Thiols thiazolidine derivatives

Penicillamine reacts with pyridoxal-5-phosphate to form a thiazolidine derivative, and is able to displace many amino acids from their Schiff base complexes, forming stable compounds of this type. The reactivity of the thiol group of penicillamine is less than that of cysteine, probably because of steric hindrance by the adjacent methyl groups of penicillamine, which in consequence is less rapidly oxidized in vivo [7]. 

The second type of weak bases for imine ligations are 1,2- or 1,3-heterosubstituted amines of amino thiols and amino alcohols. Of the two, the amino thiols appear to be the more suitable choice because they form stable thiazolidine derivatives under very mild reaction condi-tions 84"89,114 121 140 Furthermore, the 1,2-and 1,3-aminothiol moieties are found in cysteines and homocysteines that form a stable heterocyclic ring with an aldehyde within ten minutes at pH 4-5. Thiazolidine ring formation has been successfully used to ligate both linear and constrained peptides to K2K dendron types of cores and proteins containing a-oxoacyl groups. 

Hara et al. [117] demonstrated an excellent separation of the enantiomers of nine aldoses by GC as their diastereomeric thiazolidine derivatives. The sugars were derivatized with L-cysteine methyl ester (49) and subsequently silylated. This simple derivatization, including the acylation, was carried out in pyridine at 60 C. The rapid reaction of thiols with the carbonyl group of sugars was also exploited by Little [118], who used (-k)-l-phenylethanethiol (50) to form acyclic dithioacetals. 

Penicilloic acid 5, the substrate for the projected lactamization reaction, could be derived from the suitably protected intermediate 6. Retrosynthetic disassembly of 6, in the manner illustrated, provides D-penicillamine hydrochloride (7) and tert-butyl phthalimido-malonaldehydate (8) as potential building blocks. In the synthetic direction, it is conceivable that the thiol and amino groupings in 7 could be induced to converge upon the electrophilic aldehyde carbonyl in 8 to give thiazolidine 6 after loss of a molecule of water. 

As discussed in Section 4.19.2.2.2(i), imino, one or thione derivatives of thiazolidine are in tautomeric equilibrium (Scheme 60). Furthermore, many thiazolidines are in equilibrium with an acyclic thiol form or, in aqueous media, with the / -mercaptoalkylamine and the carbonyl compound from which they were formed (Scheme 71). The position of the equilibrium depends on the nature of the ring substituents. 

For the simultaneous protection of the thiol and amino functions of cysteine, Kemp and Carey116 first prepared a thiazolidine ring which was converted to its Boc derivative using di-tert-butyl dicarbonate in the presence of DIPEA [Scheme 8.47]. The conditions were critical because thiazolidines substituted at the 2-position are very susceptible to alkaline hydrolysis,... 

Thiols arising in the MaUlard reaction, mostly derived from heterocyclic compounds, such as furan, thiophene, thiazole and other heterocycles, are important flavour-active components of meat, coffee and many other foods. For example, 2-furanmethanethiol (furan-2-ylmethanethiol, furfuryl mercaptan) has an odour resembling roasted coffee, N- (2-mercaptoethyl) -1,3-thiazolidine (8-127), which is formed in the reaction of fructose with cysteamine, and has a very strong odour resembling popcorn. Its odour threshold is 0.005 ng/1 in air. 

Carbonyl Group Reduction. The flow of new methods for reduction of acid derivatives and aldehydes or ketones to alcohols continues unabated. The Report last year (4,134) featured the sodium borohydride reduction of carboxylic acid derivatives, originally thought to be 2-thiazoline-2-thiol esters (14), to give alcohols in good yields. Full details of the method have now appeared (Scheme 8), and it seems that the acid derivatives are in fact the 3-acyl thiazolidine-2-thiones (IS) dissappearance of their yellow colour is an easy way to monitor the reduction. Carboxylic acids or their chlorides can also be reduced to primary alcohols in good yields at room temperature using a titanium tetrachloride-sodium borohydride combination. ... 

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