Synthesis of N-(phosphonomethyl)glycine derivatives and studies of their immunotropic activity

Abstract

The Petasis reaction between glyoxylic acid, α amino phosphonates, and organylboronic acid afforded N phosphonomethyl α amino acids. This method has an advantage of prepara tive simplicity and high diastereoselectivity of the reactions. Immunotropic activity of the synthesized compounds was studied using the models in vivo.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…Developments reported in the past 8 years have significantly expanded the scope of the PR, leading to maturation of the reaction in five general directions. First, the reactivity and substrate scope of the classic type of three-component PR have been extensively explored through the application of masked or new carbonyl components, unconventional amines such as amides and aminophosphonates, , as well as a wide range of boronic acid and boronate reagents, such as allenylboronic acids and allenylboronates. , Second, the classic three-component PR has been elaborated into a more complex four-component variant. Third, Petasis-type reactions based on preformed imine substrates in two-component types or with noncanonical substrates in three-component types have been developed.…”

Stereoselective Syntheses of Organophosphorus Compounds

“…The Petasis reaction with aminophosphonates has been used to produce a number of specially designed compounds with additional functional groups to test their biological activity as protein tyrosine phosphatase inhibitors and immunomodulators. Using this method, α-aminophosphonates derived from N-phosphonomethylglycine were obtained in good yields and high diastereoselectivity (Figure 33 and Table 5) [59,60]. The use of α-aminophosphonates has allowed the synthesis of several N-phosphonomet hylglycine derivatives in moderate to good yields and high diastereoselectivity.…”

The main directions of scientific activity of Academician V.P. Kukhar

“…The effectiveness of the method was demonstrated by the synthesis of P-analogues tripeptides and pentapeptide of historphin P (H-Tyr-Gly-Phe-Gly-Gly P ) (Scheme 19) [58,59]. Kukhar and co-workers appear to be one of the pioneers in utilization of aminophosphonates as amine components in the Petasis boronic acid Mannich reaction (Scheme 20) [60][61][62][63]. Among multicomponent reactions, the Petasis three-component reaction has been focus of attention in the last decades due to a number of advantages.…”

“…It should be noted that the conclusions on the stereochemistry of reaction products, made on the basis of theoretical calculations and X-ray diffraction studies, completely coincide [60]. The Petasis reaction with aminophosphonates was applied to prepare a number of specially constructed compounds with additional functional groups in order to test of their biological activity as protein tyrosine phosphatase inhibitors and immunomodulatory agents (Scheme 21) [61][62][63]. In the biochemistry of aminophosphonic acids, stereochemical aspects play a very important role, since many R-amino acids (corresponding to the L-configuration of natural amino acids) change their activity when replaced with the S-configuration.…”

“…Treatment of the silyl esters with methanol at room temperature smoothly yielded the corresponding 2-aminoethylidene-1,1-bisphosphonic acids. The biological activity of functionalized 2-aminoethylidene-1,1-bisphosphonic acids as immunomodulatory agents was a subject of special investigation (Scheme 32) [76]. The Kukhar's research group in cooperation with Prof.…”