Darmstoff analogues. 2. Ring and side-chain effects on smooth-muscle contraction.
2-cis-delta 8-Heptadecenyl-4-(hydroxymethyl)-1,3-dioxolane monosodium phosphate (1b) has been shown to be present as a major component of Darmstoff in mammalian intestine and to be a potent inducer for contraction of intestinal smooth muscle. The analogous 2-pentadecyl material 1a, also found abundantly in the intestine, is inactive. In this study, synthesis of phosphorylated hydroxymethyl-1,4-dioxanes, -tetrahydrofurans, -cyclopentanes, and -oxathiolanes bearing both oleyl and palmityl side chains is reported. Of these, 2-(hydroxymethyl)-5-cis-delta 8-heptadecenyl-1,4-dioxane monosodium phosphate (2b) exhibits about 12% of the activity of 1b. Its pentadecyl analogue 2a, like 1a, is totally inactive, as are all other compounds prepared. The results indicate that Darmstoff-like compounds exhibit specific chemical requirements for activity and that where activity is encountered, the side-chain specificity noted in 1a and 1b can be preserved.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010712:Phosphatidic Acids / Q000138:chemical synthesis / Q000494:pharmacology*
D010712:Phosphatidic Acids; C015775:darmstoff