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Diastereoselective Synthesis of α,β′-Disubstituted Aminomethyl(2-carboxyethyl)phosphinates as Phosphinyl Dipeptide Isosteres

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journal contribution
posted on 02.10.2008, 00:00 by Takehiro Yamagishi, Hiroyuki Ichikawa, Terumitsu Haruki, Tsutomu Yokomatsu
A new and efficient method has been developed for the diastereoselective synthesis of unnatural dipeptide analogues containing the metabolically stable phosphinic moiety, NH2XaaΨ[P(O)OHCH2]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 α-aminoalkyl-H-phosphinates to acrylates and subsequent diastereoselective alkylation at the β′-position of the resulting Michael adducts.