2756-91-4Relevant academic research and scientific papers
Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE
Rohac, Roman,Amara, Patricia,Benjdia, Alhosna,Martin, Lydie,Ruffié, Pauline,Favier, Adrien,Berteau, Olivier,Mouesca, Jean-Marie,Fontecilla-Camps, Juan C.,Nicolet, Yvain
, p. 491 - 500 (2016)
Carbon-sulfur bond formation at aliphatic positions is a challenging reaction that is performed efficiently by radical S-adenosyl-L-methionine (SAM) enzymes. Here we report that 1,3-thiazolidines can act as ligands and substrates for the radical SAM enzyme HydE, which is involved in the assembly of the active site of [FeFe]-hydrogenase. Using X-ray crystallography, in vitro assays and NMR spectroscopy we identified a radical-based reaction mechanism that is best described as the formation of a C-centred radical that concomitantly attacks the sulfur atom of a thioether. To the best of our knowledge, this is the first example of a radical SAM enzyme that reacts directly on a sulfur atom instead of abstracting a hydrogen atom. Using theoretical calculations based on our high-resolution structures we followed the evolution of the electronic structure from SAM through to the formation of S-adenosyl-L-cysteine. Our results suggest that, at least in this case, the widely proposed and highly reactive 5′-deoxyadenosyl radical species that triggers the reaction in radical SAM enzymes is not an isolable intermediate.
Small molecule diselenide additives for in vitro oxidative protein folding
Reddy, Post Sai,Metanis, Norman
, p. 3336 - 3339 (2016)
The in vitro oxidative folding of disulfide-rich proteins can be challenging. Here we show a new class of small molecule diselenides, which can be easily prepared from inexpensive starting materials, used to enhance oxidative protein folding. These compounds were tested on a model protein, bovine pancreatic trypsin inhibitor. Two of the tested diselenides showed considerable improvement over glutathione and were on par with the previously described selenoglutathione.
Spectroscopic and theoretical investigation of the conformational space of a pyrazolo-thiazole precursor of extended dipole diazafulvenium methide intermediates
Nunes, Cláudio M.,Lopes, Susy,Pinho e Melo, Teresa M.V.D.,Fausto, Rui
, p. 101 - 108 (2009)
The structure, preferred conformers and vibrational spectra of the pyrazolo-thiazole precursor of extended dipole diazafulvenium methide intermediates, dimethyl 2,2-dioxo-1H,3H-pyrazolo[1,5-c][1,3]thiazole-6,7-dicarboxylate (DPTD) were investigated in low-temperature noble gas matrices (Ar, Xe), low temperature neat amorphous and crystalline phases and in KBr pellet (crystal and melted phases) by infrared spectroscopy, supported by quantum chemical calculations. Two types of conformers were observed spectroscopically in the matrices and in the neat amorphous solid resulting from fast condensation of the vapour of the compound onto the cold (20 K) substrate of the cryostat. These conformers correspond to the two pairs of nearly degenerated structures exhibiting skew/cis (conformers S′C and SC′) and gauche/trans (conformers G′T and GT′) arrangements of the N{double bond, long}C-C{double bond, long}O/C{double bond, long}C-C{double bond, long}O moieties. In the crystalline phase, the vibrational signature of the compound indicates that it exists in a skew/cis arrangement. After melting of the crystal, a conformational mixture is formed, where both skew/cis and gauche/trans forms exist in equilibrium and, with all probability, also conformer G′C′. This latter conformer cannot exist in the low temperature matrices and amorphous state, in view of the very low energy barrier that separates this form from the lower energy SC′ conformer, which can be easily surpassed during deposition of the compound (conformational cooling).
Asymmetric Michael reaction promoted by chiral thiazolidine-thiourea catalyst
da Silva, Tiago Lima,Rambo, Raoni Scheibler,Jacoby, Caroline Gross,Schneider, Paulo Henrique
supporting information, (2019/12/27)
In this work, we report the synthesis and characterization of three new thiazolidine- and thiourea-based chiral organocatalysts. These compounds were successfully applied in asymmetric Michael addition reactions between different ketones and nitrostyrenes leading to products in up to 85% yield, >96:4 r.d. and 97% e.e. Computational studies were used to better visualize the proposed transition state and explain the observed stereoselectivities. One of the new catalysts was also successfully applied in an aldol addition between cyclohexanone an p-nitrobenzaldehyde leading to product in 80% yield, >96:4 d.r. and 80% e.e.
Method for preparing thiazole-4-formic acid
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Paragraph 0021-0023; 0031-0033; 0041-0043; 0051-0053, (2019/04/17)
The invention discloses a method for preparing thiazole-4-formic acid. By the aid of the method, the problems of relatively high prices of raw materials used in old processes for thiabendazole which is one of important traditional pesticide and bactericide varieties and low yield of the thiabendazole can be solved. The method includes steps of generating thiazolidine-4-formic acid from L-cysteinehydrochloride, formaldehyde and pyridine; carrying out reaction on the thiazolidine-4-formic acid, methyl alcohol and HCl gas to generate thiazolidine-4-methyl formate; carrying out reaction on the thiazolidine-4-methyl formate, acetonitrile and MnO2 to generate thiazole-4-methyl formate; hydrolyzing the thiazole-4-methyl formate under the effect of sodium hydroxide to obtain the thiazole-4-formicacid which is a product. The method has the advantages of simple process synthetic route, mild reaction condition, low cost, environmental protection, safety, excellent application prospect, good social benefit and high economic benefit.
