advanced natural products chemistry research in china ......(27) is a dimeric lindenane-type...

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Chinese Journal of Natural Medicines 2018, 16(12): 08810906

Chinese Journal of Natural Medicines

Advanced natural products chemistry research in China between 2015 and 2017

YANG Guo-Xun, MA Guang-Lei, LI Hao, HUANG Ting, XIONG Juan, HU Jin-Feng*

Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China

Available online 20 Dec., 2018

[ABSTRACT] In this review, we intensively focus on the advances in research of natural products (NPs) discovery carried out by domestic scholars in China from 2015 through 2017. In general, a total of 1811 publications (1479 in English and 332 in Chinese) were accumulated regarding newly isolated NPs from plants, microorganisms, and marine sources. As a result, 277 selected papers concern-ing naturally occurring compounds with extraordinary frameworks, origins, and promising activities were discussed in this review article, mainly organized according to their structural classes and novelties.

[KEY WORDS] Natural Products Chemistry; Novel Structures; Research Progress; Review

[CLC Number] R284.3 [Document code] A [Article ID] 2095-6975(2018)12-0881-26

Introduction

Natural products (NPs) have been regarded to be greatly beneficial to human health and as important resources for drug discovery. One of the prominent events in 2015 was that the Noble Prize in Physiology or Medicine was awarded to an eminent Chinese scholar, Professor TU You-You , for the discovery of artemisinin (Qing-Hao-Su) as an effective chemo-therapy against falciparum malaria. NPs research and devel-opment went to the limelight of the world once again. In fact, Mother Nature is still the best chemist, and is still a non-exhausted source for new pharmacophores. New separa-tion and analytical systems have reduced research cost and shortened timeline nowadays, especially for those novel NPs with mass-limited materials. Unprecedented NPs will remain to be the important source of new chemical entities (NCE) and novel drug candidates.

Undoubtedly, China has become the strong force in NPs research in recent years. As far as publications are concerned, peer-reviewed articles from China are often ranked the first in most international journals in this field, such as Journal of Natural Products, Organic Letters, Phytochemistry, Tetrahe dron and Planta Medica. For example, Chinese scholars (i.e.,

[Received on] 27-May-2018 [Research funding] This work was partly supported by NSFC grants (Nos. 81773599 and 21472021). [*Corresponding author] Tel/Fax: 86-021-51980172; E-mail: jfhu@ fudan.edu.cn The authors have no conflict of interest to declare. Published by Elsevier B.V. All rights reserved

both the corresponding author’s and the first author’s affilia-tions belong to China) published 112, 103, and 103 papers in Journal of Natural Products in 2015, 2016 and 2017, respe-ctively, accounting for about 1/4 of the journal publications.

This review sums up the remarkable new findings from characteristic NPs chemistry investigations made by domestic scholars in China over a three-year period, i.e., 2015 through 2017. In order to accomplish this task, the main databases such as SciFinder Scholar, PubMed, Web of Science, China Knowledge Resource Integrated Database, Wanfang Data and VIP China Science and Technology Journal Database have been thoroughly investigated. For example, we took the fol-lowing strategies in searching SciFinder Scholar: at the ad-vanced search interface, we put “new compounds from (natu-ral sources)”, “chemical constituents from (natural sources)” or “isolation and structure elucidation” as research topic re-spectively, the [publication years] were set as 2015-2017, and the [company] was designated as China. The search term “new compounds” could be replaced by “novel compounds”, “unusual compounds”, “undescribed compounds”, “rare compounds”, or “novel structures” for further search. Mean-while, we also searched SciFinder Scholar by journal names, including Journal of Natural Products, Organic Letters, Journal of Organic Chemistry, Journal of the American Chemical Society, Angewandte Chemie-International Edition, Phytochemistry, Phytochemistry letters, Tetrahedron, Tetra-hedron letters, RSC Advances, Planta Medica, etc. To avoid omitting important papers, some specific words such as “al-kaloids”, “terpenoids”, “flavonoids” were also tried in the

YANG Guo-Xun, et al. / Chin J Nat Med, 2018, 16(12): 881906

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searches. The retrieved references have been analyzed one by one. Both the unrelated search results and duplicates were removed. Thus, 1479 papers in English and 332 papers in Chinese were collected. In particular, newly discovered com-pounds containing unusual complex structures and/or exhib-iting promising bioactivities were hand-picked. As a result, 320 selected compounds from 277 papers, organized on the basis of their chemical structure classes and novelties, were illustrated in this review article.

Newly Discovered Natural Products: Phytochem-istry, Pharmacology, and Biological Activities

Terpenoids

Monoterpenoids A new iridoid glucoside, 5-[3-(1-hydroxyethyl) pyridine],

7-loganin ester (1), has been identified from the aerial parts of Pterocephalus hookeri [1]. An unusual secoiridoid trimer, named sweriyunnanlactone A (2), was isolated from Swertia yunnanensis under the guidance of LC–MS analysis. Com-pound 2 was the first example of secoiridoid trimer featuring a C28 skeleton, showing weak inhibition on HBV DNA repli-cation with an IC50 of 60.76 μmol·L−1 (Selective index = 12.6) on HepG 2.2.15 cell line in vitro [2]. Sesquiterpenoids

8-Hydroxy-T-muurolol (3) has been isolated from the aerial parts of Chimonanthus salicifolius. It shows signifi-cantly immunosuppressive activity in a dose-dependent man-ner [3]. Kadcoccinin A (4), a cage-like sesquiterpenoid pos-sessing a tricyclo[4.4.0.03, 10]decane scaffold from the stems of Kadsura coccinea, exhibits weak antifungal effects against Fusarium oxysporum, Gaeumannomyces graminis, and Vertici-llium cinnabarium [4]. Norxanthantolide F (5) has been isolated from the fruits of Xanthium sibiricum. It exhibits antiinflam-matory activity by suppressing the lipopolysaccharide (LPS)- induced nitric oxide (NO) production in BV2 microglial cells, with an IC50 of 3.0 μmol·L−1 [5]. A phytochemical investigation on the whole plant of Salvia substolonifera has yielded seven germacrane sesquiterpenoids. Among them, substolide G (6) significantly inhibits the VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro (IC50 16.1 μmol·L−1) [6]. Cernuumolide H (7), a highly oxygenated germacranolide isolated from Carpesium cernuum, exhibits moderate cytotoxic effects against four tumor cell lines with IC50 ranging from 0.87 to 2.02 μmol·L−1 [7]. Two rare rear-ranged cuparane-type sesquiterpenoids, beshanzuenones A (8) and B, have been isolated from the shed trunk barks of Abies beshanzuensis, a critically endangered plant native to China. They show considerable activity against influenza virus A (H3N2) [8]. A few novel bisabolene-derived sesquiterpenoids have been isolated from the roots of Artabotrys hexapetalus. Among them, artaboterpenoid A (9) featured a novel carbon skeleton with a new C (2)−C (10) linkage; artaboterpenoid B was obtained as a pair of enantiomers. Moreover, (−)-8R-arta-

boterpenoid B (10) exhibited cytotoxic effects against HCT- 116, HepG2, A2780, NCI-H1650, and BGC-823 cell lines with IC50 ranging from 1.38 to 8.19 μmol·L−1 [9]. Nine new humu-lane-derived sesquiterpenoids have been isolated from the Antarctic fungus Aspergillus ochraceopetaliformis SCSIO 05702. Among them, ochracenes A (11) and B (12) featured novel carbon skeletons with corresponding methyl migration and ring cleavage. Moreover, Compound 12 exhibits inhibi-tory effect on LPS-induced NO release in RAW 264.7 cells with an IC50 of 14.6 ± 0.5 μmol·L−1 [10]. Wilfolide A (13), a rare humulanolide with an unusual bicyclo [6.3.0] undecane core and an adjoining butyrolactone moiety, has been isolated from the roots of Cynanchum wilfordii. It exhibits weak acetyl-cholinesterase (AChE) inhibitory activity [11]. Dysifragilone A (14), with a rearranged avarone skeleton, has been isolated from the South China Sea sponge Dysidea fragilis. This compound shows potent inhibitory activity against the pro-duction of NO stimulated by LPS in mouse RAW264.7 cells, with an IC50 of 6.61 μmol·L−1 [12]. Chermesin A (15), a dri-mane-type sesquiterpene, has been isolated and identified from the culture extract of Penicillium chermesinum EN-480, an endophytic fungus obtained from the inner tissue of the marine red alga Pterocladiella tenuis. It exhibits antibacterial activity against the opportunistic pathogen Micrococcus luteus, with an MIC value of 8 μg·mL−1 [13]. Another drimane-type sesquiter-penoid named polymorphine B (16) has been obtained from the ethyl acetate (EtOAc) extract of fermentation broth of fungus Xylaria polymorpha. It exhibits anti-acetylcholine-sterase and α-glucosidase inhibitory activites [14]. Daphnau-ranin A (17), a sesquiterpene with an unprecedented 5/7 oxacy-cloheptane ring system, has been isolated from the roots of Daphne aurantiaca. It shows anti-insect activity against male fruit fly with anti-feeding rate up to 46.2% ± 7.1% at 1 mmol·L−1 [15]. A rare carotane-type sesquiterpene, forkienin A (18), has been isolated from the twigs and leaves of Fokienia hodginsii [16]. Plebein A (19), a sesquiterpene with a novel skeleton has been isolated from the whole plant of Salvia plebeia [17]. Illisimonin A (20), an unprecedented sesquiterpene with a tricyclo [5.2.1.01, 6] decane skeleton, has been isolated from the fruits of Illicium simonsii. It shows neuroprotective effect against oxygen-glucose deprivation (OGD)-induced cell injury in SHSY5Y cells with an EC50 of 27.72 μmol·L−1 [18]. Aromati-cane A (21), an unprecedented guaiane-type sesquiterpene with unique cyclopropane and furan functionalities, has been isolated from the radix of Curcuma aromatica. It exhibits notable antioxidant effect on oxidative injury induced by H2O2

[19]. Nicotabin A (22), a sesquiterpene derivative pos-sessing a fused 5/6/5/5/5 ring system, has been isolated from leaves of Nicotiana tabacum. It inhibits NO production in LPS-activated RAW264.7 macrophages with an IC50 of 22.1 μmol·L−1 [20]. Commiphorane C (23), isolated from Res-ina Commiphora, possesses a 5/6/7 backbone. Biological evaluation reveals that compound 23 can significantly attenu-ate overproduction of fibronectin, collagen I, and α-SMA in TGF-β1-induced rat renal proximal tubular cells [21].


