The use of N-urethane-protected N-carboxyanhydrides (UNCAs) in amino acid and peptide synthesis.
N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactive amino acid derivatives. 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 beta amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerically pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced [4S,5S)-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 malonate in the presence of sodium hydride to yield gamma-N-benzyloxycarbonylamino-beta-oxodicarboxyl esters 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)-iodo]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.
Fehrentz
J A
JA
Laboratoire de Chimie et Pharmacologie de Molécules d'Intérêt Biologique, URA CNRS 1845, Faculté de Pharmacie, Montpellier, France.
Genu-Dellac
C
C
Amblard
M
M
Winternitz
F
F
Loffet
A
A
Martinez
J
J
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D000812:Anhydrides / Q000737:chemistry; D007202:Indicators and Reagents; D008722:Methods; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D014520:Urethane / Q000737:chemistry
D000596:Amino Acids; D000605:Amino Alcohols; D000812:Anhydrides; D007202:Indicators and Reagents; D010455:Peptides; D014520:Urethane; C013165:statine