Synthesis of sulfoxides by oxidation of thioethers

Madesclaire, M.

doi:10.1016/s0040-4020(01)88150-3

Cited by 289 publications

(93 citation statements)

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“…The binding to the protonated imidazole residue could then be superior to that of the substrate because the sulfoxide is more strongly polarized than the thioester carbonyl. The enzymic reaction with only one stereoisomer of the sulfoxide has been repeatedly demonstrated [17]. One could then expect a twofold increase in affinity if the sulfoxides VIII and X are replaced by the corresponding sulfones XI11 and XV.…”

Section: Discussionmentioning

confidence: 93%

Inhibition of 3‐Hydroxy‐3‐Methylglutaryl‐CoA Reductase and Citrate Synthase by Sulfoxides and Sulfones of Substrate‐analogue CoA‐thioether Derivatives

Karl¹,

Hupperich²,

Thomer³

et al. 1995

European Journal of Biochemistry

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Sulfoxides and sulfones were prepared by specific oxidation of 3-hydroxy-3-methylglutaryl-CoAanalogue CoA-thioether derivatives and their kinetic properties were determined with 3-hydroxy-3-methylglutaryl-CoA reductase. The oxidized CoA-thioether derivatives with a hydroxyl group at C3 were powerful competitive inhibitors, their K, values being much smaller than the K,,, for 3-hydroxy-3-methylSulfoxides and sulfones of substrate analogues of citrate synthase were also prepared. When tested in the appropriate reaction with citrate synthase, the sulfoxide and sulfone derivatives were competitive inhibitors, but their K, values were greater than the K, values of the corresponding unmodified substrates.Keywords. 3-Hydroxy-3-methylglutaryl-CoA reductase ; citrate synthase ; substrate-analogue inhibitors.glutqrl-CoA.3-Hydroxy-3-m1~thylglutaryl-CoA reductase represents the key regulatory enzyme in cholesterol biosynthesis. This enzyme catalyzes the two-step reduction of 3-hydroxy-3-methylglutarylCoA by two equivalents of NADPH to eventually yield mevalonate. In search of substrate-based inhibitors of 3-hydroxy-3-methylglutaryl-CoA, reductase, we previously reported the influence of substitutions in the acyl moiety of 3-hydroxy-3-methylglutaryl-CoA on substrate binding [l]. A further target for modification was the thioester group of 3-hydroxy-3-methylglutarylCoA. The replacement of the thioester oxygen by hydrogen yielded non-reducible substrate analogues without significantly affecting the affinity towards 3-hydroxy-3-methylglutaryl-CoA reductase [ 11. With some substrate-analogue CoA-thioethers, a drastic increase in affinity towards the reductase was found on introduction of oxygen at the thioether sulfur to yield a sulfoxide [2]. In this study, we investigate the requirements for this increased affinity with structurally related CoA-sulfoxide derivatives. Attempts are also described to enhance the inhibitory power of these compounds by introduction of a second oxygen at the sulfur to yield a CoA-sulfone derivative. To probe the oxidation of CoA-tihioethers to CoA-sulfones we used the simplest CoA-thioether, S-ethyl-CoA, and the more complicated S-(3-carboxy-3-hydroxypropyl)-CoA, substrate analogues of acetyl-CoA and malyl-CoA. Acetyl-CoA is a substrate of citrate synthase and reacts, with oxaloacetate to yield citrate via transiently formed citryl-CoA. Malyl-CoA is an analogue of this intermediate and is hydrolyzed in the presence of citrate synthase but not cleaved to acetyl-CoA and oxoacid [3]. The mechanism of hydrolysis of citryl-CoA is as yet unknown. A highaffinity analogue of malyl-CoA, interacting specifically with the Correspondence ttq H. Eggerer,

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Section: Discussionmentioning

confidence: 93%

Inhibition of 3‐Hydroxy‐3‐Methylglutaryl‐CoA Reductase and Citrate Synthase by Sulfoxides and Sulfones of Substrate‐analogue CoA‐thioether Derivatives

Karl¹,

Hupperich²,

Thomer³

et al. 1995

European Journal of Biochemistry

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“…Synthesis of sulfoxides by the oxidation of thioethers has been extensively studied, which is illustrated by the fact that the results have been compiled and discussed in sevearal review articles. [35][36][37] The relation between thioethers and dioxiranes is quite old. The peroxide content of the acetone solution of the isolated dimethyldioxirane was determined by the oxidation of methyl phenyl sulfide (thioanisole) to its sulfoxide which was quantified either by GLC 38,39 or by 1 H-NMR spectroscopy.…”

Section: Oxidation Of Thioethers and Thiol Estersmentioning

confidence: 99%

Dioxirane Oxidation of Sulfur‐Containing Organic Compounds

Lévai

2004

ChemInform

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Dedicated to Professor Branko AbstractThis short review describes the utilization of dioxiranes as convenient and extremely efficient electrophilic oxidants for the selective oxidation of sulfur-containing organic compounds. Relevant examples are included to illustrate the chemoselective and stereoselective oxidations of substances with several sites of oxidation. Electrophilic character of the dioxiranes is shown via the oxidation of compounds with two sulfur heteroatoms.

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“…A variety of oxidants have been employed for this transformation. 2 Among the more common oxidants are mCBPA, 3 The asymmetric synthesis of sulfoxides has received particular attention in recent years as the sulfoxide moiety has been shown to provide excellent stereochemical control as a chiral auxiliary. Also, many enantiopure sulfoxides are known to have high biological activity.…”

Section: Introductionmentioning

confidence: 99%