Green synthesis of some new thiopyrano[2,3-d][1,3]thiazoles using lemon juice and their antibacterial activity

A simple green method has been developed for the synthesis of a series of new 3-phenyl-6-(substituted)-thiopyrano[2,3-d]thiazole-2,5,7(6H)-triones, 6-cyano-2-oxo-3-phenyl-thiopyrano[2,3-d]thiazoles, 3-phenyl-3,5,5a,11b-tetrahydro-2H,6H-chromeno-[4′,3′:4,5]thiopyrano[2,3-d]thiazole-2,6-dione and 5-amino-6-cyano-2-oxo-3-phenyl-3,7-dihydro-2H-thiopyrano[2,3-d]thiazoles via hetero-Diels–Alder reaction by conventional method and green method using lemon juice as natural acid. The structure of all the newly synthesized compounds was interpreted by elemental analyses and spectral data. The synthesized compounds were evaluated for their in vitro antibacterial activity against some pathogenic bacteria. This study is a platform for the future design of more potent antimicrobial agents.     

Synthesis and biological evaluation of two novel 2′-substituted tiazofurin analogues

Two novel tiazofurin analogues, 2-(2-benzamido-2-deoxy-β-d-ribofuranosyl)thiazole-4-carboxamide 4 and 2-(2-azido-2-deoxy-β-d-ribofuranosyl)thiazole-4-carboxamide 5, have been synthesized starting from d-glucose and evaluated for their in vitro cytotoxicity against several human leukaemia and solid tumour cell lines.     

Titanium(IV)-mediated tandem deprotection-cyclodehydration of protected cysteine N-amides: biomimetic syntheses of thiazoline- and thiazole-containing heterocycles

The scope and limitations of TiCl(4)-mediated Delta(2)-thiazoline synthesis via tandem deprotection-dehydrocyclization of trityl-protected cysteine N-amides is presented. While chemical yields are acceptable (53-96%), the stereochemical outcomes vary on the basis of structural considerations and reaction conditions (22-99% ee). Racemization at the C(2)-exomethine position limits the utility of this method for the formation of a thiazoline within a peptide. Treatment of a tritylated Cys-Cys dipeptide with TiCl(4) afforded the corresponding thiazole-thiazoline heterocycle 12 (38% yield, 97% ee).     

Synthesis of certain exocyclic thiazole nucleosides related to tiazofurin. Formation of a unique acycloaminonucleoside

Several thiazole nucleosides structurally related to tiazofurin (1) and ARPP (2) were prepared, in order to determine whether these nucleosides had enhanced antitumor/antiviral activities. Ring closure of 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)thiourea (4) with ethyl bromopyruvate (5a) gave ethyl 2-(2,3,5-tri-O-benzoyl-β-D-ribofuranosylamino)thiazole-4-carboxylate (6a) . Treatment of 6a with sodium methoxide furnished methyl 2-(β-D-ribopyranosylamino)thiazole-4-carboxylate (9) . Ammonolysis of the corresponding methyl ester of 6a gave a unique acycloaminonucleoside 2-[(1R, 2R, 3R, 4R)(1-benzamido-2,3,4,5-tetrahydroxypentane)amino]-thiazole-4-carboxamide (7a) . Direct glycosylation of the sodium salt of ethyl 2-mercaptothiazole-4-carboxylate (12) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (11) gave the protected nucleoside 10 , which on ammonolysis provided 2-(β-D-ribofuranosylthio)thiazole-4-carboxamide (3b) . Similar glycosylation of 12 with 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride (13) , followed by ammonolysis gave 2-(2-deoxy-β-D-ribofuranosylthio)thiazole-4-carboxamide (3c) . The structural assignments of 3b, 7a , and 9 were made by single-crystal X-ray analysis and their hydrogen bonding characteristics have been studied. These compounds are devoid of any significant antiviral/antitumor activity in vitro.     

