title: Asymmetric induction of conduritols via AAA reactions: synthesis of the aminocyclohexitol of hygromycin A.
abstract: Two synthetic routes towards the construction of the aminocyclohexitol moiety of hygromycin A have been developed based on palladium-catalyzed asymmetric alkylation of conduritol derivatives. A protocol has been established whereby this biologically relevant molecule is formed from benzoquinone. A conduritol A derivative is synthesized in eight steps from benzoquinone and is then subjected to the palladium reaction. From this flexible intermediate, four epimers of the aminocyclitol, including the natural one, can be obtained with complete stereoselectivity. Racemic conduritol B derivatives are available in four steps from benzoquinone, and these are then made enantiomerically pure by a palladium-catalyzed dynamic kinetic resolution. From the chiral conduritol B, the aminocyclitol is available in six steps. Excellent levels of enantio- and diastereoselectivity highlight these strategies.
authors.affiliation: Department of Chemistry Stanford University, CA 94305-5080, USA. bmtrost@leland.stanford.edu
authors.forename: B M
authors.initials: BM
authors.lastname: Trost
authors.forename: J
authors.initials: J
authors.lastname: Dudash
authors.forename: E J
authors.initials: EJ
authors.lastname: Hembre
mesh_terms: D000478:Alkylation; D002384:Catalysis; D002934:Cinnamates; D003511:Cyclohexanols / Q000138:chemical synthesis* / Q000737:chemistry; D053138:Cyclohexenes; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002934:Cinnamates; D003511:Cyclohexanols; D053138:Cyclohexenes; C090988:conduritol B; D006921:Hygromycin B; C026273:hygromycin A; D010165:Palladium