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Dimeric sesquiterpenoids

Three cadinane dimers with multiple contiguous quarter-nary carbons have been isolated from the rhizomes of Stahli-anthus involucratus. Among them, involucratustone A (24) is a rearranged homodimer of cadinane sesquiterpene fused with a unique fully substituted 1-oxaspiro[4.4]nonane core, which is obtained for the first time in nature. It exhibits potent cyto-toxic activity. Meanwhile, involucratustone C (25), a novel 3′, 4′-seco-cadinane-dimer, possesses notable anti-inflammatory effect [22]. Chlorajaponilide F (26), isolated from the whole plant of Chloranthus japonicus (Chloranthaceae), is effective against wild type HIV-1 replication with an EC50 of 3.08 μmol·L−1. It has also been found to show inhibitory ef-fects on two NNRTI-resistant HIV strains [23]. Fortunilide A (27) is a dimeric lindenane-type sesquiterpene isolated from Chloranthus fortunei. It is noticeable that 27 exhibits low nanomolar activity against chloroquine-resistant Plasmodium falciparum with the IC50 of 5.2 ± 0.6 nmol·L−1, which is comparable to the potency of artemisinin (IC50 4.0 ± 4.2 nmol·L−1) [24]. Fortunoid B (28), representing the first example of the heterodimer of a lindenane and a eudesmane sesquiterpene, has been also isolated from C. fortunei. It shows moderate antimalarial activity [25]. Eleven new ses-quiterpene dimers have been isolated from the seeds of Sar-candra glabra. Among them, sarglabolide A (29) has been verified to exclusively possess a seventeen-membered mac-rocyclic ester ring formed by the scaffold of the sesquiterpene dimer and small organic acids. It can significantly inhibit NO production in LPS-induced macrophages, with an IC50 of 3.04 μmol·L−1 [26]. Guaianodilactone B (30), a guaianoid dimer from Carpesium faberi, exhibits potent cytotoxicity against human leukemia (CCRF-CEM) cells with an IC50 of 2.03 μmol·L−1. This compound may be served as a promising lead for a new class of antileukemic agent [27]. Another guaianoid dimer, namely selengsisnin A (31), has been isolated and identified from Artemisia selengensis [28].

Dicarabrone A (32), possessing a new skeleton featuring a cyclopentane ring connecting two sesquiterpene lactone units, has been isolated from the whole plant of Carpesium abrotanoides. It shows moderate effect on HL-60 cells, with an IC50 of 9.1 μmol·L−1 [29]. A phytochemical investigation of the whole plant of Ligularia pleurocaulis has led to the isolation of an eremophilenolide dimer named biligupleurolide (33), which shows moderate growth inhibitory activities against MCF-7, HepG2, and A549 [30]. Sterhirsutin C (34), a new heterodimeric sesquiterpene from the culture of Stereum hir-sutum, shows cytotoxicities against K562 and HCT116 cell lines [31]. Xylopiana A (35), a dimeric guaiane, has been isolated from the leaves of Xylopia vielana [32]. Artemisian B (36), the first example of [4 + 2] Diels−Alder type adducts presumably biosynthesized from a rare 1,10 : 4, 5-di-seco- guaianolide and a guaianolide diene, has been isolated from the traditional Chinese medicine Artemisia argyi. It exhibits significant anti-proliferative activity via apoptosis induction and G2/M arrest in MDA-MB-468 cells, with an IC50 of 3.21 μmol·L−1 [33].

Diterpenoids

Lagoditerpene A (37) has been isolated from a Labiatae plant, Lagochilus platyacanthus. It shows moderate hemo-static activity by shortening the values of activated partial thromboplastin time [34]. An architecturally complex spiroketal diterpenoid, leonuketal (38), has been isolated from the aerial parts of the plant Leonurus japonicas. It shows significant vaso-relaxant activity against KCl-induced contraction of rat aorta, with the EC50 of 2.32 μmol·L−1 [35]. Two labdane-type diterpe-noids, haplomintrins A (39) and B with six rings system, have been isolated from a Chinese liverwort Haplomitrium mni-oides [36]. Chlorabietin C (40) has been isolated from the roots of Chloranthus oldhamii, a rare Chloranthaceae plant, endemic to China. It shows anti-neuroinflammatory effect by inhibit-ing NO production in LPS- activated murine BV-2 microglial cells (IC50 16.4 μmol·L−1) [37]. Nepetaefolin F (41) has been isolated from the whole plant of Caryopteris nepetaefolia. It shows higher cytotoxicity than paclitaxel in one nonsmall-cell lung cancer, patient-derived xenograft (PDX) model when tested using PDX models and the adenosine triphos-phate-tumor chemosensitivity assay (ATP- TCA) with an IC50 of 6.3 μmol·L−1 [38]. The phytochemical study of Pedilanthus tithymaloides has led to the isolation of eight new and five known jatrophane diterpenoids. Subsequent structural modifi-cation has yielded 22 new derivatives. Compound 42, one of the derivatives, exhibits a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo [39].

A phytochemical investigation of the hydrophobic extract of Rabdosia serra (Lamiaceae family) has led to the isolation of two types of ent-6, 7-secokaurane diterpenoids, ent-6, 20-epoxy-6, 7-secokaur-1, 7-olide and ent-6, 7-secokaur-7, 20- olide illu-strated by rabdosins E (43) and K (44), respectively [40]. Pieris-ketolide A (45), an unusual A-homo-B-nor-ent- kaurane car-bon skeleton, has been isolated from the roots of Pieris for-mosa. It exhibits an analgesic effect with a 45% writhe inhibi-tion rate at a dose of 10.0 mg·kg−1 [41]. Scopariusol A (46), the first ent- kaurane diterpenoid featuring a 1, 11-ether bridge, together with a dimeric ent-kaurane scopariusol I (47), has been isolated from the aerial parts of Isodon scoparius [42]. An unprecedented 7, 8 : 15, 16-di-seco-15-nor-21-homo-ent- kauranoid, named laxiflorol A (48), has been isolated from the leaves of Isodon eriocalyx var. laxiflora [43]. Stelleralide F (49), obtained from the roots of Stellera chamaejasme, exhib-its extremely potent anti-HIV activity in an in vitro assay against NL4-3 virus replication in MT4 lymphocytes, with an EC50 of 0.93 nmol·L−1 [44]. Chinensipene B (50) from Trigono-stemon chinensis has been demonstrated to have inhibitory effect on LPS-induced NO production, with the IC50 of 10.2 μmol·L−1 [45]. Rhodomollacetal A (51), possessing a 2, 3 : 5, 6-di-seco-grayanane carbon skeleton, has been isolated from the leaves of Rhododendron molle [46]. Rhodomollanol A (52), a highly oxygenated diterpene, has been also isolated from the same plant. It exhibits moderate PTP1B inhibitory activity [47]. Cinnamomols A (53) and B, featuring a cage-like, rigid, and hexacyclic ring system, have been isolated from the


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leaves of Cinnamomum cassia. It exhibits significant immu-nostimulative activity [48]. Eleganstone A (54) has been iso-lated from the marine sponge Dactylospongia elegans and exhibits weak antibacterial activities against E. coli, Bacillus subtilis, and Staphylococcus aureus [49]. Euphordraculoates A (55) and B (56), featuring tigliane diterpenoids with two new carbon skeletons, have been characterized as secondary me-tabolites from Euphorbia dracunculoides. Compound 56 can inhibit Wnt pathway in a dose- and time-dependent manner [50]. Crotusin C (57), a new tigliane-type diterpenoid isolated from

the methanolic extract of the twigs and leaves of Croton caudatus, shows significant inhibitory activities against five human tumor cell lines with IC50 ranging from 0.49 to 4.19 μmol·L−1 [51]. Perovskatone B (58), an icetexane-type diterpenoid from Perovskia atriplicifolia, possesses noticeable anti-hepatitis B virus activity in vitro [52]. Eight new cafestol-type diterpenoids have been isolated from the twigs of Tricalysia fruticosa. Among them, tricalysin H (59) can significantly inhibit the NO production in LPS-activated RAW264.7 macrophages, with an IC50 of 6.6 μmol·L−1 [53]. Euphomilone A (60), a highly


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modified ent-rosane-type diterpenoid from the aerial parts of Euphorbia milii, displays inhibition on the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast for-mation (IC50 12.6 μmol·L−1) [54]. Brassicicene M (61), isolated from the fungus Alternaria brassicicola, features a unique tri-cyclo[9.2.1.03, 7]tetradecane core skeleton [55]. Xishacorene A (62) has been isolated from the Xisha soft coral Sinularia polydactyla. It exhibits an interesting dose-dependent promotion effect on the ConA- induced T lymphocyte proliferation [56].

