Collect. Czech. Chem. Commun. 1998, 63, 231-244
https://doi.org/10.1135/cccc19980231

Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond. I. Preparation of Four Diastereoisomeric (2R or 2S,4R or 4S,5S)-2-Benzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylhexanoic Acids

Jaroslav Litera, Miloš Buděšínský, Ján Urban and Milan Souček

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic

This article is part of serial Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond.

Abstract

By two separate routes were prepared four diastereoisomers of (2R or 2S,5R or 5S)-3-benzyl-5-{(1S)- [(tert-butoxycarbonyl)amino]-2-phenylethyl}tetrahydrofuran-2-ones (11, 12, 17 and 18). Since the furanones were derived from (S)-phenylalanine, absolute configurations of all chiral carbon atoms could be deduced from their 1H NMR spectra. The furanones were easily hydrolyzed to four (2R or 2S,4R or 4S,5S)-2-benzyl-5- [(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylbutanoic acids (20-23), hydroxyethylene isosteres of Phe-Phe peptide bond.

Keywords: Hydroxyethylene isostere; γ-Lactones; 5-Amino-2-benzyl-4-hydroxy-6-phenylhexanoic acids; Diastereoisomers; Transition state analogues; Peptidomimetics.