The reaction of aryl and aralkyl aldoximes with hypophosphorous acid resulted in aminophosphinic acids, which were oxidized into the corresponding aminophosphonic acids.Ke7 words: amino acids, phosphorus analogs of amino acids; c~-aminoaralkylphosphinic acids, oxidation: a-aminoaralkylphosphonic acids.Phosphonic analogs of aromatic amino acids (1, R' is aryl or aralkyl) and their N-awl derivatives, including peptides, as well as the corresponding esters are some of the most studied compounds among phosphorus analogs of amino acids. A considerable number of works and reviews are devoted to their synthesis and properties.t-4 Being structural analogs of amino acids, s-aminophosphonic acids compete with them for active enzyme centers and receptors. As inhibitors of various metabolic transformations of amino acids, c~-aminophosphonic acids exhibit antibacterial and antitumor activity, are neuroactive, and have herbicide properties (see Refs. 1,5,and 6).Phosphinic analogs of aromatic amino acids (2, R is aryl or aralkyl) have not been adequately studied. One known procedure of their synthesis is based on addition of hypophosphorous acid to N-substituted Schiff's bases obtained from aldehydes with subsequent elimination of the protection. However, the yields of phosphinic analogs of Phe, Tyr, and Trp, synthesized by this procedure, are low (5--22%). The replacement of H3PO 2 by bis(trimethytsilyloxy)phosphine allowed one to increase markedly the yield in the case of phosphinic analog of Phe. 8 This reagent was used to synthesize the same Phe analog from N-(trityl)benzylideneimine. 9Some ary'l-substituted phosphinic analogs of phenylglycine were obtained by amidoalkylation of hypophosphorous acid with N,N'-arylidenebis(acetamides) followed by hydrolysis in 40--70% yields. But this method is not convcnient Ibr phosphinic analogs of the amino acids which differ from phenylglycine. Phosphinic analogs of proteinogenic aromatic amino acids were obtained in satisfactory yields by a rather complicated way from substituted imine of ethyl aminomethyl(diethoxymet hyle ne)ph osphinite, t t The first general method for the synthesis of a-aminoalkylphosphinic acids consisted in interaction of aldoximes with hypophosphorous acid, teadi ng in one stage to phosphinie analogs of AJa, Val, Met, and G[u. lz Although the reaction of oximes with HjPO 2 remained hitherto poorly studied, the limits of their applications were unclear, and the search for the optimal conditions required additional experiments. The simplicity and mild conditions of the synthesis determined the choice of the oxime variant for obtaining phosphinic analogs of aromatic amino acids (Scheme I).Earlier, lzJ5,16,~ we demonstrated the possibility of preparing o~-aminophosphinic acids by interaction of oximes of aliphatic aldehydes and ketones with H3PO 2. The formation of/W-hydroxy-a-aminophosphinic acids was not observed, but was observed in the case of acetaldoxime, acetone oxime, and benzaldoxime. 13.1"t However, it is possible that N~-hydroxy-ct-aminophosphinic acids a...