Cassane skeletons are rare in nature, but often possess valuable medicinal properties. Neocaesalminin A (63), a fura-noditerpenoid with an unusual A-seco-rearranged cassane ske-leton, has been isolated from the seeds of Caesalpinia minax [57]. Caesalsappanin H (64), isolated from the seeds of Caesalpinia sappan, displays antimalarial activity against the chloroquine- resistant K1 strain of Plasmodium falciparum, with an IC50 value of 0.52 μmol·L−1 [58]. Boscartin A (65) has been isolated from the gum resin of Boswellia carterii. Its antiulcerative colitis activity has been evaluated in an in vitro x-box-binding protein 1 (XBP 1) transcriptional activity assay. Compound 65 significantly activates XBP 1 transcription, with an EC50 of 0.34 μmol·L−1 [59]. Scutolide D (66), a new neo-clerodane-type diterpenoid isolated from the whole plant of Scutellaria bar-bata, exhibits moderate inhibition against Epstein−Barr virus (EBV) lytic replication, with an EC50 of 3.2 μmol·L−1 [60]. A phytochemical investigation of the 70% acetone extract of Croton crassifolius roots has afforded eight new diterpenoids. Among them, crassin A (67) is a ring B-rearranged diterpenoid, whereas crassin C (68) is a ring A-rearranged diterpenoid [61]. Aphapolin A (69), a nemoralisin-type diterpenoid, has been iso-lated from Aphanamixis polystachya (Wall.) R. Parker [62]. Penioxalicin (70), the first 3-nor-2, 3-seco-labdane type diterpene, has been isolated from the fungus Penicillium ox-alicum TW01-1. It shows moderate cytotoxicity against HL-60 cell line [63]. Vitepyrroloid A (71), a new labdane diterpenoid containing a 2-cyano-substituted pyrrole-ring, has been iso-lated from the leaves of Vitex trifolia. It shows cytotoxic ac-tivity against a human nasopharyngeal carcinoma cell line (CNE1), with an IC50 of 8.7 μmol·L−1 [64]. Chloranhenryin D (72), a rare naturally occurring C-14 norabietane, has been isolated from the whole plant of Chloranthus henryi [65]. Citrinovirin (73), a novel norditerpene with an unprecedented carbon skeleton, has been isolated from the culture of a marine brown alga-endophytic strain (cf-27) of Trichoderma citrinoviride. It inhibits the growth of Staphylococcus aureus, with an MIC value of 12.4 μg·mL−1 [66]. Four polycyclic norditerpenoids have been isolated from Cephalotaxus sinensis. Among them, cephalotanins A (74) and C (75) possess two different unprece-dented carbon skeletons. Moreover, compound 74 exhibits considerable nuclear factor-kappaB (NF-κB) inhibition with an IC50 of 4.12 μmol·L−1 [67]. Cephanolide A (76) has been isolated and characterized from Cephalotaxus sinensis as the first example of A-ring-contracted cephalotane-type dinord-iterpenoid [68]. 2β-Hydroxynagilactone L (77), a dinorditerpe-

noid isolated from the seeds of Podocarpus nagi, shows cy-totoxicities against A2780 and HEY cell lines with IC50 of less than 2.5 μmol·L−1 [69]. Several new diterpenoids have been isolated from the whole plant of Ligularia fischeri. Fischericin A (78) is a new 15, 16-dinorerythroxylane-type diterpenoid possessing a C18 skeleton; while fischericin B (79) is the first example of a 6/6/6/6/5/5-fused hexacyclic ent-kaurane diterpenoid [70].

Mannolide A (80), a new kind of diterpenoid featuring a new intact carbon skeleton, has been isolated from Cephalo-taxus mannii [71]. Euryachin A (81), a new type of tetracyclic diterpenoid, has been obtained from the branches of Eurya chinensis. It exhibits anti-inflammatory activity with the potency comparable to the positive control L-N-Methylarginine, when evaluating against NO production in LPS-stimulated RAW264.7 cells [72]. Three highly modified diterpenoids, pepluacetal (82), pepluanols A (83) and B (84), have been isolated and identi-fied from Euphorbia peplus. They all inhibit Kv1.3, a vali-dated target for the treatment of autoimmune diseases. Among them, compound 84 is most effective, with an IC50 of 9.50 μmol·L−1 [73]. Sarcophytrol A (85), isolated from the South China Sea soft coral Sarcophyton trocheliophorum, bears a dodecahydrocyclopenta[6, 7]cycloundeca[1, 2-b]oxirene ring system with an unusual 1Z-configuration [74]. Euphorikanin A (86) has been isolated from the roots of Euphorbia kansui and exhibits moderate cytotoxicities against two human tumor cell lines HeLa and NCI-446 [75]. Rhodomollein XXVIII (87), a new grayanoid isolated from the roots of Rhododendron molle, has been demonstrated to have significant antino-ciceptive activity in an acetic acid-induced writhing test. Furthermore, its analogues, rhodojaponins III and VI, are more potent than morphine in both acute and inflammatory pain models [76]. Six new highly oxygenated polycyclic cy-athane-xylosides have been obtained from the cultures of the basidiomycete Cyathus striatus. Of these, striatoid F (88) can dose-dependently enhance nerve growth factor (NGF)- mediated neurite outgrowth in rat pheochromocytoma (PC-12) cells [77]. Perforalactone A (89), a new 20S quassinoid with a unique cage-like 2, 4-dioxaadamantane ring system and a migrated side chain, has been isolated from the plant Harrisonia perforata. It exhibits notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster [78]. Vulgarisin B (90) has been isolated from a medicinal plant Prunella vulgaris Linn. It has been demonstrated to have modest cytotoxicity against A549 cells [79]. Commiphorane A (91), a dinorditerpenoid characteristic of a 6/6/6/6 ring system, has been isolated from Resina Commiphora [21]. A dimeric abietane diterpenoid, biteuvisone A (92), has been isolated from the whole plant of Teucrium viscidum [80]. In fact, only about 20 dimeric abietane diterpenoids have been so far reported since 2000. Aphadi-lactone E (93) has been isolated from Aphanamixis grandifolia. It shows moderate antimalarial activity, with an IC50 of


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1.03 μmol·L−1 [81]. Taxodikaloid A (94) has been isolated from the seeds of Taxodium ascendens. It features an unprece-dented oxazoline ring linkage connecting two abietane diter-penoid monomers, which shows potential neuroprotective activity against Aβ25−35-induced damage in SH-SY5Y cells [82]. Eupractenoids A (95) and B (96), two heterodimeric diterpe-noids comprising abietane lactone and nor-rosane constituent units, have been isolated from the roots of Euphorbia ebrac-teolata. Compound 95 exhibits a moderate inhibitory effect on

α-glucosidase (IC50 7.94 μmol·L−1), with a Ki of 10.8 μmol·L−1. Whereas, compound 96 inhibits the acetyl transfer activity of Mycobacterium tuberculosis GlmU (IC50 41.85 μmol·L−1), a novel tuberculosis treatment target [83]. Neoglaucocalyxin (97), a rare dimer of ent-kauranoid with a cyclobutane ring, has been obtained from the aerial parts of Rabdosia japonica [84]. Birhodomollein A (98) has been isolated from the flowers of Rhododendron molle. It contains a rare chloro- substitution on one of the grayanane moieties [85].


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Sesterterpenoids

Erinacine S (99) has been isolated from the ethanol ex-tract of the mycelia of Hericium erinaceus. In a 30-day oral course, compound 99 could attenuate Aβ plaque burden in the brains of 5-month-old female APP/PS1 transgenic mice [86]. Aspterpenacid A (100), with an unusual 5/3/7/6/5 ring system, has been isolated from the mangrove endophytic fungus Aspergillus terreus H010 [87]. Interestingly, aspterpenacid C (101), an analogue of compound 100, has been discovered from the traditional Chinese medicinal plant Swertia bimacu-lata. Compound 101 exhibits moderate inhibitory activities on NO production (IC50 16.1 μmol·L−1) and HIV-1 replication (EC50 1.35 μmol·L−1) [88]. Sesteralterin (102) has been ob-tained from the culture extract of an Alternaria alternata strain (k21-1) isolated from the surface of the marine red alga Lomentaria hakodatensis. It represents the first nitidasane sesterterpene naturally produced by fungi [89]. (−)- Hippolide J (103) and its enantiomer, have been isolated from the ma-rine sponge Hippospongia lachne collected from the South China Sea. Both of them have been found to show potent antifungal activities against three strains of hospital-ac-quired pathogenic fungi (i.e., Candida albicans SC5314, Candida glabrata 537, and Trichophyton rubrum Cmccftla) with MIC50 of 0.125– 0.25 μg·mL−1 [90]. Triterpenoids

