title: A practical synthesis of (+)-biotin from L-cysteine.
abstract: 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.
authors.affiliation: 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
authors.forename: Masahiko
authors.initials: M
authors.lastname: Seki
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatsuda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mori
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D001710:Biotin / Q000138:chemical synthesis* / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D015394:Molecular Structure; D014803:Vitamin B Complex / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D014803:Vitamin B Complex; D001710:Biotin; D003545:Cysteine