Application of the AAA Reaction to the Synthesis of the Furanoside of C-2-epi-Hygromycin A: A Total Synthesis of C-2-epi-Hygromycin A

✍ Scribed by Barry M. Trost; Joseph Dudash; Jr.; Olivier Dirat

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 210 KB
• Volume: 8
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/1521-3765(20020104)8:1<259::aid-chem259>3.0.co;2-d

✦ Synopsis

A strategy for stereocontrolled syntheses of furanoside type of natural products is developed for a glycosyl aryl ether. This strategy resolves the issue of low diastereoselectivity typical of normal glycosidation methods for furanosides. All the stereochemistry ultimately derives from a desymmetrization of a 2,5-diacyloxy-2,5-dihydrofuran using Pd catalyzed asymmetric allylic alkylation which sets both the absolute stereochemistry and 1,4-relative stereochemistry. Diastereo-controlled elaboration of the 3,4-double bond then completes the synthesis. A new conjunctive reagent, 1-nitro-1-phenylsulfonyl-ethane, is developed to serve as an acyl anion equivalent. The utility of a phenol as a nucleophile in the Pd catalyzed glycosylation is demonstrated. From this strategy emerged a short, practical synthesis of C-2-epi-hygromycin A.