Synthesis of optically active fjord-region 11,12-diol 13,14-epoxides and the K-region 9,10-oxide of the carcinogen benzo[g]chrysene

• Published in: Journal of organic chemistry 1989-07, Vol.54 (15), p.3533-3544
• Main Authors: Bushman, Daniel R, Grossman, Scott J, Jerina, Donald M, Lehr, Roland E
• Format: Article
• Language: English
• Subjects: 400201 - Chemical & Physicochemical Properties; 550200 - Biochemistry; AROMATICS; BASIC BIOLOGICAL SCIENCES; CARCINOGENS; CHALCOGENIDES; Chemical reactivity; Chemistry; DATA; DATA ANALYSIS; EPOXIDES; Exact sciences and technology; EXPERIMENTAL DATA; HYDROCARBONS; INFORMATION; INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; MEASURING INSTRUMENTS; MEASURING METHODS; NUMERICAL DATA; Organic chemistry; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; OXIDES; OXYGEN COMPOUNDS; POLYCYCLIC AROMATIC HYDROCARBONS; Reactivity and mechanisms; SYNTHESIS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00276a009

Optically pure enantiomers of the diastereomeric pair of benzo(g)chrysene-11,12-diol 13,14-epoxides (Scheme VI) were synthesized from (11R,12R)- and (11S,12S)-dihydroxy-11,12-dihydrobenzo(g)chrysenes (16(R,R) and 16(S,S)). Two routes were employed to synthesize the racemic dihydrodiol 16. Although the Prevost method for introduction of the trans-vicinal oxygen atoms at C{sub 11} and C{sub 12} of 13,14-dihydrobenzo(g)chrysene (7) proceeded poorly, introduction of the trans-vicinal oxygen atoms was readily achieved by hydration of the tetrahydro 11,12-epoxide (9, Scheme II) or by NaBH{sub 4} reduction of benzo(g)chrysene-11,12-dione (17, Scheme IV). The latter method is the most effective for the synthesis of the racemic dihydrodiol 16, whereas the former method is preferred for the preparation of substantial amounts of the enantiomers of 16 since the diastereomeric bis-(-)-menthyloxy esters of the tetrahydrodiol 11 (Scheme V) are much more effectively separated by HPLC than are the corresponding derivatives of the dihydrodiol 16. The conformational preference of the hydroxyl groups in the series-1 diol epoxide in which the benzylic 11-hydroxyl group and the epoxide oxygen are cis (19, Figure 2) was found to be dependent upon solvent, with a quasidiequatorial conformation being preferred in DMSO-d{sub 6} and a quasidiaxial conformation being preferred in CDCl{sub 3}. As anticipated from prior studies of the rates of hydrolysis of the 3,4-diol 1,2-epoxides of benzo(c)phenanthrene, the present 11,12-diol 13,14-epoxides are relatively stable in neutral, aqueous media. Enantiomers of the K-region 9,10-oxide 24 were prepared from benzo(g)chrysene (Scheme IX).