Synthesis of prostaglandin H2

Abstract

Prostaglandin H2 (PGFL) has been prepared by chemical synthesis from PGF;,,. The synthesis proceeds from the intermediate 9/3,1 l/3-dibromo-9,l 1-dideoxyprostaglandin F2iv to the endoperoxide PGFL in 17-24% yield upon reaction of the dibromide with silver trifluoroacetate and hydrogen peroxide in diethyl ether. Synthetic PGFL was purified by high-pressure liquid chromatography and was characterized by comparison with a biological sample and by conversion to PGF2" methyl ester, PGE2, and PGFL methyl ester under appropriate reaction conditions. Synthetic PGFL aggregates human platelet rich plasma that has been preincubated with indomethacin.

Heterogeneity of thromboxane A2 (TP‐) receptors: evidence from antagonist but not agonist potency measurements

“…The following prostanoids were prepared in our laboratory and essential details of the synthetic methods are to be found in Wilson et al (1982Wilson et al ( , 1988: rac 10a-homo-15S-hydroxy-9a, La-epoxy-prosta-5Z,13E-dienoic acid (9,1 1-endoxy-lOa-homo PGH2) and its 16p-fluorophenoxy-w)-tetranor (EP 171) and 13-(m-chlorobenzyloxyimino)-w)-heptanor (EP 204) analogues; rac 9a,1 aethanocoheptanor -13 -methyl -13 -phenylthio-carbamoyl-hydrazino-prosta-5Z-enoic acid (EP 092); 1 lacarba -i5S -hydroxy -9a,1 laisopropylidenoprosta -5Z,13Edienoic acid (PTA2) and its 16p-fluorophenoxy-w)-tetranor (EP 109), wo-heptanor-13-methyl-13-phenylecarbamoylhydrazino (EP 115) and 16,20-methano (16,20-methano PTA2) analogues; 9a,1 lc-ethano-w-heptanor-lOa-homo-13-(m-chlorobenzyl-oxyimino)prosta-5Z-enoic acid (EP 167) and 4a,10adihomo -9a,1 lethanocoheptanor -3 -oxa -13 -phenylthiocarbamoyl-hydrazino-prostanoic acid (EP 169); 16-pfluorophenoxy-w-tetranor PGF2,. PGH2 was prepared from PGF2, by the method of Porter et al (1979).…”

Ligand binding to thromboxane receptors on human platelets: correlation with biological activity

“…Displacement by synthetic PGH2 and by TXA2 generated enzymatically from synthetic PGH2 was also studied. PGF2o, was converted into 93,1 113dibromo-9, 11 -dideoxy PGF2, by the method of Porter, Byers, Holden & Menzel (1979). Treatment of the dibromo derivative with 90% H202/silver trifluoroacetate gave PGH2 which was purified by silicic acid chromatography (10g Unisil, 100-200 mesh Clarkson Chemical Co., USA; gradient elution, 20% ethyl acetate in hexane to pure ethyl acetate over 3 h; -20°C).…”

“…PGF2o, was converted into 93,1 113-dibromo-9, 11 -dideoxy PGF2, by the method of Porter, Byers, Holden & Menzel (1979 , and incubated for 30 s at 0°C. The suspension was filtered rapidly at 0°C under pressure from a nitrogen gas cylinder through an Amicon MPS-1 micropartition unit (Amicon Ltd, Stonehouse).…”

Beyond Prostaglandins—Chemistry and Biology of Cyclic Oxygenated Metabolites Formed by Free‐Radical Pathways from Polyunsaturated Fatty Acids

“…[58b] Subsequently, Porter et al showed that isolated PGH 2 rearranges spontaneously in the presence of silica gel to a mixture of PGE 2 and PGD 2 . [62] However, acid-base catalysis also leads to the formation of PGD 2 or PGE 2 . [63] It is noteworthy that 15-E 2 -and 15-D 2 -IsoP (15-45 b and 15-46 b, respectively) epimerize in aqueous solution at pH 7.4 to a 4.5:1 equilibrium mixture of thermodynamically more stable, but racemic rac-PGD 2 and rac-PGE 2 diastereomers.…”