A divergent chemoenzymatic route to an intermediate for nucleoside analogues

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Abstract

Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (∼3–4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl transfer, preliminary experiments do suggest a definite but minor role of enzyme for this intramolecular acyl transfer. Compounds 1 and 2 may serve as intermediates for nucleoside analogues.

Section snippets

Selected NMR (CDCl3, 200 MHz) data:

For 6a:δ 7.35–7.27 (5H, m, Ar-H), 4.35–4.33 (2H, m, H-5, ArCH2), 4.22–4.12 (4H, m, 2 × CH2OAc), 3.90 (1H, br m, ArCH2), 3.08 (3H, m, H-3, H-4), 2.08 (3H, s, OAc), 2.05 (3H, s, OAc).

For 1a: δ 7.43–7.25 (5H, m, Ar-H), 4.28 (2H, m, H-5, ArCH2), 4.02 (2H, m, CH2OAc), 3.80 (3H, m, CH2OH, ArCH2), 3.07 (2H, m, H-3), 2.35 (1H, m, H-4), 2.05 (3H, s, OAc).

For 2a:δ 7.35–7.29 (5H, m, Ar-H), 4.71 (1H, m, H-5), 4.41 (2H, m, ArCH2), 4.19 (2H, m, CH2OAc), 3.0 (4H, m, CH2OH, H-3), 2.40 (1H, m, H-4), 2.08 (3H, s,

Acknowledgements

Author A.B. expresses thanks to Council of Scientific and Industrial Research, Government of India, for funding.

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