- Conversion of arachidonic acid to the prostaglandin endoperoxide PGG2, a chemical analog of the biosynthetic pathway
-
Reaction of the methyl ester of (15S)-hydroperoxy-5,8-11Z-13E-eicosapentaenoic acid (7) with oxygen in benzene solution in the presence of a catalyst made from samarium (II) iodide and O2 produces a mixture of the methyl esters of PGG2 (12) and its 12-epimer (15) (ratio 1:3, yield 43% based on recovered starting material).
- Corey,Wang, Zhe
-
-
Read Online
- High-performance liquid chromatography/thermospray mass spectrometry of some prostaglandins of time F series
-
Thermospray (TSP) mass-spectra and chromatographic characteristics of the prostanoids PGF(2α), 6-keto-PGF(1α), 2,3-dinor-6-keto-PGF(1α) and their methyl esters and methoximes are reported. The spectra of these compounds are dominated by ions of the type [M + H + xNH3 - nH2O]+ in the positive-ion mode and [M - H + xAcOH - nH2O]- in the negative-ion mode (n ranges from 0-4 and x is 0 or 1). The relative abundances of these ions depend on the particular structure, source and interface temperatures and eluent composition. In addition, these compounds show losses of 44 mass units, mainly due to the lass of the C-10-C-11 moiety, as demonstrated by deuterium labelling of PGF(2α). Methoximated derivatives of 6-keto-PGF(1α) also show low-abundance ions due to fragmentation in the position α to the methoxime group. The liquid-phase equilibria of tautomers of 2,3-diner-6-keto-PGF(1α) or products thereof which direct-its particular chromatographic behavior, can be effectively blocked by methoximation of the keto group thus improving its detectability. Detection limits of 20 ng on-column may be obtained for this derivative. Adsorption and hydrolysis in the interface are the principal factors responsible for this relatively high detection limit.
- Abian,Gelpi
-
-
Read Online
- Cyclopentane 1-hydroxy alkyl or alkenyl-2-one or 2-hydroxy derivatives as therapeutic agents
-
The present invention provides a novel compound represented by the general formula I; wherein R is H or COR3; R1is H, R2, phenyl, or COR3, wherein R2is C1-C5lower alkyl and R3is R2or phenyl; Z is CH2or O; Y is OH, OCOR3or ═O; x is 0 or 1; and X is C1-C5n-alkyl, C3-C7cycloalkyl, phenyl, furanyl, thienyl or substituted derivatives thereof, wherein the substituents maybe selected from the group consisting of C1-C5alkyl, halogen, CF3, CN, NO2, NR42, CO2R4and OR4wherein R4is hydrogen or C1-C5alkyl and dotted lines represent the presence or absence of a double bond and wavy lines represent a cis or trans bond. These novel compounds are especially useful for treating elevated intraocular pressure (ocular hypertension) and glaucoma.
- -
-
Page column 8
(2010/01/31)
-
- Cyclopentane 1-hydroxy alkyl or alkenyl-2-one or 2-hydroxy derivatives as therapeutic agents
-
The present invention provides a novel compound represented by the general formula I; wherein R is H or COR3;R1 is H, R2, phenyl, or COR3, wherein R2 is C1-C5 lower alkyl and R3 is R2 or phenyl;Z is CH2 or O;Y is OH or OCOR3;x is 0 or 1; andX is C1-C5 n-alkyl, C3-C7 cycloalkyl, phenyl, furanyl, thienyl or substituted derivatives thereof, wherein the substituents maybe selected from the group consisting of C1-C5 alkyl, halogen, CF3, CN, NO2, NR42, CO2R4 and OR4 wherein R4 is hydrogen or C1-C5 alkyl and dotted lines represent the presence or absence of a double bond and wavy lines represent a cis or trans bond. These novel compounds are especially useful for treating elevated intraocular pressure (ocular hypertension) and glaucoma.
- -
-
-
- Design and synthesis of 13,14-dihydro prostaglandin F(1α) analogues as potent and selective ligands for the human FP receptor
-
The in vitro evaluation of a new class of potential bone anabolic agents for the treatment of osteoporosis is described. These compounds are potent and selective ligands for the human prostaglandin F receptor (hFP receptor). The compounds lack the olefin unsaturation required for potency in the natural ligand PGF(2α) yet retain binding affinity for the hFP receptor in the nanomolar to micromolar range. Removal of the alkenes also results in a better selectivity ratio for the hFP receptor over the other prostaglandin receptors tested. A rationale for the selectivity differences of various analogues, based on ligand docking experiments to a putative hFP receptor model, is also described.
- Wang, Yili,Wos, John A.,Dirr, Michelle J.,Soper, David L.,DeLong, Mitchell A.,Mieling, Glen E.,De, Biswanath,Amburgey, Jack S.,Suchanek, Eric G.,Taylor, Cynthia J.
