Mercapto Alcohol Research Articles

A Novel Reverse Phase HPLC Method for the Quantification of Potential Genotoxic Impurities in Doripenem Monohydrate: A Broad-Spectrum Carbapenem Antibiotic Drug

A novel sensitive gradient reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the quantification of potential genotoxic impurities in doripenem monohydrate (DORIBAX) drug substance, namely mono-p-nitrobenzyl malonate, 1β-methyl bicyclic ketoester, desilylated β-keto ester, 1β-methyldiazoazetidinone, deprotected doripenem side chain, N-protected mercapto alcohol, protected doripenem and doripenem side chain. The analysis performed on Alliance Waters e2695 separation module on C18 (250 × 4.6) mm, 5 μm (make: Inertsil) column, oven temperature maintained at 40 ºC and UV detection at 270 nm. The separation was accomplished using buffer (pH 6.0 ± 0.05) and acetonitrile in the ratio of 98:2 v/v as mobile phase-A and acetonitrile as mobile phase-B, flow rate: 1.0 mL/min and injection volume: 50 μL. The proposed method was validated as per ICH guidelines in terms of limit of detection (LOD), limit of quantification (LOQ), linearity, precision, accuracy and specificity.

Highly selective and antifouling electrochemical biosensors for sensitive MicroRNA assaying based on conducting polymer polyaniline functionalized with zwitterionic peptide.

Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling. Graphical abstract Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.

Synthesis, structure and reactivity of some chiral benzylthio alcohols, 1,3-oxathiolanes and their S-oxides

ABSTRACT A series of amino acid-derived chiral benzylthio alcohols have been prepared and characterized. A chiral mercapto alcohol derived from S-leucine has been used to form three chiral 2,4-disubstituted 1,3-oxathiolanes. One of these has been oxidized to the S-oxide and another to the S,S-dioxide. The cis and trans isomers have been characterized by 1H NMR in each case and it appears that thermal epimerisation at C-2 is possible at the sulfoxide oxidation state. The X-ray structure of major trans diastereomer of 2-phenyl-4-isobutyl-1,3-oxathiolane S,S-dioxide shows an envelope conformation with oxygen at the flap and an internal angle at sulfur of just 93.8°. This compound fragments upon flash vacuum pyrolysis at 700°C to give SO2, benzaldehyde and 4-methylpent-1-ene.

Alternative corrosion inhibitor formulation for carbon steel in CO2-saturated brine solution under high turbulent flow condition for use in oil and gas transportation pipelines

A benzimidazole derivative (BPMB) was tested as inhibitor for carbon steel in CO2-saturated brine, singly (under static and turbulent conditions) and formulated with mercaptoalcohol (ME) (under turbulence). Potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), ATR-IR, SEM, XRD and AFM were employed for the study. Turbulence at short immersion time (1 h) decreased BPMB corrosion inhibition efficiency. However, prolonged immersion time (12 h) and the addition of mercaptoethanol improved its performance to 99.0%. Theoretical calculations indicate that BPMB and ME can interact strongly with the steel surface using the benzimidazole and -SH group, respectively. The ME addition enhances denser film formation on the steel surface.

A Theoretical Study of Imidazole- and Thiol-Based Zinc Binding Groups Relevant to Inhibition of Metzincins

In this report, we present a quantum chemical/density functional theory (DFT) study of possible zinc binding modes for five imidazole- and thiol-based ligands relevant to metzincin (MMP and ADAM) inhibitor design. The gas-phase DFT calculations show that, while the imidazole-based ligands may bind zinc in either a five-coordinate bidentate or a four-coordinate monodentate manner, the deprotonated thiolate-containing mercaptoketone and mercapto alcohol ligands are not strongly bidentate, in agreement with recently reported model complex structures. On the basis of modeling of ligand−water exchange reactions, we estimate that the free energy released upon coordination of these zinc binding groups to metzincins decreases in the order mercaptoketone > mercapto alcohol > imidazole-based. The range of binding free energies, however, is only about a few kcal/mol, in the gas phase. In addition, calculated proton dissociation energies show that the driving force for deprotonation of coordinated thiol is greater than that for either imidazole or water. In other words, the Zn−SRH moieties are generally more acidic than their or Zn−ImH or Zn−OH2 counterparts. These results suggest feasibility of imidazole-based chelating moieties as zinc binding groups in the design of MMP and ADAM inihibitors.

