19-Deformyl-4'-deoxydesmycosin (TMC-016): synthesis and biological properties of a unique 16-membered macrolide antibiotic.
19-Deformyl-4'-deoxydesmycosin was synthesized by the following synthetic route: 19-Deformylation of desmycosin, 3,2',4''-tri-O-trimethylsilylation, 4'-O-sulfonylation, 4'-iodination, reductive deiodination and 3,2',4''-tri-O-detrimethylsilylation. Deformylation of the aldehyde group at the C-19 position was achieved by two different methods: A) A simple one-step deformylation using Wilkinson's catalyst ((Ph3P)3RhCl). B) Reductive decarboxylation of the 19-carboxyl derivative following NaClO2 oxidation of the aldehyde. 19-Deformyl-4'-deoxydesmycosin showed very strong antimicrobial activity in vitro and in vivo.
Fujiwara
T
T
Research Laboratories, Toyo Jozo Co., Ltd., Shizuoka, Japan.
Watanabe
H
H
Kogami
Y
Y
Shiritani
Y
Y
Sakakibara
H
H
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001682:Biological Availability; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D013293:Enterococcus faecalis / Q000187:drug effects; D007933:Leucomycins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013290:Streptococcal Infections / Q000188:drug therapy; D013292:Streptococcus agalactiae / Q000187:drug effects; D015645:Tylosin / Q000031:analogs & derivatives*
D007933:Leucomycins; C060112:TMC 016; D015645:Tylosin