Efficient synthesis of Fmoc-protected phosphinic pseudodipeptides: Building blocks for the synthesis of matrix metalloproteinase inhibitors.
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.
Bhowmick
Manishabrata
M
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431-0991, USA.
Sappidi
Ravinder R
RR
Fields
Gregg B
GB
Lepore
Salvatore D
SD
D000596:Amino Acids / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005449:Fluorenes / Q000737:chemistry*; D061965:Matrix Metalloproteinase Inhibitors; D008956:Models, Chemical; D015394:Molecular Structure; D010721:Phosphinic Acids / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C496789:9-fluorenylmethoxycarbonyl; D000596:Amino Acids; D004151:Dipeptides; D005449:Fluorenes; D061965:Matrix Metalloproteinase Inhibitors; D010721:Phosphinic Acids; D011480:Protease Inhibitors