An enzymatic alternative for the synthesis of nucleoside 5′-monophosphates

Abstract

A new procedure was carried out for the synthesis of nucleoside 5′-monophosphates, involving the use of two enzymes. The first step applied phospholipase D from Streptomyces netropsis and phosphatidylcholine as phosphatidyl donor, to give 5′-(3-sn-phosphatidyl) nucleosides (C, U, A, I). These were selectively hydrolysed in the second step by the action of phospholipase C from Bacillus cereus to produce the respective 5′-nucleotides. Application of this methodology on a preparative scale conducted to 5′-adenosine monophosphate in 63% overall yield from adenosine. The regioselectivity of these enzymes avoids protection steps, the overall synthesis is performed under mild reaction conditions and product isolation is easily achieved.