Synthetic studies of neoclerodane diterpenes from Salvia divinorum:: Semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A

被引:44
作者
Harding, WW
Schmidt, M
Tidgewell, K
Kannan, P
Holden, KG
Gilmour, B
Navarro, H
Rothman, RB
Prisinzano, TE [1 ]
机构
[1] Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA
[2] Res Triangle Inst, Res Triangle Pk, NC 27709 USA
[3] Holden Labs, Carmel, CA 93923 USA
[4] NIDA, Clin Psychopharmacol Sect, IRP, DHHS, Baltimore, MD 21224 USA
来源
JOURNAL OF NATURAL PRODUCTS | 2006年 / 69卷 / 01期
关键词
D O I
10.1021/np050398i
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for K opioid receptors. One approach to better understanding the mode of binding of I at K receptors is to systematically alter the structure of 1 and examine the effects on opioid receptor affinity and activity. Currently, there is a paucity of methods described for the preparation of analogues derived from 1. Here, we report the investigation of several chemical transformations of 1 isolated from S. divinorum. In particular, this work provides a semisynthesis of salvinicins A (2) and B (3) and has identified 10a as the first neoclerodane diterpene with 6 opioid antagonist activity.
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收藏
页码:107 / 112
页数:6
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