1.2.4.5- Tetrahydrobenzo

Ethyl 3-acetyl-5-hydroxy-8-methyl-6-(phenylsulfonyl)-1,2,3,6-tetrahydrobenzo[ 1,2-b 4,3-t/]dipyrrole-1 -carboxylate... 

Dihalo- and dinitropyromellitic acids undergo cyclization when reacted with sulfur tetrafluoride and hydrogen fluoride to give high yields of 4,8-dihalo- and 4,8-dmitro-l,l,3,3,5,5,7,7-octafluoro-l,3,5,7-tetrahydrobenzo[l,2-c 4,5-c 5]difurans, respectively [218, 219, 220] (equation 112). 

However, another representative of benzo-fused tetrahydropyrimidines, 3,4,5,6-tetrahydrobenzo[/i]quinazoline 61, was reported to exist exclusively as the tautomer shown, without any indication of the annular tautomeric equilibrium (91M209). 

It is therefore orf/io-valeryl-.J -tetrahydrobenzoic acid. The anhydride is formed by the elimination of a molecule of water from the two side chains. 

Starting from l.l-dichloro-7b-ethoxy-2-methyl-1,1 a,2,7-tetrahydrobenzo[/)]cyclopropa[prepared from the corresponding benzothiopyran by addition of dichlorocarbene, the three 1-benzothiepins 6a-c are formed upon treatment with strong bases, i.e. sodium methoxide or ethoxide in dimethyl sulfoxide.73 The optimal yield of each 1-benzo-thiepin compound depends on the molar equivalents of base, as follows from different ring-opening mechanisms. 

Methyl 4-methyl-3-[(A -phenylcarbamoyl)imino]-3,4,5,6,7,8-hexahydro-2-quino-xalinecarboxylate (201) underwent cyclization to give lO-methyl-3-phenyl-6,7,8,9-tetrahydrobenzo[g]pteridme-2,4(3//, 10/7)-dione (202) (Et3N, MeOH, reflux, 20 min 80%) and subsequent catalytic aromatization to 10-methyl-3-phenylbenzo[g]pteridine-2,4(3//, 10//)-dione (203) (Pd/C, decahydronaphtha-lene, reflux, 1 h 85%) analogs likewise. ... 

The first successful transformation of protoberberines to benzo[c]-phenanthridines was reported by Onda et al. (122,123). Irradiation of the enamines 200 and 195, the Hofmann degradation products of the corresponding protoberberines, in benzene afforded the initial photoproducts 201, which immediately rearranged to the tetrahydrobenzo[c]phenanthridines 202 in 70% yield (Scheme 37). Dehydrogenation of 202 afforded dihydro-chelerythrine (203) and dihydrosanguinarine (204), which were further oxidized with dichlorodicyanobenzoquinone (DDQ) to yield chelerythrine (205) and sanguinarine (206), respectively. 

Compound 316 contains two suitable ene-diene functions that yielded two diastereomeric tetrahydrobenzo[4]qui-nolizidines in quantitative yield and in a 8 92 ratio in a TiCU-catalyzed intramolecular Diels-Alder (IMDA) reaction (Equation 9) <1998T9529>. 

The diol epoxide derivative of benzo(a)pyrene, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene also known as (+) -73,8a-dihydroxy-9ot,10a-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene,was the first diol epoxide to be synthesized. Interest in this compound was stimulated by the report by Borgen et al. (8) that a metabolite of benzo(a)pyrene, tentatively identified as the trans-7,8-diol ( 1) became covalently bound to DNA in the presence of rat liver micro-somes. Sims et al. ( ) suggested that the active metabolite was a diol epoxide derivative of unspecified stereo chemistry. 

Syntheses of the trans-7,8-dihydrodiol derivatives of 7-and 8-methylbenzo(a)pyrene via Method I have also been reported (24-26). Conversion of the latter to trans-7,8-dihydroxy-anti-9,10-epoxy-8-methyl-7,8,9,10-tetrahydrobenzo(a)pyrene, has also been described (26). 

Figure 2. Synthesis of trans-7,8-dihydroxy-anti(and syn)-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti- and syn-BPDE) via Method I ( ,2 ). Reagents (i) NaBH, (ii) H+ (iii) AgOBz, I- (iv) NBS (v) DBN (vi) NaOMe (vii) DDQ (viii) m-CPBA (ix) DMSO, H20 (x) t-BuOK.

Table III. DNA Intercalation Association Constants Reported for trans-7,8-Dihydroxy-ant i-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene...

When the 7,8-hydroxyl groups are missing, epoxide introduction occurs from both sides of the pyrene ring. Thus 7,8-dihydrobenzo(a)-pyrene is cooxidized by PGH synthase to a potent mutagen that is identified by product and nucleic acid binding studies as 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (Equation 3) (32). The structures... 

R = CN, C02Et, CONH2 Scheme 6.245 Multicomponent condensation in the synthesis of tetrahydrobenzo[b]pyrans. 

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