Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen among polycyclic aromatic hydrocarbons. Because the fjord-region diolepoxide (DE) pathway is one of the mechanisms of activation, (+/)-trans-DB[a,l]P-11,12-dihydrodiol, (+/-)-anti-DB[a,l]PDE and (+/-)-syn-DB[a,l]PDE were synthesized. The key intermediate for these syntheses, 12-methoxy-DB[a,l]P, was successfully obtained by cyclization of 6-(3-methoxybenzyl)benzanthrone with methanesulfonic acid, which in turn was prepared by 1,4 conjugate addition of 3-methoxybenzyl magnesium bromide to benzanthrone. The presence of the DB[a,l]P nucleus in the dihydrodiolepoxides and diolepoxides was proven by conversion of 12-methoxyDB[a,l]P into the parent compound in several steps. The tumor-initiating activity of the two diolepoxides in mouse skin was compared to that of DB[a,l]P-11,12-dihydrodiol and the parent DB[a,l]P. Groups of 24 8 week old female SENCAR mice were topically initiated with 12, 4 or 1.33 nmol of compound in 100 microliters of acetone. Starting 1 week later, promotion with 12-O-tetradecanoylphorbol-13-acetate (1.62 nmol in 100 microliters acetone) was begun and continued twice weekly for 30 weeks. At the 12, 4 and 1.33 nmol doses, anti-DB[a,l]PDE induced 2.0, 0.7 and 0.7 tumors per mouse (t/m) respectively, whereas syn-DB[a,l]PDE induced 1.8, 1.5 and 1.8 t/m. At the same three doses, DB[a,l]P-11,12-dihydrodiol induced 4.6, 4.3 and 2.8 t/m, and DB[a,l]P resulted in 9.3, 7.1 and 5.2 t/m. These results confirm that DB[a,l]P is more potent than its 11,12-dihydrodiol and show that the two diolepoxides are less tumorigenic than their precursors. At the medium and low doses, syn-DB[a,l]PDE is more tumorigenic than its congener anti-DB[a,l]PDE.

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Route selection, process development and large-scale preparation of selectively benzoylated and fluorinated d-glucopyranoses, required as glycosyl donors for the synthesis of the SGLT inhibitor SAR7226, are discussed.

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The thermal decompositions of several phenyl(trihalomethyl)mercury compounds in the presence of substituted benzaldehydes 1 and dimethyl acetylenedicarboxylate (7) in dry benzene at 80 °C resulted in 2-halo-5-arylfuran-3,4-dicarboxylates 9 in isolated yields (not optimized) that ranged from 13% to 64%. These products appear to be the result of selective attack by dihalocarbene on the aldehyde followed by preferential capture of the resulting carbonyl ylide by the acetylenic dipolarophile and loss of hydrogen halide. The substitution of diethyl fumarate (12) for acetylene 7 produced a mixture of the E and Z isomers of dihydrofuran 14 in a ratio of 70:30. Tetrasubstituted dipolarophiles failed to give comparable products. The intermediate dihalocarbonyl ylides were shown to undergo halogen exchange.