| Abstract
| - A short and convenient synthesis of 3‘- and 5‘-O-levulinyl-2‘-deoxynucleosides has been developedfrom the corresponding 3‘,5‘-di-O-levulinyl derivatives by regioselective enzymatic hydrolysis,avoiding several tedious chemical protection/deprotection steps. Thus, Candida antartica lipase B(CAL-B) was found to selectively hydrolyze the 5‘-levulinate esters, furnishing 3‘-O-levulinyl-2‘-deoxynucleosides 3 in >80% isolated yields. On the other hand, immobilized Pseudomonas cepacialipase (PSL-C) and Candida antarctica lipase A (CAL-A) exhibit the opposite selectivity towardthe hydrolysis at the 3‘-position, affording 5‘-O-levulinyl derivatives 4 in >70% yields. A similarhydrolysis procedure was successfully extended to the synthesis of 3‘- and 5‘-O-levulinyl-protected2‘-O-alkylribonucleosides 7 and 8. This work demonstrates for the first time application ofcommercial CAL-B and PSL-C toward regioselective hydrolysis of levulinyl esters with excellentselectivity and yields. It is noteworthy that protected cytidine and adenosine base derivatives werenot adequate substrates for the enzymatic hydrolysis with CAL-B, whereas PSL-C was able toaccommodate protected bases during selective hydrolysis. In addition, we report an improvedsynthesis of dilevulinyl esters using a polymer-bound carbodiimide as a replacement for dicyclohexylcarbodiimide (DCC), thus considerably simplifying the workup for esterification reactions.
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