title: Synthesis of α-carboxyphosphinopeptides derived from norleucine.
abstract: In the present study, we describe in detail the synthesis of a relatively rare class of phosphorus compounds, α-carboxyphosphinopeptides. We prepared several norleucine-derived α-carboxyphosphinic pseudopeptides of the general formula Nle-Ψ[PO(OH)]-Gly. These compounds could have important applications as transition state-mimicking inhibitors for methionine or leucine aminopeptidases or other enzymes. For the preparation of the key α-carboxyphosphinate protected precursors, we investigated, compared and improved two different synthetic methods described in literature: the Arbuzov reaction of a silylated N-protected phosphinic acid with a bromoacetate ester and the nucleophilic addition of a mixed O-methyl S-phenyl N-protected phosphonic acid or a methyl N-protected phosphonochloridate with tert-butyl lithioacetate. We also prepared two N-Fmoc protected synthons, Fmoc-Nle-Ψ[PO(OH)]-Gly-COOH and Fmoc-Nle-Ψ[PO(OAd)]-Gly-COOH, and demonstrated that these precursors are suitable building blocks for the solid-phase synthesis of α-carboxyphosphinopeptides.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, v. v. i., Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Pícha
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Pavel
authors.initials: P
authors.lastname: Fiedler
authors.forename: Miloslav
authors.initials: M
authors.lastname: Sanda
authors.forename: Jiří
authors.initials: J
authors.lastname: Jiráček
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009646:Norleucine / Q000737:chemistry*; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D004151:Dipeptides; D010721:Phosphinic Acids; D009646:Norleucine