Synthesis of Biologically Active Metabolites of Dibenzanthracene

Article abstract of DOI:10.1021/jo01292a007

Syntheses are described of the trans 1,2- and 3,4-dihydro diol metabolites (3a and 1a) of dibenzanthracene (DBA) and the corresponding diol epoxide derivatives 4 and 2, implicated as the ultimate carcinogenic metabolites of DBA.The synheses of 1a and 3a are accomplished from DBA via lithium-ammonia reduction to 1,4,7,8,11,14-hexahydrodibenzanthracene, base-catalyzed isomerization, Prevost reaction, dehydrogenation, and basic methanolysis.This approach involves considerably fewer steps and affords superior overall yields than obtainable by more conventional methods entailing multistep ring construction.Epoxidation of 1a affords stereospecifically the anti diol epoxide isomer 2, whereas similar reaction of 3a furnishes a mixture of the corresponding syn and anti diol epoxide isomers in 3:1 ratio.Biological evidence implicates 1a and 2 as proximate and ultimate carcinogenic forms, respectively, of DBA.Synthesis of 3-hydroxydibenzanthracene, also known to be a metabolite of DBA, is also described.