ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

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

preprint
submitted on 21.12.2017 and posted on 27.12.2017 by Ryan Shenvi, Shun Hirasawa, Min Cho, Tarsis F. Brust, Jeremy J. Roach, Larua M. Bohn
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.

Funding

GM122606, DA 038694, DA033073

History

Topic

  • Natural Products
  • Stereochemistry

Email Address of Submitting Author

rshenvi@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0001-8353-6449

Declaration of Conflict of Interest

A patent has been filed

Exports

Read the published paper

in Bioorganic & Medicinal Chemistry Letters

Logo branding

Exports