New concept for the separation of an anomeric mixture of alpha/beta-D-nucleosides through regioselective enzymatic acylation or hydrolysis processes.

ABSTRACT

An efficient and high yield protocol for the synthesis and separation of 3'- and/or 5'-protected alpha-2'-deoxynucleosides has been developed through regioselective acylation/deacylation processes catalyzed by enzymes. Pseudomonas cepacia lipase (PSL-C) was found to be highly chemo- and regioselective toward the 3'-position of the beta-2'-deoxynucleoside derivatives, whereas PSL-C displayed opposite selectivity toward the 5'-position for the corresponding alpha-anomer. The successful application of this protocol was demonstrated by a convenient separation of an alpha/beta-mixture of thymidine derivatives from an industrial waste stream. Furthermore, this technique was also applied for the separation of an anomeric mixture of 2'-deoxy-2'-fluoro-alpha/beta-arabinonucleosides that are useful building blocks for the antisense constructs.