Of rhodanine

A-2-Thiazoline-4-ones are usually obtained by the heterocydization method (38b-388). 2 Alkylthio-4(5)-thiazolones (162) are obtained by alkylation at sulfur of rhodanine (160) in nonpolar solvent (Scheme 85). 

Arylthio-5-ethyl-4(5)-thiazolone derivatives (164, 165. and 166) have been prepared by treatment of rhodanine (163) with the appropriate aryldiazonium salts (Scheme 86) (395). 

In 1877, Nencki (22) condensing ammonium thiocyanate with chloroacetic acid, attributed the name rhodaninic acid (Rhodaninsaure) to the compound he obtained. He noted the ability of rhodaninic acid to give colored derivatives with ferric salts. 

In 1879, Liebermann and Lange (20) demonstrated the formula of rhodaninic acid to be 39. 

In 1884, Nencki (70), studying the properties of rhodaninic acid, confirmed the formula proposed by Libermann and Lange (39) and noted its ability to condense with aldehydes. 

In 1886, Ginsburg and Bondzynski (71) and Berlinerblau (72) developed the reaction of rhodanine with aldehydes, but proposed a chain formula for the condensation product. 

During a relatively long period, the condensation of rhodanines with aldehydes was developed, especially by Andreasch s group (78-87). Finally, Holmberg (88, 89) described the best method to obtain rhodanines the condensation of ammonium dithiocarbamate with a sodium or potassium salt of an a-chloro acid. 

Direct allylation of rhodanine 49 (Scheme 13) under Pd(0)-catalysis with cinnamyl ethyl carbonate affords the /V-allylated compound 50. However, allylation with cinnamyl bromide and a base is not regioselective, producing a mixture of 50 and sulfide 51. Sulfide 51 isomerizes to 50 under palladium catalysis (N > S), thus indicating that Pd(0)-catalyzed allylation of 49 is thermodynamically controlled (93T1465). 

The chemistry of 4-thiazolidinones (1) was reviewed in depth by Brown in 1962.1 Since then, largely due to the wide variety of physiological activity demonstrated by this class of compounds, several thousand papers2 on the chemistry of 4-thiazolidinone derivatives, exclusive of rhodanine derivatives, have been published. This review will consider only the important literature highlights of 1, 2,4-thiazolidinediones (2), 2-imino-4-thiazolidinones (3), and 4-oxo-2-thiazolin-2-ylhydrazones (4). Neither rhodanine (5) nor the extensive patent and obscure literature references dealing with 4-thiazolidinones will be considered in any detail within this review. 

Conversion of the 4-C=0 group of 62 into a thione function creates an isomer of rhodanine (5) called isorhodanine (87 R = H), which displays enhanced chemical reactivity. Treatment of 62 with phosphorus pentasulfide in dioxane affords 87.114-117 Isorhodanines (87) react with... 

Yields in each step are in the range of 80% to 97%. The facile preparation of rhodanine in large quantity has been described along with improved directions for each step. Aliphatic, aromatic, and heterocyclic aldehydes undergo the initial condensation however, only products from the last two series are frequently carried to the final step, for example, 3,4-dimethoxyphenylacetonitrile (90% over-all), 2-ftiranaceto-... 

Gendelman, L. . Udehyde derivatives of rhodanines and their fission pro-... 

Treatment of rhodanines with an excess of zinc dust in acetic acid leads to the reduction of the thioxo group yielding 4-thiazolidinones <94TL697i>. 

Several potent AR inhibitors have been developed which, structurally, are heterocyclic alkanoic acids. Of a large series of rhodanine derivatives [88, 89], ( )-3-carboxymethyl-5-[(2 )-methyl-3-phenylpropenylidene]rhodanine (ONO-62235 epalrestat, 26) has been selected for clinical development. Epal-restat has an IC50 value of 1 x 10 8 M with AR from rat lens and an IC50 of 2.6 x 10 " 6 M with human placental AR [90]. Another series of rhodanines has been reported, the most potent of which was the aminomethylidene derivative (27), which had an IC50 value of 2.3 x 10 " 8 M with rat lens AR [91]. No in vivo results were presented. 

The condensation of rhodanine (42) with aldehydes is an important reaction closely related to the Er-lenmeyer azalactone synthesis (equation 22) the resulting condensation products are particularly useful intermediates for the preparation of various functionalized arylacetic acids and derivatives via standard manipulations of the nitrile (43), which is available as illustrated in Scheme 11. Similarly, aldehydes... 

A new method for the determination of DNA with high sensitivity and selectivity was established based on the significant enhancement of SOS intensity of 4MRASP-SDS-DNA ion-association complexes. These investigations have expanded the applications of rhodanine spectroscopy. 

The possible reaction pathway for the conversion of rhodanine and aldehyde into thionic acid is displayed here. The further transformations of thionic acid into other derivatives, including of-amino acid, aliphatic nitrile, and aliphatic acid, are not provided. 

Synthesis oxidative eleetropolymerization of rhodanine in ammonium oxalate solution [697],... 

Recent Advances in the Biological Importance of Rhodanine Derivatives... 

Keywords Rhodanine, biological activities, structure activity relationship and selectivity of rhodanine derivatives... 

Figure 2. SciFinder search for recent publications, including biological activity of rhodanines sorted by year, as determined on 10 August 2015.

Hardej et al. [22] have synthesized a series of rhodanine derivatives containing various substituents at the N3- and Cg-positions and tested for in vitro antibacterial activity against a panel of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strains. The anti-MRSA activity of compounds II (minimum inhibitory concentration (MIC)=3.9 pg/mL) and in (MIC=1.95 pg/mL) were significantly greater than that of the reference antibiotics penicillin G (MIC=31.25 pg/mL) and ciprofloxacin (MIC=7.8 pg/mL). 

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