-
p. 945 - 952
(2007/10/03)
-
- Total Synthesis of Prostaglandin F2α via Nickel-Promoted Stereoselective Cyclization of 1,3-Diene and Aldehyde
-
The total synthesis of prostaglandin F2α (PGF2α) was accomplished via nickel-promoted cyclization of 1,3-diene and aldehyde in a chain in the presence of 1,3-cyclohexadiene (1,3-CHD). The cyclization of 16 prepared in an optically active form from chiral epoxy alcohol 10 stereoselectively gave the key intermediate 18, which has both an α-chain and the four contiguous chiral carbon centers in PGF2α, in a one-pot reaction. Intermediate 18 was successfully transformed into PGF2α.
- Sato, Yoshihiro,Takimoto, Masanori,Mori, Miwako
-
p. 734 - 736
(2007/10/03)
-
- PALLADIUM(0) CATALYZED REACTIONS OF 1,4-EPIPEROXIDES
-
The Pd(PPh3)4 catalyzed reaction of 2,3-saturated and 2,3-unsaturated 1,4-epiperoxides proceeds by courses markedly different from those of the previously reported transition metal catalyses.The Pd(0)-promoted reaction of 2,3-saturated epiperoxides gives the corresponding 4-hydroxy ketones and 1,4-diols as the major products.From 2,3-dedihydroepiperoxides are formed the corresponding 4-hydroxy enones, syn-1,2;3,4-diepoxides, and 1,4-diols.The results are interpreted in terms of competing Pd(0)/Pd(II) exchange mechanisms.Exposure of prostaglandin (PG) H2 methyl esterto Pd(PPh3)4 produces a mixture of methyl esters of PGD2, PGE2, PGF2α, and (5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid.
- Suzuki, Masaaki,Oda, Yoshihisa,Hamanaka, Nobuyuki,Noyori, Ryoji
-
p. 517 - 535
(2007/10/02)
-
- The Three-Component Coupling Synthesis of Prostaglandins
-
A convergent one-pot construction of the prostaglandin (PG) framework has been accomplished by the organocopper-mediated conjugate addition of the S configurated ω side-chain unit to a protected (R)-4-hydroxy-2-cyclopentenone followed by trapping of the enolate intermediate by α side-chain alkyl halides.Transmetalation with use of triphenyltin chloride at the enolate stage serves as key operation for the succesful three-component coupling synthesis.The use of methyl (Z)-7-iodo-5-heptenoate as the α side-chain component allows short synthesis of PGE2 and PGD2.Introduction of a triple bond at the C-5-C-6 positions with methyl 7-iodo-5-heptynoate as the α side-chain synthon has opened a general entry of PGs.The protected 5,6-didehydro-PGE2 derivatives are convertible to a variety of PGs of 1 and 2 series by the controlled hydrogenation of the C-5-C-6 unsaturated bonds and α-selective (100percent) reduction of the C-9 keto function, if necessary.Lithium aluminum hydride reagents modified by (R)- and (S)-2,2'-dihydroxy-1,1'-binaphthyl exhibit a unique kinetic discrimination in reduction of PGE type compounds.A protected 5,6-didehydro-PGF2α has been transformed stereoselectively to PGI2 by using intramolecular alkoxypalladation/depalladation as the key step.
- Suzuki, M.,Yanagisawa, A.,Noyori, R.
-
p. 4718 - 4726
(2007/10/02)
-
- Synthesis of Aromatic Modified Prostaglandins from PGA2
-
A general synthetic scheme, starting from PGA2 (obtained from the marine coral Plexaura homomalla), of prostaglandins modified in the upper chain is detailed.Key aldehyde intermediates have been secured from 11-deoxy-PGF2α and PGF2α by an efficient regioselective hydroxylation procedure followed by cleavage of the 5,6-double bond.Witting reaction with these aldehydes provided the novel prostaglandins (5)-(8), belonging to the E and F families, and containing an aromatic ring in the upper chain.
- Cai, Zuyun,Nassium, Bahman,Crabbe, Pierre
-
p. 1573 - 1578
(2007/10/02)
-
- Prostaglandins. 2. Synthesis of Prostaglandin F2α in Optically Active Form from Chiral Precursors
-
A synthetic route to optically active prostaglandins is described which use chiral starting materials.Acylation of the bis(magnesiobromide) salt of methyl hemimalonate with (S)-(-)-2-acetoxysuccinyl chloride led to unstable dimethyl (S)-4-acetoxy-3,6-diox
- Johnson, Francis,Paul, K.G.,Favara, Duccio,Ciabatti, Romeo,Guzzi, Umberto
-
p. 2190 - 2198
(2007/10/02)
-
- Organoselenium-based synthesis of oxygen-containing prostacyclins
-
The application of organoselenium-induced ring closures to the synthesis of stable, oxygen-containing prostacyclins is described. The strategy involves utilization of PGF2α methyl ester (3) as a starting material in a PhSeCl-induced cyclization
- Nicolaou,Barnette,Magolda
-
p. 3480 - 3485
(2007/10/02)
-
- 8β,12α,15β-PGF2 β Compounds
-
This invention is a group of 8-beta, 12-alpha-PG2 (prostaglandin-type) analogs having variable chain length, or methyl or phenyl substitution in the hydroxy-substituted side-chain, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, and labor inducement at term.
- -
-
-