asymmetric total synthesis and biosynthetic implications
TRANSCRIPT
Literature 08/20/2021
Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B
Yu Wang
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
ROMe
MeH
O
O
MeMe
H
Me
Me
R
R
n, n=1 or 2
R
Introduction
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
• Triterpenoids isolated from Salvia plants• Featuring a complex heptacyclic framework
• Hydrangenone - analogues to the family of
triterpenoids with unprecedented 6/7/6/5/5 skeleton
OMe
MeH
O
O
MeMeH
Me
Me
Perovskone
Me
MeH
O
O
MeMeH
Me
Me
OHO Me
OH
Hydrangenone
Me
Introduction
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
• Triterpenoids isolated from Salvia plants• Featuring a complex heptacyclic framework
• Hydrangenone - analogues to the family of
triterpenoids with unprecedented 6/7/6/5/5 skeleton
OMe
MeH
O
O
MeMeH
Me
Me
Perovskone
Me
MeH
O
O
MeMeH
Me
Me
OHO Me
OH
Hydrangenone
Me
Proposed Biosynthesis
Parve. A, Iqbal Choudhary. M, Akhter. F, Norwalk. M, Mohammad. F. V, Hasan. N. M, Zamir. T, Ahmad. V, J. Org. Chem. 1992, 57, 16, 4339-4340
Perovskone
Me
MeH
O
OMe
MeOH
Precursor of icetexone
MeMe
Me
O
H
PO
OH
OP OH
O OH
Geranyl pyrophosphate
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
Proposed Biosynthesis
Tabefam. M, Farimani. M, Danton. O, Ramseyer. J, Ebrahimi. S, Neuburger. M, Kaiser. M, Salehi. P, Potterat. O, Hamburger. M, J. Nat. Prod. 2018, 81, 2682-2691
Hydrangenone B
Me
OOP
OH
OH
1-deoxy-D-xylulose 5-P
Dehydration Me
OOP
OH
+PO
Me
Me
DMAPP
POO Me
Me
OMeH
B
Me
MeH
O
OMe
MeOH
Me
MeH
OH
Me
O
O
Me
Me
Me
HO
O
3+2 Cycloaddtion
Me
MeH
OH
Me
O
O
Me
Me
Me
HO
Ene-reaction
Me
MeH
O
O
MeMe
H
OO
O
Me
Me
Me
O
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
MeReduction
Hydrangenone B
Synthetic Overview
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
MeOMe
MeH
O
O
MeMe
H
Me
Me
OPerovskone C
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone D
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone F
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
Me
MeH
Perovskatone D
O
OMe
MeOH
OH
Synthetic Plan
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
Perovskatone D
O
OMe
MeOH
OH
Me Me
trans-α-ocimene
Asymmetric Photoenolization Diels-Alder Reaction
Me MeCHO
OBnOMe
Me
Me
OMeOMe
Me
OHC
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
cycloaddition, cyclization
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
oxidativecleavage
recyclization
MeOMe
MeH
O
O
MeMe
H
Me
Me
olefinmigration
oxidativecleavage
recyclizationPerovskone C, D, F
selective oxidation
Synthetic Plan
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
Perovskatone D
O
OMe
MeOH
OH
Me Me
trans-α-ocimene
Asymmetric Photoenolization Diels-Alder Reaction
Me MeCHO
OBnOMe
Me
Me
OMeOMe
Me
OHC
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
cycloaddition, cyclization
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
oxidativecleavage
recyclization
MeOMe
MeH
O
O
MeMe
H
Me
Me
olefinmigration
oxidativecleavage
recyclizationPerovskone C, D, F
selective oxidation
Synthetic Plan
