John H. Fried

Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

In order to improve the modest oral activity of PGE2 as an inhibitor of gastric acid secretion, analogs were prepared and tested orally in histamine-challenged rats. Insertion of a double bond at C-4, resulting in the 4,5-allene analog of PGE1, gave a small increase in activity. Introduction of the omega-tetranor-16-phenoxy lower sidechain, a modification known to enhance activity in the PGF series, gave an eight-fold increase in activity. The analog having both modifications (enprostil, 2) showed a six hundred-fold increase in oral antisecretory activity over PGE2, which may reflect a potentiation effect. Modification of enprostil at C-1 (various esters) and at C-11 (11-methyl, 11-deoxy) generally resulted in compounds of high activity while modifications at other sites generally resulted in significant reductions in activity.

Synthesis of lower chain allenic prostaglandins (1)

Abstract The synthesis of four lower chain allenic prostaglandin F α analogues IXA-D is described. The allenyl moiety has only occasionally been incorporated into the prostanoid skeleton and in all the examples thus far reported ·(2,3), this functionality is located in the upper side chain at carbons 4–6. This communication describes the synthesis of four isomeric allenyl PGF α derivatives wherein the cumulated diene system is situated at positions 13–15.

Synthesis of 2′,2′-difluoro-6,7-dihydro-16-methylenecyclopropa[6,7]progesterone analogues

17α-Acetoxy-2′,2′,6β-trifluoro-6β,7β-dihydro-16-methylenecyclopropa[6,7]progesterone (9) and its Δ1-analogue (10) have been synthesised by a ten-step reaction sequence from 3-hydroxy-16-methylpregna-5,16-dien-20-one (1).