Novel Amino Acid Derivatives. Preparation and Properties of Aminoacylphosphonates and Amino Hydroxyimino Phosphonates

Article abstract of DOI:10.1021/jo00312a021

Reaction of N-(benzyloxycarbonyl)prolyl chloride with (MeO)3P followed by treatment of the resulting acylphosphonate 5 with LiBr in MeCN gave lithium methyl Cbz-prolylphosphonate (6a).Didemethylation of 5 by treatment with Me3SiBr led to sodium Cbz-prolylphosphonate (6b).Fmoc-alanyl chloride and Fmoc-phenylalanyl chloride were converted similarly to the corresponding dimethyl Fmoc-aminoacylphosphonates 7, which were monodemethylated to methyl ester lithium salts 8.Phthalimidoacyl 9 derived from β-Ala, τ-aminobutyric acid, and DL-Ala gave dimethyl phthalimidoacylphosphonates 10, which were converted to oximes 11 by NH2OH, to methyl phthalimidoacylphosphonate lithium salts 12 and methyl phthalimido α-hydroxyimino phosphonate lithium salts 13 by LiBr demethylation of compounds 10 and 11, respectively.Diisopropyl phthalimidoacylphosphonates 14 derived from Gly, β-Ala, τ-aminobutyric acid, DL-Ala, and L-Phe were prepared by the Arbuzov reaction of their N-phthaloyl chlorides with (2-PrO)3P, which in turn yielded oximes 16.These were deblocked by hydrazine to yield diisopropyl amino-α-(hydroxyimino)alkylphosphonates 17.Similarly oxime derivatives 18 of diethyl phthalimidoacylphosphonates 15 derived from amino acids Ala and Phe could be hydrazinolyzed to diethyl amino hydroxyimino phosphonates 19.