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2011 | OriginalPaper | Chapter

Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

Authors : Kimberly M. Lovell, Katherine M. Prevatt-Smith, Anthony Lozama, Thomas E. Prisinzano

Published in: Chemistry of Opioids

Publisher: Springer Berlin Heidelberg

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Abstract

Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.

Graphical Abstract

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Title: Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects
Authors: Kimberly M. Lovell
Katherine M. Prevatt-Smith
Anthony Lozama
Thomas E. Prisinzano
Publisher: Springer Berlin Heidelberg
Book: Chemistry of Opioids
Print ISBN: 978-3-642-18106-1

Electronic ISBN: 978-3-642-18107-8

Copyright Year: 2011
DOI: https://doi.org/10.1007/128_2010_82