Synthesis of three potential inhibitors of leukotriene biosynthesis

Pfister, J. R.; Murthy, Devangachinta

doi:10.1021/jm00362a002

Cited by 22 publications

(2 citation statements)

References 5 publications

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“…Oxidation of 10 using pyridinium chlorochromate gave the aldehyde 11 (73%). The phosphonium salt 12 for the Wittig reaction was prepared from methyl 8-hydroxy-5-octenoate . The Wittig condensation of 11 with 12 gave the TBDPS-protected 10( S )-HETE methyl ester 13 in 49% yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 10(S)-Hydroxyeicosatetraenoic Acid: A Novel Cytochrome P-450 Metabolite of Arachidonic Acid

et al. 1996

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10(S)-(−)-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid methyl ester (2) was synthesized in eight steps starting from enantiomerically pure (R)-glyceraldehyde acetonide. The 10(R)-(+)-enantiomer was prepared using an identical method except that the starting material was (S)-glyceraldehyde acetonide. By use of these authentic standards, it was possible to confirm that arachidonic acid was converted to a mixture of 10(S)-(−)-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid (1) and the 10(R)-(+)-enantiomer by phenobarbital-induced rat liver microsomes.

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Section: Resultsmentioning

confidence: 99%

Synthesis of 10(S)-Hydroxyeicosatetraenoic Acid: A Novel Cytochrome P-450 Metabolite of Arachidonic Acid

et al. 1996

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“…Such an agent might be of value in the therapy of diseases in which these potent lipid mediators have been implicated, such as asthma, psoriasis, allergic disorders, myocardial ischemia, and inflammation. The enzyme 5-lipoxygenase controls the entry of free arachidonic acid into the oxidative pathways which can lead to the formation of the peptidoleukotrienes (LTC4, LTD4, and LTEI) 5,la-diHETEs and LTB4, and lipoxins, as shown in Scheme I. Substrate recognition and subsequent catalysis require a 1,4-diene system that is 5-9 carbons removed from the carboxylic acid group in polyenoic acid substrates such as 5,8,11-eicosatrienoic acid, 5,8,11,14-eicosatetraenoic acid (arachidonic acid), and 5,8,11,14,17-eicosapntenoic acid.3.4 In 5-lipoxygenation of arachidonic acid, the reaction appears to proceed via the coordinate addition of oxygen across the 5,g-double bond, with a double-bond shift from 5,6-to 6,7-positions to form 5- Their results prompted us to report our findings on the syntheses and inhibitory activities of 9-(4-chlorophenyl)-7,7-dimethyl-5(2), 8-nonadienoic acid (7) and its methyl ester (6). We speculated that the aryl group could isosterically replace the C-10 to C-20 diene segments of arachidonic acid.…”

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confidence: 94%

Inhibition of Leukotriene and Thromboxane Biosynthesis by a 9-(4-chlorophenyl) Analogue of Arachidonic Acid

Hageman

Mohrbacher

et al. 1988

Journal of Pharmaceutical Sciences

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Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides: TheMoffatt,Swern, and Related Oxidations

Tidwell

1990

Organic Reactions

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The use of dimethyl sulfoxide as an oxidizing agent began with the discoveries by Kornblum and co‐workers that certain α‐bromo ketones were converted into glyoxals under mild conditions by treatment with dimethyl sulfoxide, and that primary tosylates such as n ‐octyl tosylate were converted into the corresponding aldehydes using dimethyl sulfoxide and sodium bicarbonate at 150° for 3 minutes. The initial step of the reactions involves a displacement by dimethyl sulfoxide giving an alkoxysulfonium ion and this species undergoes a 1,2 elimination assisted by base to give the carbonyl product A few years later it was discovered that alcohols were oxidized at room temperature to carbonyl compounds by dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC), and phosphoric acid. This reaction was immediately recognized as an effective and mild procedure for sensitive substrates, and the extensive studies by this group and the development of alternative variations elsewhere have been the subject of several earlier reviews. The course of the Moffatt procedure is summarized. The key intermediate in this process is the oxysulfonium ylide, which appears to be common to all of the variations of dimethyl sulfoxide oxidations, and which reacts intramolecularly to give the products. Other related procedures that were soon developed utilize dimethyl sulfoxide activated by acetic anhydride, phosphorus pentoxide, sulfur trioxide/pyridine complex, and chlorine. Reaction of alcohols with phosgene to give chloroformates which react with dimethyl sulfoxide to give alkoxysulfonium ions, followed by reaction with triethylamine, also effects oxidation. The reaction of the complexes of dimethyl sulfide and chlorine or N ‐chlorosuccinimide (NCS) with alcohols is proposed to give the same alkoxysulfonium complexes, which are efficiently converted into carbonyl products upon addition of triethylamine. Electrochemical activation of sulfides has also been successfully utilized. The activation of dimethyl sulfoxide is effected by many reagents, and these reactions as well as those involving activated sulfides evidently involve the alkoxysulfonium ion and the decisive oxidation step which occurs via the alkoxysulfonium ylide in all the reactions. Activation of dimethyl sulfoxide by oxalyl chloride, has become the most used of these oxidation procedures, but several of the other methods are also convenient and efficient.

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Synthesis of three potential inhibitors of leukotriene biosynthesis

Cited by 22 publications

References 5 publications

Synthesis of 10(S)-Hydroxyeicosatetraenoic Acid: A Novel Cytochrome P-450 Metabolite of Arachidonic Acid

Synthesis of 10(S)-Hydroxyeicosatetraenoic Acid: A Novel Cytochrome P-450 Metabolite of Arachidonic Acid

Inhibition of Leukotriene and Thromboxane Biosynthesis by a 9-(4-chlorophenyl) Analogue of Arachidonic Acid

Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides: TheMoffatt,Swern, and Related Oxidations

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