Synthesis of 3′-azido/-amino-xylobicyclonucleosides

Abstract

Lipozyme® TL IM mediated the selective deacetylation of one of the two acetoxy groups in 4-C-acetoxymethyl-5-O-acetyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-d-xylofuranose, leading to the first efficient syntheses of 3′-azido/3′-amino-xylobicyclonucleosides T, U, C and A.

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

“…The Vorbrüggen coupling [ 17 ] of 7a , b with uracil in the presence of N,O -bis(trimethylsilyl)acetamide (BSA) and trimethylsilyltrifluoromethane sulfonate (TMS-triflate) in acetonitrile yielded the triacetylated nucleoside 8 in 94% yield. Subsequently, deacetylation of acetoxy groups in nucleoside 8 with 2 M NaOH solution in water/dioxane (1:1) also led to the concomitant cylization between suitably placed C-3′-OH and C-1′′-tosyl groups to afford 3′- O ,4′- C -methyleneuridine ( 9 ) in 82% yield ( Scheme 3 ) in similar manner as described in our earlier report [ 18 ].…”

“…Acetolysis of compound 11 yielded the glycosyl donor 12a , b in 95% yield, which on Vorbrüggen coupling with uracil under earlier used base-coupling conditions afforded the corresponding acetylated nucleoside 13 in 92% yield. Subsequent deacetylation of nucleosides 13 followed by concomitant cyclization with 2 M NaOH solution in water/dioxane (1:1) afforded 2′- O ,4′- C -methylene-xylouridine ( 14 ) in 95% yield ( Scheme 4 ) in a similar manner as described in our earlier report [ 18 ]. The structure of compound 2′- O ,4′- C -methylene-xylouridine ( 14 ) was confirmed by X-ray diffraction studies on its single crystal which also confirms the possibility of restriction of ring puckering in bicyclic nucleoside and the sugar ring puckering is locked in N -type conformation ( Fig.…”

“…General procedure for biocatalytic acetylation of ribo - and xylotrihydroxyfuranosides 3a,b: synthesis of compounds 4a,b. Similar as described in [ 18 ] to a solution of the mixture of compounds 3a , b (2 g, 9.08 mmol) in 2-methyl-THF (40 mL), vinyl acetate (1.26 mL, 13.6 mmol) was added followed by the addition of Novozyme ® -435 (0.2 g, 10% w/w of the compound 3a , b ). The reaction mixture was stirred at 35 °C in an incubator shaker for 1 h and the progress of the reaction was monitored periodically by TLC.…”

“…General procedure for the tosylation of monoacetylated sugar derivatives 4a and 4b: synthesis of compounds 5 and 10. Similar as described in [ 18 ] to a stirred solution of compound 4a (2 g, 7.6 mmol) in pyridine (20 mL), p -toluenesulfonyl chloride (2.18 g, 11.4 mmol) was added at 0 °C. The progress of the reaction was monitored by TLC and on completion after 2 h, the reaction mixture was neutralized by 10% ice-cold hydrochloric acid solution (80 mL) and extracted with chloroform (3 × 100 mL).…”

“…General procedure for the acetolysis of compounds 6 and 11: synthesis of tetraacetate compounds 7a,b and 12a,b. Similar as described in [ 18 ] acetic anhydride (6.2 mL, 65.43 mmol) and concentrated sulfuric acid (0.03 mL, 0.65 mmol) was added to a stirred solution of compound 6 (3 g, 6.5 mmol) in acetic acid (37.4 mL, 654.33 mmol) at 0 o C and mixture was stirred for 6 h at 30 °C. On completion, the reaction was quenched by addition of water (200 mL) and the product was extracted with chloroform (3 × 100 mL).…”