An improved synthesis of a key intermediate for (+)-biotin from D-mannose.
An efficient and reproducible process for the synthesis of methyl 2,3,4,5-tetradeoxy-7,8-O-isopropylidene-D-arabino-nanonate (2), a key intermediate in the total synthesis of (+)-biotin (1), starting from readily available D-mannose is described. The crucial part of this synthesis was the development of a practical route to a novel O-benzyl protected unsaturated ester methyl (benzyl 5,6,7,8-tetradeoxy-2,3-O-isopropylidene-alpha-D-lyxo-nona-5,7-dienofuranosid) uronate (7), allowing the one-step preparation of hydroxy ester methyl 5,6,7,8-tetradeoxy-2,3-O-isopropylidene-alpha-D-lyxo-nanofuranuronate (8) by the catalytic debenzylation and hydrogenation over palladium on carbon catalyst. This procedure requires no chromatographic purification, which makes it ideal for synthetic preparation on an industrial scale.
Chen
Fen-Er
FE
Fudan-DSM Joint Laboratory for Synthetic Methods and Chiral Technology, Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China. rfchen@fudan.edu.cn
Zhao
Jian-Feng
JF
Xiong
Fang-Jun
FJ
Xie
Bin
B
Zhang
Ping
P
D001710:Biotin / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry*; D015394:Molecular Structure
D001710:Biotin; D008358:Mannose