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The use of N ‐urethane‐protected N ‐carboxyanhydrides (UNCAs) in amino acid and peptide synthesis
Author(s) -
Fehrentz JeanAlain,
GenuDellac Corine,
Amblard Muriel,
Winternitz Franclois,
Loffet Albert,
Martinez Jean
Publication year - 1995
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.310010204
Subject(s) - chemistry , sodium borohydride , hydrolysis , amino acid , sodium hydride , yield (engineering) , decarboxylation , enantiopure drug , peptide , peptide synthesis , organic chemistry , stereochemistry , enantioselective synthesis , catalysis , biochemistry , materials science , metallurgy
N ‐Urethane‐protected N ‐carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N ‐protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4 S ,5 S )‐ N ‐alkoxycarbonyl‐4‐hydroxy‐5‐alkylpyrrolidin‐2‐ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)‐iodol]‐benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.