Development of new methods in asymmetric reactions and their applications

Several novel methods using chiral reagents and biocatalysts for asymmetric reactions are described. Among those reactions, asymmetric reduction via a novel tandem Michael addition/Meerwein-Ponndorf-Verley reduction of acyclic alpha,beta-unsaturated ketones using a chiral mercapto alcohol, asymmetric synthesis of allene-1,3-dicarboxylate via crystallization induced asymmetric transformation, and improved asymmetric nitroolefination of lactones and lactames at alpha-carbon using new chiral reagents were developed. In the reactions using biocatalysts, asymmetric dealkoxycarbonylation of bicyclic beta-keto diesters having sigma-symmetry with lipase or esterase to give optically active beta-keto esters, the asymmetric reduction of bicyclic 1,3-diketones having sigma-symmetry with Baker's yeast to give optically active keto alcohols, and the asymmetric aldol reaction of glycine with threonine aldolase were also developed. The above mentioned products were effectively utilized as chiral building blocks for the asymmetric synthesis of natural products and drugs.

Long-Range Electronic Coupling between Ferrocene and Gold in Alkanethiolate-based Monolayers on Electrodes

High-speed cyclic voltammetry was used to measure rates for ferrocene oxidation/reduction in a series of self-assembled monolayers formed by coadsorption of N-(mercaptoalkyl)ferrocenecarboxamide ((C5H5)Fe(C5H4)CONH(CH2)nSH where n = 7−10, and 15) with mercapto alcohol (HO(CH2)n+1SH where n = 7−10, and 15) on gold. Standard electron-transfer rate constants were obtained as a function of chain length and from these rate constants, a β value (describing the exponential decay of rate with adsorbate chain length) of 1.1 methylene-1 or 0.85 A-1 was obtained. The rate data were also used to estimate coupling factors, |VAB|, describing the long-range electronic coupling between the immobilized ferrocene groups and the underlying gold electrode. Electronic coupling factors varied from a low of 0.06 cm-1 for the long-chain monolayer (18 bonds in the pathway linking ferrocene to the electrode) to a high of 6.5 cm-1 for the short-chain monolayer (10 bonds linking ferrocene to the electrode). The latter value is in go...

Glyconothio‐O‐lactones. Part III. Thermolysis of a 4,5‐Dihydro‐1,2,3‐ and a 2,5‐Dihydro‐1,3,4‐thiadiazole

AbstractAddition of CH2N2to 2,3:5,6‐di‐O‐isopropylidene‐1‐thio‐mannono‐1,4‐lactone (1) gave the 2,5‐dihydro‐1,3,4‐thiadiazole2and the 4,5‐dihydro‐1,2,3‐thiadiazole3. First‐order kinetics were observed for the thermolysis of3(Scheme 3) at 80–110° in C6D5Cl solution and of 2 (Scheme 3) at 20–35° in CDC13, respectively. The 1,2,3‐thiadiazole3led to mixtures of the thiirane9, the starting thionolactone1, the thiono‐1,5‐lactone8, and the enol ether7, while the isomeric 1,3,4‐thiadiazole2led to mixtures of the anomeric thiiranes9and12, the O‐hydrogenS,O,O‐ortholactone α‐D‐14, theS‐methyl thioester15, theS,S,O‐ortholactone13, and the 2,3:5,6‐di‐Oisopropylidene‐mannono‐1,4‐iactone (16). Pure products of the thermolysis were isolated by semipreparative supercritical fluid chromatography (SFC), whereas preparative HPLC led to partial or complete decomposition. Thus, the β‐D‐mannofuranosyl β‐D‐mannofuranoside10, contaminated by an unknown S species, was isolated by preparative HPLC of the crude product of thermolysis of3at 115–120° and partially transformed in CD3OD solution into the symmetric di(α‐D‐mannofuranosyl) tetrasulfide11. Its structure was evidenced by X‐ray analysis. Similarly, HPLC of the thermolysis product of2gave the enethiol17, the sulfide19, and the mercapto alcohol18as secondary products. Thermolysis of the thiirane9at 110–120° (Scheme 4) led to the anomeric thiirane12which was transformed into mixtures of the enethiol17and the enol ether7.Addition of H2O to17and7gave the corresponding hemiacetals18and20.The mechanism of the thermolysis of the dihydrothiadiazoles2and3, and the thiiranes9and12is discussed.

