Biocatalytic route to C-3′-azido/-hydroxy-C-4′-spiro-oxetanoribonucleosides. (19th November 2015)

• Record Type: Journal Article
• Authors: Kumar, Manish; Sharma, Vivek K.; Kumar, Rajesh; Prasad, Ashok K.
• Is Part Of: Carbohydrate research. Volume 417(2015)
• Page Start: 19
• Page End: 26
• Publication Date: 2015-11-19
• Subjects: Biocatalysis -- Lipase -- Novozyme®-435 -- Diastereoselectivity -- Azido-spironucleosides; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2015.08.015
• Languages: English
• ISSNs: 0008-6215

Abstract

Highlights: Novozyme ® -435 catalyzed deacetylation methodology has been optimised for exclusive diastereoselective monodeacetylation of diacetoxy α-D-ribofurano-sugar derivative. The developed methodology has been successfully used for the efficient synthesis of 3′-azido-/3′-amino-C-4′-spiro-oxetanoribonucleosides T, U, C and A. Further, recently developed enzymatic diastereoselective decaetylation methodology has been used for the synthesis of C-4′-spiro-oxetanoribonucleosides A and C. The X-ray crystal data analysis on 3′-O-benzyl-C-4′-spiro-oxetanoribouridine revealed that the presence of spiro carbon restricts the conformational flipping of furanose ring. Thus the sugar puckering in C-4′-spiro-oxetanoribonucleosides attains N-type conformation which is in consonance with the literature report. Graphical abstract: Abstract: The lipase, Novozyme ® -435, exclusively deacetylates the 5- O -acetyl over 4- C -acetyloxymethyl group of almost identical reactivity in 5- O -acetyl-4- C -acetyloxymethyl-3-azido-3-deoxy-1, 2- O -isopropylidene- α -D-ribofuranose that led to the development of first and efficient synthesis of 3′-azido-/3′-amino- C -4′-spiro-oxetanoribonucleosides T, U, C and A in 20–24% overall yields. The X-ray study on the compound obtained by tosylation of lipase-mediated monodeacetylated product unambiguously confirmed the point of diastereoselective monodeacetylation on diacetoxy-azido-ribofuranose derivative. The capability of Novozyme ® -435 for selective deacylation of 5- O -acetyl group in 5- O -acetyl-4- C -acetyloxymethyl-3- O -benzyl-1, 2- O -isopropylidene- α -D-ribofuranose recently discovered by us has been successfully used for the synthesis of C -4′-spiro-oxetanoribonucleosides A and C in good yields. These results clearly indicate that the broader substrate specificity and highly selective capability of Novozyme ® -435 for carrying out acetylation/deacetylation reactions can be utilized for the development of environment friendly selective methodologies in organic synthesis.