Structure-activity relations of polyfunctional diterpenes of the daphnane type. I. Revised structure for resiniferatoxin and structure-activity relations of resiniferonol and some of its esters [Euphorbia resinifera, Euphorbia unispina, Euphorbia poisonii]

• Published in: Journal of natural products (Washington, D.C.) Vol. 45; no. 3; p. 347
• Main Authors: Adolf, W, Sorg, B, Hergenhahn, M, Hecker, E
• Format: Journal Article
• Language: English
• Published: United States 01.05.1982
• Subjects: Animals; Chemical Phenomena; Chemistry; Diterpenes - toxicity; Irritants; Methylation; Mice; Structure-Activity Relationship
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np50021a018

Base catalyzed transesterifications of resiniferatoxin afforded the 9, 13, 14-orthophenylacetate (III), as well as (4-hydroxy-3-methyoxyphenyl) acetic acid methyl ester (II). Reesterification of III with homovanillic acid showed that the previously proposed structure for resiniferatoxin has to be revised to resiniferonol-9, 13, 14-orthophenylacetate-20-(4-hydroxy-3-methoxyphenyl) acetate (I). From III, different 20 esters (I, IV-IX) were prepared. The orthophenylacetate III was cleaved by Acidic hydrolysis to yield the 14-phenylacetate X. Subsequent alkaline transesterifications of X afforded the parent alcohol resiniferonol (XI), Starting from XI, the 14, 20-diesters XII and XV and the 9, 13, 20-diesters xii and XV and the 9, 13, 14-orthoesters XIII, XIV, XVI, XVII and XVIII were obtained. All esters were tested for irritant activity on the mouse ear. Some aspects of structure-activity relations of irritancy of resiniferonol esters are established and discussed.