Development of a Novel Synthetic Process for 2-Deoxy-3,5-di-O-p-toluoyl-α-l-ribofuranosyl Chloride:  A Versatile Intermediate in the Synthesis of 2‘-Deoxy-l-ribonucleosides

Abstract

A novel synthetic route to 2-deoxy-3,5-di-O-p-toluoyl-α-l-ribofuranosyl chloride (1) from inexpensive d-xylose (3) is described. 1 is a key intermediate in the synthesis of the antiviral agent 1-(2-deoxy-β-l-ribofuranosyl)thymine (β-l-thymidine) (2) and other 2‘-deoxy-l-ribonucleosides. This seven-step synthesis employs a key conversion of the d to the l configuration of the sugar moiety (6 to 7 in Scheme ) using simple reagents and reaction conditions. The entire process involves only three isolation steps. The key compound (1) was produced in 11% overall yield without chromatography.

Highly Stereocontrolled and Regiocontrolled Syntheses of 2,3,4-Trisubstituted Alkanoates and Lactones

“…The new chloro diols (±)- 3 and (±)- 5 were treated with hydrochloric acid in dioxane to form the all-cis 2-chloro-3-hydroxy γ-lactone (±)- 6 in 85% yield on a 1 / 2 g scale and the homologous all-cis lactone (±)- 7 in 70% yield (Scheme ). The proton NMR spectra of lactones (±)- 6 and (±)- 7 have the coupling constant J 2,3 = 4.4 and 4.0 Hz, respectively, consistent with the cis stereochemistry of the hydrogen atoms at positions 2 and 3; this result was confirmed via X-ray crystallography. The racemic chloro diol (±)- 5 was treated with 2,2-dimethoxypropane and catalytic p -toluenesulfonic acid in THF to form acetonide α-chloro ester (±)- 8 in 95% yield (Scheme ).…”

Total Synthesis of Leupyrrins A1 and B1, Highly Potent Antifungal Agents from the Myxobacterium Sorangium cellulosum

“…As shown in Scheme , an alternative sequence involved a diastereoselective hydroxyalkylation of lactone 97 , which may be obtained by two different routes. The first sequence started from known d ‐xylose ( 91 ) derivative 92 and involved TBS‐protection of the primary alcohol and stereoselective methylation of 93 . Alternatively, the methyl‐bearing stereogenic center was first introduced by an asymmetric Crimmins syn aldol reaction of 95 with aldehyde 94 .…”

“…As shown in Scheme15, an alternative sequence involved ad iastereoselective hydroxyalkylation of lactone 97,w hich may be obtainedb yt wo different routes.T he first sequence started from known d-xylose (91)d erivative 92 [45] and involved TBS-protection of the primary alcohol and stereoselective methylation of 93.A lternatively,t he methyl-bearings tereogenic center was first introduced by an asymmetric Crimmins syn aldol reaction of 95 with aldehyde 94. [46] Simultaneous Lewis acid mediated transesterification of the auxiliary carbamate group and removal of the acetonide group of aldol product 96 led to the desired lactone, which wass ubsequently TBS-protected at the primary hydroxyl.…”

Synthesis of α‐Chiral Butyrolactones by Highly Stereoselective Radical Transfer or Sequential Asymmetric Alkylations: Concise Preparation of Leupyrrin Moieties

“…Lactone 39 lacks the hydroxymethylene group and has no protecting group on the secondary hydroxyl moiety.L actone 39 was obtained by TBS protection of known lactone 38,w hich was available in four steps from xylose 37 (Scheme 6) following ak nown route. [30] Importantly,m ethylation of 40 could now be effected to give a-methyl lactone 39 as ad iastereomeric mixture (R/S = 9:1). [31] These results demonstrated that as elective alkylation can indeed proceed if the adjacent hydroxyl group is not protected.…”