A Stereoselective Approach to S-Vinyl Thioesters from Alkynes,Elemental Sulfur and Acyl Chlorides

A facile, stereoselective synthesis of S-vinyl thioesters from easily available starting compounds and reagents is showed.

FeCl3-6H2O-Catalyzed Synthesis of β-Ketothioesters from Chain α-Oxo Ketene Dithioactals

A FeCl3-6H2O-catalyzed synthesis of β-ketothioesters from the hydrolysis reaction of chain α-oxoketene dithioacetals was carried out. Subsequently, we explored the FeCl3-6H2O-catalyzed Friedel-Crafts alkylation of the synthesized fl-ketothioesters with alcohols in CH3CN at 25 ℃, affording the desired α-alkylated fl-ketothioesters in excellent yields. Wide scope of the substrates, use of inexpensive reagents, high yields under mild reaction conditions are notable features of these reactions.

Theoretical study on formation of thioesters via O-to-S acyl transfer

Peptide thioester preparation via intramolecular O-to-S acyl transfer is a recently developed method for protein chemical synthesis through Fmoc chemistry. Theoretical calculations have been carried out to study the mechanism for the formation of thioesters via O-to-S acyl transfer. It is found that the O-to-S acyl transfer occurs via an anionic stepwise mechanism in which the cleavage of the C-O bond is the rate-limiting step. The side reaction of hydrolysis also proceeds through an anionic stepwise process, and its rate-limiting step is the attack of the hydroxide ion on the carbonyl carbon. Increase of the chain length between the ester O atom and the S atom can increase the energy barrier of the O-to-S acyl transfer. On the other hand, substituents at the α-position of the ester can reduce the energy barrier.

Palladium-catalyzed diarylative dearomatization of indoles with aryl thioesters

We report herein a palladium-catalyzed diarylative dearomatization of indole by employing thioester and arylboronic acid as the aryl electrophiles.The reaction involved a decarbonylation/migratory insertion/terminal Suzuki coupling procedure.Substrates bearing various functional groups are well tolerated in the reaction,affording the diarylated indoline skeletons in moderate to good yields.

Theoretical investigations on the thiol–thioester exchange steps of different thioesters

As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect（i.e. conjugation and hyper-conjugation effects） becomes important when the steric hindrance is insignificant.

Effect of the Position of Reaction-Site in Amphipathic-Type Thioester in Aqueous Amidation Reaction

Amphipathic-type thioesters CH3(CH2)mCOS(CH2)nCOONa (m + n = 12) were synthesized and their reaction with various alkylamines was examined. Compounds having thioester moiety close to carboxylate (m = 10, n = 2) afforded the corresponding amides in good yields, while the substrate having thioester moiety distant from carboxylate (m = 2, n = 10) afforded the amides in relatively low yield. In all cases, the difference in yield due to the chain length of amine was not observed. The results indicated that the reaction took place effectively near the surface of micelle. However, the reaction was found to occur not only on micelle surface but also in solution.

SYNTHESIS OF LIQUID CRYSTALLINE POLYACRYLATES WITH THIOESTER AS BRIDGE-BOND

A new series of acrylates with the same mesogens containing thioester as bridge-bond were synthesized, and the acrylates were characterized by H-1 NMR, IR and MS. The polymers were obtained by radical polymerization using AIBN as initiator. The monomers and polymers exhibit thermotropic-enantiotropic Liquid crystalline behavior.

Recent Progress of Thioester Method

Introduction The availability of site-specifically modified peptides is of vital importance for biochemical and biophysical studies. Biological methods, such as expression using bacteria, are useful. They are, however, not always applicable to the synthesis of peptides with sitespecific modifications. Chemical methods can be viable alternatives to those biological approaches. Peptides obtained by chemical and biological means,

Improvement of Thioester Method by Using Pac Ester for Synthesis of Cyclopentapeptides

Thioester method was improved by using Pac (phenacyl group) ester as protecting group of 3-mercaptopropionic acid. Two cyclopentapeptides c(Ala-Tyr-Leu-Ala-Gly) and c(Pro-Tyr-Leu- Ala-Gly) were synthesized successfully by this method.

Encouraging Solution to the Problem of Synthesizing Protein α-Thioester

Expressed protein ligation(EPL)provides a powerful tool to access large-size proteins with precise structures.Existing methods for constructing the critical protein thioester for EPL have predominantly relied on the recombinant intein fusion expressed in Escherichia coli(E.coli).Despite its powerful applications,the expression of thioester derived from eukaryotic protein in E.coli inherently suffers from its limited solubility,the inactivity of intein,premature hydrolysis and low yields.To overcome these obstacles,we present herein the facile one-flask synthesis of inaccessible proteinα-thioester via a SUMO-protein-intein(SPI)sandwich model.The utility of SUMO enhances the protein fusion yield and solubility,prevents premature hydrolysis and simplifies the purification process.The inaccessible protein thioester with internal Cys residues can be readily produced and is compatible with the EPL-desulfurization protocol used to prepare complex proteins,which is otherwise difficult to obtain using traditional methods.Its utility has been highlighted through the synthesis of human granulocyte colony-stimulating factor(G-CSF).

