Synthesis of 2-(ethylsulfanyl)aniline derivatives through the unexpected ring opening of N-substituted-2(3H)-benzothiazolones

Lebegue, Nicolas; Charrier, Gaetan; Carato, Pascal; Yous, Saı̈d; Berthelot, Pascal

doi:10.1016/j.tetlet.2004.10.141

Cited by 3 publications

References 13 publications

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The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Krapcho

Ciganek

2013

Organic Reactions

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The Krapcho reaction involves esters with α‐electron‐withdrawing substituents such as malonates, β‐keto esters, and α‐cyano esters, which undergo dealkoxycarbonylation on being heated in polar aprotic solvents (such as DMSO, DMF, or HMPT) in the presence of water, or in polar aprotic solvents with water in the presence of added salts (such as NaCN, NaCl, LiCl, LiI, or MgCl 2 ). This procedure avoids the use of strongly aqueous acidic and alkaline conditions and tolerates many functional and protecting groups. The chapter presents the mechanistic aspects of this procedure, which include reaction parameters such as solvents, salts, other additives, and the use of microwave irradiation. The diastereoselectivity of protonation of the enolate intermediate leading to the dealkoxycarbonylated products is discussed. Trapping of the intermediate enolate by electrophiles other than a proton is illustrated. Potential side reactions and same‐pot subsequent reactions of substrates are discussed along with functional‐group compatibility for halogens and nitrogen, oxygen, sulfur, selenium, and carbon functional groups. Several examples of applications of this methodology for the synthesis of natural products along with experimental conditions and procedures are presented. Closely related methods are discussed in the Comparison with Other Methods section. The tables, which consist of 371 pages, are grouped according to substrate structure. Selective entries for other methods (excluding classical aqueous acidic or basic methods) are included in the tabular survey for comparative purposes.

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The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Krapcho

Ciganek

2013

Organic Reactions

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Synthesis of 2‐(Ethylsulfanyl)aniline Derivatives Through the Unexpected Ring Opening of N‐Substituted‐2(3H)‐benzothiazolones.

Lebegue¹,

Charrier²,

Carato³

et al. 2005

ChemInform

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Synthesis of 2-(Ethylsulfanyl)aniline Derivatives Through the Unexpected RingOpening of N-Substituted-2(3H)-benzothiazolones. -A very simple method for the ring opening of benzothiazolones (I) is presented utilizing diethyl 2,2-diethylmalonate and KCN in DMSO/water. In an attempt to transform diester (VI) to the monoester using the system KCN/H2O/DMSO, additional ring-opening to an aminothiophenol is observed. This process is optimized and applied to benzothiazole substrates (I) and (IV) in the presence of diester (II). -(LEBEGUE*, N.; CHARRIER, G.; CARATO, P.; YOUS, S.; BERTHELOT, P.; Tetrahedron Lett. 45 (2004) 52, 9509-9511; Lab. Chim. Ther., Fac. Sci. Pharm. Biol., F-59006 Lille, Fr.; Eng.) -Mais 14-137

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Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections

García

Chua

Low

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for antifungal drug discovery. First, we show that several AHAS inhibitors developed as commercial herbicides are powerful accumulative inhibitors of Candida albicans AHAS (Ki values as low as 800 pM) and have determined high-resolution crystal structures of this enzyme in complex with several of these herbicides. In addition, we have demonstrated that chlorimuron ethyl (CE), a member of the sulfonylurea herbicide family, has potent antifungal activity against five different Candida species and Cryptococcus neoformans (with minimum inhibitory concentration, 50% values as low as 7 nM). Furthermore, in these assays, we have shown CE and itraconazole (a P450 inhibitor) can act synergistically to further improve potency. Finally, we show in Candida albicans-infected mice that CE is highly effective in clearing pathogenic fungal burden in the lungs, liver, and spleen, thus reducing overall mortality rates. Therefore, in view of their low toxicity to human cells, AHAS inhibitors represent a new class of antifungal drug candidates.

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Synthesis of 2-(ethylsulfanyl)aniline derivatives through the unexpected ring opening of N-substituted-2(3H)-benzothiazolones

Cited by 3 publications

References 13 publications

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Synthesis of 2‐(Ethylsulfanyl)aniline Derivatives Through the Unexpected Ring Opening of N‐Substituted‐2(3H)‐benzothiazolones.

Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections

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