A phytochemical investigation of the methanolic extract of the fruiting bodies of Fomes officinalis has afforded a number of 24-methyl-lanostane triterpenoids. Among them, officimalonic acid A (104) represents a previously unknown triterpene type with a 24-methyl-7(89)abeo-lanostane skel-eton; officimalonic acid D (105) shows a potent inhibitory effect (IC50 6.8 μmol·L−1) on NO production in LPS-induced RAW264.7 cells [91]. Tsugalide A (106), a new rearranged lanostane triterpenoid, has been isolated from the MeOH ex-tract of the stem of Tsuga longibracteata [92]. Six lanostane- related triterpenoids have been isolated from Kadsura coccinea. Among them, kadcoccinone A (107) has an infrequent 14 (13→12)-abeo-6/6/5/6-fused rearranged lanostane-type skeleton; kadcoccinone C (108) possesses a novel 6/6/9-fused carbo-cyclic core containing a rare oxabicyclo [4.3.1] decane system; kadcoccinones D (109) and E represent the first two examples of the 18 (13→12)-abeo-26-norlanostane triterpenoids [93]. Eu-viscin A (110) has been isolated from the whole plant of Teucrium viscidum. It possesses a rare 7 (8→9)-abeo-9R-D: C-friedo-B′: A′-neo-gammacerane skeleton [94]. Ganoboninone A (111), a new 3, 4-seco-27-norlanostane triterpenoid, has been isolated from the fruiting bodies of the medicinal mush-room Ganoderma boninense. It shows antimalarial effect with an IC50 of 27.36 μmol·L−1 [95]. Balanterpene A (112), featuring a ring-expanded triterpenoid skeleton with the C-19 methyl involved in the ring formation, has been isolated from the leaves of Casearia balansae [96]. Cimiheraclein A (113) has been isolated from the aerial parts of Cimicifuga heracleifolia and exhibits weak inhibitory activity against the STAT 3 sig-naling pathway [97]. Four iridals with an unprecedented

α-terpineol moiety have been isolated from the ethanol extract of rhizomes of Iris tectorum. Among them, polycycloiridal A (114) exhibits pronounced hepatoprotective activity at a con-centration of 10 μmol·L−1 [98]. Lancolide E (115), featuring a complex tetracyclo [5.4.0.02,4.03, 7] undecane-bridged system, has been obtained from a “talented” schinortriterpenoid pro-ducer Schisandra lancifolia [99]. Schincalide A (116), a schi-nortriterpenoid possessing a tricyclo [5.2.1.01, 6]decane- bridged system, has been isolated from the stems and leaves of Schisandra incarnate [100]. Spiroschincarin A (117), featuring a unique 1-oxaspiro[6.6]tridecane motif, has been isolated from the fruits of Schisandra incarnata [101].

Alismanin A (118), an aromatic triterpenoid with a C34 skeleton, has been isolated from Alisma orientale. It displays significant activation effect on pregnane X receptor (PXR) at 10 nmol·L−1 [102]. Picraquassin A (119), obtained from the stems of Picrasma quassioides, has an unprecedented 21, 24-cycloapotirucallane skeleton [103]. Spirochensilide A (120), isolated from Abies chensiensis, is regarded as the first rear-ranged triterpenoid skeleton featuring an unprecedented spiro-[5, 6] ring system [104]. Several highly modified triter-penoids have been isolated from Phyllanthus hainanensis. They exhibit exceptionally potent in vitro immunosuppressive activities against the proliferation of T and B lymphocytes. Among them, phainanoid F (121) has been the most potent, with the IC50 of 2.04 nmol·L−1 [positive control cyclosporin A (CsA) 14.21 nmol·L−1] and < 1.60 nmol·L−1 (CsA 352.87 nmol·L−1), respectively [105]. In addition, phainanolide A (122) exhibits remarkable cytotoxic activity against HL-60 cells with an IC50 of 0.079 μmol·L−1 [106].

Twenty new liminoids have been isolated and identified from Cipadessa cinerascens. Among the isolates, cipacinoid A (123) shows moderate protein tyrosine phosphatase 1B (PTP1B) inhibition [107]; ciparasins B (124) and P (125) exhibit significant anti-HIV activity with the EC50 of 5.5 μmol·L−1 and 6.1 μmol·L−1, respectively [108]. Fourteen new limonoids have been isolated from the whole plant of Munronia henryi. Among them, munronin A (126) exhibits cytotoxic effects on a small panel of cancer cell lines, with IC50 ranging from 0.4 to 2.3 μmol·L−1; while munronin H (127) shows significant anti-TMV activity, with an IC50 of 19.6 μg·mL−1 [109]. Walrobsin A (128) has been isolated from the root barks of Walsura robusta. It shows significant anti-inflammatory activity with an IC50 of 7.8μmol·L−1 and also inhibits the expression of iNOS and IL-1β in a dose- dependent manner [110]. Walsuronoid F (129), featuring an 18 (13/14)-abeo limonoid skeleton, has been isolated from the fruits of Walsura robusta [111]. Trichilia species of the Meli-aceae family are well-known for metabolizing structurally diverse limonoids. From the fruits of Trichilia connaroides, several novel ones have been obtained. Among them, spiro-trichilin A (130) shows weak anti-inflammatory activity on NO production in LPS-induced RAW264.7 cells [112]. In contrast, trichiconlide A (131) bears an unprecedented 5/6/5/6/5 carbon skeleton; trichiconlide B (132) possesses a cage- like structure located between rings A and C. Furthermore,


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131 shows a moderate inhibitory effect on LPS-induced NO production in the RAW264.7 cell line [113]. Triconoids A (133) and D (134), representing two rearranged limonoid skeletons, have been isolated from the leaves and twigs Trichilia con-naroides collected from the capital area of Nepal [114]. Chukve-lutilide Y (135), a new C-15 enolic acyl phragmalin- type limonoid orthoester, has been isolated from the ethanol ex-tract of seeds of Chukrasia tabularis [115]. Xylomexicanin I (136), a tetranortriterpenoid with bridged B- and C-rings, has

been isolated from seeds of the Chinese mangrove, Xylocarpus granatum [116]. Three new ring B-seco limonoids, ciliatonoids A−C, have been isolated from Toona ciliata. Both ciliatonoids A (137) and B possess an unprecedented limonoid architecture, while ciliatonoid C (138) belongs to a rare class of limonoid and displayed modest cytotoxic effects against HL-60 and P-388 cell lines, with IC50 of 1.19 and 2.50 μmol·L−1, respec-tively [117]. Perforanoid A (139) has been isolated from the leaves of Harrisonia perforata (Blanco) Preliminary studies


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show that Compound 139 has been cytotoxic towards HEL, K562, and CB3 tumor cell lines, with IC50 of 6.17, 4.24 and 3.91 μmol·L−1, respectively [118].

Krishnadimer A (140), a C2-symmetric limonoid dimer representing a new class of axially chiral nonbiaryl natural products, has been isolated from the seeds of a mangrove, Xylocarpus moluccensis [119]. Meroterpenoids

(+)-Rhodonoid C (141) and (−)-rhodonoid C, an enantio-meric pair of meroterpenoids isolated from the aerial parts of

Rhododendron capitatum, are the first examples of meromo-noterpenes incorporating an unprecedented 6/6/6/5 ring sys-tem. Compound 141 shows antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro [120]. (±)-rasumatranin A (142), a pair of bibenzyl-based meroterpenoid enantiomers have been isolated from the adnascent Chinese liverwort, Radula sumatrana [121]. Seven monoterpene−shikimate−con-jugated meroterpenoids with a spiro ring system have been isolated from Guignardia mangiferae. Among them, manginoid A (143) represents the first example of spiro meroterpenoid


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bearing a bridged spirocyclohexanedione moiety. Manginoid E (144) possesses an unexpected 2, 4-dioxatricyclo[3.3.1.03, 7] nonane motif. Compound 143 exhibits inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 with an IC50 of 0.84 μmol·L−1 [122]. The endophytic fungus Guignardia mangiferae isolated from Ilex cornuta leaves has been shown to produce a family of meroterpenes with toll-like receptor 3 regulating activity. Among the isolates, compound 145 could selectively upregulate the toll-like receptor 3 expression in mouse dendritic cells at 10.0 μmol·L−1 [123]. Frutescone A (146), a tasmanone-based meroterpenoid from the aerial parts of Baeckea frutescens L., exhibits moderate cytotoxicities [124]. Chrysogenolide A (147) has been isolated from the solid sub-strate fermentation cultures of a Huperzia serrata endophytic fungus, Penicillium chrysogenum MT-12 [125].

Two enantiomeric pairs of meroterpenoids have been isolated from Rhododendron capitatum. Among them, (−)- rhodonoid B (148) and its enantiomer both have been found to show PTP1B inhibitory activities [126]. Five pairs of dimeric meroterpenoid enantiomers have been characterized from Ganoderma cochlear. Among the isolates, (+)-cochlearoid A (149) significantly inhibits Cav3.1 T-type calcium channel (TTCC) with noticeable selectivity [127]. Ganoleucin A (150) has been isolated from the fruiting bodies of Ganoderma leu-cocontextum. It presents potent noncompetitive inhibitory activ-ity against a-glucosidase from both yeast and rat small intesti-nal mucosa [128]. A new curcuminoid, curcuterpene G (151), has been isolated from the low polar fraction of methanol extracts from the rhizome of Curcuma longa. Compound 151 exhibits the inhibitory effect to HepG2, A549, and CT-26 tumor cells with the IC50 of 4.82, 8.81, and 5.40 μmol·L−1, respectively [129]. Spiroaspertrione A (152), a novel terpene- polyketide hybrid spiromeroterpenoid, has been isolated from cultures of Aspergillus sp. TJ23. It has been demonstrated to have potent resensitization of oxacillin against methicil-lin-resistant Staphylococcus aureus by lowering the oxacillin MIC up to 32-fold from 32 to 1 μg·mL−1 [130]. Two novel meroterpenoids including yaminterritrem B (153), have been discovered from Aspergillus terreus. Compound 153 exhibits a dose-dependent inhibitory effect on COX-2 expression in LPS-stimulated RAW264.7 macrophages [131]. Dysiherbol A (154), a new tetracyclic meroterpene isolated from a Dysidea sp. marine sponge collected from the South China Sea, pos-sesses an intriguing 6/6/5/6-fused tetracyclic carbon skeleton. The NF-κB inhibitory and cytotoxic activity evaluation dis-closed that compound 154 shows potent activity with IC50 of 0.49 and 0.58 μmol·L−1, respectively [132]. Sarglaperoxide A (155), an unusual sesquiterpene−normonoterpene conjugates with a peroxide bridge, has been isolated from the seeds of Sarcandra glabra. It exhibits 64.5% inhibitory effect against Staphylococcus aureus at 25 μg·mL−1 and displayed 53.6% in-hibitory effects on NO production in LPS-induced RAW264.7 at 25 μmol·L−1. The results match the traditional applications of S. Glabra [133]. Two novel immunosuppressive unsymmet-rical cyclobutane derivatives, including scopariusicide A

