Synthesis of Simplified Azasordarin Analogs as Potential Antifungal Agents

28 January 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

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 activity 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 C. albicans for these early de novo analogs, the synthetic route reported here permits more comprehensive modifications of the bicyclic core, and SAR studies that were not heretofore possible.

Keywords

antifungal
sordarin
Diels-Alder
[4+2]-cycloaddition
glycosidation
nitrile

Supplementary materials

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Title
2019 01 25 Azasordarins SI
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