Synthesis of a Central Intermediate in the Biosynthesis of Di- and Trideoxysugars

✍ Scribed by Müller, Thomas ;Schmidt, Richard R.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 943 KB
• Volume: 1997
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199719970916

✦ Synopsis

Abstract

The synthesis of disodium (6‐deoxy‐α‐D‐ribo‐hexopyran‐3‐ulosyl) (2′‐deoxythymidin‐5′‐yl) diphosphate (1) is described. To this end, D‐glucose is transformed into known furanose derivative 2 possessing a 3‐C‐methylene group as latent functionality for 3‐ulose generation. From 2, 3,6‐dideoxy derivative 6 was synthesized; ensuing acid catalyzed cleavage of the 1,2‐O‐isopropylidene group and then O‐acetylation furnished the required pyranose 8α,β, which could be selectively deacetylated at the anomeric oxygen to afford 9α,β. Treatment with phosphitylating agent 13e and then oxidation led to dibenzylphosphate derivative 15e which could be chemoselectively debenzylated by hydrogenolysis without affecting the olefinic double bond (→ 17); de‐O‐acetylation and then ozonolysis afforded the unprotected phosphate intermediates 18 and 19, respectively. Both compounds could be successfully used for the synthesis of 1 by employing the nucleoside phosphate morpholidate procedure for the generation of nucleoside diphosphate sugars. Ozone cleavage of the olefinic double bond in 20 could be successfully performed even in the presence of the thymine moiety.