(156), have been isolated from the aerial parts of Isodon sco-parius [134]. Chartarolide A (157), a phenylspirodrimane-based meroterpenoid, has been isolated from a sponge (Niphates recon-dite) associated fungus Stachybotrys chartarum WGC-25C-6. It exhibits significant cytotoxic activities against a small panel of human tumor cell lines, showing strong inhibitory activi-ties against the human tumor related protein kinases of FGFR3, IGF1R, PDGFRb, and TrKB [135]. Phloroglucinol-terpene adducts

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs) have been isolated from the whole plant Hypericum uralum. Among them, uralione A (158) has been found to ex-hibit significant protective effect against induced injury in PC12 cells [136]. Hyperuralone D (159), a 1, 9-seco-bicyclic PPAP isolated from the aerial parts of Hypericum uralum, exhibits moderate inhibition against AChE with an IC50 of 7.1 μmol·L−1 [137]. Hyperattenin K (160), isolated from Hy-pericum attenuatum Choisy and identified as a new ada-mantyl-like PPAP, exhibits inhibitory effect on HIV-1 repli-cation in C8166 cells and moderate cytotoxic effects against the HL-60 and A-549 cell lines [138]. Another two adamantane type PPAPs have been isolated from Hypericum subsessile. Of them, hypersubone B (161) exhibits significant cytotox-icities against four human cancer lines [139]. Garcinia L. is a rich source of PPAPs. (+)-Garcimulin A (162) and its enanti-omer, isolated from Garcinia multiflora, exhibits cytotoxic activities against five human cancer cell lines [140]. Garmultin A (163) has been obtained as a pair of enantiomers from the same plant. In an assay for its cytotoxic activities against five human tumor cell lines, the levo isomer exhibits stronger inhibitory activity than the dextro isomer [141]. Hypercohin K (164), the first PPAP possessing a unique spiro-fused cyclopropane ring, has been isolated from Hypericum co-haerens. It has been found to significantly increase the activity of AChE [142]. Callisretone A (165), a rearranged phloroglu-cinol-monoterpenoid adduct, has been isolated from Calli-stemon rigidus. It shows inhibitory effects on NO produc-tion with an IC50 of 15.3 μmol·L−1 [143]. Viminalin F (166), a

hybrid of acylphloroglucinol and -phellandrene isolated from the fruits of Callistemon viminalis, exhibits moderate cytotoxic activity [144]. Hypersampsonone A (167) has been isolated from the aerial parts of Hypericum sampsonii. It exhibits inhi-bition against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease, with an IC50 of 8.08 μmol·L−1 [145]. Garciyunnanimine A (168), a polycyclic polyprenylated acylphloroglucinol imine (PPAP imine), has been isolated from Garcinia yunnanensis [146].

Callistrilone A (169), the first triketone−phloroglucinol− monoterpene hybrid, has been isolated from the leaves of Callis-temon rigidus. It exhibits moderate antibacterial activity against Gram-positive bacteria including multiresistant strains [147]. Drychampone A (170), a sesquiterpenoid-based meroterpenoid, has been isolated from Dryopteris championii. It possesses a novel carbon skeleton constructed by an 11/6/6 ring system coupled with a pyronone moiety [148]. Guapsidial A (171),


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a sesquiterpene- based psidium meroterpenoid, has been iso-lated from the leaves of Psidium guajava [149]. Hyperjapone A (172) has been obtained as a racemic mixture from Hy-pericum japonicum. It exhibits moderate cytotoxic activities against HeLa and HepG2 cell lines [150]. A couple of meroter-penoids have been isolated from the leaves of Rhodomyrtus tomentosa. Among them, tomentodiones A (173) and B are a pair of C-11' epimers of caryophyllene-conjugated phloroglu-cinols. [151]; rhodomyrtial A (174) is an unprecedented trike-

tone-sesquiterpene- triketone adduct [152]; tomentodione E (175) represents the first example of β-calacorene-based meroterpenoid [153].

Nine new conjugates of sesquiterpenoids and acylphloro-glucinols have been isolated from the leaves of Eucalyptus robusta. Among them, eucarobustol A (176) represents the first example of conjugate of aristolane and acylphloroglucinol unit. In turn, eucarobustol C (177) features a new coupling model of guaiane and acylphloroglucinol via the C-4−C-7′


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bond. Furthermore, compound 176 shows inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 of 1.3 μmol·L−1 [154]. Rhodomentones A (178) and B (179) bearing an unprecedented caryophyllene-conjugated oxa-spiro[5.8] tetradecadiene skeleton, have been isolated from the leaves of Rhodomyrtus tomentosa [155]. A few meroterpenoids with new skeletons have been isolated from the leaves of Myrtus communis. Among them, compound 180 features a new carbon skeleton with an unprecedented octahydrospiro[bicyclo[7.2.0] undecane-2,

2′-chromene] tetracyclic ring system. A variable temperature NMR spectroscopy experiment suggested it existed as a mixture of two conformers (180a and 180b) in solution [156].

Guajavadimer A (181), a dimeric sesquiterpene-based meroterpenoid, has been isolated from the leaves of Psidium guajava L. It shows moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells [157]. Dimericbiscognienyne A (182), an unusual diisoprenyl- cyclohexene-type meroterpenoid dimer, has been isolated


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from Biscogniauxia sp. [158]. Three pairs of dimeric meroter-penoid enantiomers have been isolated from the fruiting bodies of Ganoderma applanatum. All of them have been proved to be JAK3 inhibitors. In addition, the enantiomers of applana-tumine B (183) are active towards discoidin domain receptor 1 (DDR1) with IC50 of 8.2 μmol·L−1 and 6.9 μmol·L−1 [159], respe-ctively. Three interesting phloroglucinol-diterpene adducts have been isolated from the roots of a rare Chloranthaceae plant, Chloranthus oldhamii. Among them, chlorabietol C (184) shows inhibitory activity against PTP1B with an IC50 of 4.9 μmol·L−1 [160].

Lignans

Four new butyrolactones have been isolated from the fermentation product of the endophytic fungus Aspergillus versicolor. Among them, versicolactone A (185) displays sig-nificant antitobacco mosaic virus activity with the inhibition rate of 46.4%, even more potent than the positive control ningnanmycin (30.8%) [161]. Two pairs of racemic spirodienone neolignans have been isolated from the bark of Cinnamomum subavenium. Of all isolates, (−)-subaveniumin B (186) exhibits moderate inhibitory effect against LPS-induced NO production in RAW264.7 mouse macrophages (IC50 4.3 μmol·L−1) [162]. Gastradefurphenol (187), a minor 9, 9′-neolignan, has been isolated from an aqueous extract of the Gastrodia elata rhi-zomes [163]. The bioassay-guided separation of the dried root of Campylotropis hirtella has led to the isolation of one neura-minidase inhibitor (188) with the IC50 of 16.76 μmol·L−1 [164].

Coumarins

Anisucoumaramide (189) has been isolated from Clausena anisumolens. It shows high selectivity for the MAO-B (human monoamine oxidase) isoenzyme and inhibitory activity in the nanomolar range [165]. The racemic mixture (±)-cnidimonin A (190), isolated from the fruits of Cnidium monnieri, exhibits stronger antiviral activity against HSV-1 (IC50 1.23 μmol·L−1) than its corresponding optically pure enantiomers [166]. Two pairs of oligomeric coumarin enantiomers, including (+)-spirotris-coumarin A (191), have been isolated from Toddalia asiatica. Interestingly, the racemic mixtures exhibits 3- to 6-fold stronger antiviral activity against H3N2 than their corresponding optically pure enantiomers [167]. Andafocoumarin B (192), isolated from the roots of Angelica dahurica cv. Hangbaizhi, exhibits a potent inhibition on NO production in LPS-activated RAW264.7 macrophages, with an IC50 of 13.9 μmol·L−1 [168]. Cochlearoid F (193), isolated from the fruiting bodies of Ganoderma cochlear, exhibits potent inhibitory activity on

fibronectin overproduction in TGF-1-induced HKC-8 cells [169].

Flavonoids

From the 95% EtOH extract of the leaves of Garcinia oligantha, oliganthin I (194) has been identified as a new xanthone derivative. It exhibits inhibitory effects on four human tumor cell growth, with IC50 ranging from 3.2 to 6.2 μmol·L−1 [170].

