M. E. Dmitriev

Synthesis of P,N-protected phosphinic pseudoprolylglycine block

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.

One-pot synthesis of N-Cbz-α-aminophosphonic acids

GRAPHICAL ABSTRACT ABSTRACT The paper describes the synthesis of N-protected-α-aminoalkylphosphonic acids, phosphoisosteres of amino acids, from phosphorous acid. A simple, milder and effective one-pot procedure for the amidoalkylation of phosphorous acid in a mixture of acetic anhydride and acetyl chloride at room temperature allows to combine the formation of amino phosphorylic function with the protection on the nitrogen atom.

Synthesis of phosphorus isosters of β-amyloid peptides fragments

We have developed a synthetic route to pseudo dipeptides, analogs of certain fragments of β-amyloid peptides (products of the APP protein hydrolysis). These compounds can be used for preparation of phosphinic acidic oligopeptides representing the peptide sequence of the β-amyloid but containing the phosphorus isoster peptide fragment. Synthesis of pseudo ornityl-glutamate, pseudo arginyl-glutamate, pseudo glycyl-leucine, and pseudo isoleucyl-glycine via amino- and amidoalkylation of phosphonic acids containing the structural isoster of the corresponding amino acid is described.

Amidoalkylation of phosphorous acid

A convenient approach to prepare N-protected α-aminophosphonic acids (phospho-isosteres of natural amino acids) via amidoalkylation of phosphorous acid in a mixture of acetic anhydride and acetyl chloride upon cooling has been developed.

Synthesis of prolyl-glutamate phosphoisostere

A method for the synthesis of prolyl-glutamate phosphoisostere by cyclic amidoalkylation of phosphonous acid containing a structural isostere of glutamic acid was developed. A combination of amide and carbonyl moieties in the 4-N-Cbz-aminobutyraldehyde molecule allows cyclization with in situ generation of a cyclic pyrrolidine Schiff base followed by its Arbuzov type phosphorylation.

Cyclic Amidoalkylation of Hydrophosphorylic Compounds. Synthesis of Proline Analogs

A method for the synthesis of N-Cbz-protected phosphorylic analogs of proline by cyclic amidoalkylation of various hydrophosphorylic compounds was developed. Combination of amide and carbonyl fragments in the 4-N-Cbz-aminobutyraldehyde molecule allows to realize the three-center two-component amide version of the Kabachnik–Fields reaction.