A novel synthesis of (+)-biotin from L-cysteine.
(+)-Biotin (1) was synthesized in 25% overall yield over 11 steps from L-cysteine. The contiguous asymmetric centers at C-3a and C-6a were formed through a novel and highly stereoselective Lewis base-catalyzed cyanosilylation of alpha-amino aldehyde 3 to provide anti-O-TMS-cyanohydrin 4 with high stereoselectivity and in high yield (anti/syn = 92:8, 96%). Treatment of 4 with a di-Grignard reagent, 1,4-bis(bromomagnesio)butane, followed by carbon dioxide, efficiently installed the 4-carboxybutyl chain at C-4 to give keto acid 5. The final cyclization to bicyclic compound 7b, a precursor to 1, was realized by a palladium-catalyzed intramolecular allylic amination of cis-allylic carbonate 6b that was elaborated from 5.
Seki
Masahiko
M
CMC Research Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa-ku, Osaka, 532-8505, Japan. m-seki@tanabe.co.jp
Mori
Yoshikazu
Y
Hatsuda
Masanori
M
Yamada
Shin-ichi
S
D001710:Biotin; D003545:Cysteine / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D007202:Indicators and Reagents; D001710:Biotin; D003545:Cysteine