Neobraclactone A (195) has been isolated from the leaves of Garcinia bracteata. It shows significant growth inhibition activities against the human leukaemia HL-60 and K562 cell lines with GI50 of 0.50 and 0.40 μmol·L−1, respectively [171]. Four pairs of prenylated flavan enantiomers have been isolated from the stem and root bark of Daphne giraldii. The isolates have a selective cytotoxicity towards hepatic carcinoma cell lines. Among them, (2R)-kazinol B (196) shows a more potent inhibitory effect on Hep3B cells than its racemate [172]. Sopho-pterocarpan A (197) has been isolated from the roots of Sophora flavescens Ait. It is a potential autophagy activator and exhibits cytotoxic activity in MCF-7 cells [173]. Caesalpinnone A (198), a hybrid of flavan and chalcone, has been isolated from the twigs and leaves of Caesalpinia enneaphylla. It shows the highest cytotoxicities against the HL-60, SMMC-7721, A549, MCF-7, and SW-480 human tumor cell lines with IC50 in the range of 0.54−0.87 μmol·L−1 [174]. (+)-Ascomlactone A (199) and (−)-ascomlactone A, a pair of enantiomeric polyketide dimers, have been obtained from a mangrove endophytic fungus Ascomycota sp. SK2YWS-L. Both of them exhibit

significant inhibitory effect against -glucosidase with IC50 of 63.7 and 27.μmol·L−1, respectively [175]. Nine unexpected new flavonol glycoside cyclodimers in the truxinate- or truxillate- form have been isolated as minor components from the ex-tract of Ginkgo biloba leaves. Of them, biginkgoside E (200) significantly inhibits NO production in LPS-activated BV-2 microglial cells, with an IC50 of 2.91 μmol·L−1 [176].

Steroids

Gloeophyllin A (201), featuring a rare C-nor-D-homo-steroid skeleton, has been isolated from the solid cultures of Gloeophyllum abietinum. It shows strong antiproliferative activity against K562 cells with an IC50 of 4.73 μg·mL−1 [177]. A new steroidal ketone (202), with an ergosta-22, 25-diene side chain, has been obtained from the South China Sea marine sponge Xestospongia testudinaria. It exhibits significant in-hibitory activity against PTP1B, with an IC50 of 4.27 μmol·L−1 [178]. Two new functionalized ergostane-type steroids, phomopsterones A (203) and B (204), have been isolated from the plant de-rived Phomopsis sp. TJ507A. Compound 203 is an unprece-dented ergosteroid featuring a rearranged bicyclo[3.3.1]nonane motif. Compound 204 exhibits anti-inflammatory activity [179]. Ganotheaecolin A (205) has been isolated from the fruiting bodies of Ganoderma theaecolum. It represents a 6/6/7/5-fused carbon skeletal ergosterol [180]. Chantriolide D (206), isolated from the whole plants of Tacca chantrieri, exhibits selective cytotoxicity against A2780 cells with an IC50 of 4.61 μmol·L−1 [181]. Four new C21 steroids with an open-chain sugar moiety have been isolated from the canes of Marsdenia tenacissima. Two of them including compound 207 exhibits a wide spectrum of chemoresistance reversal activity [182].

Bufospirostenin A (208) and bufogargarizin C (209), two novel steroids with rearranged A/B rings, have been isolated from the toad Bufo bufo gargarizans [183]. 2′S-Arenobufagin-3-O-


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lactate (210), isolated from the eggs of the toad Bufo bufo gar-garizans, exhibits potent cytotoxic effects against human gastric cancer cells BGC-823 and human lung cancer cells A549 with IC50 of 12.19 and 8.86 nmol·L−1, respectively [184]. Aspafilisine (211), featuring a unique rearranged seven- membered B ring formed by the C (7)–C (14) linkage, has been isolated from the roots of Asparagus filicinus [185]. Neocyclocitrinol E (212), an unusual C25 steroid, has been isolated from solid fermentation products of the fungus Chaetomium sp. M453 assosiated with

Huperzia serrata (Thunb. Ex Murray) Trev. [186]. Ganoderin A (213) has been isolated from the Ganoderma lucidum spores oil [187]. A novel withanolide, aromaphysalin A (214), possessing an exceptional C (11)–C (15) bond and an unprecedented 4, 9-cyclized aromatic ring (ring A), has been isolated from the stems and leaves of Physalis angulata L. It exhibits inhibitory activity on NO production with an IC50 of 51.64 μmol·L−1 [188]. Two novel physalins, physalin X (215) and aromaphysalin B (216), have been isolated from Physalis angulata L. They both


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exhibit inhibitory activities on NO production with IC50 of 68.50 and 29.69 μmol·L−1, respectively [189]. Withapubeside B (217), possessing a cage segment and an enolic glucoside moiety, has been isolated from the stems of Physalis pubes-cens L. [190]. Matsutakone (218), a novel sterol with an un-precedented polycyclic ring system, has been isolated from the fruiting bodies of Tricholoma matsutake. It exhibits in-hibitory activity against AChE [191].

Alkaloids

Three novel 7, 8-seco-lycopodane-derived 8, 5-lactones, namely annotinolides A (219), B (220), and C (221), have been isolated from the club moss Lycopodium annotinum. They exhibit considerable antiaggregation activities against Aβ1-42 peptide at 50 μmol·L−1 [192]. A novel C16N2 Lycopodium alkaloid, phlefargesiine A (222), has been isolated from the club moss Phlegmariurus fargesii. It exhibits inhibitory effect against AChE with an inhibitory ratio of 36.2% at 40 μmol·L−1 [193]. A little later, a very closely related alkaloid, phleghenrine D (223), together with neophleghenrine A (224) containing a 9-azaprotoadamantane moiety, has been isolated from another club moss Phlegmariurus henryi. Compound 223 shows po-tent AChE inhibitory activity but no inhibition against BuChE in comparison with tacrine (the positive control) [194]. Squar-rosusine A (225) has been isolated from the aerial parts of Phlegmariurus squarrosus. It is the first example of aldol condensation in fawcettimine-type Lycopodium alkaloids [195]. Lycoplanine A (226) has been isolated from the club moss Lycopodium complanatum. It is a potent Cav3.1 T-type calcium channel (TTCC) inhibitor with an IC50 of 6.06 μmol·L−1 [196].

Sporulaminal A (227), an unusual spiroaminal derived from bergamotane sesquiterpenoid, has been isolated from a marine- derived fungus Paraconiothyrium sporulosum YK-03 [197]. Pericoannosin A (228) and periconiasin F (229) have been isolated from the endophytic fungus Periconia sp. F-31 of the medicinal plant Annona muricata. Both of them shows anti- HIV activity with IC50 of 69.6 and 29.2 μmol·L−1, respectively [198]. (−)-Sinensilactam A (230) has been isolated from the fruiting bodies of Ganoderma sinensis. It has been found to be a Smad3 phosphorylation inhibitor in TGF-β1 induced human renal proximal tubular cells [199]. A couple of matrine-based alkaloids have been discovered from the seeds of Sophora alopecuroides. Sophalines A (231) and B (232) possess un-precedented 6/6/6/4 and 6/5/6/6 ring systems, respectively; while sophaline C (233) is a matrine−acetophenone alkaloid. Compounds 232 and 233 significantly inhibited HBsAg secretion by more than 50.0% at non-cytotoxic concentration of 0.4 mmol·L−1, which is more potent than the positive control lamivudine (3TC) (31.5% at a concentration of 1.0 mmol·L−1) [200].

Three new Myrioneuron alkaloids have been isolated from Myrioneuron faberi. Among them, myrifamine B (234) shows significant in vitro inhibitory activity towards the hep-atitis C virus; myrifamine C (235) is the first example of a symmetric dimer among the Myrioneuron alkaloids [201]. Arthpyrone A (236), a 4-hydroxy-2-pyridone alkaloid, has been

isolated from the sponge-derived fungus Arthrinium arundinis ZSDS1-F3. Compound 236 possesses a 2-pyridone core fea-tured with a decalin moiety linked via a carboxide bridge bearing a novel oxabicyclo[3.3.1]-nonane ring system [202].

Khasuanine A (237), a novel monoterpenoid indole alka-loid, has been isolated from the roots of Melodinus khasianus. It markedly inhibits the proliferation of PC3 cell with an IC50 of 0.45 μmol·L−1 and was able to induce the apoptosis of PC3 cells by activation of caspase 3 and p53, and by inhibition of Bcl-2 [203]. Versicoamide F (238), has been isolated from the fungus Aspergillus tennesseensis. It shows weak antiprolifera-tive activity against the H460 cell line [204]. New monoterpe-noid indole alkaloids, kopsinidine C (239) and 11, 12-methy-lenedioxychanofruticosinic acid (240), have been obtained from the twigs and leaves of Kopsia officinalis [205]. Alstro-stine G (241) possessing an unprecedented 6/5/6/6/5/6-ring system has been isolated from Alstonia rostrata [206]. Rauvomine B (242), isolated from the aerial parts of Rauvolfia vomitoria, is a novel C18 normonoterpenoid indole alkaloid with a sub-stituted cyclopropane ring. It exhibits significant anti-infla-mmatory activity [207].

Diaporisoindole A (243), a novel isoprenylisoindole al-kaloid, has been isolated from the endophytic fungus Di-aporthe sp. SYSUHQ3. It exhibits inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B with an IC50 of 4.2 μmol·L−1 [208]. Three pairs of new enan-tiomeric alkaloids with an unprecedented spiro indolinone- naphthofuran skeleton have been isolated from a marine Streptomyces sp. Among them, (±)-pratensilin A (244) shows moderate cytotoxicities towards a small panel of cell lines [209].

