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Published on: September 20, 2016
Synthesis of streptolydigin, a potent bacterial RNA polymerase inhibitor
Sergey V Pronin1, Sergey A Kozmin
1University of Chicago, Department of Chemistry, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Abstract:
Streptolydigin is a highly potent, broad-spectrum antibiotic produced by Streptomyces lydicus, which inhibits bacterial RNA polymerase. We describe the first synthesis of streptolydigin, which was assembled in a highly convergent and fully stereocontrolled fashion with a longest linear sequence of 24 steps starting from commercially available precursors. The assembly process entailed preparation of fully elaborated streptolic and ydiginic subunits of the natural product, followed by a highly efficient union in a three-step one-pot procedure, which included Dieckmann cyclization with a concomitant imide opening, Horner-Wadsworth-Emmons olefination, and desilylation.
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