Jyotirmoy Maity

Efficient and selective enzymatic acylation reaction: separation of furanosyl and pyranosyl nucleosides.

Candida antarctica lipase-B (CAL-B) immobilized on lewatite selectively acylated the primary hydroxyl group of the furanosyl nucleoside in a mixture of 1-(alpha-D-arabinofuranosyl)thymine and 1-(alpha-D-arabinopyranosyl)thymine. This selective biocatalytic acylation of furanosyl nucleoside has enabled us an easy separation of arabinofuranosyl thymine from an inseparable mixture with arabinopyranosyl thymine. The primary hydroxyl selective acylation methodology of arabinonucleoside has also been successfully used for the separation of 1-(beta-D-xylofuranosyl)thymine and 1-(beta-D-xylopyranosyl)thymine from a mixture of the two, which demonstrate the generality of the enzymatic methodology for separation of furanosyl and pyranosyl nucleosides.

Benzoyl Cyanide: A Mild and Efficient Reagent for Benzoylation of Nucleosides

Abstract Efficient benzoylation of various nucleosides has been accomplished in pyridine with a catalytic amount of DMAP and benzoyl cyanide under mild conditions.

Gel-immobilized enzymes as promising biocatalysts: Results from Indo-Russian collaborative studies

Chemo-enzymatic methods constitute a promising approach to obtain various biologically active compounds, including enantiomerically pure substances. Entrapment in gels is one of the most convenient methods to stabilize enzymes for their application in water/organic media. Proteases and lipases are widely used for enantioselective transformations of various organic compounds in water-poor media. In this study, chymotrypsin was entrapped into a composite poly(N-vinyl caprolactam)-calcium alginate (PVCL-CaAlg) and covalently attached to poly(vinyl alcohol) (PVA) cryogel beads. Lipase was immobilized by covalently attaching to aldehyde-bearing PVA cryogel beads. The activities of the entrapped biocatalysts were studied. Both entrapped α-chymotrypsin and lipase retained high activity in acetonitrile/water medium (water content 0.5–20 %) and displayed high storage stability for several months. The high operational stability of immobilized α-chymotrypsin and lipase in a cyclic process (up to 912 h in total) was also demonstrated. Gel-immobilized enzymes were successfully used to obtain optically pure L-phenylalanine (ee 98.6 and 83 % in the case of α-chymotrypsin and lipase, respectively) by enantioselective hydrolysis of Schiff’s base of amino acid ethyl ester in an acetonitrile/water system.

Chemo-enzymatic synthesis of 3′-O,4′-C-methylene-linked α-L-arabinonucleosides

Lipozyme® TL IM catalyzed the diastereoselective acetylation of C-4′-hydroxymethyl over the other three hydroxyl groups of C-4′-hydroxymethyl-β-D-xylofuranosylnucleosides using vinyl acetate as acetyl donor to afford the corresponding C-4′-acetoxymethylnucleosides in 88 to 95% yields. The developed biocatalytic methodology has been successfully used for the efficient and environmentally friendly synthesis of 3′-O,4′-C-methylene-linked α-L-arabinofuranosylnucleosides from enzymatically monoacetylated nucleosides in 63 to 79% overall yields. The screening of vinyl esters of different alkyl chain lengths, i.e. vinyl acetate, vinyl propanoate and vinyl butanoate as acylating agent for biocatalytic diastereoselective acylation of the C-4′-hydroxymethyl group of tetrahydroxy-β-D-xylofuranosylthymine revealed that the rate of butanoylation and propanoylation is 2.0 and 1.5 times faster than that of acetylation, respectively.

N2-tert-Butoxycarbonyl-N5-[N-(9-fluorenylmethyloxycarbonyl)-2-aminoethyl]-(S)-2,5-diaminopentanoic Acid

N2-tert-Butoxycarbonyl-N5-[N-(9-fluorenylmethyloxycarbonyl)-2-aminoethyl]-(S)-2,5-diaminopentanoic acid (5) has been synthesized by the reaction of N2-tert-butoxycarbonyl-L-2,5-diaminopentanoic acid (Boc-L-ornithine, 3) and N-Fmoc-2-aminoacetaldehyde (N-Fmoc-glycinal, 4) in the presence of sodium cyanoborohydride in methanol containing 1% acetic acid at room temperature.

