Sodium borohydride disulfides reduction

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Reductive amination of benzaldehyde with (R)-81 provided the corresponding benzyl amine, which was reductively alkylated with formaldehyde to give 82 (Scheme H) " Compound 82 was debenzylated by hydrogenation in the presence of Pearlman s catalyst to afford frovatriptan ((/J)-6). Alternatively, monomethylation of amine (/ )-81 was affected by treatment with carbon disulfide and dicyclohexylcarbodiimide in pyridine to provide isothiocyanate 83, which was reduced with sodium borohydride to give (l )-6. 

The interest in papain increased enormously after the publication by Kimmel and Smith D ] of a modification of the purification procedure of Balls and Lineweaver [5j. This modification permitted the isolation of pure papain from papaya dried latex and was used for many years as the standard method for the production of papain. The crystalline papain of Kimmel and Smith consists of three components active papain, reversibly oxidized papain, and irreversibly oxidized papain. Reversibly oxidized papain can be converted into active papain by reduction of the active-site thiol by low molecular weight thiols [10], sodium borohydride [11], or CN [12]. In active papain, the Cys-25, which is essential far catalytic activity, is present in a reduced form, while in reversibly oxidized papain the Cvs-25 forms a mixed disulfide with cysteine. Drenth et al. reported that in irreversibly oxidized papain the Cys-25 has been oxidized to the sulfuric acid... 

Gallenbeck et al. (25) has summarized the work on reductive alkylation using formaldehyde and sodium borohydride to yield dimethylated proteins. Oxidation and reduction reactions involving thiol and disulfide groups have been discussed by Ryan (13) and Feeney (11). 

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

Sodium borohydride reduces disulfides to thiols, which can then be used to reduce nitro groups. Based on the redox properties of 1,2-dithiolane, lipoamide (17) was used for the selective reduction of mono-substituted nitrobenzenes to the corresponding anilines. Lipoamide (17) can also be immobilized on hydrophilic polymers such as polyvinylamine, polyethyleneimine and chitosan. These polymeric reducing catalysts can be recycled and are easy to separate from the reaction mixture. The system has been used to reduce nitroarenes to anilines. ... 

Reduction of 308 with sodium borohydride gives 24% tetraphenylethylene with lithium borohydride, 75% of 2,2-diphenylethanol and 16% of 2,2-diphenylethyl disulfide with di-isobutylaluminum hydride, 39% l,l,3,3-tetraphenyl-2-propanone and 30% of benzophenone. Lithium aluminum hydride gives four products that may be formed by way of cyclopropanone intermediates. ... 

It has been found possible to construct the 1,4-benzothiazine ring by direct interaction of bis-(2-aminobenzene) disulfide (96) with carbonyl compounds.139,140 The reaction is most efficient when conducted under a nitrogen atmosphere with a 1 1 ratio of reactants otherwise, the principle products are benzothiazoles. While reduction of the benzothiazine 97 with sodium borohydride gives a stable dihydro derivative, the unsaturated benzothiazines themselves were prone to autoxidation, giving rise to benzothiazoles and benzothiazine sulfoxides.141... 

Radioactive [35S]-phosphorothioates have been used for in vivo evaluation of chronic or cumulative toxicity of oligonucleotides. To achieve site-specific 35S-labeling in phosphoramidite chemistry, either a mixture of [35S]/carbon disulfide/pyridine/triethylamine [329] or 35S-la-beled Beaucage reagent [330] have been used in the sulfurization step. 3H- and 14C-labeled compounds have been tools in investigations of the metabolic fate of the nucleobases of an oligomer [331]. 3H may be inserted at the 5 -end by formation of the 5 -carboxyaldehyde by Mofatt-Pfitzner reagent, followed by reduction with [3H]-sodium borohydride in 2-propanol... 

Reduction of disulfides to thiols. Disulfides are reduced to the corresponding thiols in high yields under mild conditions. The selenium can be reused, so that essentially only sodium borohydride is consumed. 

The 14,15-double bond present in tabersonine was introduced into the /3-ethyl isomer of lactam 491 by treatment with LDA-diphenyl disulfide followed by oxidation and elimination to give the a,fl-unsaturated lactam 492. Murphy s law operated at this point, for upon lithium aluminum hydride reduction, 492 gave only a 5% yield of the amino alcohol 493. An alternative procedure was therefore developed. Hydrolysis gave a carboxylic acid, and treatment with ethyl chloroformate and triethylamine followed by sodium borohydride in aqueous THF gave a lactam alcohol 494, which after silylation was reduced with lithium aluminum hydride to amino alcohol 493 in 58% overall yield from 492. Mesylation and elimination of HC1 in refluxing chloroform gave the unsaturated mesylate salt 482. The same salt was prepared previously by Ziegler and Bennett... 

