Synthesis of the phenolic derivatives of highly tumorigenic trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene

Journal Article · Fri Oct 27 04:00:00 EDT 1989 · Journal of Organic Chemistry; (USA)

DOI:https://doi.org/10.1021/jo00283a020· OSTI ID:7155795

Kumar, S; Kole, P L; Sehgal, R K ^[1]

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1. State Univ. of New York, Buffalo (USA)

Two isomeric phenolic derivatives of trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (42), 3,7,8-trihydroxy-trans-7,8-dihydrobenzo(a)pyrene (40), and 1,7,8-trihydroxy-trans-7,8-dihydrobenzo(a)pyrene (41), have been prepared in order to probe their relevance in the carcinogenesis of benzo(a)pyrene. Two methods have been developed for the synthesis of the key intermediates 3-acetoxy-9,10-dihydrobenzo(a)pyrene (25) and 1-acetoxy-9,10-dihydrobenzo(a)pyrene (26). In one method, known 1-methoxypyrene-6-carboxaldehyde (5) and 1-methoxypyrene-8-carboxaldehyde (6) were homologated, and the resulting 4-(methoxypyrene)butanoic acids 14 and 18 were cyclized with polyphosphoric acid (PPA) at 105{degree}C to produce 3-methoxy- and 1-methoxy-7,8,9,10-tetrahydrobenzo(a)pyren-7-one (19 and 21, respectively). The PPA cyclization at low temperature (90{degree}C) produced primarily the undesired seven-membered ring ketones 23 and 24, respectively. Demethylation of methoxy ketones 19 and 21 followed by successive reduction, dehydration, and acetylation afforded the key intermediates 25 and 26. The second method involves bromination of the trimethylsilyl cyanide derivative 27 of 7,8,9,10-tetrahydrobenzo(a)pyren-7-one followed by removal of the protecting group. 1-Bromo-7,8,9,10-tetrahydrobenzo(a)pyren-7-one (28) was obtained as a major and 3-bromo-7,8,9,10-tetrahydrobenzo(a)pyren-7-one (29) as a minor products of this synthesis.

• OSTI ID: 7155795
• Journal Information: Journal of Organic Chemistry; (USA), Journal Name: Journal of Organic Chemistry; (USA) Vol. 54:22; ISSN JOCEA; ISSN 0022-3263
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400201* -- Chemical & Physicochemical Properties
550200 -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AROMATICS
CONDENSED AROMATICS
DATA
DATA ANALYSIS
EXPERIMENTAL DATA
HYDROCARBONS
HYDROXY COMPOUNDS
INFORMATION
MEASURING INSTRUMENTS
MEASURING METHODS
NUMERICAL DATA
ORGANIC COMPOUNDS
PHENOLS
POLYCYCLIC AROMATIC HYDROCARBONS
PROMOTERS
PYRENE
SYNTHESIS
TUMOR PROMOTERS