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
Perovskatone D
O
OMe
MeOH
OH
Me Me
trans-α-ocimene
Asymmetric Photoenolization Diels-Alder Reaction
Me MeCHO
OBnOMe
Me
Me
OMeOMe
Me
OHC
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
cycloaddition, cyclization
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
oxidativecleavage
recyclization
MeOMe
MeH
O
O
MeMe
H
Me
Me
olefinmigration
oxidativecleavage
recyclizationPerovskone C, D, F
selective oxidation
Synthetic Plan
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
Perovskatone D
O
OMe
MeOH
OH
Me Me
trans-α-ocimene
Asymmetric Photoenolization Diels-Alder Reaction
Me MeCHO
OBnOMe
Me
Me
OMeOMe
Me
OHC
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
cycloaddition, cyclization
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
oxidativecleavage
recyclization
MeOMe
MeH
O
O
MeMe
H
Me
Me
olefinmigration
oxidativecleavage
recyclizationPerovskone C, D, F
selective oxidation
Synthesis of Perovskones and HydrangenonesForward Synthesis-Key Step
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me MeCHO
OBnOMe
Me
Me
OMeOMe
Me
OHC+
3 steps from commercial material
4 steps from commercial material
OBn
O
H
O
MeO OMe
Me
Me
TiiPrO
Ti
OMeOiPr
O iPrOiPrO OOiPr*L1
Me
Me
hv (λ=366nm)2.4 equiv Ti(OiPr)4
0.15 equiv TADDOL type ligand L1DCM, 1.5 h
94% yield d.r.=20:1
endo-selectivity
OBnOH
OMe
OMe
Me
MeOMe
MeMe
OHC
94.5:5.5 er97.7:2.3 er after recrystallization
MeO
MeOOHOH
F3C
CF3 F3C
CF3
CF3
F3C
F3C
CF3
L1
X-ray analysis
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OBnOH
OMe
OMe
Me
MeOMe
MeMe
OHCIBX, DMSO
80 °C, 10h
OBnO
OMe
OMe
Me
MeOMe
MeMe
OHC
73% yield
1) PdCl2, H2, EtOH/DCM(1:1)
r.t., 18h2) Li(t-BuO)3AlH, THF
-78°C to 0 °C
OHO
OMe
OMe
Me
MeOMe
MeMe
HO
92% yield over 2 steps
I2, PPh3, quinoline
toluene(dry), 60 °C, 3.5h91% yield
OHO
OMe
OMe
Me
MeOMe
MeMe
I
AIBN, Bu3SnHtoluene(dry and degassed)
90 °C, 8h
OH
OMe
OMe
Me
MeOMe
MeMe
O
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+
68% yield total
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OBnOH
OMe
OMe
Me
MeOMe
MeMe
OHCIBX, DMSO
80 °C, 10h
OBnO
OMe
OMe
Me
MeOMe
MeMe
OHC
73% yield
1) PdCl2, H2, EtOH/DCM(1:1)
r.t., 18h2) Li(t-BuO)3AlH, THF
-78°C to 0 °C
OHO
OMe
OMe
Me
MeOMe
MeMe
HO
92% yield over 2 steps
I2, PPh3, quinoline
toluene(dry), 60 °C, 3.5h91% yield
OHO
OMe
OMe
Me
MeOMe
MeMe
I
AIBN, Bu3SnHtoluene(dry and degassed)
90 °C, 8h
OH
OMe
OMe
Me
MeOMe
MeMe
O
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+
68% yield total
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OBnOH
OMe
OMe
Me
MeOMe
MeMe
OHCIBX, DMSO
80 °C, 10h
OBnO
OMe
OMe
Me
MeOMe
MeMe
OHC
73% yield
1) PdCl2, H2, EtOH/DCM(1:1)
r.t., 18h2) Li(t-BuO)3AlH, THF
-78°C to 0 °C
OHO
OMe
OMe
Me
MeOMe
MeMe
HO
92% yield over 2 steps
I2, PPh3, quinoline
toluene(dry), 60 °C, 3.5h91% yield
OHO
OMe
OMe
Me
MeOMe
MeMe
I
AIBN, Bu3SnHtoluene(dry and degassed)
90 °C, 8h
OH
OMe
OMe
Me
MeOMe
MeMe
O
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+
68% yield total
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OBnOH
