Enantioselective Transfer Hydrogenative Cycloaddition Unlocks the Total Synthesis of SF2446 B3: An Aglycone of Arenimycin and SF2446 Type II Polyketide Antibiotics

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Jul 26

PMID 37494281

Authors

Nancy O Huynh

Tomas Hodik

Michael J Krische

Affiliations

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Abstract

The first total synthesis and structure validation of an arenimycin/SF2446 type II polyketide is described, as represented by construction of SF2446 B3, the aglycone shared by this family of type II polyketides. Ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition, which occurs via successive stereoablation-stereoregeneration, affects a double dynamic kinetic asymmetric transformation wherein two racemic starting materials combine to form the congested angucycline bay region with control of regio-, diastereo-, and enantioselectivity. This work represents the first application of transfer hydrogenative cycloaddition and enantioselective intermolecular metal-catalyzed C-C bond activation in target-oriented synthesis.

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