Synthesis of streptolydigin, a potent bacterial RNA polymerase inhibitor.
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.
Pronin
Sergey V
SV
University of Chicago, Department of Chemistry, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Kozmin
Sergey A
SA
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000737:chemistry*
D000617:Aminoglycosides; C100307:streptolydigin; D012321:DNA-Directed RNA Polymerases