Affordable Access

Publisher Website

Synthesis and epimerization of phenylalanyl 4-aminocyclophosphamides

Authors
Journal
Tetrahedron
0040-4020
Publisher
Elsevier
Publication Date
Volume
63
Issue
43
Identifiers
DOI: 10.1016/j.tet.2007.08.009
Keywords
  • Cyclophosphamide
  • Prodrug
  • Proteolysis
  • Epimerization
Disciplines
  • Design

Abstract

Abstract Peptide and amino acid conjugates of (4 R)- and (4 S)-4-aminocyclophosphamides (4-NH 2-CPA, 3) were designed as prodrug forms of phosphoramide mustard. Four diastereomers of Boc-Phe-4-NH-CPA ( 6) were synthesized stereospecifically from homoserine ( R or S) and the protection strategy was optimized for the homoserine hydroxyl group during the construction of the 1,3,2-oxazaphosphorinane ring. The Phe-4-NH-CPA isomers of the trans-configuration ((2 S,4 R)- and (2 R,4 S)-) were found to be less stable than the corresponding isomers of the cis-configuration ((2 R,4 R)- and (2 S,4 S)-) and to undergo epimerization of the C-4 chiral center in the presence of 25% TFA used during Boc deprotection. The synthetic route developed should be applicable to the synthesis of a variety of peptide and amino acid conjugates of 4-aminocyclophosphamide.

There are no comments yet on this publication. Be the first to share your thoughts.