Biocatalytic Separation of <i>N</i>-7/<i>N</i>-9 Guanine Nucleosides

Singh, Sunil Kumar; Sharma, Vivek; Olsen, Carl Erik; Wengel, Jesper; Parmar, Virinder S.; Prasad, Ashok K.

doi:10.1021/jo101565e

Cited by 12 publications

(3 citation statements)

References 32 publications

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“…Lipases have been used for selective esterification/transesterification reactions in the enzyme-mediated organic synthesis. , Furthermore, one of the lipases, viz. Novozyme-435 ( Candida antarctica lipase immobilized on polyacrylate), has been explored for carrying out selective reactions necessary for carbohydrate modifications − and polymer synthesis. − Taking lead from our previous experience of using lipases for discrimination between the two ester functions of triacylated pentofuranose derivatives with an aim to synthesize bicyclonucleosides, ,, Novozyme-435 lipase was used to affect the copolymerization reaction of hydroxy sugar monomers 2 , 5 , or 8 with the PEG dimethyl ester 10 under high vacuum and solventless conditions at 70 °C to synthesize poly[polyoxyethylene-oxy- bis (carboxymethyl)-4-methylene-1,2- O -isopropylidene-β- l - threo -pentofuranosyl] ( 11 ), poly[polyoxyethylene-oxy- bis (carboxymethyl)-4-methylene-1,2- O -benzylidene-β- l - threo -pentofuranosyl] ( 12 ), and poly[polyoxyethylene-oxy- bis (carboxymethyl)-4-methylene-1,2- O -isopropylidene-3- O -pentyl-β- l - threo -pentofuranosyl] ( 13 ) in 72, 54, and 67% yields, respectively. All three polymerization reactions when performed under identical conditions but without adding lipase did not yield any product.…”

Section: Resultsmentioning

confidence: 99%

Biocatalytic Route to Sugar-PEG-Based Polymers for Drug Delivery Applications

et al. 2011

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Sugar-PEG-based polymers were synthesized by enzymatic copolymerization of 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-benzylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-isopropylidene-3-O-pentyl-β-L-threo-pentofuranose with PEG-600 dimethyl ester using Novozyme-435 (Candida antarctica lipase immobilized on polyacrylate). Carbohydrate monomers were obtained by the multistep synthesis starting from diacetone-D-glucose and PEG-600 dimethyl ester, which was in turn obtained by the esterification of the commercially available PEG-600 diacid. Aggregation studies on the copolymers revealed that in aqueous solution those polymers bearing the hydrophobic pentyl/benzylidene moiety spontaneously self-assembled into supramolecular aggregates. The critical aggregation concentration (CAC) of polymers was determined by surface tension measurements, and the precise size of the aggregates was obtained by dynamic light scattering. The polymeric aggregates were further explored for their drug encapsulation properties in buffered aqueous solution of pH 7.4 (37 °C) using nile red as a hydrophobic model compound by means of UV/vis and fluorescence spectroscopy. There was no significant encapsulation in polymer synthesized from 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose because this sugar monomer does not contain a big hydrophobic moiety as the pentyl or the benzylidene moiety. Nile red release study was performed at pH 5.0 and 7.4 using fluorescence spectroscopy. The release of nile red from the polymer bearing benzylidene moiety and pentyl moiety was observed with a half life of 3.4 and 2.0 h, respectively at pH 5.0, whereas no release was found at pH 7.4.

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Section: Resultsmentioning

confidence: 99%

Biocatalytic Route to Sugar-PEG-Based Polymers for Drug Delivery Applications

et al. 2011

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“…In the convergent synthesis, a common glycosyl donor is synthesized for coupling with different nucleobases. ,, The earlier use of diol sugar precursor 3- O -benzyl-4- C -hydroxymethyl-1,2- O -isopropylidene-α- d -ribofuranose ( 3 ) for the synthesis of a common glycosyl donor is limited because it requires selective protection of one of the two primary hydroxyl groups . To overcome this limitation, di- O -mesylated derivative of the diol 3 has been employed, but this necessitates an additional two steps to remove the mesyl function toward the end of the synthesis (Supporting Information SI-Scheme 1). , It is at this juncture that the selectivity of lipases can be explored for discrimination between two primary hydroxyl groups in the precursor diol 3 . We herein report efficient and novel chemoenzymatic synthesis of bicyclic nucleosides T, U, A, and C via lipase-mediated regioselective acetylation of diol sugar precursors 3 .…”

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Chemoenzymatic Convergent Synthesis of 2′-O,4′-C-Methyleneribonucleosides

et al. 2014

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Novozyme-435-catalyzed efficient regioselective acetylation of one of the two diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d-ribofuranose has been achieved. The enzymatic methodology has been successfully utilized for convergent synthesis of bicyclic nucleosides (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme-435 can be used for 10 cycles of the acylation reaction without losing selectivity and efficiency.

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“…Similar applications of lipases have been reported for the separation of mixtures of arabinofuranosyl and -pyranosyl nucleosides [ 12 ], O -aryl α,β-D-ribofuranosides, etc. [ 13 – 15 ]. We herein report for the first time the use of Novozyme ® -435 for the separation of an epimeric mixture of xylo - and ribofuranosides.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

Rana

Kumar

Khatri

et al. 2017

Beilstein J. Org. Chem.

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Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility.

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Biocatalytic Separation of N-7/N-9 Guanine Nucleosides

Cited by 12 publications

References 32 publications

Biocatalytic Route to Sugar-PEG-Based Polymers for Drug Delivery Applications

Biocatalytic Route to Sugar-PEG-Based Polymers for Drug Delivery Applications

Chemoenzymatic Convergent Synthesis of 2′-O,4′-C-Methyleneribonucleosides

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

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