a'-Hydroxy-ct,f~-unsaturated cyclic ketones occupy a central position in the synthesis of complex natural products I. No enzymatic resolution of a'-hydroxy-a,[i-unsaturated ketones has been reported. In connection with out work on the development of new chiral building blocks for the synthesis of optically active natural products, we report here out results on the PLE-catalyzed preparation of (+)-6-hydroxy-3mcthylcyclohex-2-en-l-one 2 (Scheme I). 0 0 0 0.1M phosphate buffeffDMSO
(.+)-1 (-)-1 (+)-2
Scheme 1
The results of enzymatic hydrolysis of (+)-1 catalyzed by PLE are summarized in Table 1. Lipases isolated from porcine pancrease (PPL) and from the yeast Candida cylindracea (CCL) show low selectivity (< 20% e.e.). PLE exhibited the highest enantioselectivity among the other lipases tested. The broad substrate specificity and high stereoselectivity of pig liver esterase (PLE) is well documented. Many examples of the use of PLE in the stereoselective hydrolysis of racemiΒ’ monoesters have been reported 2'a . The important feature of this transformation is that the enantioselectivity is highly dependent on the co-solvent and the temperature.
Dimethylsulphoxide-phosphatΒ’ buffer system was the most effective for enhancing the enantioselectivity. Table 1 Results of the PLE catalyzed Hydrolysis of (+)-1 Entry Coav(%) Temp Solv Time A~oUol AeeU~e ! 0 IS soue 36