First Regioselective Enzymatic Alkoxycarbonylation of Primary Amines. Synthesis of Novel 5′- and 3′-Carbamates of Pyrimidine 3′,5′-Diaminonucleoside Derivatives Including BVDU Analogues

摘要

The first regioselective enzymatic alkoxycarbo-nylation of primary ammo groups has been achieved in pyrimidine 3′,5′-diaminonucleoside derivatives. Thus, Candida antarctica lipase B (CAL-B) catalyzed this reaction with nonactivated homocarbonates allowing the selective synthesis of several N-5′ carbamates, including (E)-5-(2-bromovi-nyl)-2′-deoxyuridine (BVDU) analogues, with moderate-high yields, whereas immobilized Pseudomonas cepacia lipase (PSL-C) afforded mixtures of alkoxycarbonylated regioiso-mers. To obtain N-3′ carbamates selectively, a short and efficient chemoenzymatic route was used employing some of the N-5′-protected derivatives previously synthesized.