Darmstoff Analogues. 2. Ring and Side-Chain Effects on Smooth-Muscle Contraction

Article abstract of DOI:10.1021/jm00344a006

2-cis-Δ⁸-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-Δ⁸-heptadecenyl-1,4-dioxane monosodium phosphate (2b) exhibits about 12percent 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.