Part II.: Two enzymatic procedures for the selective synthesis of malic acid monoesters

Two different enzymatic procedures have been developed for selectively obtaining two different regioisomers of malic acid monoesters; These procedures are based on differences in the reactivities of the carboxylic groups of malic acid in the presence of a Candida antarctica lipase. 1-dodecyl hydrogen 2-hydroxy-succinate was obtained via direct esterification of the alpha-hydroxy acid and 1-dodecyl hydrogen 5-hydroxy-succinate was synthesised via partial hydrolysis of the corresponding diester of malic acid. In both cases, the use of an organic solvent (dioxane and acetone, respectively) is required. In the esterification reaction, the polarity of the organic solvent has a great influence on the product distribution; more apolar organic media increase the yield of the diester byproduct. Initially, the reactions for the selective synthesis of the mono- and diester require addition of water to the solvent (2.9% and 0.75% [w/w] for dioxane and n-hexane, respectively). However, the selectivity and the conversion of the process increases markedly upon addition of a desiccant after 24 h of reaction (from 51 to 80% yield of 1-dodecyl hydrogen 2-hydroxy-succinate). In acetone the hydrolysis reaction was more selective than in n-hexane, but required the addition of 6.3% (w/w) water. Hydrolysis gives a relatively high yield of 4-dodecyl malate (79%). (C) 1999 Elsevier Science Inc. All rights reserved.