The synthesis of heterocyclic compounds of pharmaceutical interest from conjugated acetylenic and allenic nitriles

The reaction of hydroxyacetylenic nitriles with 2-aminoethanethiol gives 3-(2-aminoethylthio)-4-hydroxy-alkyl-2-enenitriles. These do not cyclise directly to a furan but isomerise directly to the corresponding N-adducts which then cyclise to give 5-amino-3-(2-thioethylamino)-2,2-dialkyl-2,3-dihydrofurans in > 90 percent yield. After protecting the hydroxyl function of a 3-(2-aminoethylthio)-4-hydroxyalkyl-2-enenitrile as a tetrahydropyranyl derivative, this S-adduct isomerised to the corresponding N-adduct on keeping. Three new 5,6-dihydro-3H-furo [3,4-b]-1,4-thiazines were prepared from the 5-(1-alkyl-1-tetrahydropyranyl-oxyalkyl)-6-cyano-2,3-dihydro-4H-1,4-thiazines by hydrolysis to the corresponding 5-(1-hydroxyalkyl)-6-cyano-2,3-dihydro-1,4-thiazines followed by base catalysed cyclisation. The addition of half molar amounts of a-phenylethylamine to two allenic nitriles resulted in the isolation of recovered allenic nitrile with low optical purity. In both cases the absolute configuration of the recovered allene was related to that of the resolving agent(Summary)

Microscopic and enzyme histochemical studies on the liver and kidney of rats treated with fulvine, the toxic alkaloidal constituent of crotalaria fulva

Histochemical changes in the liver of rats, treated with the pyrrolizidine alkaloidal constituent of Crotalaria fulva, indicated primarily damage of the hepatic parenchymal cells. The observed differences in activity of enzymes suggested functional inpairment of the cell membrane, mitochondria, endoplasmatic reticulum, and lysosomes in the liver cells. In large doses, fulvine produced a hyaline droplet degeneration in the epithelium of the proximal convoluted tubules of the kidney. Stability of the mitochondrial and changes in activity of the lysosomal enzymes would imply a functional adaptation, rather than primary damage of the epithelium.(AU)