Enzymes in organic chemistry, part 2: Lipase-catalysed hydrolysis of 1-acyloxy-2-arylethylphosphonates and synthesis of phosphonic acid analogues of L-phenylalanine and L-tyrosine

Abstract

α-Hydroxyphosphonates (±)- 3, prepared by base catalysed addition of phosphites 2 to aldehydes 1, were acylated to give esters (±)- 4. Diethyl 1-acyloxy-2-arylethylphosphonates (±)- 4a, 4b, and 4e were hydrolysed by lipase from Aspergillus niger in a biphasic system to afford ( R)- α-hydroxyphosphonates of low enantiomeric purity. The corresponding diisopropyl phosphonates (±)- 4c, 4f and 4g gave ( S)- α-hydroxyphosphonates with an ee of up to 78%. The absolute configuration of the α-hydroxyphosphonates was assigned by 31P NMR spectroscopy of their ( R)-MTPA-esters. (S)- 3 b and 3e were chemically transformed via their azides to phosphonic acid analogues of L-phenylalanine and L-tyrosine, respectively.