Commercial hexythiazox is a racemic mixture of the two trans enantiomers Scheme 26.2.2 shows the main synthetic pathways [11, 17, 19]. Starting from 4-chloro propiophenone the key intermediate erythro amino alcohol may be obtained by stereoselective catalytic reduction of the corresponding hydroxy imi-noketone or by sodium borohydride reduction of the aminoketones obtained via Gabriel synthesis. Different routes lead from this aminoalcohol to the trans-thiazolidinone system the basis of all routes is activation of the hydroxy group, e.g., in form of the sulfonate and a ring forming reaction with carbon disulfide or carbonyl sulfide. The final acylation of the NH group with cyclohexyl isocyanate leads to hexythiazox. 

Disulfides can be reduced chemically, electrochemically or enzymatically. Chemical reduction is often used prior to derivatisation of thiols to fluorophores, but it can also be used with HPLC-ED. Common reducing agents are mercapto-ethanol, DTT, dithioerythritol, cyanide and sodium borohydride, but their efficiency varies towards different disulfides. Cyanide or borohydride rapidly reduce cystine at room temperature, but require over 24 h to reduce cysteine-D-penicillamine disulfide completely, whilst the sterically hindered D-penicillamine disulfide is not reduced at all. ... 

Methods of Preparation. Two methods for the synthesis of 4-benzyloxazolidine-2-thione from 2-amino-3-phenyl-l-propanol (phenylalaninol) have been described. The appropriate amino alcohol is readily prepared from (/ )-phenylalanine or (. -phenylalanine by reduction with sodium borohydride and iodine in THF. Exposure of phenylalaninol to carbon disulfide and aqueous sodium carbonate for 15 min at 100 °C provided 4-benzyloxazolidine-2-thione in 63% yield (eq 1). Alternatively, the treatment of the amino alcohol with thiophosgene and triethy-lamine in dichloromethane for 30 min at 25 °C provided 95% of the oxazolidinethione (eq 2) The former method often results in the oxazolidinethione contaminated with varying amounts of the corresponding thiazolidinethione. 

Preparation. Sodium diisopropylphosphonate generates 5-methyl diisopropoxyphosphinyldithioformate when treated with carbon disulfide and methyl iodide. The reduction of this compound with sodium borohydride followed by trapping of the thiolate with methyl iodide leads to diisopropyl methylsulfanyl-methylphosphonate(eq 1). ... 

Another improvement implemented over the past years deals with sample preparation. In plasma and blood, only 5-15% of the total homocysteine is free. The rest is bound to disulfide bridges, either to other thiols or to various proteins. A reduction step is thus necessary for a meaningful monitoring of the homocysteine concentration. By switching from sodium borohydride to tris(2-carboxyethyljphosphine (TCEP), the disulfide reducing agent most widely used today [595], sample preparation was simplified. 

Cysteine is readily converted to the corresponding disulfide, cystine, even under mild oxidative conditions, such as treatment with I2 or potassium hexacyanoferrate (III). Reduction of cystine to cysteine is possible using sodium borohydride or thiol reagents (mercaptoethanol, dithiothreitol) ... 

A -Protected amino acids and peptides are rapidly converted to the corresponding amino alcohols in high yields with complete retention of optical purity via reduction of the mixed anhydride by cold Sodium Borohydride in THE with dropwise addition of methanol (eq 16). The disulfide bridges of cystine, the methyl and benzyl esters of w-carboxyl-protected glutamic and aspartic acids of peptides, and Ai-Cbz and IV-Boc protection are compatible with the methodology. The anhydrides derived from ethyl chloroformate are superior to isobutyl and benzyl carbonates both in terms of yield and retention of optical purity. 

Note Some protocols do not call for a reduction step. The addition of borohydride at this level may result in disulfide bond cleavage and loss of protein activity in some cases. As an alternative to reduction, add 50pi of 0.2M lysine in 0.5M sodium carbonate, pH 9.5 to each ml of the conjugation reaction to block excess reactive sites. Block for 2 hours at room temperature. Other amine-containing small molecules may be substituted for lysine—such as glycine, Tris buffer, or ethanolamine. 

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