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Total synthesis of thiocillin I

University of British Columbia

This thesis describes the first total synthesis of Thiocillin I, a thiopeptide antibiotic that is structurally similar to Micrococcin P1. Our group has recently completed the first total synthesis of the latter natural product. In that connection, new methodology had to be devised for the assembly of the central pyridine-thiazole cluster of the molecule. The present work details the development of a considerably more efficient "second generation approach" to that crucial molecular subunit. The new technique relies upon a three-component condensation to form the pyridine core with the full complement of thiazoles already in place. This transformation is recognized as a variant of the Bohlmann-Rahtz reaction that has heretofore eluded the synthetic community. Minor modification of this chemistry is likely to facilitate the synthesis of several other thiopeptide antibiotics, naturally occurring or otherwise. This presages the advent of technology for the conduct of medicinal chemistry studies of thiopeptide substances and promises to lead to new generations of chemotherapeutic resources.

Text

2010-10-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/29493

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/