Total synthesis of the ansamycin antibiotic (+)-thiazinotrienomycin E.
The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved. Key features of the synthetic strategy include (a) the efficient construction of sulfone 7 incorporating TBS protection of the aniline, (b) an improved synthesis of allyl chloride (-)-6, the advanced intermediate employed in our trienomycins A and F total syntheses, (c) application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit in a stereo-controlled fashion, (d) an efficient union of sulfone 7 with advanced iodide 62, and (e) Mukaiyama macrolactamization to access the thiazinotrienomycin macrocyclic ring.
Smith
A B
AB
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Wan
Z
Z
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D007202:Indicators and Reagents; D013302:Streptomyces; D013450:Sulfones; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D013450:Sulfones; D013843:Thiazines; C094829:thiazinotrienomycin E