Recent advances in the preparation of Fmoc-SPPS-based peptide thioester and its surrogates for NCL-type reactions

Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in comparison to Boc-SPPS.With the fast development in the emerging field of protein chemical synthesis,many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation reactions.This review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides,which can be used as the N-terminal fragments in a native chemical ligation(NCL)or NCL-type ligation reactions.

Synthesis of c-Myb Protein(38-89)-NH_2 Using a Partially Protected Peptide Thioester

The method of selective modification of eysteine SH group with 4-methylbenzylchloride is developed,c-Myb protein (38-89)-NH_2 is synthesized by using a partially protected peptide thioester.The 4-methylbenzyl (MeBzl) protecting group of cysteine in the building block is stable during the segment cou- pling.The method can be used in the chemical synthesis of some protein containing cysteine.

Mechanism of Imidazole-Promoted Ligation of Peptide Phenyl Esters

Imidazole-promoted ligation of peptide phenyl esters was recently found to be a complementary method for protein chemical synthesis. Theoretical calculations have been carried out to understand the detailed mechanism of this particular ligation process. It is found that both the reaction of the phenyl ester with imidazole and the reaction of the acyl imidazole intermediate with cysteine proceed through an addition-elimination mechanism. The cleavage of the C--O bond in the reaction between the phenyl ester and imidazole is the rate-limiting step of the overall liga- tion process. Interestingly, although the imidazole-promoted phenyl ester ligation has a higher free energy barrier than the conventional thiophenol-promoted native chemical ligation for a sterically less hindered C-terminal amino acid （e.g. gylcine）, for a sterically hindered C-terminal amino acid （e.g. proline） the imidazole-promoted phenyl ester ligation is calculated to be more favorable than the conventional thiophenol-promoted native chemical ligation.

Application of Pac Ester in Thioester Method for the Synthesis of Cyclopentapeptides

Thioester method for the synthesis of cyclopeptides is improved by using Pac (Pac = phenacyl, CH2COC6H5) ester as a protecting group of 3-mercaptopropionic acid. The Pac group is easy to be removed from C-terminal with zinc in acetic acid. The protected glycine thioester and peptide thioesters synthesized by the unproved method, are easy to be purified, so the final linear peptides are pure enough for the following cyclization. Furthermore, this method is flexible for peptide chain elongation, either from C-terminal or from N-terminal. So it is an efficient and practical method for synthesis of bioactive peptides. Two N-protected pentapeptide thioesters, Boc-Pro-Tyr-Leu-Ala-GlySCH2CH2COOPac and Boc-Ala-Tyr-Leu-Ala-Gly-SCH2CH2-COOPac were synthesized by the improved thioester method. After deprotecting Pac ester with zinc in aqueous acetic acid and Boc group with trifluoroacetic acid in CH2C12, two free pentapeptide thioesters were obtained. Ag+ -assisted cyclization in acetate buffered solution afforded two cyclic pentapeptides c(Pro-Tyr-Leu-Ala-Gly) and c(Ala-Tyr-Leu-Ala-Gly). Effects of different buffer pH, different Ag+ concentrations, etc. on the cyclization were studied.

Structure of Cyclic Aryl Thioester Dimer Based on o-Phthaloyl Dichloride and Bis(4-mercaptophenyl) Sulfide

A cyclic aryl thioester dimer was prepared by the reaction of o phthaloyl dichloride and bis(4 mercaptophenyl) sulfide in good yield under pseudo high dilution conditions via interfacial polycondensation. The structure of the cyclic dimer was confirmed by a combination of MALDI TOF MS, FTIR, gel permeation chromatography and NMR analyses. The X ray diffraction study of the single crystal of cyclic thioester dimer obtained from two solutions reveals no severe internal strain on the cyclic structure.

Improvement in the synthesis of 2-(5-amino-1,2,4-thiadiazol-3- yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester

2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(I)with 2,29-dibenzothiazole disulfide(II)in the presence of triphenylphosphine.Effects of reaction time,temperature,solvents,catalysts and feeding molar ratio on the yield and quality of products were investigated,and an im-proved procedure suitable for industrial production was established.Using 1,2-dichloroethane as solvent,triphe-nylphosphine as reducer,and triethylamine as catalyst,n(I):n(II):n(triphenylphosphine)51.0:1.0:1.0,the product was obtained at room temperature in 98.1%yield.The purity of the product without further purification is 98.7%determined by HPLC method.This procedure could be a suitable alternative to the traditional processes because of its easy handling,high yield and low cost.