Thionation with the Reagent Combination of Phosphorus Pentasulfide and Hexamethyldisiloxane

Curphey, Thomas J.

doi:10.1021/jo0256742

Cited by 208 publications

(105 citation statements)

References 40 publications

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“…Ethyltrifluoroacetate (3.0 mmol, 1.5 eq) was subsequently added, providing (after workup and purification) the desired ␤-ketoester. This ester was then converted according to protocols in the literature, first to a 1,2-dithiole-3-thione (17)(18)(19) and subsequently, by the use of Hg(OAc) 2 , to the corresponding 1,2-dithiole-3-one (36). 4-Chloro-5-methyl-1,2-dithiole-3-thione (compound 7) was produced from ethyl 2-chloroacetoacetate (12% yield).…”

Section: Methodsmentioning

confidence: 99%

1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

Reeve

Desai

et al. 2004

Antimicrob Agents Chemother

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The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type II dissociated fatty acid synthase. The pivotal role of this essential enzyme, combined with its unique structural features and ubiquitous occurrence in bacteria, has made it an attractive new target for the development of antibacterial and antiparasitic compounds. We have searched the National Cancer Institute database for compounds bearing structural similarities to thiolactomycin, a natural product which exhibits a weak activity against FabH. This search has yielded several substituted 1,2-dithiole-3-ones that are potent inhibitors of FabH from both Escherichia coli (ecFabH) and Staphylococcus aureus (saFabH). The most potent inhibitor was 4,5-dichloro-1,2-dithiole-3-one, which had 50% inhibitory concentration (IC 50 ) values of 2 M (ecFabH) and 0.16 M (saFabH). The corresponding 3-thione analog exhibited comparable activities. Analogs in which the 4-chloro substituent was replaced with a phenyl group were also potent inhibitors, albeit somewhat less effectively (IC 50 values of 5.7 and 0.98 M for ecFabH and saFabH, respectively). All of the 5-chlorinated inhibitors were most effective when they were preincubated with FabH in the absence of substrates. The resulting enzyme-inhibitor complex did not readily regain activity after excess inhibitor was removed, suggesting that a slow dissociation occurs. In stark contrast, a series of inhibitors in which the 5-chloro substituent was replaced with the isosteric and isoelectronic trifluoromethyl group were poorer inhibitors (IC 50 values typically ranging from 25 to >100 M for both ecFabH and saFabH), did not require a preincubation period for maximal activity, and generated an enzymeinhibitor complex which readily dissociated. Possible modes of binding of 5-chloro-1,2-dithiole-3-ones and 5-chloro-1,2-dithiole-3-thiones with FabH which account for the role of the 5-chloro substituent were considered.Fatty acid biosynthesis, an essential process for all organisms, is catalyzed in plants and bacteria by a series of discrete dissociable enzymes and a central acyl carrier protein (ACP) (43). This set of enzymes is known collectively as a type II fatty acid synthase (FAS) and differs significantly from the type I FAS of metazoans, in which all of the enzymatic activities are contained on one or two polypeptides (12,31,67). The structural and mechanistic differences between the two FAS systems, in conjunction with the fact that the type I FAS is down regulated in well-nourished mammals (38, 39), have led to significant interest in components of the type II FAS as targets for the development of new antibacterial agents. Such agents may also have promise as novel antimalarials because protozoan parasites of the genus Plasmodium have been shown recently to contain a type II FAS in their apicoplast (53,62,63).Significant efforts and progress have been made in the understanding of small-molecule inhibition of two different components of the type II FAS. FabI (InhA), the enoyl ACP reductase that c...

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Section: Methodsmentioning

confidence: 99%

1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

Reeve

Desai

et al. 2004

Antimicrob Agents Chemother

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“…7 A large number of methods have been developed for the thionation of carbonyl groups to their thiocarbonyl analogues, where the main reagents include Lawesson's reagent, 8 Berzelius' reagent 9 , more recently Curphey's method. 10 The use of a P4S10-pyridine complex was also reported by Bergman and co-workers in 2011.…”

Section: Fmochnmentioning

confidence: 62%

“…Finally Curphey's method, 10 using P4S10 (1.1 molar equiv.) in the presence of hexamethyldisiloxane (HMDO, 5.5 molar equiv.)…”

mentioning

confidence: 99%

Synthesis of orthogonally protected thioamide dipeptides for use in solid-phase peptide synthesis

Manzor¹,

Kelleher²

2016

Tetrahedron Letters

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“…Recently, functionalized-thioamide fluorescent dyes were also employed as metal ion sensors [13]. Diverse synthetic methods have been discovered for the synthesis of thioamides [14][15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

L-Proline: An Efficient and Selective Catalyst for Transamidation of Thioamides with Amines

Adimurthy¹

2016

J Biomol Res Ther

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Thionation with the Reagent Combination of Phosphorus Pentasulfide and Hexamethyldisiloxane

Cited by 208 publications

References 40 publications

1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

Synthesis of orthogonally protected thioamide dipeptides for use in solid-phase peptide synthesis

L-Proline: An Efficient and Selective Catalyst for Transamidation of Thioamides with Amines

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