Synthetic and biotransformation studies on prochiral non-proteinogenic amino acids: Diethyl α-acetamido, α-alkylmalonates

Abstract

Nine diethyl α-acetamido, α-alkylmalonates 3-11 (alkyl=methyl, benzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl and 3-chlorobenzyl) have been synthesised in three steps starting with diethyl malonate in overall yields of 49-90%. The structures of <i>C</i>-alkylated acetamidomalonates have been established on the basis of their spectral data, the structures of two compounds <b>9</b> and <b>11</b> are also confirmed on the basis of their X-ray crystallographic studies. Further, the X-ray crystal structure of the chiral monoethyl ester of α-acetamidomalonic acid <b>1</b> has been studied. None of our <i>C</i>-alkylated acetamidomalonate has been found to be a substrate for lipase-catalysed enantiodifferentiating deesterification/ hydrolysis of the symmetric diester groups.