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.
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.
Trost
Barry M
BM
Department of Chemistry, Stanford University, CA 94305-5080, USA. bmtrost@stanford.edu
Dudash
Joseph
J
Dirat
Olivier
O
D000447:Aldehydes / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D001685:Biological Factors / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000737:chemistry; D005285:Fermentation / Q000502:physiology; D005663:Furans / Q000737:chemistry*; D006031:Glycosylation; D006921:Hygromycin B / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010165:Palladium / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry
D000447:Aldehydes; D001565:Benzoates; D001685:Biological Factors; C448001:C-2-epi-hygromycin A; D002934:Cinnamates; D005663:Furans; D010636:Phenols; D013450:Sulfones; D006921:Hygromycin B; C026273:hygromycin A; D010165:Palladium