Artigo Acesso aberto Revisado por pares

Synthetic Studies of Neoclerodane Diterpenes from Salvia d ivinorum : Semisynthesis of Salvinicins A and B and Other Chemical Transformations of Salvinorin A

2005; American Chemical Society; Volume: 69; Issue: 1 Linguagem: Inglês

10.1021/np050398i

ISSN

1520-6025

Autores

Wayne W. Harding, Matthew Schmidt, Kevin Tidgewell, Pavitra Kannan, Kenneth G. Holden, Brian P. Gilmour, Hernán A. Navarro, Richard B. Rothman, Thomas E. Prisinzano,

Tópico(s)

Pharmacological Receptor Mechanisms and Effects

Resumo

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 κ opioid receptors. One approach to better understanding the mode of binding of 1 at κ 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 δ opioid antagonist activity.

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