Safe and Alternate Process for the Reductions of Methanesulfonates: Application in the Synthesis of 1,2,3-Triacetyl-5-deoxy-d-ribofuranoside

Abstract

Diethylene glycol dimethyl ether, diglyme, and 1,2-bis­(2-methoxyethoxy)­ethane, triglyme, are found to be suitable and safe alternate solvents to DMSO for the reduction of methanesulfonate in sodium borohydride. Addition of anhydrous lithium chloride led to the complete reduction of methanesulfonate esters to the corresponding alkanes in the presence of sodium borohydride in these solvents (diglyme and triglyme). This protocol is useful in the preparation of 1,2,3-triacetyl-5-deoxy-d-ribofuranoside, 7, a key intermediate of Capecitabine, 1, on the commercial scale.

Hybrid Chemoenzymatic Synthesis of C7‐Sugars for Molecular Evidence of in vivo Shikimate Pathway Inhibition

“…Protected as acetonide, the unique deoxy group of 5dR (12) was formed via methanesulfonate and sodium borohydride following the synthetic approach leading to the chemotherapeutic agent capecitabine. [26][27][28] In contrast, the pentose 13 received its fluorine group from TBAF (tetrabutylammonium fluoride), for targeted C-7 alteration of 7d7FSh (2). [29] Final deprotection gave the deoxy sugars 12 and 13, both, ready to use for chemoenzymatic synthesis of 1 and 2.…”

“…Here, d ‐ribose served as the starting carbohydrate. Protected as acetonide, the unique deoxy group of 5dR ( 12 ) was formed via methanesulfonate and sodium borohydride following the synthetic approach leading to the chemotherapeutic agent capecitabine [26–28] . In contrast, the pentose 13 received its fluorine group from TBAF (tetrabutylammonium fluoride), for targeted C‐7 alteration of 7d7FSh ( 2 ) [29] .…”

3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation

“…Glycosylation of the silylated 4-(arylhydrazono)-3-(trifluoromethyl)-4,5dihydro-pyrazolones (4-7) with 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose (17) [17] in the presence of SnCl 4 in dry CH 2 Cl 2 , under Vorbr€ uggen glycosylation conditions provided the corresponding N 2 -b nucleosides (18)(19)(20)(21), respectively in good yields (Scheme 1). The downfield chemical shift of the anomeric protons (6.24-6.28 ppm), as a result of the anisotropic effect of the 2-oxo moiety of the hydrazopyrazolone ring, confirms the glycosylation at the N 2 -position in 18-21.…”

“…1,2,3-Tri-O-acetyl-5 0 -deoxy-b-D-ribofuranose (22) was synthesized according to literature procedure. [18] Coupling of 4-7 with 22 under Vorbr€ uggen glycosylation conditions provided the 5 0 -deoxyribonucleoside derivative 23-26, respectively in good yields (Scheme 2). Deprotection of 23-26 was performed with NaOMe in MeOH to give the free nucleosides 12-15 in good yields (Scheme 2).…”

“…The crude residue was purified by silica gel column chromatography (eluate: Hexane/dichloromethane, 1/1 to 100% dichloromethane) to give 18-21. 2-[(2,3,5-tri-O-benzoyl-b-D-ribofuranosyl](Z)-4-(2-(3-nitrophenyl)hydrazono)-5-(trifluoromethyl)-2,4-dihydro-3H-pyrazol-3-one (18). Compound 18 was prepared by coupling of 4 with 17 according to general procedure (B).…”