The taumycin A macrocycle: Asymmetric total synthesis and revision of relative stereochemistry

The symbiotic association of marine microorganisms with their host sponges continues to be an extraordinary source of hybrid polyketide/non-ribosomal secondary metabolites that often possess unique structures in conjunction with interesting biological activity. Recently, taumycin A was isolated from a Madagascar sponge of genus Fascaplysinopsis. This work describes the first asymmetric total synthesis and revision of the relative configuration of the 12-membered macrocycle via the synthesis of taumycin A aldehyde. Key to the success of this work is a novel alpha-keto ketene macrocyclization that provided an efficient means by which to access two diastereomers of the desired macrolide without the need to employ additional coupling agents or unnecessary oxidation state adjustments.