The University of New Mexico

Seminar:

The Taumycin A Macrocycle: Asymmetric Total Synthesis and Revision of Relative Stereochemistry

February 6, 2015

William Maio

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, taumycins A and B, were isolated in extremely small amounts, from a Madagascar sponge of genus Fascaplysinopsis.  Of particular note, taumycin A was shown to inhibit UT-7 cell growth in the micromolar range, whereas taumycin B, which lacks the terminal oxazole moiety at C(12), is completely devoid of this activity.  To date, extensive biological evaluation has not yet been performed on either metabolite.  At the onset of our synthetic campaign, we believed that the prudent approach might be to first target taumycin aldehyde--a compound initially accessed via reductive ozonolysis of taumycin A -- as a means to address both the unknown relative and absolute stereochemistry of the taumycin macrocycle.  This work describes the first asymmetric total synthesis and revision of the relative configuration of the 12-membered macrocycle.  Key to the success of this work is a novel a-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.