A Facile and Practical Synthesis of Peracylated 4-Thio-d-ribofuranoses from d-Glucose

Abstract

A practical synthesis of a peracylated 4-thio-D-ribofuranose 14 starting from inexpensive d-glucose is described. The C2-C6 portion of D-glucose was utilized, in which sulfur was introduced to C5 in two consecutive displacement reactions with net retention of configuration under mild conditions.

Chemical synthesis of 4′-thio and 4′-sulfinyl pyrimidine nucleoside analogues

“…Simple trituration from MeOH isolated the β-anomer of 1 exclusively in a satisfactory 50% yield from 5 , with analytical data confirming those reported previously for d - ribo thiofuranoses. 9 The development of this synthetic route to 1 required no column chromatography and was completed starting from 100 g of 2 , delivering 1 in an overall yield of 25% for the seven steps and in 25 g quantity.…”

“…Bioisosteric replacement of furanose oxygen with larger sulfur seeks to explore the biological effect, imparted through changes to furanose ring conformation and the hydrolytic stability of a thiohemiaminal glycosidic linkage. Insertion of a sulfur atom to access thiofuranose components generally start from available chiral pool materials and the use of thiourea to convert 4,5-epoxides to 4,5-thiiranes, 8,9 alongside sodium sulfide-mediated formation of 2,5-bicyclic systems are notable examples of key intermediates developed to enable this. [10][11][12] Open chain systems have also been used, 13 for example, effecting double displacement of a 1,4-bismesylate with Na 2 S to access 1-deoxy thiofuranoses, 14 and both C1 aldehyde and thioacetal oxidation levels have delivered access to anomeric thioglycosides.…”

“…in a satisfactory 50% yield from 5, with analytical data confirming those reported previously for Dribothiofuranoses. 9 The development of this synthetic route to 1 required no column chromatography and was completed starting from 100 g of 2, delivering 1 in an overall yield of 25% for the seven steps and in 25 g quantity. The chemistry developed in Scheme 1 was next mapped onto a 2-deoxy-2,2-gem-difluoro ribose system to access 4'-thiogemcitabine and analogues thereof (Scheme 2).…”

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

“…Depending on this observation, we postulated a mechanistic pathway for this cyclization process, where two consecutive inversions of configuration at the C5′ centre enabled the retention of stereochemistry. Thus, formation of 5,6-epoxide moieties was common in case of hexose carbohydrates, where the C6-OH group attacked the C5 centre and substituted the mesyl group present at C5 to form 5,6-epoxide moieties [32][33][34]. Herein, we elucidated the mechanistic pathway for conversion of 16a,b into 9a,b through the formation of an intermediate epoxide II, which has (S) stereochemistry at the C5′ due to first inversion of configuration by attack from the C6′-OH group (Scheme 6).…”

Synthesis and anticancer evaluation of 4’-thio and 4’-sulfinyl pyrimidine nucleoside analogues

“…Simple trituration from MeOH isolated the β-anomer of 1 exclusively in a satisfactory 50% yield from 5, with analytical data confirming those reported previously for Dribothiofuranoses. 9 The development of this synthetic route to 1 required no column chromatography and was completed starting from 100 g of 2, delivering 1 in an overall yield of 25% for the seven steps and in 25 g quantity.…”