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A Practical Synthesis of (+)‐Biotin from L ‐Cysteine
Author(s) -
Seki Masahiko,
Hatsuda Masanori,
Mori Yoshikazu,
Yoshida Shinichi,
Yamada Shinichi,
Shimizu Toshiaki
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400733
Subject(s) - chemistry , aldehyde , cysteine , yield (engineering) , strecker amino acid synthesis , nitrile , amide , adduct , sodium bisulfite , reagent , protecting group , thiolactone , coupling reaction , organic chemistry , catalysis , enantioselective synthesis , alkyl , materials science , metallurgy , enzyme
α‐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 α‐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.