Solid-phase synthesis and stereochemical assignments of tenuecyclamides A-D employing heterocyclic amino acids derived from commercially available Fmoc alpha-amino acids

[reaction: see text] The solid-phase assembly of heterocyclic amino acids enabled the total synthesis of numerous diastereoisomers of tenuecyclamides A-D, establishing or correcting the stereochemistry of each natural product. This strategy provides a very efficient route to synthesize thiazole- and oxazole-containing macrolactams from heterocyclic amino acids that are readily prepared from Fmoc-alpha-amino acids. This methodology appears to be broadly applicable to the synthesis of natural product libraries incorporating unnatural heterocyclic amino acid residues for the purpose of drug discovery.     

Tryptamine derived amides with thiazole ring system from Thermoactinomyces strain TA66-2

A moderately thermophilic actinomycete strain, which was identified as Thermoactinomyces strain TA66-2, was isolated from hot-spring water. Fermentation, followed by solvent partition and chromatographic separations, resulted in the isolation of two new and two known molecules. The structures of the new compounds were elucidated as 2-(1-Propionylaminoethyl)thiazole-4-carboxylic acid [2-(1H-indol-3-yl)ethyl]amide and 2-(1-Acetylaminoethyl)thiazole-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]amide by using spectral methods (1D-, 2D-NMR and LC-ESI-MS).     

Synthesis,anticancer and antiviral activities of novel thiopyrano[2,3-d]thiazole-6-carbaldehydes

Novel rel-(6R,7R)-2-oxo-7-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehydes were synthesized via regio- and diastereoselective hetero-Diels-Alder reaction of 5-arylidene-4-thioxo-2-thiazolidinones with acrolein. The synthesized compounds were evaluated for anticancer and antiviral activities by the National Institutes of Health (NIH) following US NCI and AACF protocols. Anticancer activity screening on NCI60 cell lines allowed identification of 7-phenyl-2-oxo-7-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehyde 3a with the highest level of antimitotic activity against leukemia with mean GI₅₀/TGI values 1.26/25.22 μM. The screening of antiviral activity lead to identification of 7-(4-methoxyphenyl)-2-oxo-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehyde 3b with a promising influence on EBV virus (EC₅₀ = 0.07 μM, SI = 3279) and moderate effect on Herpes simplex virus type 1 and Varicella zoster virus and 7-[4-(benzyloxy)phenyl]-2-oxo-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d][1,3]thiazole-6-carbaldehyde 3e with a promising influence on Hepatitis C virus (EC₅₀ = 12.6 μM, SI = 43.1).     

The Versatile Synthesis of Azulenothiazole Derivatives

6-Methoxy-2-methylazuleno[6,5-d]thiazole 5 , 2-benzamidoazuleno[6,5-d]thiazole 13 and its 6-methoxy derivative 10 were obtained by the decarbethoxylation of the diethyl 6-methoxy-2-methylazuleno[6,5-d]thiazole-5,7-dicarboxytate 4, diethyl 2-benzamidoazuleno[6,5-d]thiazole-5,7-dicarboxylate 12 and ite 6-methoxy derivative 9 , respectively. The latter compounds were synthesized from diethyl 6-amino-2-hydroxyazulene-l,3-dicarboxylate 1 , diethyl 5-bromo-6-amino-2-acetylaminoazulene-l,3-dicarboxylate 6b and diethyl 5-bromo-6-amino-2-hydroxyazulene-l,3-dicarboxylate 6a in a few steps, by previous methods.     

Mechanism selection for regiocontrol in base-assisted, palladium-catalysed direct C-H coupling with halides: first approach for oxazole- and thiazole-4-carboxylates

Both base-assisted non-concerted metallation-deprotonation (nCMD) and concerted metallation-deprotonation (CMD) have been identified as two potent operating mechanisms in palladium-catalysed direct C-H coupling of oxazole and thiazole-4-carboxylate esters with halides through base- and solvent-effect experiments. Novel C2- and C5-selective CMD direct arylation procedures in oxazole- and thiazole-4-carboxylate series were then designed by controlling the balance between electronic and steric factors. Notably, charge interactions between the palladium catalyst and substrate were identified as a parameter for controlling selectivity and reducing the impact of steric factors in the CMD reaction.     

