Total Synthesis of (-)-7-Epicylindrospermopsin,a Toxic Metabolite of the Freshwater Cyanobacterium Aphanizomenon ovalisporum,and Assignment of Its Absolute Configuration

摘要

The Z and E nitrnnes 38 and 39 from condensation of aldehyde 20 with hydroxylamine 36 underwent intramolecular dipolar cycloaddition to give the substituted l-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.