4-Thiazolidinones structure

Dehuri and Nayak (83JIC970) reported that 3,4,5,6,7,8-hexahydro-l,3-diazocine-2-thione (213), obtained from 1,5-dibromopentane and thiourea in boiling ethanol, reacts with chloroacetic acid or its ethyl ester followed by basification to give 5//-6,7,8,9-tetrahydrothiazolo[3,2-a]-[ 1,3]diazocin-3(2//)-one (214). The reaction of 213 with ethyl chloroacetate was not smooth and the yield was low. The thione 213, on reaction with ethyl chloroacetate and aromatic aldehydes in the presence of pyridine and piperidine, furnishes the arylidene product 215 which is also obtained from 214 and aromatic aldehydes. No spectral data are cited to confirm the thiazolidinone structures 214 and 215 (Scheme 50). 

Reaction of thione 276 (R = H) with diethyl acetylenedicarboxylate in acetic acid or ethanol similarly gives both thiazolidinone (277) and thiazinone (278) as expected (79TL53) (Scheme 67). Condensation of 276 (R = Me, Cl, NO2, CO2H) and 280 with acetylenedicarboxylic esters gives a cyclized product in each case for which respective thiazolidinone structures 279 and 281 were assigned (77M11). This work warrants reinves-... 

A single crystal X-ray study (78TL2621) of one of the products obtained from the reaction of benzimidazolyl-2-thione (247) with DMAD confirms thiazolidinone structure 23, which was earlier tentatively assigned on the... 

Hexythiazox, tra/2s 5-(4-chlorophenyl)-N cyclohexyl-4-methyl-2 Oxothiazolidine-3-carboxamide, is a new potent acaricide which has a unique thiazolidinone structure. It has broad acaricidal spectrum and excellent ovicidal, larvicidal and nymphcidal actions. Its synthesis requires stereoselective processes because the trans configuration at positions 4- and 5- in the thiazolidinone structure is essential for acaricidal activity. We have studied the stereoselective synthesis of phenylpropanolamines as key-intermediates of hexythiazox derivatives and established the novel stereoselective synthetic methods for trans thiazolidinones from phenylpropanolamines. 

As mentioned above, the stereochemistry of the thiazolidinone structure is quite important for acaricidal activity. In order to regulate the stereochemistry, a number of synthetic pathways were considered as shown in Scheme 1. In this scheme, we focused our attention on aziridines, chloroamines and aminoalcohols as key-intermediates. We investigated the synthetic process to obtain both cis and trans or erythro and threo isomers of these intermediates (5-6). Here we intend to describe the stereoselective synthesis of the trans isomers which are important for the acaricidal activity ( Schemes 2-4 ). 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

The structure of the toxins was elucidated by NMR and approved by X-ray diffraction analysis (Fig. 7). The two compounds were found to contain a new class of 16- and l4-membered macrolides attached via 6-membered lactol to the rare 2-thiazolidinone moiety. Both toxins are... 

Some of the other scaffolds used to synthetize Kvl.5 channel inhibitors are prototypes of vicinally substituted heterocycles, such as the tetrazole 2f shown in Table 1. This series was developed to circumvent a metabolic liability of thiazolidinone derivatives previously identified as potent Kvl.5 blockers [54]. Some chemistry efforts have been directed toward novel structures that provide practical advantages in addition to Kvl.5 potency. This is the case of Kvl.5 inhibitors based on a diisopropyl amide scaffold [50]. 

This sponge, found in the Red Sea, produces a number of toxins, three of which have been isolated and identified as possessing a thiazolidinone ring that is connected to a fourteen-membered macrolide ring.47 Latrunculins A and B have been assigned structures (42) and (43), and latrunculin C is a stereoisomer of (42). 

Structure-based design has been effectively utilized in synthesis of inhibitors of non-proteolytic enzymes. Inhibitors of MurB, an essential bacterial enzyme required for biosynthesis of peptidoglycan, were identified using the X-ray structure of the enzyme for library design. Thiazolidinone inhibitors (8) thus identified are the first examples of small molecule inhibitors of MurB. 

Symmetrical dialkylthioureas react with 7 to give a single product. Un-symmetrical substituted thioureas (11) have been condensed with 7 to afford two isomeric 2-imino-4-thiazolidinones (12a,b) however in most cases, a predominant isomer has been obtained. Structural configurations of 12 have been deduced by hydrolysis to the corresponding diones (13a,b),... 

The isolation and E,Z-configurational assignments of 2-cyanomethylene-3-methyl-4-thiazolidinone have been reported,70 thus correcting previous structural assignments.73... 

Phenylhydrazono-4-thiazolidinones (124) and their 5-substituted derivatives are cyclized upon treatment with formaldehyde or aromatic aldehydes to give the bicyclic structure 125.169 5-Arylidene derivatives of 126 have been cyclized to 127 by initial treatment with chloroacetic acid, followed by hot acetic anhydride or concentrated sulfuric acid.170... 

The structures of isomeric 2-methylenethiazolidin-4-ones have been ascertained by NMR analysis.69 Recently, several papers on 13C-NMR spectra of 4-thiazolidinones have been reported.184... 

In a different study, Vigorita et al. used the docking experiments to analyze and understand the configuration preferences of the optical isomers of 3,3 -(l,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] (Fig. 5) in relation to the available structures of COX-1 and COX-2 enzymes [85]. 

Dandia A, Singh R, Khaturia S et al (2006) Efficient microwave enhanced regioselective synthesis of a series of benzimidazolyl/triazolyl spiro [indole-thiazolidinones] as potent antifungal agents and crystal structure of spiro[3H-indole-3, 20-thiazolidine]-30(l, 2, 4-triazol-3-yl)- 2, 40(lH)-dione. Bioorg Med Chem 14 2409-2417... 

Thiones 123 react with chloroacetic acid in the presence of anhydrous sodium acetate in acetic acid and acetic anhydride to give a cyclized product for which structure 124 has been assigned (82MI1). The cyclized product could be isomeric structure 125. The same workers similarly obtained a product formulated as 126 from the reaction of the thione 123 (n = 6) with chloroacetic acid (8IM12). Compound 126 reacts with aromatic aldehyde to furnish the arylidene product 127 which is also obtained from the reaction of thione 123 (n = 6), chloroacetic acid, and aldehydes as well as from the condensation reaction of thiazolidinone 124 ( = 6)... 

Although the synthesis of condensed thiazolidinones (214,220,223,226, 229 and 232) are accomplished in a straightforward manner, structures must await spectral studies. Moreover, structures of thiones 213,219,222, 225,228 and 231 used as the starting materials are not established beyond doubt. 

Bis-(4-thiazolidinones) (234), on treatment with concentrated sulfuric acid, undergo cyclodehydration to furnish 7//-bis-(thiazolo)-[3,4-f 3, 2 -J]-5-triazol-3(2//)-ones (235) (85JIC147) (Scheme 57). Compounds 235 in general were found to be more potent herbicides than their precursors, 234, suggesting that 235 must be compact and possess planar structure. 

Reaction of 4-oxoquinazolinyl-2-thione (332) with DMAD gives four major products (359-362) and one minor product (363) whose structures were unequivocally established by C-NMR spectroscopy and X-ray crystallographic analysis [86JCS(P1)2095] (Scheme 83). Surprisingly, no condensed thiazolidinone (364 or 365) was isolated from the reaction mixture. This is in contrast to the behavior of other thiones (20,28,53,65, 155, 185, 247, 276 (R = H), 276, 280, and 352) that react with DMAD to give the corresponding condensed thiazolidinones (21,48,54,67,160,188, 23, 277, 279, 281, and 357). 

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