CHEMOENZYMATIC SYNTHESIS OF AMINO ACID-BASED SURFACTANTS

The application of lipases to the synthesis of amino acid-based surfac tants was investigated. Low yields (2-9%) were obtained in the acylati on of free amino acids, such as L-serine and L-lysine, as well as thei r ethyl esters and amides with fatty acids, owing in part to low misci bility of the reactants. When the N-carbobenzyloxy (Cbz)-L-amino acids were used in an effort to improve miscibility of the amino acid deriv atives with the acyl donor, a dramatic improvement was observed for N- Cbz-L-serine (92% yield) but not for N-alpha-Cbz or N-zeta-Cbz-L-lysin e sine (7 and 2% yield, respectively). As an alternative, an efficient synthesis of N-zeta-acyl-L-lysines was developed, based on the regios pecific chemical acylation of copper(II) lysinate. In pursuit of a gen eral route to amino acid-fatty acid surfactants, the utility of a poly ol linker was investigated. Thus, the glycerol ester of NalphaNzeta-di -Cbz-L-lysine was prepared and evaluated as a substrate for acylation. As expected, this and other glycer-1-yl esters of N-protected amino a cids were excellent substrates for lipase-catalyzed acylation. Their r eaction with myristic acid in the presence of Novozyme resulted in the regioselective acylation of the primary hydroxyl group of the glycero l moiety to afford the corresponding 1-O-(N-Cbz-L-aminoacyl)-3-O-myris toylglycerols with conversions of 50-90%. These were readily deprotect ed to give a range of 1-O-(aminoacyl)-3-O-myristoylglycerols with over all yields of 27-71%.