The enantioselective total syntheses of (+)-7-oxohinokinin, (+)-7-oxoarcitin, (+)-conicaol B and (?)-isopolygamain?

Organic & Biomolecular Chemistry Pub Date: 2022-03-17 DOI: 10.1039/D2OB00336H

Abstract

A flexible approach to C7 keto dibenzyl butyrolactone lignans was developed and the synthesis of several natural products and their related derivatives is described herein. The developed pathway proceeds through enantioenriched β-substituted butyrolactones, from which facile aldol addition and subsequent oxidation affords the desired benzylic ketone moiety. This methodology was used to complete the first enantioselective total syntheses of three natural products, (+)-7-oxohinokinin, (+)-7-oxoarcitin and (+)-conicaol B, and a further five analogues. The utility of this method was further demonstrated through a 1–2 step modification to access another class of natural product, aryltetralin lignans, allowing the asymmetric total synthesis of (?)-isopolygamain and a polygamain derivative. Anti-proliferative testing determined (?)-isopolygamain was the most active of the compounds prepared, with IC50 values of 2.95 ± 0.61 μM and 4.65 ± 0.68 μM against MDA-MB-231 (triple negative breast cancer) and HCT-116 (colon cancer) cell lines, respectively.

Graphical abstract: The enantioselective total syntheses of (+)-7-oxohinokinin, (+)-7-oxoarcitin, (+)-conicaol B and (?)-isopolygamain
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