21597-12-6Relevant articles and documents
Insights into the Mechanism of Thiol-Triggered COS/H2S Release from N-Dithiasuccinoyl Amines
Zhou, Shengchao,Mou, Yujie,Liu, Miao,Du, Qian,Ali, Basharat,Ramprasad, Jurupula,Qiao, Chunhua,Hu, Li-Fang,Ji, Xingyue
, p. 8352 - 8359 (2020/09/07)
The hydrolysis of carbonyl sulfide (COS) to form H2S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H2S in a biological system. Herein, we describe N-dithiasuccinoyl amines as thiol-triggered COS/H2S donors. Notably, thiol species especially GSH and homocysteine can trigger the release of both COS and H2S directly from several specific analogues via an unexpected mechanism. Importantly, two representative analogues Dts-1 and Dts-5 show intracellular H2S release, and Dts-1 imparts potent anti-inflammatory effects in LPS-challenged microglia cells. In conclusion, N-dithiasuccinoyl amine could serve as promising COS/H2S donors for either H2S biological studies or H2S-based therapeutics development.
Use of Dithiasuccinoyl-Caged Amines Enables COS/H2S Release Lacking Electrophilic Byproducts
Cerda, Matthew M.,Mancuso, Jenna L.,Mullen, Emma J.,Hendon, Christopher H.,Pluth, Michael D.
, p. 5374 - 5380 (2020/03/19)
The enzymatic conversion of carbonyl sulfide (COS) to hydrogen sulfide (H2S) by carbonic anhydrase has been used to develop self-immolating thiocarbamates as COS-based H2S donors to further elucidate the impact of reactive sulfur species in biology. The high modularity of this approach has provided a library of COS-based H2S donors that can be activated by specific stimuli. A common limitation, however, is that many such donors result in the formation of an electrophilic quinone methide byproduct during donor activation. As a mild alternative, we demonstrate here that dithiasuccinoyl groups can function as COS/H2S donor motifs, and that these groups release two equivalents of COS/H2S and uncage an amine payload under physiologically relevant conditions. Additionally, we demonstrate that COS/H2S release from this donor motif can be altered by electronic modulation and alkyl substitution. These insights are further supported by DFT investigations, which reveal that aryl and alkyl thiocarbamates release COS with significantly different activation energies.
Mechanism of sulfur transfer from 1,2,4-dithiazolidine-3,5-diones to triphenylphosphines
Ponomarov, Oleksandr,Padelkova, Zdenka,Hanusek, Jiri
, p. 560 - 564 (2013/07/26)
The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5-diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25°C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. From the Hammett correlations and from the solvent dependency, it was concluded that the transition-state structure is very polar and resembles the zwitter-ionic intermediate. The extent of P-S bond formation and S-S bond cleavage is very similar in the solvents series, but the latter gradually decreases with the decreasing polarity of the solvent. Copyright 2013 John Wiley & Sons, Ltd. The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5- diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25°C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. The transition-state structure is very polar and resembles the zwitter-ionic phosphonium intermediate. Copyright
Efficient synthesis of 1,2,4-dithiazolidine-3,5-diones [dithiasuccinoyl- amines] from bis(chlorocarbonyl)disulfane plus bis(trimethylsilyl)amines
Barany, Michael J.,Hammer, Robert P.,Merrifield,Barany, George
, p. 508 - 509 (2007/10/03)
The 1,2,4-dithiazolidine-3,5-dione heterocycle, also referred to as a dithiasuccinoyl (Dts)-amine, serves as a readily removable amino protecting group for building blocks used in syntheses of peptides, glycopeptides, and PNA; it is also useful as a masked isocyanate and (inversely) as a sulfurization reagent for trivalent phosphorus. Bis(chlorocarbonyl)disulfane, the two-sulfur analogue of succinyl chloride, has been envisioned as a reagent for facile single-step elaboration of the heterocycle. However, reactions of bis(chlorocarbonyl)disulfane directly with primary amines fail to yield Dts-amines for reasons that are discussed. Inspired by several precedents from the organosilicon chemistry literature that a trimethylsilyl group may serve as a "large proton," a successful, high-yield preparation of Dts-amines through reactions of bis(chlorocarbonyl)disulfane with bis(trimethylsilyl)amines has been developed. Studies aimed at elucidating mechanistic reasons for these observations are also presented. Copyright
Efficient Synthesis of 1,2,4-Dithiazolidine-3,5-diones (Dithiasuccinoyl-amines) and Observations on Formation of 1,2,4-Thiadiazolidine-3,5-diones by Related Chemistry
Slomczynska, Urszula,Barany, George
, p. 241 - 246 (2007/10/02)
An efficient synthesis of 1,2,4-dithiazolidine-3,5-diones (1) from chlorocarbonylsulfenyl chloride (3) plus O-dimethylaminoethyl-N-alkyl or aryl thiocarbamates (4) has been worked out.In this synthesis, 1,2,4-thiadiazolidine-3,5-diones (5) have been shown to arise as low-level-by-products, and experiments were conducted to elucidate the mechanism of the side reaction.N,N'-Dimethyl-1,2,4-thiadiazolidine-3,5-dione (5a) was prepared in one step from N,N'-dimethylurea plus 3, or from 4a plus one equivalent of sulfuryl chloride.A general route to 5 involved reaction ofequimolar amounts of isocyanates (6), isothiocyanates (7) and sulfuryl chloride followed by hydrolysis of intermediate 9.Heterocycles reported have been characterized by nmr, ir, uv, ms, and hplc.
