title: Total synthesis of azumamide A and azumamide E, evaluation as histone deacetylase inhibitors, and design of a more potent analogue.
abstract: The unprecedented diastereoselective Mannich reaction of a Z-allylsulfoximine was a key step in the total synthesis of the marine natural products azumamide A and E, and an unnatural analogue. Their relative potency as histone deacetylase inhibitors was evaluated and found to correlate with predicted zinc-binding affinity. [reaction: see text]
authors.affiliation: School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom.
authors.forename: Shijun
authors.initials: S
authors.lastname: Wen
authors.forename: Krystle L
authors.initials: KL
authors.lastname: Carey
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakao
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fusetani
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry; D001665:Binding Sites; D001688:Biological Products / Q000138:chemical synthesis / Q000494:pharmacology; D003622:Dapsone / Q000031:analogs & derivatives / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D008956:Models, Chemical; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D000498:Allyl Compounds; D001688:Biological Products; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C516228:azumanide A; C516229:azumanide E; C036115:sulfoxone; D003622:Dapsone; D015032:Zinc