Synthesis of new thiazole-2, -4, and -5-yl-(amino)methylphosphonates and phosphinates: unprecedented cleavage of thiazole-2 derivatives under acidic conditions

An efficient and reliable synthesis of new thiazole-(amino)methylphosphonic, phosphinic acids, and phosphine oxides is reported. The synthetic protocol is based on nucleophilic addition of phosphorous species to thiazole derived imines. Unexpectedly, it was discovered that heating of thiazole-2-yl-(amino)methylphosphonates and phosphinates with aqueous HCl leads to their decomposition resulting in a rupture of the C-P bond, rejecting of the phosphorus containing fragment and formation of the corresponding secondary N-(thiazole-2-yl-methyl)-alkylamines. Two alternative mechanisms for this cleavage are postulated.     

Total synthesis of anithiactins A-C and thiasporine A

The total syntheses of anithiactins A-C (1–3) and thiasporine A (4) have been achieved in good overall yields. The key reaction in the synthetic sequence was the Suzuki-Miyaura cross-coupling between 2-aminophenylboronic acid hydrochloride and methyl 2-bromothiazole-4-carboxylate forming the common intermediate methyl 2-(2-aminophenyl)thiazole-4-carboxylate (8), which could be further transformed by hydrolysis, alkylation, and aminolysis to give the four title natural products. This work represents the first total synthesis of anithiactin B (2) and C (3).     

Predicting the binding capability of benzothiazoline-2-thione and its derivatives with gold: a DFT and FT-Raman combined studies

The activities of chemical systems can be evaluated successfully by combining vibrational spectroscopic analysis and quantum chemical calculation based on density functional theory (DFT). Two tautomers of 5-fluorobenzo[d]thiazole-2(3H)-thione (FBTT), 7H-[1,3]dioxolo[4',5',4,5]benzo[1,2-d]thiazole-6-thione (DBTT) and 5-chloro-6-methylbenzo[d]thiazole-2(3H)-thione (CMBTT) were investigated by FT-Raman spectroscopy and DFT calculations at B3LYP/6-311+G** level. The molecular properties and activity relationships were determined by the HOMO energies, Mulliken charges and the binding energies with metal. It is concluded that three derivatives exhibited stable conformation of the thione form both in the isolated powder monomers and in their complexes with gold. The binding capability with gold was in the order of DBTT>BTT approximately CMBTT>FBTT. The derivatives with the electron-donor substitutes in benzene ring were favorable to metal for the p-pi conjugate effect.     

Nitrosation and hydrolysis studies of some thiazole-4-acetic esters

Nitrosation of hydrazino substituted thiazole-4-acetates has been shown to occur on the ring, rather than the α-methylene carbon, as previously reported. Thus nitrosation of ethyl 2-isopropylidenehydrazono-, 2-benzylidenehydrazono-, 2-(2-benzoylhydrazino)-, and 2-(2-acetylhydrazino)thiazole-4-acetates yielded the corresponding 2-hydrazino-4-carbethoxymethylidene-4,5-dihydrothiazoline-5-oximes. Basic hydrolysis of the thiazoline-5-oxime esters, followed by decarboxylation gave tautomeric mixtures of the 2-hydrazino-4-methyl-2,5-dihydrothiazoline-5-oxime and 2-hydrazino-4-methyl-5-nitrosothiazol derivatives. These tautomeric mixtures were also prepared by nitrosating the 2-hydrazino-4-methylthiazoles. The α,β-unsaturated acids, 2-isopropylidenehydrazono-, 2-benzylidenehydrazono-, and 2-(2-benzoyl-hydrazino)-4-carboxymethylidene-4,5-dihydrothiazoline, were isolated after basic hydrolysis of the corresponding 2-hydrazinothiazole-4-acetic esters. Dinitrosation of the 2-isopropylidenehydrazono-4-carboxy-methylidene-4,5-dihydrothiazoline, followed by decarboxylation, generated 2-isopropylidenehydrazono-5-nitrosothiazole-4-formyloxime.     

