摘要:

266 CHEMICAL COMMUNICATIONS The Biosynthesis of Epistephanine and the Structure of Stebisimine By D. H. R. BARTON, G. W. KIRBY, and A. WIECHERS (Imperial College, London, S. W.7) THE ideal that bisbenzylisoquinoline alkaloids might be formed in Nature by the oxidative coupling of coclaurine (I ; R= R’= R”=H) deriva- tives has so far lacked experimental support.2 We now report appropriate tracer studies on episteph- mine3 (11). R O / (I) 6’ ( f ) - [ Z-W] Tyrosine was incorporated (0.17 yo) into epistephanine in Stefihania japonica Miers. Cleavage of the alkaloid with sodium in liquid ammonia gave, after methylation with diazo- methane, ( &- )-00-dimethylcoclaurine (I ; R= H, R’= R”= Me) and (-)-N00-trimethylcoclaurine (I ; R = R’= R”= Me). These compounds con- tained, respectively, 50 and 51% of the total activity.In the following season incorporation of ( ) - [2-14C] tyrosine (0.08@)$), ( f ) - [ 8,3’, 5’-3H3] - coclaurine4 (I; R=R’=R’’=H) (0.008~0), and (&)- [N-methyl-14C]N-methylcoclaurine (0.050%) was observed. These and later incorporations have been corrected for loss of tritium from positions involved in the oxidative couplings. Herzig- Meyer demethylation of epistephanine, derived from the N-methyl labelled precursor, located 98% of the activity in the N-methyl group. Both enantiomers of [8,3’,5’,-3H,]N-methyl- coclaurine were fed, in parallel, to S. japonica. The (-)-enantiomer ( I ; K=Me, R’=R”=H) was incorporated ( 0 ~ 0 6 0 ~ 0 ) into epistephanine much more efficiently than its antipode (0.003~0). This confirm^^-^ the absolute configuration (11) of the alkaloid and shows that racemisations of the precursor is unimportant in this plant.Degrada- tion of epistephanine derived from ( -) -N-methyl- coclaurine gave ( - ) -N00-trimethylcoclaurine con- taining 95% of the total activity. The other fragment, ( & ) -00-dimethylcoclaurine, was in- active. Clearly N-methylcoclaurine provides only half the epistephanine molecule and is not de- methylated in the plant to give coclaurine or any other metabolically active derivative. During work with S. juponica we isolated a newNUMBER 9, 1966 267 minor alkaloid, stebisimine, m.p. 233-235”, C,,H,,N,O,, m/e 590 (molecular ion and base peak), [aID = 0” (cI 1.26 in CHCl,), Vmax (CHC1,) 1610 crn.-l, A,,, (EtOH) 238 and 279 mp (E, 51,900 and 24,200), and hinr 308 mp ( E , 12,500).The n.m.r. spectrum (in CDCl,) showed methoxyl signals at r 6.04, 6.10, 6.12, and 6.75 and no N-methyl signal. These properties suggested that stebisimine might be N-nor- 1,Z-dehydroepistephanine and this was confirmed chemically. Reduction of stebisimine with sodium in liquid ammonia gave, after N- methylation of the product mixture, ( f)-arme- pavine (I; R=R’=Me, R”=H) and the (&)-NO- dimethylcoclaurine (I; R= R”=Me, R’=H). Both components were identified by comparison with the synthetic race mate^.^ (Received, l i a y c l z 21stI 1966; Corn. 175.) F. Faltis and H. Frauendorfer, Bey., 1930, 63, 806. Dr. I. R. C. Bick (Univ. of Tasmania) has kindly informed us of his unpublished work on the biosynthesis of The feeding of ( &)- [2-14C] tyrosine gave radioactive berbamine containing berbamine in Atherosperrna moschatum. equal amounts of radioactivity in the two halves of the molecule. M. Tomita and E. Fujita, Pharm. Bull. (Japan), 1954, 2, 378. I,. J. Haynes, I<. L. Stuart, D. H. R. Barton, D. S. Bhakuni, and G. W. Kirby, Chent. Comm., 1965, 141. H. Yamaguchi, J . Pharm, Soc. Japan, 1958, 78, 678. C. Ferrari and V. Deulofeu, Tetrahedron, 1962, 18, 419. M. Tomita and J. Kunimoto, J . Pharm. SOC. Japan, 1962, 82, 734. $1. Tomita and H. Yamaguchi, Pharm. Bull. (Japan), 1953, 1, 10; we thank Prof. M. Tomita for several authentic * A . R. Battersby, D. M. Foulkes, and R. Binks, J . Chem. SOC., 1965, 3323. specimens.

ISSN:0009-241X    

DOI:10.1039/C19660000266

出版商:RSC    

年代:1966

数据来源: RSC