11,12-Secoprostaglandins. 1. Acylhydroxyalkanoic acids and related compounds

Abstract

The synthesis is described of a series of acylhydroxyalkanoic acids which embody structural modifications of that class of secoprostaglandins which are formally derived from the natural substances by scission of the cyclopentane ring between carbon atoms 11 and 12. These analogues have been tested for their ability to stimulate cAMP formation in the mouse ovary, a characteristic action of the (E)-prostaglandins, and for their ability to bind to the rat lipocyte prostaglandin receptor. Certain members of the series that most closely resemble the prostaglandins in structure (e.g., 8-acetyl-12-hydroxyheptadecanoic acid) markedly stimulate cAMP formation at concentrations in the pharmacological range and show a significant affinity for the prostaglandin receptor. Conversely, these compounds are not substrates for prostaglandin 15-hydroxydehydrogenase which catalyzes a major reaction in the biological deactivation of the prostaglandins.

Unsaturated Polyhydroxy Acids having Prostaglandin-Like Activity from Bryonia alba II. Major Components

“…In the meantime, the problem of the possibility of the occurrence of prostaglandins themselves in plants remains unsolved. It should be mentioned, that the presence of a five-membered ring is not a necessity for the manifestation of affinity towards prostaglandin receptors, as was pointed out earlier in a series of papers concerning synthetic seco-prostaglandins [39][40][41][42]. It is not certain yet which of the isomers of the described trihydroxyoctadecadienoic acids possesses the greatest affinity for the receptors and displays the highest activity.…”

[3,3]-Sigmatropic Rearrangements in the Enantioselective Synthesis of (-)-Methylenolactocin

“…Zn(OTf) 2 was dried overnight at 120°C under vacuum prior use. Tetradeca-6,8-diene 17b and compounds (S)-6, 26 (S)-7, 27 (S)-10, 28 and were prepared according to published procedures. (-)-N-Methylephedrine and (S)-oct-1-yn-3-ol are commercially available.…”

“…1.25-1.33 (m, 14 H, CH 2 ), 2.20 (m, 2 H, CH 2 C≡C), 4.35 (t, 1 H, J = 6.0 Hz, CHOH). 13 C NMR (CDCl 3 ): d = 14.0 (CH 3 ), 18.2 (CH 2 C≡C), 22.5,22.6,24.9,28.5,28,6,31.5,38.2,62.7 (CHOH), 85.9 (C≡C).…”

11,12-Secoprostaglandins. 5. 8-Acetyl- or8-(1-hydroxyethyl)-12-hydroxy-13-aryloxytridecanoic acids and sulfonamide isosteres as inhibitors of platelet aggregation

“…Subsequently, we showed that acids in several series3,4 isosteric with these acylhydroxyalkanoic acids display similar biological properties. The most thoroughly studied of these series is that of the sulfonamide isosteres4 of which 7-[JV-(4hydroxynonyl)methanesulfonamido]heptanoic acid (2) is an active representative.…”