Synthesis of P,N-protected phosphinic pseudoprolylglycine block

Abstract

The phosphine block N-Cbz-Pro-ψ[P(O)(OAd)CH₂]-GlyOH has been synthesized for subsequent peptide assembly. A procedure has been proposed for the preparation of phosphorus prolylglycine isostere by three-center two-component amide version of the Kabachnik–Fields reaction. A combination of amide and carbonyl fragments in the molecule of 4-N-Cbz-aminobutyraldehyde makes it possible to accomplish cyclization with generation in situ of a cyclic pyrrolidine Schiff base, followed by Arbuzov phosphorylation of the latter with diacetyl 2-(ethoxycarbonyl)ethyl phosphonite generated in situ.