Polycondensed heterocycles. III. Synthesis of 5,11‐dioxo‐1,2,3,1 1a‐tetrahydro‐5H,11H‐ and 5‐oxo‐2,3,11,1 1a‐tetrahydro‐1H,5H‐pyrrolo[2,1‐c][1,4]benzothiazepine

AbstractThe syntheses of 5,11‐dioxo‐1,2,3,11a‐tetrahydro‐5H11H‐ and 5‐oxo‐2,3,11,11a‐tetrahydro‐1H,5H‐pyrrolo‐[2,1‐c][1,4]benzothiazepine 10 and 11 have been studied.The former was obtained by intramolecular cyclization with CDI of N‐(2‐mercaptobenzoyl)‐L‐proline 19, prepared on one hand by demethylation of N‐(2‐methylthiobenzoyl)‐L‐proline t‐butyl ester 15, obtained via the Pummerer rearrangement of the corresponding sulphoxide 17 and successive alkaline hydrolysis, and by deprotection of the mercapto ester 18 with TFA or trimethylsilyl iodide. The ester 15 was achieved by reaction of o‐(methylthio)benzoic acid 12 with L‐proline t‐butyl ester or by treatment of the corresponding acid chloride 13 with L‐proline and successive esterification of N‐(2‐methylthiobenzoyl)‐L‐proline 16. On the other hand the proline 19 was also obtained by reduction with sodium dithionite of (S)‐bis[2‐[[2‐(hydroxycarbonyl)‐1‐pyrrolidinyl]carbonyl]phenyl] disulphide 20, prepared by condensation of bis(2‐chlorocarbonylphenyl) disulphide 14 with L‐proline. The reduction of (S)‐bis[2‐[[2‐(chloromethyl)‐1‐pyrrolidinyl]carbonyl]phenyl] disulphide 28 with sodium borohydride in boiling ethanol afforded directly the benzothiazepinone 11 in 85% yield. The disulphide 28 was synthesized treating the corresponding alcohol 24 or N‐(2‐mercaptoben‐zoyl)‐L‐prolinol 25 with thionyl chloride. Compound 25 was obtained by demethylation of the corresponding methylthio ether 26 oxidized to sulphoxide 27 via the Pummerer rearrangement. The acid chloride 14 by condensation with (S)‐2‐(chloromethyl)pyrrolidine hydrochloride gave disulphide 28 as well. The acid chlorides 13 and 14 by reaction with L‐prolinol provided respectively alcohols 26 and 24.Attempts to cyclodehydrate the mercapto alcohol 25, obtained also by reduction of disulphide 24, failed.

ChemInform Abstract: Molecular Requirements of the Recognition Site of Cholinergic Receptors.

AbstractStarting from the reaction between the ketones (I) and the mercapto alcohol (II), compounds of type (VI) (no yields given) are synthesized and tested together with (VII) and (VIII) for their cholinergic activities.

Desulphurisation and Reduction Studies of Epithio Fatty Acids and Alcohols

AbstractThe cis and trans epithio fatty acids and alcohols with Raney Ni give the corresponding saturated derivatives. Lithium aluminium hydride reduction of cis epithio fatty acids either in tetrahydrofuran or in ether yields both mercapto alcohol isomers which can be separated and identified by thin‐layer chromatography. The trans isomer on similar treatment however furnishes the mercapto alcohols in tetrahydrofuran only, while in ether medium the epithio group remains unaffected. The isomeric mercapto alcohols on desulphurisation likewise afford the saturated alcohols.