Elsevier

Tetrahedron Letters

Volume 49, Issue 6, 4 February 2008, Pages 937-940
Tetrahedron Letters

Short synthesis of a novel class of salvinorin A analogs with hemiacetalic structure

https://doi.org/10.1016/j.tetlet.2007.12.041Get rights and content

Abstract

Novel semisynthetic analogs of salvinorin A, a full agonist having extraordinary affinity as well as selectivity for the κ-opioid receptor (KOR), were obtained in good yields. The derivatives are remarkable for their unusual and unique hemiacetal structure in the salvinorin series of compounds. The formation of the hemiacetal occurs with epimerization at C-12, thus preserving the original configuration of salvinorin A. The dimethyl ester derivative of the hemiacetal was found to have an affinity for both KOR and MOR (μ-opioid receptor).

Graphical abstract

Novel semisynthetic analogs of salvinorin A with dual affinity for κ- and μ-opioid receptors are obtained by hydrolysis with 5% aq KOH, subsequent hemiacetalization, and epimerization at C-12.

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Acknowledgments

The authors would like to acknowledge Lukasz Kutrzeba for help in extraction of salvinorin A from plant material, and Dr. Paulo Carvalho for providing crystallographic data. This work was supported by NIH Grant R01 DA017204, and conducted in a facility constructed with support from research facilities improvement program Grant C06 RR-14503-01 from National Center for Research Resources, National Institutes of Health, Bethesda, MD, USA.

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