Document Type

Article

Language

eng

Publication Date

3-28-2019

Publisher

American Chemical Society

Source Publication

Journal of Organic Chemistry

Source ISSN

0022-3263

Abstract

A new series of simplified azasordarin analogs was synthesized using as key steps a Diels–Alder reaction to generate a highly substituted bicyclo[2.2.1]heptane core, followed by a subsequent nitrile alkylation. Several additional strategies were investigated for the generation of the key tertiary nitrile or aldehyde thought to be required for inhibition at the fungal protein eukaryotic elongation factor 2. This new series also features a morpholino glycone previously reported in semisynthetic sordarin derivatives with broad spectrum antifungal activity. Despite a lack of activity against Candida albicans for these early de novo analogs, the synthetic route reported here permits more comprehensive modifications of the bicyclic core and structure–activity relationship studies that were not heretofore possible.

Comments

Accepted version. The Journal of Organic Chemistry, Vol. 84, No. 9 (March 28, 2019): 5292-5304, DOI. © 2019 American Chemical Society. Used with permission.

Available for download on Saturday, March 28, 2020

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