The synthesis of chiral arene oxide metabolites of benz[a]anthracene: optically active benz[a]anthracene 10,11- and 5,6-oxides

Abstract

(+)-Benz[a]anthracene 10,11-oxide (9) has been obtained in optically pure form by a four-step synthesis from (–)-trans-(10R,11R)-10-bromo-11-(menthyloxyacetoxy)-8,9,10,11-tetrahydrobenz[a]anthracene (1A) which was separated from diastereoisomer (1B) by recrystallization. The absolute configuration of (+)-(9) was established as (10S,11R) by application of the exciton-chirality method to the circular dichroism curve of the benzoate (+)-(6) and by a correlation of stereochemistry between (+)-(6),(–)-(4), and (+)-(9). (+)-Benz[a]anthracene 5,6-oxide (15) has been synthesised in 30% optical yield using partially resolved (+)-cis-5,6-dihydroxy-5,6-dihydrobenz[a]anthracene (11) obtainable by chromatographic resolution of the (–)-cis-5,6-dimenthyloxyacetoxy-5,6-dihydrobenz[a]anthracene diasteroisomers (12A) and (12B). Both arene oxides, (+)-(9) and (+)-(15), showed configurational stability at ambient temperature in accord with perturbation molecular orbital calculations.