A rare arcutine-type C20-diterpenoid alkaloid, aconicar-micharcutinium A, has been obtained as hydroxide (245) from the lateral roots of Aconitum carmichaelii [210]. Apetaldine A (246), a C19-diterpenoid alkaloid, has been isolated from Aco-nitum apetalum [211]. Sinomontadine (247), a C18-diterpenoid alkaloid, has been isolated from Aconitum sinomontanum. It features an unprecedented skeleton containing a seven-membered ring (A-ring) [212]. Pericolactine A (248), obtained from a fungus Periconia sp. (No. 19-4-2-1) isolated from the lichen Parmelia sp., is a new class of diterpenoid alkaloid with an unusual fused 5-5-8-5 tetracyclic ring system [213]. Walujewine A (249) and walujewine C (250), two new isosteroidal alka-loids, have been isolated from the bulbs of Fritillaria walu-jewii. Compound 249 shows highly selective AChE inhibition and compound 250 was potent dual AChE-BuChE inhibitors [214]. A spinaceamine- bearing pregnane, named scleronine (251), has been isolated from a Chinese soft coral Scleronephthya sp., showing significant inhibitory effects against the migration of tumor cells A549 and B16 [215].

Flueggether A (252) and virosinine A (253) have been isolated from Flueggea virosa. Both show mild in vitro an-ti-HIV activity [216]. Chemical investigation of the Nepalese Daphniphyllum himalense has yielded two compounds, hi-malensines A (254) and B (255). Compound 254 is the first natural C19 Daphniphyllum alkaloid; while 255 bears a


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22-nor-1, 13-secodaphnicyclidin skeleton and exhibits mar-ginal inhibitory activities against two kinases, PTP1B and IKK- β [217]. Scholarisine H (256), a new monoterpenoid indole alkaloid possessing a rare cage carbon skeleton, has been isolated from the leaves of Alstonia scholaris [218]. Plantadeprate A (257), a monoterpene zwitterionic guanidium from the seeds of Plantago depressa, exhibits potential antihyperglycemic ef-fect attributed to suppression of hepatic gluconeogenesis with an inhibitory rate of 8.2% at 40 μmol·L−1 [219]. N-4-Demethyl- 21-dehydrokoumine (258), has been isolated from the leaves

and vine stems of Gelsemium elegans. It exhibits moderate cytotoxic effects against five human tumor cell lines, with IC50 ranging from 4.6 to 9.3 μmol·L−1 [220]. (+)-Tishaviolamine A (259), featuring an unprecedented 6/5/5/6/5 nitrogen contain-ing heterocyclic skeleton, has been isolated from Viola tian-schanica [221]. Conipyridoin E (260) has been identified from the solid culture of the fungus Coniochaeta cephalothecoides. It exhibits strong activity against the growth of both Staphy-lococcus aureus and MRSA with MIC of 0.97 μmol·L−1 [222]. Gunnilactam A (261), a novel macrocyclic tetralactam, has


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been isolated from the submerged fermentation broth of Pae-cilomyces gunnii which is an entomogenous fungus identified as the anamorph of Cordyceps gunnii. Compound 261 exhib-its selective cytotoxic activity against human prostate cancer C42B cells with an IC50 of 5.4 μmol·L−1 [223]. From the fer-mentation broth of the marine-derived Actinoalloteichus cyanogriseus WH1-2216-6, a new 5, 5, 6-polycyclic tetramate macrolactam (PTM) named 16-hydroxymaltophilin (262) has been isolated. It is active against a panel of human cancer cell lines with the IC50 of 4.5-9.7 μmol·L−1 [224]. One novel hybrid

peptide−polyketide, dahurelmusin A (263), has been isolated from Elymus dahuricus infected by the Epichloë bromicola endophyte. It exhibits significant insecticidal activities against Rhopalosiphum padi and Brevicoryne brassicae with LC50 of 0.092 and 0.251 mmol·L−1, respectively [225]. Nivelactam (264), a new macrolactam derivative, has been isolated from the fermentation broth of Streptomyces niveus. Compound 264 displayed moderate cytotoxic activities against a panel of human tumor cell lines in vitro [226]. Emericellolide A (265), featuring the unprecedented macrolide skeleton composed of


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an unusual L-glutamate fragment, an isoindolone unit, and a sesquiterpene moiety, has been isolated from a plant endo-phytic fungus Emericella nidulans HDN12-249 [227].

Aglaodoratin C (266), a rare C-10 carbonylated aglain- type flavonol-diamide [3+2] adduct, has been isolated from the leaves of Aglaia odorata (Meliaceae). It has been demon-strated to inhibit liver carcinoma HepG2 cell proliferation [228]. Versiquinazoline B (267), a fumiquinazoline-type alkaloid from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1, exhibits inhibitory activities against thioredoxin reductase (TrxR) [229]. Flueggenines E (268) and F (269) have been isolated from the ethanolic extract of Flueggea virosa. Both are Securinega alkaloid hybrids incorporating tryp-tamine or piperidine residues. Compound 268 shows a mod-erate anti-HIV activity [230]. Speradine C (270), a highly oxy-genated hexacyclic cyclopiazonic acid (CPA) alkaloid, has been isolated from the sponge derived fungus Aspergillus flavus MXH-X104 [231]. Curvularia sp. IFB-Z10, a white croaker-associated fungus, has yielded a skeletally unprece-dented indolizine alkaloid named curindolizine (271), which displays an anti-inflammatory action in LPS-induced RAW264.7 macrophages with an IC50 of 5.31 μmol·L−1 [232].

(+)-Nigegladine A (272) and (–)-nigegladine A, a pair of enantiomers of thymoquinone dimer, have been isolated from the seeds of Nigella glandulifera. They both exhibitsignificant protective effects against hypoxia/reoxygenation-induced H9c2 myocardial cell injury [233]. Two pairs of enantiomeric alkaloid dimers have been isolated from the aerial parts of Mac-leaya cordata. Among them, (−)-macleayin A (273) exhibits modest cytotoxic activity against the HL-60 cell line with an IC50 of 3.51 μmol·L−1 [234]. Geleganidine B (274), an unusual dimeric monoterpenoid indole alkaloid, has been isolated from the roots of Gelsemium elegans. It shows moderate cy-totoxic activity against MCF-7 and PC-12 cells [235]. Exotine A (275), a heterodimer of isopentenyl-substituted indole and coumarin derivative linked through a fused heptacyclic ring system, has been isolated from the roots of Murraya exotica. It shows inhibition of NO production in LPS-induced BV-2 microglial cells [236]. Fistulain A (276), a new type of dimeric chromone alkaloid, has been isolated from the bark of Cassia fistula. It displays anti-TMV activity and weak cytotoxicities [237]. Duclauxamide A1 (277), a new polyketide-derived heptacyclic oligophenalenone dimer with a N-2-hydroxyethyl moiety, has been isolated from Penicillium manginii YIM PH30375 and shows moderate cytotoxic effects against a small panel of cancer cell lines [238]. Four pairs of partially racemized β-carboline alkaloids have been isolated from the extract of Peganum harmala. Among them, pegaharmine D (278) shows signifi-cant cytotoxic activities against HL-60, PC-3 and SGC-7901 cell lines [239]. (+)-Pestaloxazine A (279), consisting of 22 carbons and 12 heteroatoms, has been isolated along with its enantiomer from a Pestalotiopsis sp. fungus derived from a soft coral. Compound 279 exhibits potent antiviral activity against EV71 (enterovirus 71) with an IC50 of 14.2 μmol·L−1,

stronger than that of the positive control ribavirin (IC50 256.1 μmol·L−1) [240]. (±)-Uncarilin B, a pair of unusual dimeric isoechinulin-type enantiomers with a symmetric four-membered core, have been isolated from Uncaria rhyn-chophylla. (−)-Uncarilin B (280), at a concentration of 0.25 mmol·L−1, shows activities on MT1 and MT2 (melatonin) receptors with agonistic rates of 11.26% and 52.44%, respec-tively [241]. Tabercorymines A (281) and B, two new vobas-inyl−ibogan-type bisindole alkaloids with an unprecedented skeleton, have been isolated from Tabernaemontana corym-bosa. Both of them show potent antiproliferative activities against several human cancer cell lines, including vincristine- resistant KB [242]. A new bisindole alkaloid, hunterizeyline F (282), has been isolated from the twigs and leaves of Hunteria zeylanica [243]. (±)-Peharmaline A (283), existing as a pair of

rare -carboline–vasicinone hybrid alkaloid enantiomers, have been isolated from the seeds of Peganum harmala. They exhibit significant cytotoxic activities against HL-60, PC-3, and SGC-7901 cancer cell lines with IC50 of 9.2, 21.6, and 25.4 μmol·L−1, respectively [244]. Six unusual matrine-type alkaloid dimers have been isolated from the roots of Sophora flavescens. Among them, flavesine A (284) is the first natural matrine-type alkaloid dimer, while flavesine F (285) repre-sents an unprecedented dimerization pattern constructed by matrine and (−)-cytisine [245].

Gelsekoumidine B (286), obtained as a pair of atropi-someric bisindole alkaloids (286a/286b), has been isolated from the roots of Gelsemium elegans. Compound 286 rep-resents the first example of seco-koumine−gelsedine type alkaloid. It exhibits a moderate inhibitory effect against NO production [246].

Pseudellone A (287), together with its diastereomer, has been isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3 [247]. Four new diketopiperazines have been characterized from the mangrove-derived Penicillium brocae MA-231. Of the isolates, spirobrocazine A (288) possesses a rare spirocyclic 6/5/6/5/6 cyclic system; brocazine G (289) exhibits potent cytotoxicities against both sensitive and cis-platin-resistant human ovarian cancer cells and antimicrobial activity against pathogenic Staphylococcus aureus [248]. One bisthiodiketopiperazine derivative, named adametizine A (290), has been isolated from the marine-sponge derived fungus Penicillium adametzioides AS-53. It exhibits lethality against brine shrimp (Artemia salina) with an LD50 of 4.8 μmol·L−1 [249]. Penicisulfuranol A (291), a new epipolythiodioxopiperazine (ETP) alkaloid, has been isolated from the mangrove endo-phytic fungus Penicillium janthinellum HDN13-309. It shows cytotoxicities against HeLa and HL-60 cell lines with IC50 of 0.1 and 0.5 μmol·L−1, respectively [250]. Streptopertusacin A (292), a unique indolizinium alkaloid existing as a zwitterion, has been isolated from a culture of the seaweed-derived Streptomyces sp. HZP-2216E. It shows moderate activity against the growth of methicillin-resistant Staphylococcus aureus (MRSA) [251].


