Diastereoselective synthesis of alpha,beta'-disubstituted aminomethyl(2-carboxyethyl)phosphinates as phosphinyl dipeptide isosteres.
A new and efficient method has been developed for the diastereoselective synthesis of unnatural dipeptide analogues containing the metabolically stable phosphinic moiety, NH 2XaaPsi[P(O)OHCH 2]XaaOH, which mimics the transition state of tetrahedral geometry of a scissile peptide bond in hydrolysis by protease. The method is based upon stereospecific Michael addition of stereodefined alpha-aminoalkyl- H-phosphinates to acrylates and subsequent diastereoselective alkylation at the beta'-position of the resulting Michael adducts.
Yamagishi
Takehiro
T
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Ichikawa
Hiroyuki
H
Haruki
Terumitsu
T
Yokomatsu
Tsutomu
T
D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
D004151:Dipeptides; D010721:Phosphinic Acids