A simple enzymatic preparation of 2',3'-di-O-acetylnucleosides through a lipase catalyzed alcoholysis

Article abstract of DOI:10.3390/50300533

Several 2',3'-di-O-acetylnucleosides (2a-d) were obtained regioselectively through a Candida antarctica B lipase catalyzed alcoholysis.

Full text of DOI:10.3390/50300533

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Molecules 2000, 5
A Simple Enzymatic Preparation of 2’,3’-Di-O-
Acetylnucleosides Through a Lipase Catalyzed Alcoholysis
1
1
2
1
1,2
Alejandra Zinni , Alejandro Schmidt , Mariana Gallo , Luis Iglesias and Adolfo Iribarren
1
Centro de Estudios e Investigaciones, Universidad Nacional de Quilmes - Roque Sáenz Peña 180 -
1876) Bernal - Buenos Aires, Argentina
(
2
INGEBI (CONICET) - Vuelta de Obligado 2490 - (1428) - Buenos Aires, Argentina
E-mail: leiglesias@unq.edu.ar
Abstract: Several 2’,3’-di-O-acetylnucleosides (2a-d) were obtained regioselectively
through a Candida antarctica B lipase catalyzed alcoholysis.
Introduction
Much effort has been devoted to the synthesis of nucleoside analogues as most of the antiviral
agents used at present against extensive viral affections belong to this family of compounds [1]. Due to
the polyfunctional nature of nucleosides, selective transformations are usually required to prepare these
molecules in good yields. However, such reactions are frequently difficult to carry out satisfactorily by
means of traditional synthetic procedures [2]. For instance, in the synthesis of oligonucleotides and nu-
cleosides prodrugs, regioselective protection and deprotection of hydroxyl groups are carried out
through multy-steps processes.
Enzymes have become nowadays well-recognized regio- and stereoselective catalysts in synthetic
chemistry [3], and lipases are one of the most useful biocatalysts due to their efficiency, easy work up
and stability in organic solvents. These facts prompted us to study lipase-catalyzed deacylation of nu-
cleosides 1a-d through a Candida antarctica B lipase (CAL) catalyzed alcoholysis:
AcO
B
HO
O
B
O
EtOH
CAL
OAc OAc
OAc OAc
1
a-d
2 a-d
Scheme. a R= H, B= 1-uracyl; b R= CH , B= 1-uracyl; c R= H, B=9-hypoxantyl; d R= H, B=9-guanyl.
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Molecules 2000, 5
Experimental
The alcoholysis shown in the Scheme were performed at 200 rpm and 28º C. The reaction mixtures
were analyzed by both TLC and HPLC, using a C-18 column. After a convenient time was reached,
the enzyme was filtered off and products 2a-d were isolated by column chromatography, affording
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satisfactory spectral data ( H and C NMR).
Results and Discussion
R
Although the reactions depicted in the Scheme were studied employing three lipases: Lipozyme
(
Mucor miehei lipase), Candida rugosa lipase and CAL, only the latter exhibited activity. With this
biocatalyst, compounds 2a-d could be obtained regioselectively in good yields. The ethanol/nucleoside
ratio and the solvent showed a dramatic effect on the selectivity and the yield of the biotransformation.
In contrast to the non enzymatic synthesis of compounds 2a,c,d, which requires three steps, the re-
gioselective enzymatic alcoholysis presented herein avoids one step and is carried out under simple
and mild conditions.
References and Notes
1.
2.
3.
Périgaud, C.; Gosselin G.; Imbach, J.L. Nucleosides Nucleotides 1992, 11, 903.
Hanrahan J.R.; Hutchinson, D.W. J .Biotechnol. 1992, 23, 193.
Wong C.H.; Whitesides, G.M. Enzymes in synthetic organic chemistry; Elsevier Science Ltd.: Ox-
ford, 1994, Cap. 2.
4
.
.
Sachder, H.S.; Starkovsky, N.A. Tetrahedron Letters 1969, 7, 33.
Iglesias, L.E.; Zinni, A.; Gallo, M.; Iribarren, A. Submitted for publication.
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