Greener Biocatalytic Approach to the Synthesis of Nucleosides and their Precursors

Novel, efficient and selective biocatalytic acylation / deacylation strategies have been used for the greener synthesis of precursors of different bicyclonucleosides. Biocatalytic methodology has also been developed for the separation of pyrano- and furanonucleosides, which is otherwise almost impossible to achieve by usual chemical approach.

MILD, EFFICIENT, SELECTIVE AND “GREEN” BENZOYLATION OF NUCLEOSIDES USING BENZOYL CYANIDE IN IONIC LIQUID

Use of benzoyl cyanide (BzCN) for benzoylation of nucleosides has been studied, both in pyridine and in ionic liquid. BzCN in 1-methoxyethyl-3-methylimidazolium methanesulfonate as ionic liquid has been found to be a “green” alternative compared to the pyridine-BzCN system. An efficient and selective benzoylation of nucleosides of both, the 2′-deoxy- and the ribo-series at ambient temperature was accomplished.

Synthesis of novel 3′-azido-3′-deoxy-α-L-ribo configured nucleosides: A comparative study between chemical and chemo-enzymatic methodologies

GRAPHICAL ABSTRACT ABSTRACT Syntheses of novel 3′-azido-3′-deoxy-2′-O,4′-C-methylene-α-L-ribofuranosyl nucleosides have been carried out from 3′-azido-3′-deoxy-4′-C-hydroxymethyl-β-D-xylofuranosyl nucleosides following both chemical and chemo-enzymatic methodologies. The precursor nucleoside in turn was synthesized from a common glycosyl donor 4-C-acetoxymethyl-1,2,5-tri-O-acetyl-3-azido-3-deoxy-α,β-D-xylofuranose, which was obtained by the acetolysis of 4-C-acetoxymethyl-5-O-acetyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-D-xylofuranose in 96% yield. It has been observed that a chemo-enzymatic pathway for the synthesis of targeted nucleosides is much more efficient than a chemical pathway, leading to the improvement in yield for the synthesis of 3′-azido-3′-deoxy-α-L-ribofuranosyl thymine and uracil from 49 to 89% and 55 to 93%, respectively.

Synthesis of novel 3-[(1-glycosyl-1 H -1,2,3-triazol-4-yl)- methylamino]ket-2-en-1-ones

Nine 3-[(1-β-D-ribofuranosyl- and 3-[(1-β-D-glucopyranosyl-1H-1,2,3-triazol-4-yl)methylamino]ket-2-en-1-ones have been synthesized by copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction between propargylamine derivatives and 1-azido-2,3,5-tri-O-benzoylβ-D-ribofuranose or 2,3,4,6-tetra-O-acetyl-1-azido-β-D-glucopyranose, followed by deprotection of the resulting tri-O-benzoyl- or tetraO-acetyl-1-β-D-glycosyltriazoles in good yields. The precursor propargylamine derivatives were synthesized by Sonogashira reaction of substituted acetylenes and benzoyl chloride followed by Michael-type addition of propargylamine to the resulting substituted alkynes in good yields. The precursor azido sugars, 1-azido-2,3,5-tri-O-benzoyl-β-D-ribofuranose and 2,3,4,6-tetra-O-acetyl-1-azido-β-D-glucopyranose, were synthesized by azidation of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose and β-D-glucopyranose pentacetate, respectively, with azidotrimethylsilane in the presence of tin(IV) chloride. All products were unambiguously characterized on the basis of the spectral data analysis.

Biocatalytic route to C-4′-spiro-oxetano-xylofuranosyl pyrimidine nucleosides

Abstract A facile access to C-4′-spiro-oxetano-xylofuranosyl nucleosides has been demonstrated for the first time through Lipozyme® TL IM-mediated regioselective acetylation of one of the primary hydroxyl group over the other primary and secondary hydroxyl groups in 3′-O-benzyl-4′-C-hydroxymethyl-β-D-xylofuranosyl nucleosides. Attempts to optimize a convergent route for these spironucleosides via selective manipulation of hydroxyl groups in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose were unsuccessful. Nevertheless; the present linear biocatalytic route efficiently afforded the C-4′-spiro-oxetanoxylofuranosyl nucleosides T and U in 47 and 38% overall yields, respectively, starting from corresponding furanose diol.