Chemo-enzymatic synthesis of bicyclic 3-azido- and 3-amino-nucleosides

Manish Kumar; Vivek K. Sharma; Carl Erik Olsen; Ashok K. Prasad

doi:10.1039/c4ra06805j

Chemo-enzymatic synthesis of bicyclic 3-azido- and 3-amino-nucleosides

Manish Kumar, Vivek K. Sharma, Carl Erik Olsen, Ashok K. Prasad

Section for Plant Biochemistry

5 Citations (Scopus)

Abstract

Conformationally locked 3′-azido-3′-deoxythymidine analogues of T, U, A and C containing a 2′-O,4′-C-methylene linked bicyclic furanose moiety has been efficiently synthesized following a greener chemo-enzymatic convergent route. Thus, one of the two diastereotopic hydroxyl groups of 3-azido-3-deoxy-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d- ribofuranose has been regioselectively acetylated using Novozyme®-435 in quantitative yield. The selective enzymatic acetylation can be carried out with the same efficiency using Novozyme®-435 for 10 cycles of reaction. The monoacetylated sugar derivative was converted to bicyclic 3′- azidonucleosides in four steps in overall yields of 60 to 68%. It has been demonstrated that 3′-azido-3′-deoxy-2′-O,4′-C- methylenethymidine can easily be converted into 3′-amino-3′-deoxy- 2′-O,4′-C-methylenethymidine in 95% yield, which is an important monomer for the synthesis of therapeutically useful sugar-modified oligonucleotides.

Original language	English
Journal	R S C Advances
Volume	4
Issue number	70
Pages (from-to)	37231-37235
Number of pages	5
ISSN	2046-2069
DOIs	https://doi.org/10.1039/c4ra06805j
Publication status	Published - 2014

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title = "Chemo-enzymatic synthesis of bicyclic 3-azido- and 3-amino-nucleosides",

abstract = "Conformationally locked 3′-azido-3′-deoxythymidine analogues of T, U, A and C containing a 2′-O,4′-C-methylene linked bicyclic furanose moiety has been efficiently synthesized following a greener chemo-enzymatic convergent route. Thus, one of the two diastereotopic hydroxyl groups of 3-azido-3-deoxy-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d- ribofuranose has been regioselectively acetylated using Novozyme{\textregistered}-435 in quantitative yield. The selective enzymatic acetylation can be carried out with the same efficiency using Novozyme{\textregistered}-435 for 10 cycles of reaction. The monoacetylated sugar derivative was converted to bicyclic 3′- azidonucleosides in four steps in overall yields of 60 to 68%. It has been demonstrated that 3′-azido-3′-deoxy-2′-O,4′-C- methylenethymidine can easily be converted into 3′-amino-3′-deoxy- 2′-O,4′-C-methylenethymidine in 95% yield, which is an important monomer for the synthesis of therapeutically useful sugar-modified oligonucleotides.",

author = "Manish Kumar and Sharma, {Vivek K.} and Olsen, {Carl Erik} and Prasad, {Ashok K.}",

year = "2014",

doi = "10.1039/c4ra06805j",

language = "English",

volume = "4",

pages = "37231--37235",

journal = "RSC Advances",

issn = "2046-2069",

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TY - JOUR

T1 - Chemo-enzymatic synthesis of bicyclic 3-azido- and 3-amino-nucleosides

AU - Kumar, Manish

AU - Sharma, Vivek K.

AU - Olsen, Carl Erik

AU - Prasad, Ashok K.

PY - 2014

Y1 - 2014

N2 - Conformationally locked 3′-azido-3′-deoxythymidine analogues of T, U, A and C containing a 2′-O,4′-C-methylene linked bicyclic furanose moiety has been efficiently synthesized following a greener chemo-enzymatic convergent route. Thus, one of the two diastereotopic hydroxyl groups of 3-azido-3-deoxy-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d- ribofuranose has been regioselectively acetylated using Novozyme®-435 in quantitative yield. The selective enzymatic acetylation can be carried out with the same efficiency using Novozyme®-435 for 10 cycles of reaction. The monoacetylated sugar derivative was converted to bicyclic 3′- azidonucleosides in four steps in overall yields of 60 to 68%. It has been demonstrated that 3′-azido-3′-deoxy-2′-O,4′-C- methylenethymidine can easily be converted into 3′-amino-3′-deoxy- 2′-O,4′-C-methylenethymidine in 95% yield, which is an important monomer for the synthesis of therapeutically useful sugar-modified oligonucleotides.

AB - Conformationally locked 3′-azido-3′-deoxythymidine analogues of T, U, A and C containing a 2′-O,4′-C-methylene linked bicyclic furanose moiety has been efficiently synthesized following a greener chemo-enzymatic convergent route. Thus, one of the two diastereotopic hydroxyl groups of 3-azido-3-deoxy-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d- ribofuranose has been regioselectively acetylated using Novozyme®-435 in quantitative yield. The selective enzymatic acetylation can be carried out with the same efficiency using Novozyme®-435 for 10 cycles of reaction. The monoacetylated sugar derivative was converted to bicyclic 3′- azidonucleosides in four steps in overall yields of 60 to 68%. It has been demonstrated that 3′-azido-3′-deoxy-2′-O,4′-C- methylenethymidine can easily be converted into 3′-amino-3′-deoxy- 2′-O,4′-C-methylenethymidine in 95% yield, which is an important monomer for the synthesis of therapeutically useful sugar-modified oligonucleotides.

U2 - 10.1039/c4ra06805j

DO - 10.1039/c4ra06805j

M3 - Journal article

SN - 2046-2069

VL - 4

SP - 37231

EP - 37235

JO - RSC Advances

JF - RSC Advances

IS - 70

ER -

Chemo-enzymatic synthesis of bicyclic 3-azido- and 3-amino-nucleosides

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