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Cytochalasan-type secondary metabolites are generally produced by fungi. Armochaetoglobin L (293) has been isolated from the solid culture broth of Chaetomium globosum TW1-1 and shows anti-HIV activity with an EC50 value of 0.48 μmol·L−1 [252]. Armochaeglobines A (294) and B (295), another two indolebased cytochalasan alkaloids with new carbon skeletons, have been obtained from the fungus Chae-tomium globosum TW1-1 which has been first isolated from the arthropod Armadillidium vulgare [253]. Arthriniumnin A (296) has been isolated and identified from the fungus Arthrinium

arundinis ZSDS1-F3 derived from the sponge Phakellia fusca [254]. A novel polycyclic aspochalasin, aspochalazine A (297), has been isolated from the culture broth of Aspergillus sp. found in the gut of a marine isopod Ligia oceanica. It is the first aspochalasin derivative with an azabicyclo [255]. A series of merocytochalasans have been isolated from the culture broth of Aspergillus flavipes. Among them, aspergilasine A (298) possesses a uniquely caged pentacyclo[7.2.0.14, 11.02, 7.05, 10] dodecane skeleton with an unexpected cyclobutane ring [256]; epicochalasines A (299) and B, possessing a hendecacyclic


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ring system, can induce G2/M-phase cell cycle arrest signifi-cantly [257]; asperflavipine A (300), possessing two cytochala-san moieties and two epicoccine moieties, is the first cyto-chalasan heterotetramer; asperflavipine B (301) contains a cytochalasan and two epicoccine moieties. Compound 300 shows moderate cytotoxic effects and induced apoptosis in Jurkat, NB4, and HL60 cells through the activation of caspase-3 and degradation of poly (ADP-ribose) polymerase (PARP) [258].

Polyketides

Penicilfuranone A (302), a novel furancarboxylic acid, has been isolated from the cultures of the fungus Penicillium sp. sh18 endophytic to the stems of Isodon eriocalyx var. laxiflora [259]. Six new 16-membered macrolides with a rare branched octose unit have been isolated from Streptomyces sp. HK-2006-1. Among the isolates, aldgamycin O (303) shows antibacterial activity against Staphylococcus aureus 209P with an MIC of 16 μg·mL−1 [260].

Miscellaneous

A new spiroketal, chlorotheolide B (304), has been iso-lated from the solid substrate fermentation of the plant endo-phytic fungus Pestalotiopsis theae (N635). It shows an anti-proliferative effect against the human tumor HeLa cell line and induces an autophagic process in the cells [261]. (+)-Deno-bilone A (305), together with its enantiomer, has been isolated from Dendrobium nobile. Both of them show moderate in-hibitory effects against HeLa, MCF-7, and A549 cells [262]. Diasteltoxin A (306), asteltoxin-bearing dimers, has been isolated from a mutated strain of a sponge-derived fungus Emericella variecolor XSA-07-2. It exerted certain inhibitory effects against two tumor cell lines (H1299 and MCF-7) and exhibits inhibition against thioredoxin reductase (TrxR) [263]. Grisemycin (307), the first sulfur angucyclinone with an un-usual ether- bridged system, has been isolated from a ma-rine-derived Streptomyces griseus strain M268. It exhibits modestly selective activity against HL-60 [264]. Selesconol (308), an inducer for the differentiation of rat bone marrow mesenchymal stem cells into neural cells, has been obtained from the culture of Daldinia eschscholzii IFB-TL01 [265]. Di-hydrotrichodimer ether A (309), a rare bisorbicillinoid with a γ-pyrone moiety, has been isolated from the fungus Clono-stachys rosea YRS-06. It displays potent inhibition activity against E. Coli with an MIC value of 25 μg·mL−1 [266]. Citrifuran A (310), metabolized by an Aspergillus sp., shows moderate inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages with an IC50 of 18.3 μmol·L−1 [267]. Three novel aromatic azoxy compounds including azoxymycin A (311) have been isolated and identified from Streptomyces chattanoogensis L10 [268]. Forsythenethoside A (312) has been isolated from the fruits of Forsythia suspensa. It shows strong neuroprotective activity against serum-deprivation-induced PC12 cell damage [269]. Rifamorpholine B (313) has been isolated from the culture of a locust associated rare actinoba-cteria, Amycolatopsis sp. HCa4, showing potent activity against

MRSA with an MIC of 4.0 μmol·L−1 [270]. A new griseofulvin derivative, 4′-demethoxy-4′-N-isopentylisogriseofulvin (314), has been isolated from Penicillium griseofulvum CPCC 400528. It exhibits anti-HIV activity with an IC50 of 33.2 μmol·L−1 [271]. Chrysanthemorimic acid A (315) has been isolated and char-acterized from the flowers of Chrysanthemum morifolium. It displays significant effect against hydrogen peroxide-induced neurotoxicity in SH-SY5Y cells at 10 μmol·L−1 [272]. The phy-tochemical investigations on the rhizomes of Atractylodes lancea have led to the isolation of compound 316. It shows weak inhibitory effects on α-glucosidases and protein tyrosine phosphates 1B (PTP1B) at a concentration of 10 μmol·L−1 [273]. Lecanicillone A (317), an unusual dimeric spiciferone with acyclobutane ring via a [2 + 2] cycloaddition, has been iso-lated from an entomopathogenic fungus Lecanicillium sp. PR-M-3. Compound 317 shows moderate cytotoxicity against the HL-60 cell line [274]. Tadehaginoside D (318), obtained from Tadehagi triquetrum, significantly increases the basal and insulin-elicited glucose uptake [275]. The biosynthesis gene clus-ter (fls) for atypical angucycline fluostatins has been identi-fied from the marine derived Micromonospora rosaria SCSIO N160. Heterologous expression of the intact fls-gene cluster in Streptomyces coelicolor YF11 in the presence of 3% sea salts yielded difluostatin A (319) which exhibits antibacterial activities [276]. By genome wide deletions of epigenetic regu-lators in entomopathogenic fungus Metarhizium robertsii, unexpected activations of orphan secondary metabolite genes have been found upon the disruption of a histone acetyltrans-ferase (HAT) gene Hat1. This led to the characterization of 8 isocoumarin derivatives including meromuside A (320) [277].

Discussion and Perspective

Natural products (NPs) are rich source for novel com-pounds that are of great value, not only for organic chemistry but also for drug discovery. In the years of 2015, 2016, and 2017, with the development of separation and analytical techniques, a bunch of more complex natural products with/without better bioactivities have been identified by Chinese researchers. Because of the limitation of length, we deeply feel sorry that this review could not cover all achievements in NPs chemistry made by Chinese scholars. Nevertheless, the selected findings could represent the advanced NPs chemistry researches in the past three years, and would greatly enrich our knowledge about NPs and help accelerate the process for drug discovery. The newly discovered chemical structures provide new ideas for drug researchers. At the same time, some of NPs can be just served as lead compounds for drug discovery. For example, fortunilide A (27), showing antimarial activity at low nanomolar level, could be a promising drug candidate like arteminsinin; stelleralide F (49) shows significant anti-HIV activity about 34 times better than AZT in an in vitro assay; phainanoid F (121), the immunosuppressive triterpene with new carbon skeleton, exhibits exceptionally potent immunosuppressive activities in vitro against the proliferation of T and B lymphocytes, which is about 7 and 221 times as active as cyclosporin A.


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The biosyntheses studies and genetic regulations are of great help for understanding the biosynthetic pathway of NPs. As a branch of NPs research, such studies provide a future view for NPs scientific direction: with the help of biologists, chemists can manufacture any interesting compounds or try to get novel compounds by gene manipulation.

However, there are still some critical limitations conce-rning NPs research in China. First, how can we elucidate the interactions between the compounds existing in one plant/ organism? It’s difficult while it’s imperative to identify real active compounds from crude extracts. Second, how can we discover the mass-limited NPs with novel skeletons and po-tent bioactivities from unexploited nature sources (e.g., en-dangered plants native to China [8])? Meanwhile, how can we rapidly achieve the miniaturization (microgram scale) of the structure elucidation using new analytical technologies (e.g., advanced NMR probes [278, 279])? Third, how can we develop more reliable and more sensitive screening methods? China is a large nation with tradition of prescribing herbal medicines. Thousands of years of practice accumulates enormous clinical data that are treasures for human beings. By cooperating with scientists all over the world, Chinese scholars will for sure make greater achievements in NPs research in the years to come.

Acknowledgements

We thank Prof. YE Yang (Shanghai Institute of Materia Medica, Chinese Academy of Sciences) for suggestions and discussions in preparation of this review. We are grateful to our lab members for assistance in literature search and prepa-ration of this review.

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Cite this article as: YANG Guo-Xun, MA Guang-Lei, LI Hao, HUANG Ting, XIONG Juan, and HU Jin-Feng. Advanced natural products chemistry research in China between 2015 and 2017 [J]. Chin J Nat Med, 2018, 16(12): 881-906.

advanced natural products chemistry research in china ......(27) is a dimeric lindenane-type...

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