OMe
OMe
Me
MeOMe
MeMe
OHCIBX, DMSO
80 °C, 10h
OBnO
OMe
OMe
Me
MeOMe
MeMe
OHC
73% yield
1) PdCl2, H2, EtOH/DCM(1:1)
r.t., 18h2) Li(t-BuO)3AlH, THF
-78°C to 0 °C
OHO
OMe
OMe
Me
MeOMe
MeMe
HO
92% yield over 2 steps
I2, PPh3, quinoline
toluene(dry), 60 °C, 3.5h91% yield
OHO
OMe
OMe
Me
MeOMe
MeMe
I
AIBN, Bu3SnHtoluene(dry and degassed)
90 °C, 8h
OH
OMe
OMe
Me
MeOMe
MeMe
O
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+
68% yield total
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+1) Li, NH3/THF (1:1), -100 °C, 1h
2) DDQ, toulene, r.t., 3hMe
MeH
MeO
OMeMe
MeOMe
OH
47% yield over 2 stepsdr=4.7:1 (trans:cis)
AgO
dioxane/6N HNO3, 10 °C69% yield total
Me
MeH
O
OMe
MeOMe
OH Me
MeH
O
OMe
MeOH
OH+
Product Ratio: 6.7:1
Perovskatone DMethyl-Perovskatone D
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
MeO
OMeMe
MeOMe
OH
O
Me
MeH
MeO
OMeMe
MeOMe
O
OH
+1) Li, NH3/THF (1:1), -100 °C, 1h
2) DDQ, toulene, r.t., 3hMe
MeH
MeO
OMeMe
MeOMe
OH
47% yield over 2 stepsdr=4.7:1 (trans:cis)
AgO
dioxane/6N HNO3, 10 °C69% yield total
Me
MeH
O
OMe
MeOMe
OH Me
MeH
O
OMe
MeOH
OH+
Product Ratio: 6.7:1
Perovskatone DMethyl-Perovskatone D
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
OMe
MeOR
OH
R=H, Perovskatone DR=Me, Methyl-Perovskatone D
+MeMe
1 step from commercial material
Eu(fod)3, toluene
60°C
Me
Me
O
OR
iPr
Me
Me
H
OHODiels-Alder
Reaction
endo-selectivity
Me
MeH
OH
Me
Me
O
O
Me
MeOR
hemiacetalization
Me
MeH
O
Me
Me
O
HO
Me
MeOH LiCl
DMSOonepot
OCF3CF2CF2
OMe
MeMe
Eu
3
Synthesis of Perovskones and HydrangenonesCascade Cyclization- Perovskone and Derivative
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHBi(OTf)3, DCM
20°C, 4hMe
MeH
O
Me
Me Me
O
Me
MeOH
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
+
63% yield over 2 steps
Product ratio: 1.5:1Me
Me
Synthesis of Perovskones and HydrangenonesCascade Cyclization- Perovskone and Derivative
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHBi(OTf)3, DCM
20°C, 4hMe
MeH
O
Me
Me Me
O
Me
MeOH
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
+
63% yield over 2 steps
Product ratio: 1.5:1Me
Me
Synthesis of Perovskones and HydrangenonesCascade Cyclization- Perovskone and Derivative
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHBi(OTf)3, DCM
20°C, 4hMe
MeH
O
Me
Me Me
O
Me
MeOH
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
+
63% yield over 2 steps
Product ratio: 1.5:1Me
Me
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHCu(OTf)2, DCM,
80°C, 4.5-5 hO
Me
MeH
O
O
MeMe
H
Me
Me
Me
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
43% yield over 2 steps from perovskatone56% yield over 2 steps from methyl-perovskatone
cation intermediate
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
O3, Me2S, DCM
-78°C, 2 min OOMe
MeH
O
O
MeMe
H
Me
Me
Me O
50% yield
Pyrrolidine, AcOH
toluene, 90 °C, 1.5 h Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
91% yield
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHCu(OTf)2, DCM,
80°C, 4.5-5 hO
Me
MeH
O
O
MeMe
H
Me
Me
Me
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
