363-24-6Relevant articles and documents
A NEW SYNTHETIC ROUTE TO PROSTAGLANDINS
Corey, E. J.,Niimura, Koichi,Konishi, Yoshitaka,Hashimoto, Shinsuke,Hamada, Yasumasa
, p. 2199 - 2202 (1986)
A short synthetic route to prostaglandins is described which depends on oxime-based methodology and which involves the joining of intermediates 9, 11, and 12 in a one-flask operation.
Total synthesis of prostaglandins F2-alpha and E2 as the naturally occurring forms.
Corey,Schaaf,Huber,Koelliker,Weinshenker
, p. 397 - 398 (1970)
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Schneider
, p. 304 (1969)
Inhibition of cyclooxygenase and prostaglandin E2 synthesis by γ-mangostin, a xanthone derivative in mangosteen, in C6 rat glioma cells
Nakatani, Keigo,Nakahata, Norimichi,Arakawa, Tsutomu,Yasuda, Hideyuki,Ohizumi, Yasushi
, p. 73 - 79 (2002)
The fruit hull of mangosteen, Garcinia mangostana L., has been used for many years as a medicine for treatment of skin infection, wounds, and diarrhea in Southeast Asia. In the present study, we examined the effect of γ-mangostin, a tetraoxygenated diprenylated xanthone contained in mangosteen, on arachidonic acid (AA) cascade in C6 rat glioma cells. γ-Mangostin had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a Ca2+ ionophore. The inhibition was concentration-dependent, with the IC50 value of about 5 μM. γ-Mangostin had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, γ-mangostin concentration-dependently inhibited the conversion of AA to PGE2 in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, γ-mangostin inhibited the activities of both constitutive COX (COX-1) and inducible COX (COX-2) in a concentration-dependent manner, with the IC50 values of about 0.8 and 2 μM, respectively. Lineweaver-Burk plot analysis indicated that γ-mangostin competitively inhibited the activities of both COX-1 and -2. This study is a first demonstration that γ-mangostin, a xanthone derivative, directly inhibits COX activity.
Characterization of aldo-keto reductase 1C subfamily members encoded in two rat genes (akr1c19 and RGD1564865). Relationship to 9-hydroxyprostaglandin dehydrogenase
Satoshi Endo,Matsunaga, Toshiyuki,Hara, Akira
, (2021/02/02)
Rat genes, akr1c19 and RGD1564865, encode members (R1C19 and 20HSDL, respectively) of the aldo-keto reductase (AKR) 1C subfamily, whose functions, however, remain unknown. Here, we show that recombinant R1C19 and 20HSDL exhibit NAD+-dependent dehydrogenase activity for prostaglandins (PGs) with 9α-hydroxy group (PGF2α, its 13,14-dihydro- and 15-keto derivatives, 9α,11β-PGF2 and PGD2). 20HSDL oxidized the PGs with much lower Km (0.3–14 μM) and higher kcat/Km values (0.064–2.6 min?1μM?1) than those of R1C19. They also differed in other properties: R1C19, but not 20HSDL, oxidized some 17β-hydroxysteroids (5β-androstane-3α,17β-diol and 5β-androstan-17β-ol-3-one). 20HSDL was specifically inhibited by zomepirac, but not by R1C19-selective inhibitors (hexestrol, flavonoids, ibuprofen and flufenamic acid), although the two enzymes were sensitive to indomethacin and cis-unsaturated fatty acids. The mRNA for 20HSDL was expressed abundantly in rat kidney and at low levels in the liver, testis, brain, heart and colon, in contrast to ubiquitous expression of R1C19 mRNA. The comparison of enzymic features of R1C19 and 20HSDL with rat PG dehydrogenases and other AKRs suggests not only a close relationship of 20HSDL with 9-hydroxy-PG dehydrogenase in rat kidney, but also roles of R1C19 and rat AKRs (1C16 and 1C24) in the metabolism of PGF2α, PGD2 and 9α,11β-PGF2 in other tissues.
15-Hydroperoxy-PGE2: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis
Jagusch, Hans,Werner, Markus,Werz, Oliver,Pohnert, Georg
supporting information, p. 17641 - 17645 (2019/11/13)
Arachidonic-acid-derived prostaglandins (PGs), specifically PGE2, play a central role in inflammation and numerous immunological reactions. The enzymes of PGE2 biosynthesis are important pharmacological targets for anti-inflammatory drugs. Besides mammals, certain edible marine algae possess a comprehensive repertoire of bioactive arachidonic-acid-derived oxylipins including PGs that may account for food poisoning. Described here is the analysis of PGE2 biosynthesis in the red macroalga Gracilaria vermiculophylla that led to the identification of 15-hydroperoxy-PGE2, a novel precursor of PGE2 and 15-keto-PGE2. Interestingly, this novel precursor is also produced in human macrophages where it represents a key metabolite in an alternative biosynthetic PGE2 pathway in addition to the well-established arachidonic acid-PGG2-PGH2-PGE2 route. This alternative pathway of mammalian PGE2 biosynthesis may open novel opportunities to intervene with inflammation-related diseases.
In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. the Concept, Methodological Implications, and Applications to Synthesis of Biologically Active Compounds
Xu, Chaofan,Shen, Xiao,Hoveyda, Amir H.
supporting information, p. 10919 - 10928 (2017/08/15)
In situ methylene capping is introduced as a practical and broadly applicable strategy that can expand the scope of catalyst-controlled stereoselective olefin metathesis considerably. By incorporation of commercially available Z-butene together with robust and readily accessible Ru-based dithiolate catalysts developed in these laboratories, a large variety of transformations can be made to proceed with terminal alkenes, without the need for a priori synthesis of a stereochemically defined disubstituted olefin. Reactions thus proceed with significantly higher efficiency and Z selectivity as compared to when other Ru-, Mo-, or W-based complexes are utilized. Cross-metathesis with olefins that contain a carboxylic acid, an aldehyde, an allylic alcohol, an aryl olefin, an α substituent, or amino acid residues was carried out to generate the desired products in 47-88% yield and 90:10 to >98:2 Z:E selectivity. Transformations were equally efficient and stereoselective with a ~70:30 Z-:E-butene mixture, which is a byproduct of crude oil cracking. The in situ methylene capping strategy was used with the same Ru catechothiolate complex (no catalyst modification necessary) to perform ring-closing metathesis reactions, generating 14- to 21-membered ring macrocyclic alkenes in 40-70% yield and 96:4-98:2 Z:E selectivity; here too, reactions were more efficient and Z-selective than when the other catalyst classes are employed. The utility of the approach is highlighted by applications to efficient and stereoselective syntheses of several biologically active molecules. This includes a platelet aggregate inhibitor and two members of the prostaglandin family of compounds by catalytic cross-metathesis reactions, and a strained 14-membered ring stapled peptide by means of macrocyclic ring-closing metathesis. The approach presented herein is likely to have a notable effect on broadening the scope of olefin metathesis, as the stability of methylidene complexes is a generally debilitating issue with all types of catalyst systems. Illustrative examples of kinetically controlled E-selective cross-metathesis and macrocyclic ring-closing reactions, where E-butene serves as the methylene capping agent, are provided.