2 alkanoate ester

Compounds of type 184 were prepared similarly with R, = methyl and R2 = alkanoic esters (136, 229, 304) or carboxyethyl (4, 10, 13, 22, 220) (Table 11-27). Dichloroacetone reacts with ammonium thiocyanate, but... 

In Candida sp., degradation of the CoA-alkanoic esters to the alkenoic acid esters is catalyzed by an acyl-CoA oxidase and results in the production of H2O2 that is converted into O2 by catalase activity. The enzyme from C. tropicalis contains FAD (Jiang and Thorpe 1983), and in C. lipolytica carries out a stereospecific antielimination of hydrogen (Kawagnchi et al. 1980). 

A bifnnctional enol-CoA hydratase and 3-hydroxyacetyl-CoA dehydrogenase are used in the degradation of CoA-alkenoic esters to the p-keto acid. This is then degraded to acetyl-CoA and the lower alkanoate ester by 3-ketoacetyl CoA thiolase and acetyl-CoA thiolase. 

Additional BHT-derived 5-LO inhibitors bear heteroatom-linked 4-substituents. Searle s SC-45662 (50) was selective (25 1) for 5-LO over CO in cRBL (3.7 /iM) and in A23187-stimulated RBL-1 cells (7.1 yuM) [146]. Besides NSAID-like activity in RAA (down to 10 mg/kg p.o.), SC-45662 also inhibited GPB (ED30 16.7 mg/kg p.o.), and LTB4 release from ulcerative colitis rectal mucosal biopsy samples was decreased [147]. Several patents have described similar compounds where the alkyl substituent on sulphur is varied quite widely [148 151]. Oxidation of the distal sulphur was consistent with activity, while replacement of this sulphur with oxygen gave reduced potency. Simple alkyl groups, alkylene-linked esters and amides, and disulphide-linked alkanoic esters were also active in cRBL with similar potency free carboxylic acids were somewhat less potent. Oxidation of the sulphur attached to the phenolic ring destroyed the activity. 

JOC 50 3408 (1985) (2,2-dihalo-alkanoate ester to 2-halo-alkanoate ester)... 

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