43% yield over 2 steps from perovskatone56% yield over 2 steps from methyl-perovskatone
cation intermediate
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
O3, Me2S, DCM
-78°C, 2 min OOMe
MeH
O
O
MeMe
H
Me
Me
Me O
50% yield
Pyrrolidine, AcOH
toluene, 90 °C, 1.5 h Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
91% yield
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
Me
MeH
O
Me
Me
O
HO
Me
MeOHCu(OTf)2, DCM,
80°C, 4.5-5 hO
Me
MeH
O
O
MeMe
H
Me
Me
Me
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
43% yield over 2 steps from perovskatone56% yield over 2 steps from methyl-perovskatone
cation intermediate
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
O3, Me2S, DCM
-78°C, 2 min OOMe
MeH
O
O
MeMe
H
Me
Me
Me O
50% yield
Pyrrolidine, AcOH
toluene, 90 °C, 1.5 h Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
91% yield
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
Me
O3, Me2S, DCM
-78°C, 1.5 min
42% yield
OMe
MeH
O
O
MeMe
H
Me
Me
OMeOHC
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
Na2CrO4, NaOAc, 60°Ctoluene, AcOH/Ac2O
MeOMe
MeH
O
O
MeMe
H
Me
Me
OPerovskone C
1)NaBH4, CeCl3, MeOH, -78°C,20min
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone F
17% yield
1) SeO2, dioxane 100°C, 1.5h
2) DMP, DCM16°C, 30min
19% yield over 2 steps
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone D82% yield, d.r.=1.8:12) m-CPBA, NaHCO3DCM, 0°C, 1h67% yield
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
Na2CrO4, NaOAc, 60°Ctoluene, AcOH/Ac2O
MeOMe
MeH
O
O
MeMe
H
Me
Me
OPerovskone C
1)NaBH4, CeCl3, MeOH, -78°C,20min
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone F
17% yield
1) SeO2, dioxane 100°C, 1.5h
2) DMP, DCM16°C, 30min
19% yield over 2 steps
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone D82% yield, d.r.=1.8:12) m-CPBA, NaHCO3DCM, 0°C, 1h67% yield
Synthesis of Perovskones and HydrangenonesForward Synthesis
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
OMe
MeH
O
O
MeMe
H
Me
Me
Perovskone derivative
Me
Na2CrO4, NaOAc, 60°Ctoluene, AcOH/Ac2O
MeOMe
MeH
O
O
MeMe
H
Me
Me
OPerovskone C
1)NaBH4, CeCl3, MeOH, -78°C,20min
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone F
17% yield
1) SeO2, dioxane 100°C, 1.5h
2) DMP, DCM16°C, 30min
19% yield over 2 steps
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone D82% yield, d.r.=1.8:12) m-CPBA, NaHCO3DCM, 0°C, 1h67% yield
Synthesis of Perovskones and Hydrangenones
Baochao Yang, Guoen Wen, Quan Zhang, Min Hou, Haibing He, Shuanhu Gao, J. Am. Chem. Soc. 2021, 143, 6370-6375
MeOMe
MeH
O
O
MeMe
H
Me
Me
Perovskone
MeOMe
MeH
O
O
MeMe
H
Me
Me
OPerovskone C
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone D
MeOMe
MeH
O
O
MeMe
H
Me
Me
O
OH
Perovskone F
Me
MeH
O
O
MeMe
H
Me
Me
OHO Me
OH
Hydrangenone
Me
MeH
O
O
MeMe
H
OOHH
O
Me
Me
Me
Hydrangenone B
- 19-24 steps from commercial avaliable materials
-asymmetric PEDA
- stereospecific Diels-Alder reaction followed by cascade cyclization
produced perovskone
-selective oxidations produced other members in the natural product
family