title: Enantioselective total synthesis of ustiloxin D.
abstract: Ustiloxin D and phomopsin A are potent antimitotic agents that bind to tubulin and interfere with cellular microtubule function. A synthetic strategy has been developed to allow access to both of the natural products as well as a variety of variants of the ustiloxin and phomopsin family members in order to provide sufficient quantities for biological studies. Herein we report the enantioselective total synthesis of ustiloxin D using a longest linear sequence of 20 steps. Four of the five stereocenters were set using catalytic asymmetric methodologies. In particular, Evans's new Al-catalyzed asymmetric aldol reaction facilitated access to both syn and anti products corresponding to the different benzylic stereochemistries found in ustiloxins and phomopsins. In addition, due to its high functional group tolerance, Trost's Pd-mediated etherification was used to construct the chiral tertiary alkyl-aryl ether. Taken together, these synthetic strategies allow us to use densely functionalized intermediates to realize an efficient synthesis of ustiloxin D.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tanaka
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Sawayama
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wandless
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D010455:Peptides; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C089079:ustiloxin D