A practical synthesis of (+)-biotin from L-cysteine.
Alpha-amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded alpha-amino nitrile 5 with high diastereoselectivity (syn/anti=11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.
Seki
Masahiko
M
Export & Import Group, Purchasing Department, Logistics Division, Tanabe Seiyaku Co., Ltd. 3-2-10, Dosho-Machi, Chuo-Ku, Osaka 541-8505, Japan. m-seki@tanabe.co.jp
Hatsuda
Masanori
M
Mori
Yoshikazu
Y
Yoshida
Shin-ichi
S
Yamada
Shin-ichi
S
Shimizu
Toshiaki
T
D001710:Biotin / Q000138:chemical synthesis* / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D015394:Molecular Structure; D014803:Vitamin B Complex / Q000138:chemical synthesis / Q000737:chemistry
D014803:Vitamin B Complex; D001710:Biotin; D003545:Cysteine