Opening Of Thiazolidine Ring Research Articles

One Pot Catalyst‐free Synthesis of Substituted Di‐amino N‐tosyl Benzoyl Thiazoles byRegioselective C−N Bond Cleavage and Its Anticancer Activity

AbstractThe synthesis of hitherto unknown thiazole derivatives have been disclosed via purely green approach. This proposed work is novel in terms of C−C bond formation at guanidino carbon in 2‐amino benzimidazole moiety. The unstable benzimidazol‐hemiaminals have been used as a source of reactive intermediates.The catalyst‐free synthesis of diamino benzoyl N‐tosyl thiazole governed bythe sequential chemical conversions, which was steered by simple N‐tosylation of benzimidazol‐hemiaminal. The reaction was internally edge forward by thiazolidine ring opening, N‐tosylation, C−C bond formation and regioselective cleavage of C−N bondat guanidino carbon in a single step. Oxidation of tertiary alcohol to ketone with ring opening by C−N bond cleavage and N‐tosylation are the valuable conversions to accomplish the regioselectivity in the development of new desired thiazole ring. Moreover benzimidazol‐hemiaminal used as a storage of 2‐oxo‐2‐phenylethyl N′‐(1H‐benzo[d]imidazol‐2‐yl)‐N‐phenylcarbamimidothioate which is again highly unstable intermediate. The reverse back step mechanism was developed for the synthesis of thiazoles unlike other hemiaminals. The protocol is free of catalyst and toxic solvents.Use of ionic liquid, shorter reaction time, high yielding and easy isolation of products makes this strategy more environmental‐friendly. The importance of products attributed to the presence of active benzoyl and amino groups. Product thiazoles (T3) (IC50=7.906 μM), (T4) (IC50=5.250 μM) and (T7) (IC50=4.709 μM) were found potent anticancer agents against lung cancer with reference to doxorubicin as standard.

A novel ring opening reaction of peptide N-terminal thiazolidine with 2,2′-dipyridyl disulfide (DPDS) efficient for protein chemical synthesis

In the protein chemical synthesis via native chemical ligation (NCL) method with three peptide segments, the N-terminal cysteine residue of middle segment is generally protected by thiazolidine ring. In this paper, we show the novel method for thiazolidine ring opening using 2,2′-dipyridyl disulfide (DPDS). The N-terminal thiazolidine was converted into S-pyridylsulfenylated cysteine residue with DPDS under acidic conditions, and this N-terminally Cys peptide protected with disulfide was applicable to NCL reaction without purification and deprotection steps. DPDS treatment did not remove other Cys protecting groups generally used for regioselective disulfide bond formation reactions. These results indicate that this thiazolidine ring opening reaction is quite useful for the protein chemical synthesis with three-segment NCL strategy.

Spectrophotometric Analysis of the Cyanide Metabolite 2-Aminothiazoline-4-Carboxylic Acid (ATCA)

Methods of directly evaluating cyanide levels are limited by the volatility of cyanide and by the difficulty of establishing steady-state cyanide levels with time. We investigated the measurement of a stable, toxic metabolite, 2-aminothiazoline-4-carboxylic acid (ATCA), in an attempt to circumvent the challenge of directly determining cyanide concentrations in aqueous media. This study was focused on the spectrophotometric ATCA determination in the presence of cyanide, thiocyanate (SCN−), cysteine, rhodanese, thiosulfate, and other sulfur donors. The method involves a thiazolidine ring opening in the presence of p-(hydroxy-mercuri)-benzoate, followed by the reaction with diphenylthiocarbazone (dithizone). The product is spectrophotometrically analyzed at 625 nm in carbon tetrachloride. The calibration curve was linear with a regression line of Y = 0.0022x (R2 = 0.9971). Interference of cyanide antidotes with the method was determined. Cyanide, thiosulfate, butanethiosulfonate (BTS), and rhodanese did not appreciably interfere with the analysis, but SCN− and cysteine significantly shifted the standard curve. This sensitive spectrophotometric method has shown promise as a substitute for the measurement of the less stable cyanide.

2 + 2] Cycloaddition Reactions of Imines with Cyclic Ketenes: Synthesis of 1,3‐Thiazolidine Derived Spiro‐β‐Lactams and Their Transformations.

AbstractFor Abstract see ChemInform Abstract in Full Text.

2+2] Cycloaddition Reactions of Imines with Cyclic Ketenes: Synthesis of 1,3‐Thiazolidine Derived Spiro‐β‐lactams and Their Transformations

AbstractUnsymmetric cyclic ketenes were generated from N‐acyl‐1,3‐thiazolidine‐2‐carboxylic acids 1a–c by means of Mukaiyama's reagent, and then reacted with imines 2a–c to the new, isomeric spiro‐β‐lactams 3 and 4 via [2+2] cycloaddition (Staudinger ketene–imine reaction; Scheme 1). The reactions were stereoselective (Table 1) and mainly afforded the spiro‐β‐lactams with a relative trans configuration. The spiro‐β‐lactams could be transformed into the corresponding monocyclic β‐lactams by means of thiazolidine ring opening or into substituted thiazolidines via hydrolysis of the β‐lactam ring.

