Cysteine scheme

The 2-isoxazolidine nitriles (540b) and (540a) obtained, were further converted into the enantiomeric target compounds (541) and (542) by producing the thiazole ring via condensation with L-cysteine (Scheme 2.254) and (Scheme 2.255) (753). 

S-methylation involves the methylation of cysteine (Scheme 12). While there are no current studies on the S-methylation of cysteine, it is thought to be involved in the aging process of enzymes. ... 

Perhaps more significantly they were also able to isolate a polar, water-soluble compound that they believed was 55 in which the cysteine residue had been incorporated into the artemisinin backbone. The broadness of the signals in the proton NMR spectrum made characterization problematic, but treatment of 55 with acetic anhydride afforded 56, which was fully characterized (Scheme 16A). More recently, the same group has isolated and characterized another product from artemether. Adduct 57 was derived from the C4 secondary radical and cysteine (Scheme 16B). 

The reaction of diazomethane with 2-phenyM-(sulfanylmethylene)-5(4//)-oxazolone 665, readily obtained from 4-(chloromethylene)-2-phenyl-5(4//)-oxazo-lone 394, generates the intermediate spirocyclopropane oxazolones 666 and 667, respectively. Both 666 and 667 were independently elaborated to the 2-sulfanyl-1-aminocyclopropanecarboxylic acid derivatives 668 and 669—a novel class of conformationaUy constrained masked cysteines (Scheme 7.210). Representative examples of spirocyclopropane oxazolones are shown in Table 7.47 (Fig. 7.58). 

Biochemical oxidation of the ellipticine derivative 241 to the o-quinone 242 has been achieved using hydrogen peroxide and horseradish peroxidase (HRP) as a catalyst (83JMC574). Compound 242 was easily protonated to form a tautomeric equilibrium between 243 and 244 it gave an addition product with methanol and was reduced by cysteine (Scheme 41). 

If the reduced and oxidized peptides do not separate on RP-HPLC, the separation can be improved by modifying the reduced conformer, if still present, by using the thiol-specific reagent NEM to modify the reduced peptide (Scheme 5). This modification results in the formation of a stable covalent linkage between the thiol and NEM, after attack of the thiolate anion on one of the double-bonded carbon atoms in NEM, to form (N-ethylsuc-cinimido)cysteine (Scheme 5). The covalently modified reduced peptide becomes more hydrophobic and is eluted off the column later than the reduced peptide. Thus, baseline resolution can now be obtained between the oxidized conformer and the NEM-modified peptide.11921 The time course of the oxidation can be followed by the disappearance of the NEM-modified peptide with time and the concomitant appearance of the peak corresponding to the oxidized peptide. 

A milder method for the preparation of H-Cys(Acm)-OH is based on benzotriazole as a synthetic auxiliary.O The acetamidomethylating agent is prepared from benzotriazole, formaldehyde, and acetamide, and is then reacted with cysteine (Scheme 16) in aqueous dioxane at 50 °C for three to five hours in the presence of sodium hydroxide the desired product is obtained free of thiazolidine-2-carboxylic acid. 

Methoxycarbonylsulfenyl chloride (SMoc-Q)P is a valuable reagent for the synthesis of asynunetric disulfides via reasonably stable, isolable 5-(methoxycarbonylsulfanyl) derivatives. This procedure has been successfully transferred to cysteine peptides for selective intrachain and interchain disulfide formation (see Vol.E22b, Section 6.1.3.1). Due to the high reactivity of 5-(methoxycarbonylsulfanyl)cysteine derivatives 9 (Scheme 21), and complications arising from their base lability and the risk of S N nnigration, this type of protection is not suitable for multistep peptide synthesis. The more recently proposed AT-methyl-AT-phenylcarbamoylsulfanyl (SMpc) derivative of cysteine (Scheme 21) is apparently less prone to sulfur to nitrogen shift. ... 

Cysteine has also been found to add at C-5 of the 1,2,4-triazine ring. Panfuran, the pharmacologically active 1,2,4-triazine derivative 39, gives adduct 40 when mixed with cysteine (Scheme 27) (78HC(33)189). 

It is usual to effect cleavage of disulphide bonds by reduction or oxidation. Addition of a large excess of a thiol such as 2-mercaptoethanol or 1,4-dithiothreitol to a polypeptide reduces cystine residues to cysteine (Scheme 5.1). In order to prevent reoxidation in air, the generated thiol groups are blocked, usually by reaction with iodoacetic acid. The product yields S -carboxymethylcysteine (5.9) on hydrolysis for amino-acid analysis. Alternatively, oxidative cleavage of disulphide bonds can be achieved with performic acid each half of the cysteine residue is converted into a residue of cysteic acid (5.10). 

Recently, a-halogenated acetophenones (phenacyl groups) have been reported as a novel, membrane-permeant, non o-nitrobenzyl-based class of caging reagents. They are capable of covalent, photoreversible (350 nm) inhibition of PTPs at the catalytic cysteine (Scheme 3.2-7) [72,73]. The different... 

The chemoselective Michael addition of sulfhydryl group to the maleimido group is a well-known conjugation reaction tmder neutral pH, which has been commonly used for the coupling of fiuorophores to proteins with surface-exposed cysteine residues. The reaction was used to conjugate a maleimidocaproyl (MIC) peptide to a C-terminally truncated Ras protein bearing a C-terminal cysteine (Scheme 12). 

As shown, the DHPAlks can also react with SH groups found in more soluble components like glutathione and cysteine (Scheme 13.4 VIII). High levels of glutathione and cysteine therefore reduce the toxic potential of PAs [88,100-102]. 

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