Industrialized scale preparation method for pidotimod
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Paragraph 0018; 0020; 0022; 0024; 0026, (2018/11/03)
The invention discloses an industrialized scale preparation method for pidotimod, and belongs to the technical field of medicine synthesis. The industrialized scale preparation method comprises the following steps of performing ring closure and esterification on L-cysteine, so as to obtain L-thiazolidine-carboxylic ester; then, condensing with L-pyroglutamic acid under the action of a condensing agent; then, performing ester hydrolysis, and crystallizing, so as to obtain a product meeting the medicinal standard. The industrialized scale preparation method has the advantages that the intermediate, such as L-thiazolidine-carboxylic ester hydrochloride, is not separated, the water is removed by a co-boiling method in the condensing reaction process, and the separating and drying steps of theintermediate are omitted; compared with other preparation methods, the technology is optimized, so as to shorten the large-scale production time, improve the yield rate, and reduce the production cost; the operability in the scale production of the pidotimod is realized.
X-ray crystal structures and anti-breast cancer property of 3-tert -butoxycarbonyl-2-arylthiazolidine-4-carboxylic acids
Jagtap, Rohidas M.,Thorat, Shridhar H.,Gonnade, Rajesh G.,Khan, Ayesha A.,Pardeshi, Satish K.
, p. 1078 - 1086 (2018/02/06)
Diastereomeric '2RS,4R'-2-arylthiazolidine-4-carboxylic acids (ATCAs) were synthesized and their resolution to chiraly pure N-BOC derivatives was attempted by column chromatography. The absolute stereochemistry of the resolved compounds was ascertained by X-ray single crystal structures. Further application of the synthesized compounds was studied for their in vitro anti-breast cancer activity against MCF7 cell line using DOX as a standard by MTT assay method. Cell morphology analysis was carried out by fluorescence microscopy. The compounds containing '2S' absolute configuration in thiazolidine ring and presence of 2-NO2, 2,6-Cl groups on '2R'-aryl substituent showed significant anti-breast cancer activity where some of the compounds were found to be more active than DOX in terms of induced apoptosis mode of MCF7 cell death.
New aspects of the formation of 2-substituted thiazolidine-4-carboxylic acids and their thiohydantoin derivatives
Mahdy, Ahmed R.E.,Elboray, Elghareeb E.,Fandy, Ragab F.,Abbas-Temirek, Hussien H,Aly, Moustafa F.
, p. 105 - 121 (2018/05/14)
Aromatic aldehydes reacted readily with (R)-cysteine in boiling acidified methanol to give diastereomeric mixtures of the corresponding 2-(aryl substituted) thiazolidine-4-carboxylic acids. 4-Nitrobenzaldehyde under similar conditions afforded one isomer of 2-(4-nitrophenyl)-thiazolidine-4-carboxylic acid, which epimerized in the NMR solvents into a diastereomeric mixture. 2-Nitrobenzaldehyde reacted with (R)-cysteine to afford 3,5-bis-(2-nitrophenyl)-tetrahydro-1H-thiazolo[3,4-c]oxazol-1-one as the sole product, which collapsed in the NMR solvent into a diastereomeric mixture of the thiazolidine-4-carboxylic acids. The thiazolidine derivatives reacted smoothly with phenyl isothiocyanate to give single isomers of the corresponding thiohydantoins.
Thiazolidine esters: New potent urease inhibitors
Lodhi, Muhammad Arif,Shams, Sulaiman,Khan, Khalid Mohammad
, p. 858 - 864 (2015/01/30)
A variety of esters of thiazolidine-4-caboxylic acid were synthesized and investigated for their urease inhibitory properties. A significant increase in urease inhibitory activities of these ester derivatives has been observed. The order of activity increases from methyl ester to heptyl ester but further prolongation of the alkyl chain was proved to be detrimental for receptor binding. These findings provide evidence that the nature of the alkyl chain has a significant impact on the coordination of thiazolidine esters with bi-metallic nickel center of urease. It was also observed that inhibition potentiated by lower pH and with increase in time.
A highly enantio- and diastereoselective direct aldol reaction in aqueous medium catalyzed by thiazolidine-based compounds
Rambo, Raoní Scheibler,Gross Jacoby, Caroline,Da Silva, Tiago Lima,Schneider, Paulo Henrique
, p. 632 - 637 (2015/08/03)
Taking l-aminoacids as starting materials, a new set of enantiopure thiazolidine-based organocatalysts were prepared using a simple synthetic approach and successfully applied in the asymmetric direct aldol reaction between various cyclic ketones and aldehydes in a saturated aqueous medium. The aldol adducts were obtained with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (dr >20:1).
