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Efficient synthesis of Fmoc‐protected phosphinic pseudodipeptides: Building blocks for the synthesis of matrix metalloproteinase inhibitors
Author(s) -
Bhowmick Manishabrata,
Sappidi Ravinder R.,
Fields Gregg B.,
Lepore Salvatore D.
Publication year - 2011
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21425
Subject(s) - chemistry , matrix metalloproteinase inhibitor , combinatorial chemistry , matrix metalloproteinase , matrix (chemical analysis) , stereochemistry , biochemistry , chromatography
A convenient route for the synthesis of Fmoc‐protected phosphinic dipeptide building blocks is described. The protected amino acid isosteres benzyloxycarbonyl aminomethyl phosphinic acid (glycine surrogate), benzyl α‐isopropyl acrylate (valine surrogate), and benzyl α‐isobutyl acrylate (leucine surrogate) were synthesized starting from commercially available materials. Reaction of either the valine or leucine surrogate with bis(trimethylsilyl) phosphonite generated the pseudodipeptide bond. The synthesis concluded with an efficient one‐pot three‐step procedure involving a bis‐deprotection of the N‐ and C‐termini under catalytic hydrogenation conditions followed by selective capping of the N‐terminus with an Fmoc group to yield either Fmoc‐NHCH 2 PO(OAd)CH 2 CH(Pr i )CO 2 H or Fmoc‐NHCH 2 PO(OAd)CH 2 CH(Bu i )CO 2 H. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 1–3, 2011.