title: Total synthesis of the myxobacterial macrolide ripostatin B.
abstract: This article describes the total synthesis of ripostatin B, which is a 14-membered macrolide of myxobacterial origin that inhibits E. coli RNA polymerase by a different mechanism of action than the first-line anti-tuberculosis drug rifampicin. Structurally, ripostatin B features a labile and synthetically challenging doubly skipped triene motif embedded in the macrolactone ring. Key steps in the synthesis were a Paterson aldol reaction, a low-temperature Yamaguchi esterification and an alkene metathesis reaction to close the macrolide ring. The natural product was synthesized in a longest linear sequence of 21 steps and 3.6% overall yield.
authors: Swiss Federal Institute of Technology (ETH) Zürich, Institute of Pharmaceutical Sciences, HCl H 405, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich.
authors: Florian
authors: F
authors: Glaus
authors: Karl-Heinz
authors: KH
authors: Altmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D009231:Myxococcales
chemical_list: D000900:Anti-Bacterial Agents; D007783:Lactones; C096601:ripostatin B; D012321:DNA-Directed RNA Polymerases