Mercapto acids

HYDROXYTHIAZOLE DERTVATIVES FROM NITRILES AND a-MERCAPTO ACIDS... 

Another class of new ligands was prepared in quantitative yields by Feringa et al., in 1997, by reaction between a-mercapto acids, aniline and 2-pyridine-carboxaldehyde." These pyridyl-substituted thiazolin-4-one ligands were further involved in the copper-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone,... 

A logical extension of the synthetic strategy underlying our solid-phase approach toward 1,5-benzothiazepinones was to replace the [3-mercapto acids (cysteine, penicillamine) by a-mercapto acids, such as mercaptoacetic acid 54a or thiolactic acid 54b. This change would facilitate access to the corresponding [6,6]-fused systems, i, e. 1,4-benzothiazin-3-ones 57. As with the benzothiazepines, no solid-phase synthesis of benzothiazines has been reported to date. 

From a pharmaceutical discovery perspective, it could be fruitful to embark on a library synthesis using cyclic hydroxamic acid templates. There are several reports describing interesting bioactivities for such compounds, particularly as inhibitors of metal-dependent enzymes 48-52 However, only three a-mercapto acid monomers are currently available from commercial sources hence the structural diversity of products that could be easily prepared is limited. Several approaches to introducing additional points of diversity into the benzothiazinone scaffold are currently under investigation. 

Heterocyclization of a-mercapto acids with (azolylimino)indolones 182 (Scheme 36) afforded the spirocyclic thiadiazepinones 183 <1989IJB639, 1994PS27>. gem-Dithiol addition to bis(methylene)-substituted diketopiper-azine 168 afforded the bridged bicyclic structure 169 featuring two dithiazepane rings (Scheme 33) <1981JHC1545>. 

Analogously, a number of bis-benzo-TAs 61 were obtained (75JHC783) by an interaction of cyanogen with substituted mercapto acids 58 (Scheme 17). The suggested scheme was confirmed by the isolation of a small amount of amide 60, which was formed from intermediate 59 via hydrolysis by the water liberated in the first step of the condensation. 

Resin-bouda-amino esters, besides being traditionally used for making peptides, have served as key intermediates for the construction of various heterocyclic scaffolds. Thus, they react smoothly with isocyanates to form ureas, which upon heating under acidic conditions cyclize to form hydantoins 53 [27]. A one-pot, three-component condensation of resin-bound a-amino esters with aldehydes and a-mercapto acids affords 4-thiazolidi-... 

The AA has also been used in the preparation of analogues of the paclitaxel side chain 32 like protected a,[3-diamino acids 35a and 35b from 33 [59,60], 0-amino-a-mercapto acids 36a and 36b from 33 [59,61], derivatives bearing a ni-... 

Recent oxidations to be studied include those of p-mcthoxytoluene,962 glutathione963 and cysteine and related mercapto acids.964... 

Reaction of a-mercapto acids with hexafluoroacetone gives the oxathiolanones 192 (Equation 62) <2003JHC435> which provide a useful protected form of the acid <2004S1821> and also allow introduction of a mercapto acid unit into peptides <2004S1088>. 

The first (3-thiolactone was prepared according to Scheme A by Knunyants and co-workers. A mixed anhydride of )3-mercaptocarboxylic acid and carbonic-acid ester is obtained by treatment of a salt of the mercapto acid with a chlorocarbonate ester.Cyclization to the 3-thiolactone occurs during the reaction this synthetic method is exemplified by the preparation of 302 from 301. A mixed carboxylic-sulfonic acid anhydride is involved in the formation of the thiolactone ring in 303. ... 

Extension of this synthetic strategy to the preparation of 1,5-benzothiazepin-4-ones and 4-alkyloxy-l,4-thiazin-3-ones by using suitably protected forms of cysteine and a-mercapto acids in nucleophihc aromatic substitution reactions of 7 has been envisaged by the authors. 

SA " r R1 aliphatic and aromatic amines, hydroxy, ester, protected [109] a- and p-amino acids amino, furyl, thienyl aromatic and heteroaromatic aldehydes 2-mercapto acids... 

The reported synthesis and properties of poly(thiol esters) of the A-B and A-A/B-B types are reviewed for these classes of compounds 2 poly(a-mercapto acids), 7 poly(/3-mercapto acids), 4 poly (e-mercapto acids) and 44 A-A/B-B type poly(thiol esters). The melting points of poly(thiol esters) are generally lower than those of the corresponding polyamides and higher than those of the polyesters. They are readily hydrolyzed by alkali, which seems to be the main reason for the lack of commercial interest in these materials. 

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