title: Total synthesis of (-)-7-epicylindrospermopsin, a toxic metabolite of the freshwater cyanobacterium aphanizomenonovalisporum, and assignment of its absolute configuration.
abstract: [reaction: see text] The Z and E nitrones 38 and 39 from condensation of aldehyde 20 with hydroxylamine 36 underwent intramolecular dipolar cycloaddition to give the substituted 1-aza-7-oxobicyclo[2.2.1] heptanes 40 and 41 in a ratio of 2:1, respectively. Reductive N-O bond cleavage of 40 followed by carbonylation gave cyclic urea 47 in which inversion of the secondary alcohol was effected via an oxidation-reduction sequence. After conversion of the p-bromobenzyl ether 50 to azide 54, activation of the cyclic urea as its O-methylisourea and reduction of the azide led to spontaneous cyclization to afford the tricyclic nucleus 59 of cylindrospermopsin. Global deprotection, including hydrolysis of the 2,4-dimethyoxypyrimidine appendage to a uracil, and then monosulfation of the resultant diol 60 afforded a substance identical with natural (-)-7-epicylindrospermopsin (1). The asymmetric synthesis of (-)-7-epicylindrospermopsin defines its absolute configuration as 7S,8R,10S,12S,13R,14S.
authors.affiliation: Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: White
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hansen
mesh_terms: D000470:Alkaloids; D001427:Bacterial Toxins; D000458:Cyanobacteria / Q000737:chemistry*; D000087522:Cyanobacteria Toxins; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000470:Alkaloids; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D014867:Water; C089595:cylindrospermopsin; D014498:Uracil