Thiols alkylation

SH thiols (or mercaptans ) sulfanyl (mercapto ) -thiol alkyl mercaptan... 

Thiols Alkyl thiocarbonates Alkyl dithiocarbonates (xanthates) Alkyl thionocarbamates... 

Detwiler and co-workers were the first to demonstrate a role for csPDI in platelet physiology (Chen et al, 1995 Essex et al, 1995). Essex and co-workers (1999, 2001) and Hogg and co-workers (Burgess et al., 2000) showed that the inactivation of csPDI with anti-PDI antibodies and thiol alkylating agents inhibited platelet activation and aggregation. Recent studies have identified two distinct activities for csPDI. 

Two major synthetic strategies have been applied for the synthesis of S-prenylated peptides as shown in Scheme 1. In the first approach (method A), S-alkylation is performed on the final peptide in a protected or unprotected form.13641 In method B, which has produced better results in terms of overall yield, thiol alkylation is carried out on the cysteine residue or on a small peptide fragment and then the S-prenylated synthons are coupled to the remaining peptide fragment to produce the final products.[45 501 Most of the procedures reported for the synthesis of farnesylated peptide derivatives, can also be applied to the synthesis of geranylgeranylated peptides. 

The range of organic compounds which have been subject to the Simons process is wide and includes aliphatic and aromatic hydrocarbons, halocarbons, ethers, aliphatic and aromatic amines, heterocyclics, thiols, alkyl sulphonic and carboxylic acids, and their derivatives, among others. 

Alkyl halides react with nucleophiles, reagents that can supply an electron pair to form a covalent bond, to give a product in which the nucleophile takes the place of the halogen. Table 6.1 gives fifteen examples of such nucleophilic substitution reactions, which can be used to convert alkyl halides to alcohols, ethers, esters, amines, thiols, alkyl cyanides, or acetylenes. 

Methyl mercaptan (= Methane thiol) (alkyl thiol)... 

Motte L. and Pileni M. P., Self-assemblies of silver nanocrystals influence of length of thiol-alkyl chains used as coating agent. Applied Surface Science 164 (2000) pp. 60-67. 

To date, four bioorthogonal reactions have been used to label glycans on cells and in lysates hydrazone/oxime formation with ketones, thiol alkylation with maleimides, Staudinger ligation of azides with triaryl phosphines, and copper-catalyzed or strain-promoted [3+2] cycloadditions of alkynes and azides (Figure 5) (25, 26, 32, 34, 35). While each reaction has been used extensively, most recent applications have employed azido- or alkynyl-sugars due to their superior metabolic incorporation and efficient ligations. 

In addition to n-alanine and n-glutamate, many bacterial cell walls also contain meso-diaminopimelate (DAP) [2]. DAP is produced by epimerization from l,l-DAP to d,l-DAP by the cofactor independent diaminopimelate epimerase [97, 98]. The structure of this enzyme has been solved and two cysteines in the active site were proposed to be the acid-base catalysts [99]. The pattern of label incorporation from tritiated water is consistent with a two-base mechanism [97]. The enzyme has been shown to be stoichiometrically inhibited by the thiol alkylating agent aziDAP [97]. Interestingly, DAP epimerase has an equilibrium constant of 2 (Keq = [d,l]/[l,l]) duc to the statistically expected higher concentration of the [d,l] form at equilibrium between these species [100]. 

Baker, L. M., P. R. Baker, F. Golin-BiseUo et al. 2007. Nitro-fatty acid reaction with glutathione and cysteine. Kinetic analysis of thiol alkylation by a Michael addition reaction. J Biol Ghent 282 (42) 31085-93. 

Thiol chemistry exploits the extraordinary reactivity of sulphhydtyls in alkylation with ct-halocarbonyls, in addition to conjugated olefins and sulphur-sulphm exchange with disulphides. In practice, in thiol alkylation and addition to conjugated olefins, disulphides have frequently been used for chemoselective ligation in both peptide synthesis and semi-synthesis because of the stability of the products. 

Important variants of procedure have been tested, providing wider possibilities for thio-Claisen rearrangements in synthesis like any other method for forming carbon-carbon bonds whose scope exceeds its limitations, there is the likelihood of studies of the type described in this Section being taken up in many more laboratories. Lithiation of allyl sulphides is followed by rearrangement, providing a very efficient method for the synthesis of thiols, alkyl sulphides, and hydrocarbons of the squalene type, or based upon the artemisyl skeleton. Typically, benzyl yy-dimethylallyl sulphide (65) gives (66) with four equivalents of... 

Figure 9 New inhibitors of CAII are genraated using the enzyme itself as a template for irrevrasible (a) thiol alkylation and (b) azide-acetylene cycloaddition. Exemplary hit compounds and their potencies are shown on the right...

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