Mercapto acids applications

Hexafluoroacetone as protecting and activating reagent new routes to amino, hydroxy, and mercapto acids and their application for peptide and glyco- and depsipeptide modification 06CRV4728. 

In contrast to the a-oxy- or a-amino-substituted allylic esters, not many examples for a-thio substituted substrates and their application in Claisen rearrangements are described so far (Scheme 5.2.63). Lythegoe et al. applied the Ireland-Claisen rearrangement to the synthesis of a-mercapto acids such as 199 starting from allylic esters 198 [116]. 199 was oxidized and further converted into a,j8-unsaturat-ed esters or subjected to an oxidative degradation. Jones et al. used the Ireland-Claisen rearrangement of 200 in their syntheses of thietan oxides [117]. 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

The application of CPO, HRP and CiP is limited to sterically unencumbered substrates and all these peroxidases produce the same absolute configuration of the chiral hydroperoxide. To overcome this limitation, the semisynthetic enzyme selenosubtilisin, a mimic for glutathione peroxidase, with the peptide framework of the serine protease subtilisin was developed by Bell and Hilvert. This semisynthetic peroxidase catalyzes the reduction of hydrogen peroxide and hydroperoxides in the presence of 5-mercapto-2-nitrobenzoic acid. It was utilized by Adam and coworkers and Schreier and coworkers for the kinetic resolution of racemic hydroperoxides (equation 17) . The results obtained were very promising. 

The synthesis of 3-benzyl-2-phenylthiazolidin-4-one (47, Fig. 21) demonstrates the mercaptane scavenging applicability of the aminoethanethiol resin (48). Benzaldehyde is allowed to react with benzylamine in the presence of mercapto acetic acid (49) in toluene under refluxing conditions. 

In some cases the application of a basic catalyst can be followed by further oxidation of dihydropyrimidene-2-thiones, yielding heteroaromatized heterocycles [60, 61]. For example (Scheme 3.14), it was shown that the reaction of 4-oxo-4-arylbut-2-enoic acids 45 with thiourea 28 in the presence of sodium hydroxide led to 2-mercapto-6-arylpyrimidine-4-carboxylic acids 46 [60], while their dihydro analogues were not isolated. 

Malem, E, and Mandler, D. Self-assembled monolayers in electroanalytical chemistry -application of to-mercapto carboxylic-acid monolayers for the electrochemical detection of dopamine in the presence of a high-concentration of ascorbic acid. Anal. Chem. 1993, 65, 37-41. 

The oxidation-reduction method, developed initially by Mukaiyama et al. [133] and related to the previously described organophosphorus methods, has permitted a variety of important solid-phase applications. The mechanism of the activation is complex and involves the oxidation of the triaryl/ alkyl-phosphine to the oxide as well as reduction of the disulfide to the mercapto derivative. However, different active species, such as 81 (Fig. 11), the 2-pyridyl thioester, or even the symmetrical anhydride, have been postulated to form. For the intermediate 81, the peptide bond formation may proceed through a (cyclic transition state. The method has been used for conventional stepwise synthesis [134], acylation of the first protected amino acid to a hydroxymethyl resin, and to achieve segment condensation on a solid support in the opposite direction (N C) [135,136]. Lastly, it has been used for efficient grafting of a polyethylene glycol (molecular weight 2000) derivative to an aminomethyl resin to prepare PEG-PS resins [137]. 

Thiazolidones are another class of heterocycles that attract much attention because of their wide ranging biological activity [106], They are usually synthesized by three-component condensation of a primary amine, an aldehyde, and mercapto-acetic acid with removal, by azeotropic distillation, of the water formed [107]. The reaction is believed to proceed via imine formation then attack of sulfur on the imine carbon. Finally, an intramolecular cyclization with concomitant elimination of water occurs, generating the desired product. The general applicability of the reaction is limited, however, because it requires prolonged heating with continuous removal of water. To circumvent these difficulties and to speed up the synthesis, Miller et al. developed a microwave-accelerated three-component reaction for the synthesis of 4-thiazolidinones 63 [108]. In this one-pot procedure, a primary amine, an aldehyde, and mercaptoacetic acid were condensed in ethanol under MW conditions for 30 min at 120 °C (Scheme 17.44). The desired 4-thiazolidinones 63 were obtained in 55-91% yield. 

Electrochonical Sensors, Biosensors and Their Biomedical Applications 5 -Mercapto -2 -nitrobenzoic acid (yellow)... 

Contents J. M. BRAND, J. CHR. YOUNG, and R. M. SILVERSTEIN, Insect Pheromones A Critical Review of Recent Advances in Their Chemistry, Biology, and Application - M. McNEIL, A. G. DARVILL, and P. ALBERSHEIM, The Structural Polymers of the Primary Cell Walls of Dicots - U. SCHMIDT, J. HAUSLER, ELISABETH OHLER, and H. POISEL, Dehydroamino Acids, a-Hydroxy-a-amino Acids and a-Mercapto-a-amino Acids — Author Index — Subject Index. 

Harsanyi et al. [64] improved and combined the efficiency and applicability of the classic SrnI type methods for S -trifluoromethylation (Scheme 31). This method is simplified compared to the previously reported ones as neither UV irradiation or pressure safe equipment is needed. It is somewhat similar to the second part of the Tandem CF3I process , which has been introduced by Dolbier [63] and coworkers. In the case of other acidic group containing thiols such as 2-mercapto-benzimidazole the inhibition of the radical chain reaction was observed. 

An (-)-Ephedrine voltammetric sensor prepared through the immobilization of an MIP imprinted polymer for ephedrine in the range of 0.5-3 mM [426], and the MIP-coated gold electrode modified by chitosan-platinum nanoparticles (CS-PtNPs) and graphene-gold nanoparticles (GR-AuNPs) nanocomposites for the determination of erythromycin are other examples of the application of MIPs for the analysis of pharmaceutical species. The latter report used erythromycin as template and 2-mercapto-nicotinic acid functional monomers and yielded a linear response in the range of 7.0 x 10 -9.0 X 10 M and a detection limit of 2.3 x 10 M [378]. 

Sinha, N D and Cook, R. M (1988) The preparation and application of functionalized synthetic oligonucleotides III. Use of H-phosphonate derivatives of protected amino-hexanol and mercapto-propanol or -hexanol. Nucl Acids Res 16, 2659-2669... 

Thioesters are known to be cleaved by addition of 20% 1 M aqueous NaOH in dioxane to give carboxylic acids and thio-Wang resins [80] but they have also been cleaved under acidic conditions. An approach of Villain et al. describes the synthesis of thioacids by acidic cleavage of thioesters on solid support [81]. This procedure depends on a special type of linker (38) which is synthesized via addition of a mercapto-benzophenone derivative to aminomethyl-polystyrene. Cleavage of the resulting C-terminal thioacids 41 is induced by addition of HP (Scheme 5, for another application of thioester linkers for thioacid synthesis see Canne et al. [82]). 

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