Chemo-enzymatic route to bridged homolyxofuranosyl-pyrimidines

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

“…In our earlier research work, bridged homolyxofuranosylpyrimidines were synthesized following a chemoenzymatic methodology where biocatalyst Novozyme 435 was used for regioselective acetylation of the primary hydroxy group present in 3′-Obenzyl-β-ᴅ-glucofuranosylpyrimidines [27]. In this article, regioselective acylation at the primary hydroxy group of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylpyrimidines was carried out with the different biocatalyst Lipozyme TL IM using the same acylating agent, i.e., vinyl acetate but in a different solvent, i.e., 2-Me-THF instead of THF and at a different temperature, i.e., 40 °C instead of 45 o C as mentioned in the previous reaction conditions.…”

“…Further, Zhang et al [ 23 ] synthesized the tricyclic azido-isonucleoside analogue 5 and Imanishi et al [ 24 ] synthesized the azido-nucleoside 6 with a conformationally restricted sugar moiety. Recently, we have developed a greener and efficient chemoenzymatic synthetic methodology for the synthesis of conformationally restricted bicyclic azido-nucleosides 6 [ 25 ] and 7 [ 26 ], and bicyclic homonucleosides 8 [ 27 ]. Herein, we report an efficient chemo-enzymatic and chemical route to synthesize two novel conformationally restricted azido-homoarabino nucleosides 9a , b in excellent overall yields ( Figure 1 ).…”

Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides

“…Finally, debenzylation of nucleosides 7a,b was achieved using 20% Pd(OH) 2 /C/HCO 2 H to yield the titled bicyclic nucleosides, that is, 1- 8b) in 82% and 85% yield, respectively, by following the literature procedure. 41 (Scheme 2). Herein, yields of the chemical reactions of this series and corresponding C-3′ epimers were compared.…”

“…Finally, debenzylation of nucleosides 7a , b was achieved using 20% Pd(OH) 2 /C/HCO 2 H to yield the titled bicyclic nucleosides, that is, 1-((1 S ,3 R ,4 S ,7 R )-7-hydroxy-6-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)pyrimidine-2,4(1 H ,3 H )-dione ( 8a ) and 1-((1 S ,3 R ,4 S ,7 R )-7-hydroxy-6-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-5-methylpyrimidine-2,4(1 H ,3 H )-dione ( 8b ) in 82% and 85% yield, respectively, by following the literature procedure. 41 (Scheme 2 ). Herein, yields of the chemical reactions of this series and corresponding C-3′ epimers were compared.…”

“…In our earlier studies, the nucleoside monomer of locked-nucleic acid (nucleoside D , Figure 1 ) was found to be locked into C3′- exo sugar puckering with pseudorotational phase angle ( P = 193.74 and 201.13°), indicating the S -type conformation of the nucleoside. 41 The pseudorotational phase angle ( P ) calculated 44 for the 1-((1 S ,3 R ,4 S ,7 R )-7-hydroxy-6-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-5-methylpyrimidine-2,4(1 H ,3 H )-dione ( 8b ) was found to be 196.11° implying C3′- exo sugar puckering and S -type conformation of the nucleoside. The calculated values of dihedral angles (ν 0 = –2.45, ν 1 = 38.64, ν 2 = –55.59, ν 3 = 55.59, ν 4 = –34.91) confirmed the conformation of the nucleoside 8b to be C3′- exo , that is, S -type conformation.…”