New Demethylated Derivatives of Carolacton and Structure–Activity Relationship (SAR) Studies on Their Biofilm Inhibitory Properties

Abstract

The total synthesis of a series of new carolacton derivatives that mainly lack selected methyl substituents along the polyketide backbone is reported. Their inhibitory activity towards bacterial biofilms revealed that selective removal of the methyl group at C10 does not have a major effect on biological activity, whereas additional removal of the methyl group at C14 in carolacton results in a large decrease in antibacterial activity. A key new feature of this work is the replacement of the Nozaki–Hiyama–Kishi (NHK) vinylation with a titanium-mediated protocol for the fusion of the two main fragments.

Key words

antibiotics - biofilms - carolacton - Nozaki–Hiyama–Kishi reaction - polyketides - structure–activity relationship studies - total synthesis

Publication History

Received: 10 December 2022

Accepted after revision: 16 January 2023

Accepted Manuscript online:
16 January 2023

Article published online:
24 March 2023

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