Incubation of 2,4-diethyl-1,2-dihydro-2-methylquinoline (DMDQ) with hepatic microsomes from rats pretreated with phenobarbital, 3-methylcholanthrene, pregnenolone-16 alpha-carbonitrile, or dexamethasone results in minor loss of the cytochrome P-450 chromophore and accumulation of a hepatic pigment. The hepatic pigment consists of the four regioisomers of N-ethylprotoporphyrin IX and minor amounts of the corresponding N-methyl regioisomers. Exposure of chick embryo liver cells to DMDQ results in inhibition of their ferrochelatase activity, induction of their 5-aminolevulinic acid synthase activity, and accumulation of protoporphyrin IX. 1,2-Dihydro-2,2,4-trimethylquinoline (TMDQ) causes negligible loss of cytochrome P-450 in rat liver microsomes but in vivo still produces the four N-methylprotoporphyrin IX regioisomers in low yield. Furthermore, it inhibits ferrochelatase activity, elevates 5-aminolevulinic acid synthase activity, and causes protoporphyrin IX accumulation in cultured chick embryo hepatocytes. One-electron oxidation of the 2,2-dialkyl-1,2-dihydroquinolines to radical cations is postulated to result in N-alkylation of the prosthetic heme group of cytochrome P-450. The N-alkylprotoporphyrins IX thus formed are potent inhibitors of ferrochelatase. Inhibition of ferrochelatase causes the induction of 5-aminolevulinic acid synthase and the accumulation of protoporphyrin IX. Heme alkylation and ferrochelatase inhibition may be generally associated with substrates that are subject to cytochrome P-450 mediated oxidative extrusion of alkyl radicals.
The thermal, nonphotochemical isomerization of vitamin A aldehydes plays a central role in vertebrate and invertebrate vision as well as in light-driven proton pumping in certain halophilic bacteria. In vertebrate vision, 1 l-ris-retinal bound to opsin via a protonated Schiff base (rhodopsin) is photochemically isomerized to its all-trans congener, which then is hydrolyzed to form alltrans-reúnal and opsin.1 In order for rhodopsin regeneration to occur, all-trans-retinal, or a derivative thereof, must be thermally isomerized to its 11-cis congener. In certain halophilic bacteria, a photochemical transformation of the all trans to the 13retinylidine Schiff base (probably in the protonated form), coupled with a thermal back reaction, is of importance in the proton pumping cycle.2 Therefore, the mechanism(s) by which the retináis and their Schiff bases are thermally interconverted is of great importance.
Three bisolefinic carbamates and five NJf-diallyl N-substituted amines have been subjected to hydroformylation conditions under catalysis by HCo(CO)4, Co(CO)8, and (Ph3P)3Rh(H)CO in an attempt to prepare heterocyclic ketones. The products differ with amines and carbamates and with the catalyst. Carbamate 3 and HCo(CO)4 gave 3-pyrrolidinone (4) in 45% yield. The cobalt-catalyzed reaction of 8 and rhodium-catalyzed reaction of 3 and of 8 afforded products arising from hydroformylation at the terminal olefinic carbon. These mixtures usually included 2-pyrrolidinone; cobalt-catalyzed hydroformylation of chlorinated allylamines 10-12 provided Nbenzyl-2-pyrrolidinone ( 14) and /V^V-dibutylbenzylamine ( 16). Direct synthesis of potential intermediates including 18 has permitted the delineation of mechanistic rationale.
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