Chemoenzymatic approach toward the pure enantiomers of 2-methyl-1,3-propanediol mono (p-methoxybenzyl ether)

In a route towards the enantiomerically pure 2-methylpropane-1,3-diol mono( p-methoxybenzyl ether), which is an important starting material for natural product synthesis, a kinetic resolution approach by means of lipase-cataly zed hydrolysis as well as acylation has been elaborated. Candida antarctica lipase-catalyzed hydrolysis of the corresponding racemic acetate proceeded with high enantioselectivity (E 35). During the studies, a curious phenome non was observed, namely, that the enantioselectivity gradually declined ac companying the progress of the hydrolysis. This was due to inhibition of th e enzyme-catalyzed reaction caused by the accumulation of the resultant alc ohol. The rate of reaction of the more reactive enantiomer became lower. Th is situation prompted a new process, which would minimize the contamination or the undesired enantiomer, prior to the enzyme-catalyzed hydrolysis. Thi s was successfully achieved with the aid of another Pseudomonas cepacia lip ase-catalyzed desymmetrization, taking advantage of the prochiral nature of the starting material, 2-methyl-1,3-propanediol, and the subsequent p-meth oxybenzylation under mild conditions.