The disposition of14C-levamisole in the lactating cow

1. 14C-Levamisole 1(-)-2,3,5,6-tetrahydro-6-phenyl[U-14C]imidazo[2,1-b]-thiazole was administered orally and subcutaneously to lactating cows (8 mg/kg body weight). Urine, faeces, milk and blood samples were collected from 0-48 h after dosing and tissues were collected 48 h after dosing. 2. 14C-Labelled residues (ppm 14C-levamisole equivalents) in blood were highest at 3 h (2.2 ppm, oral dose) or 6 h (2.1 ppm, subcutaneous dose) and then declined to less than 0.5 ppm 48 h after dosing. 3. 14C-Labelled residues in milk were highest in samples collected from 0-12 h after dosing (1.55 ppm and 1.86 ppm of levamisole equivalents from oral and subcutaneously dosed animals, respectively) and declined to 0.06 ppm in milk collected from 36-48 h after dosing. Milk collected from 0-48 h after dosing accounted for 0.2% (oral dose) and 0.6% (subcutaneous dose) of the total 14C-activity administered as 14C-levamisole. The parent compound, 14C-levamisole, accounted for 12% or less (declined with time after dosing) of the total 14C-activity in the milk. Three 14C-labelled metabolites (formed by oxidation of imidazoline ring and/or opening of thiazolidine ring) in the milk were isolated and identified. 4. Urinary excretion accounted for 83% and 84% and faecal excretion accounted for 11% and 9% of the total 14C-activity given orally and subcutaneously, respectively, as 14C-levamisole. No 14C-levamisole was detected in the urine; the major urinary metabolite (formed by opening of thiazolidine ring) was isolated and identified. 5. The 14C-activity remaining in the animals 48 h after dosing was widely distributed in body tissues; however, the concentration in the liver was substantially higher than in all other tissues examined. Less than 5% of the 14C-activity in the liver was present as 14C-levamisole.

Thiazolidine ring opening in penicillin derivatives. Part 1. Imine formation

The rate of epimerisation of (3S,5R,6R)-benzylpenicilloic acid at C-5 shows three distinct dependencies upon pH in aqueous solution. Below pH 6 the rate shows a sigmoidal dependence upon pH, whereas it is pH-independent between pH 6 and 12, and above pH 12 the rate is hydroxide-ion dependent. These different regions of pH dependence are interpreted in terms of three mechanistic pathways all of which involve opening the thiazolidine ring by C–S bond fission and re-closure to generate the epimer. At low pH the reaction occurs by unimolecular ring opening of the S-conjugate acid which is kinetically equivalent to the N-conjugate acid of pKa 5.14. The pH-independent pathway involves formation of a zwitterion by unimolecular opening of the neutral thiazolidine. At high pH the unprotonated imine intermediate is formed by concerted hydroxide-ion-catalysed ring opening. The mono- and di-methyl esters of benzylpenicilloate also epimerise at C-5. At low pH the rates are similar for all three compounds but above pH 6 the mono- and di-esters are, respectively, 21 and 1700 times less reactive than the dianion of the diacid.

Thiazolidine ring opening in penicillin derivatives. Part 2. Enamine formation

The alkaline hydrolysis of (3S,5R,6R)-methyl benzylpenicilloate, and the corresponding carboxamide and N-ethylamide, is accompanied by an absorbance increase at 285 nm. This is attributed to a competing elimination reaction across C6–C5 to open the thiazolidine ring and reversibly generate an enamine intermediate. Kinetic analysis and hydrolysis in D2O do not indicate a significant build-up of this intermediate during hydrolysis of the methyl ester. However, over the pH range 4–11 the rate of thiazolidine ring opening is competitive with hydrolysis of the ester function. The deuterium solvent kinetic isotope effect on the ring closure reaction is 7.5.

Reactivity Parameters of the Metal Assisted 1,2-Cleavage of Penicillins

A straigtforward and smooth conversion of penicillins into 1,2-secopenicillanates is described. The thiazolidine ring opening is brought about by the co-operative effect of strong non-nucleophilic bases and thiophilic heavy metal salts. The nature of the latter and the polarity of the solvent profoundly affect the reaction rate.Best general conditions can be drawn for the conversion of numerous 6-substituted penicillanates with various protecting groups on the carboxy function.

Opening of the thiazolidine ring of penicillin derivatives

Penicilloic acid derivatives undergo two types of reversible thiazolidine ring opening reactions; in aqueous alkaline solution methyl benzylpenicilloate ring opens to give an enamine intermediate by a base-catalysed elimination process involving C-6-H whereas benzylpenicilloic acid epimerises at C-5 by unimolecular ring opening to form an intermediate iminium ion.

Reductive opening of the thiazolidine ring. Selective N‐methylation of cysteamines

AbstractThe reaction of thiazolidines 2 and 7 with borane was investigated. It gave N‐methylcysteamines 3 and 8 through thiazolidine ring opening. Sodium borohydride and lithium aluminum hydride were ineffective.

PREPARATION OF 6-THIA-3,8-DIAZABICYCLO/3,2,1/OCTAN-2-ONES

Abstract Study of the isomerisation of penilloic acid in aprotic solvents revealed the epimerisation at position C-4, when opening of thiazolidine ring was prevented by N-acetyl group(I).