Total synthesis of the thiopeptide antibiotic amythiamicin D

The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thiopeptide natural product amythiamicin D, which utilizes a biosynthesis-inspired hetero-Diels-Alder route to the pyridine core of the antibiotic as a key step. Preliminary studies using a range of serine-derived 1-ethoxy-2-azadienes established that hetero-Diels-Alder reaction with N-acetylenamines proceeded efficiently under microwave irradiation to give 2,3,6-trisubstituted pyridines. The thiazole building blocks of the antibiotic were obtained by either classical Hantzsch reactions or by dirhodium(II)-catalyzed chemoselective carbene N-H insertion followed by thionation, and were combined to give the bis-thiazole that forms the left-hand fragment of the antibiotic. The key Diels-Alder reaction of a tris-thiazolyl azadiene with benzyl 2-(1-acetylaminoethenyl)thiazole-4-carboxylate gave the core tetrathiazolyl pyridine, which was elaborated into the natural product by successive incorporation of glycine and bis-thiazole fragments followed by macrocyclization.     

2-(p-氯苯)-5,8-二氢螺咪唑并〔2,1-b〕苯并〔d〕噻唑7(6H),1′-环己烷的合成及晶体结构

合成了2－（p-氯苯）-5，8-二氢螺咪唑并[2，1-b]苯并[d]噻唑7（6H），1’-环乙烷5，并测定了其晶体结构。晶体分子式晶体属单科晶系，空间群为结构的偏离因子分子结构中有一个大的平面部分，是由噻唑五员环（A）和咪唑五员环（B）构成。     

One-pot synthesis of thiazole-2-imine derivatives by CoFe2O4@SiO2-PA-CC-Guanidine-SA MNPs as an efficient and recyclable catalyst

A novel and atom-economic protocol for the synthesis of thiazole-2-imine derivatives was developed. Synthesis of thiazole-2-imine derivatives from primary amines, phenyl isothiocyanate and phenacyl bromide derivatives by the CoFe₂O₄@SiO₂-PA-CC-Guanidine-SA magnetic nanocatalyst in excellent yields was reported. This nanocatalyst is easily separated from the reaction mixture and can be reused for several times. For the characterization of the catalyst used of Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and vibrating-sample magnetometry (VSM) techniques.     

Aminoalkyl derivatives of 2,4′-bithiazole-4-carboxylic acid,the intercalating part of bleomycin

The synthesis of three 2,4′-bithiazole derivatives related to the antibiotic antitumor bleomycin is reported. These compounds substituted by aminoalkyl chains on 2′ and/or 4-positions were prepared by the Hantzs synthesis between new thioamides and methyl 2-(2-bromoacetyl)thiazole-4-carboxylate and will be useful for the study of the intercalative moiety of bleomycin.     

Isoquinoline-mediated S-vinylation and N-vinylation of benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol

An effective route to 5-vinylated and N-vinylated benzo[d]oxazole-2(3H)-thiones and benzo[d]thiazole-2(3H)-thiones is described via reaction of acetylenic esters and benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol in the presence of 15 mol%of isoquinoline.     

Synthesis of New 1,4-Dihydropyridine Derivatives Containing Thiazolyl Substituents

A series of 4-[2-methyl (or aryl) thiazole-4-yl]-2,6-dimethyl-3,5-diacetyl (or dibenzoyl) 1,4-dihydropyridines were synthesized using a modified Hantzsch reaction involving the condensation of the corresponding aldehyde with acetyl acetone or benzoyl acetone. The preparation of the corresponding aldehydes (2-methylthiazole-4-carboxaldehyde and some 2-arylthiazole-4-carboxaldehydes) was achieved by a simplified protocol of the published synthesis.     

A Facile Synthesis of 1,3-Thiazole-4-sulfonyl Chlorides

A four-step preparative-scale synthesis of eight 2-alkyl- and arylsubstituted thiazole-4-sulfonyl chlorides from chloralamides is reported. Good yields and easy availability of starting materials are valuable advantages of the procedure that gives access to formerly unattainable building blocks.