Synthèse et amination réductrice de phosphonopyruvates: préparation d'acides amino-2 carboxy-2 alkylphosphoniques (β-phosphonoalanine)

Abstract

The reaction of α-copper(I)alkanephosphonates with methyl and ethyl oxalyl chlorides gives methyl or ethyl dialkylphosphonopyruvates which, submitted to reductive amination in ethanol at pH 6–7 with sodium cyanohydridoborate (NaBH3CN) and ammonia, or primary amines, lead to phosphonic amino esters; hydrolysis with diluted HCl gives phosphonic amino acids. These three reactions constitute a general way to β-phosphonoalanine and β-alkyl β-phosphonoalanine.

ω -Phosphinyl-α -Amino Acids: Synthesis, and Development towards Use as Therapeutic Agents

“…Reductive amination with sodium cyanoborohydride and ammonia in ethanol (or methanol) furnishes phosphonate 25 which yields the AP3 derivative (26) with acid hydrolysis (Scheme 3) [17].…”

“…In an initial preparation of the AP5 analogue, (R)-4-oxo-5-phosphononorvaline 80, cuprate 99 [17,59] was generated from the reaction of CuI with diethyl lithiomethylphosphonate (THF, -65 o C), for a coupling reaction with the acid chloride of N-(benzyloxycarbonyl)-4-oxazolidone [100, derived in three steps from (R)-aspartic acid] to give ketophosphonate 101. While treatment with TMSI/MeCN yielded enantiopure 80 in 47% yield at laboratory scale [60], deprotection of the oxazolidone function proved problematic on scale-up, necessitating an alternative approach involving initial protection of (R)-aspartic acid as the -alkyl--methyl-(R)-N-(triphenylmethyl)aspartate 102.…”

Phosphorus-containing amino acids with a P–C bond in the side chain or a P–O, P–S or P–N bond: from synthesis to applications

“…Finally, the corresponding phosphonic a-amino acids 156a-e were obtained aer hydrolysis with hydrochloric acid (6 N) in satisfactory yields. 55 3.2.2. Via the alkylation of a nickel(II) complex of a glycine Schiff base.…”

Chemistry of Aminophosphonic Acids and Phosphonopeptides

“…One of the most effective strategies in the synthesis of complex g-aminophosphonic acids is based on the use of phosphonate carbanions to form CÀP bonds in the corresponding protected substrate. Thus, chiral amino acid esters can be introduced through the reaction with lithium dimethyl methylphosphonate easily generated from BuLi in THF to yield g-amino-b-keto-phosphonic acids with high stereocontrol [211][212][213]. The compounds 100 were used as reagents in the Horner-Wadsworth-Emmons reaction to synthesize stereoselectively unsaturated amino keto acids [211] and aminoalkohols [214].…”