Enzymatic alcoholysis of 3′,5′-di-O-acetyl-2′-deoxynucleosides
Introduction
Biotransformations catalysed by hydrolytic enzymes provide convenient methods to achieve regioselective reactions in the sugar moiety of nucleosides. In addition to the usefulness of the described and reviewed enzymatic regioselective acylation and alkoxycarbonylation of nucleosides [1], [2], the hydrolase-catalysed deacylation of nucleosides has also been studied through enzymatic hydrolysis of peracylated deoxynucleosides [3], [4], [5], [6], [7] and ribonucleosides [6], [8], [9].
Over the last years we have been studying the enzymatic deacylation of peracylated ribonucleosides through enzymatic alcoholysis and we have found that Candida antarctica-B (CAL-B) lipase catalyses efficiently the formation of the corresponding 2′,3′-di-O-acylribo-nucleosides [10], [11], [12].
Taking into account these results, we considered of interest to study the behaviour of 3′,5′-di-O-acetyl-2′-deoxynucleosides (1a–e, Scheme 1) in the CAL-B catalysed alcoholysis (Scheme 2) and herein we report the results of these biotransformations.
Section snippets
General
Lipase B from Candida antarctica (CAL-B, Novozym 435, 10,000 PLU/mg solid; PLU: propyl laurate units) was a generous gift from Novozymes (Brazil). The enzyme was used straight without any further treatment or purification.
All employed reagents and solvents were of analytical grade and obtained from commercial sources. (2′S)-2′-deoxy-2′-C-methyluridine (1f, Scheme 1) and (2′R)-2′-deoxy-2′-C-methyluridine (1g) were prepared following a previously reported protocol developed by us [13].
Preparation of the substrates 1a–i (Scheme 1)
3′,5′-di-O
Results and discussion
Taking into account our previous results on CAL-B catalysed alcoholysis of peracylated ribonucleosides [10], [11], [12], which showed that the best regioselectivity could be reached by carrying out the biotransformations in a very high excess of ethanol, experiments of enzymatic alcoholysis of the diacetylated substrates 1a–i were performed using a similar nucleoside/alcohol ratio (see Experimental).
Under these conditions, only one monoacetylated product was formed, giving 3′-O
Conclusions
CAL-B lipase-catalysed alcoholysis of 3′,5′-di-O-acetyl-2′-deoxynucleosides gave the corresponding 3′-O-acetyl-2′-deoxynucleoside in yields ranging from 50 to 96%. In most cases, lower product yields were obtained compared to those afforded by CAL-B lipase-catalysed alcoholysis of peracetylated ribonucleosides [10], [11], [12]. The choice of the alcohol affected the rate of the enzymatic reaction and the yield of the 3′-O-acetylated product, but in all cases only this regioisomer was formed.
Acknowledgements
We thank UNQ, CONICET, SECyT and Fundación Antorchas for partial financial support. AMI and JMM are research members of CONICET. We are grateful to Novozymes (Brazil) for the generous gift of CAL.
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