O6C-20-nor-SalA is a stable and potent KOR agonist

27 December 2017, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its C8 epimer, so much so that epimerization is completely suppressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR.

Keywords

salvinorin
kappa opioid receptor
total synthesis
Heck reaction
conformational analysis
Chemistry

Supplementary materials

Title
Description
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CarboNor20SalA Supporting Information
Description
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Shenvi120
Description
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Shenvi127
Description
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