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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
Author(s) -
Trost Barry M.,
Dudash, Jr. Joseph,
Dirat Olivier
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020104)8:1<259::aid-chem259>3.0.co;2-d
Subject(s) - hygromycin b , chemistry , radiochemistry , biochemistry , gene , mutant
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. Diastereocontrolled 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.