Novel sulfur-containing rapamycin analogs prepared by precursor-directed biosynthesis.
[reaction: see text] Two novel sulfur-containing analogs of the immunosuppressive natural product rapamycin (1) were obtained by feeding cultures of Streptomyces hygroscopicus with l-nipecotic acid (4) and either (S)-1,3-thiazane-4-carboxylic acid (5) or (S)-1,4-thiazane-3-carboxylic acid (6). The structures of the two new compounds, 20-thiarapamycin (2) and 15-deoxo-19-sulfoxylrapamycin (3), were determined by spectroscopic methods.
Graziani
Edmund I
EI
Department of Chemical & Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. graziaei@wyeth.com
Ritacco
Frank V
FV
Summers
Mia Y
MY
Zabriskie
T Mark
TM
Yu
Ker
K
Bernan
Valerie S
VS
Greenstein
Michael
M
Carter
Guy T
GT
D007166:Immunosuppressive Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry*
D007166:Immunosuppressive Agents; D013455:Sulfur; D020123:Sirolimus