7/29/2019 0010-0014

1/5

WATURALLYOCCURRIWG OXYGENRETEROCYCLICSV.MUmEm

Carl Djewaa_81,. J. Elrenbraun, . A. FInnwan and B. GilbertDepartment f Chomietry, Ww State niversity,

(Retoeived February 1959)

RECENT paper0 have been oonoerned ith the isolation and oharaoterlza-

Detroit 2, Miohlgan

tion 3 of memaein, a orystalline neeotioidal onatituent f the see& ofMamma amerloana . We should nor like to record oertain observationswhioh lead to the aaaignment f structure to thie rubstanoe. ammeinrepresents he first naturally ocurring owin 4 with a n-propyl aub-stituent at C-4 and It is aleo interesting o note that a number of ayn-thetlo ooumarlns ave been shorn to exhibit ineeotioidal ctivitye5

Dlhydromammein II), In whloh the lsopropylidene ouble bond 3 ofmameln (I) has been reduoed, upon heating with yk aqueous alkali led to

1 Paper IV: D. Herb&, W. B. More, O.R. Gottlleb and C. Djerarsl,J. Amer. Chem. Soo,& in press (1959).

2 M. P. Morris and C. Pagan, J. Amer. Chew SOO, 12, 1489 (1953).' C. Djerami, E. J. Eiaenbraun, . Gilbert, . J. Lemln, S. P.4 Marfey and M. P. Morris, J. Amer. Chem. SOOT 80, 3686 (1956).For pertinent eviews lee: F. Y. Dean In L. Zeohmeister'e, ro-greet3 n the Chemistry f Or nio Natural Produote Vol. IX, pp.225-291. Springer, ienna (1952); . Reppel,(1954); . Karrer, Kormtitutlon nd Vorkomnen er omanlsohenPflamenstoffe,pp. 532-562 Birlch&eer, aael (1958).

5 P. L&gem, B. Martin and P. H&r, Eelv. Chim. dote 21, 892(1944). 10

7/29/2019 0010-0014

2/5

Baturally ocourring xygen heterocyclica . maeuaein 11methyl ;-propyl ketone, isovaleric cid and iaovalerylphloroglucinolV).7Theee three oleavage products account for 21 out of the 22 carbon atomsof mammein an&together with the earlier reported3 spectral esults,suggest strongly that mammein is a substituted oumarln. ethylation fthe residual material, after removal of the above cleavage roducts,furnished crystalline, luorescent imethyl ether, m.p, 109-109,5, fthe oomposition 19H2604, hose ultraviolet bsorption pectrum asvirtually superimposable pon that S of 5,7-dimethoxyooumarin,hestructure (XII) of this crucial degradation roduct was established ythe following ynthetio equenoer

Peahmann condensation f ieovaleroylphlorogluainolVII)7 withethyl butyroaaetate VIII) furnished -n-propyl-5, -dlhydroq-6-leovaleroylooumarln IX) ' (m.p. 228-229'r ound:C, 67.308 H, 7.32; 0,26.23. 5$2o 5 requires C, 67.09; H, 6.62; 0, 26.29), which was trana-formed by Clemmensen eduction into 4-;-propyl-5,7-dihydroxy-6-ieovalerylcoumarln X) (m.p. 183.5-186'; ound: C, 66.45; H, 7.98.C17H2204,H20 equires C, 66.21; H, 7.85.) Methylation ith dimethyl sulfateand potassium arbonate rovided the non-fluorescent -E-propyl-5, -dimethoxy-6-isovalerylcoumarlnXI) (m.p. 51-53'r found: C, 71.52~

6 Thio subetanoe as first isolated in this laboratory y Dr.S.P. Marfey.7 T.S. Kenny, A. Robertson nd S.W. George, J. Chem. Soa, 1601(1939).' 8. F&me and T. Severin, rch. Pharm* SE, 486 (1957).9 We believe that ring oloeure in the direction of IX (rather thanyielding the isomerlc S-ieovaleroyl oumarin) s favored bysterio considerations s well aa by hydrogen bonding betweenthe oarbonyl group and the two ortho-hydroxyl roups.

7/29/2019 0010-0014

3/5

12 rJsturally ooourrlng oxygen heterooyollos V. mameln

H(CH~ZCH(CH~)~ /

dHO \ OHRl R

I R=(CH3j2C=CHCH ; Rl=(CH ) CHCH CO V R=HU R=(CH3)2CHCH2C 2,l Rl=(C&HCk,CO

III R=(CH3)2CHCH2CO; R =(GH )2CICHCH2VI R=(GH3)2CHCH2CH2

IV R=Rl=(CH3)2CHCH2Cd2; OI4OCOCH,

IX R=OX R=H2

t3H7o=