Thiol esters, hydrolysis reduction

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

Hydroxydec-2-enoic acid 397 was identified in the fodder juice of the Weisel cells (gelee royale) of honey bees. One of the synthesis of 397 starts from suberic acid ethylester 393 222) which was first converted into the hydroxyacid 394 and then into the thiol ester 395. Raney nickel reduction of the latter yields an intermediate aldehyde which, in statu nascendi, reacts with the phosphorane 67 to give 396. Subsequent hydrolysis of396affords the ( )-a,0-unsaturated hydroxy acid 397 222) (Scheme 70). 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

But we can assign to GSH more specific functions also. It participates in transpeptidations and oxidation reductions as well as in hydration-dehydration reactions. Perhaps this large variety of reactions has more in common than appears at first sight. Many of the transpeptidation reactions have been shown to occur with enzymes such as the cathepsins which require SH groups for activity. Hydrolysis of thiol esters by papain has been recently demonstrated (66) and the formation of thiol esters as intermediates in transpeptidations still remains to be explored. In the glyoxalase reaction the actual substrate may be the hydrated form of the aldehyde, in which case the reaction mechanism would be one of dehydration and hydrolysis rather than of a hydrogen shift. Thus the reaction will bear some similarity to the aconitase reaction which is stimulated by SH compounds and ferrous ions (67). 

Reduction of the ketone function to a methylene group follows. The resulting butanoic thiol ester repeatedly undergoes a similar sequence of reactions elongating the chain, always by two carbons. The eventual product is a long-chain acyl group, which is removed from the protein by hydrolysis. 

The enzymatic reduction of a thiocarbonyl compound has been investigated [159] for the first time, in order to provide a new route for enan-tiopure thiols, molecules which are currently needed for asymmetric synthesis. Reaction of easily available /1-thioxoesters with baker s yeast under classical conditions did furnish the expected thiols, but with lower enantiomeric purity and moderate conversion rate, due to the competitive hydrolysis of the thioxo group into a carbonyl leading to an alcohol. However, conditions (ethyl acrylate, dry yeast) were found to improve the production of (S)-ethyl 3-mercaptobutanoate. Cyclic thioxo esters led to high stereoselectivity of cis (1S,2S) products, but with moderate chemical yields. 

Removal of protecting groups. A combination of DBU with a thiol can be used in the removal of an Fmoc group in a large scale process. Regeneration of alcohols from trichloroacetimidates is accomplished by treatment with DBU in MeOH (other methods involve acid-catalyzed hydrolysis and Zn dust reduction)." Alcohols temporarily protected as trichloroacetimidates permit their differentiation from others that are masked in acetonide, ester (acetate, benzoate, etc.), and ether (allyl, TBS, etc.) forms. 

In bicyclic adducts (eq 1), thiol enol ethers are the direct products of oxidative decarboxylation reduction of the ester and subsequent hydrolysis of the thiol enol ethers affords a-methylene ketones (eq 5). Thus eqs (eq 4) and (eq 5) demonstrate the utility of (1) as a methoxycarbonylketene (2) or methyleneketene (3) synthon in [4 + 2] cycloaddition reactions. 

A variety of terminal functional groups and their chemical transformations on SAMs have been examined for example, (i) olefins—oxidation [23,24,131,132], hydroboration, and halogenation [23,24] (ii) amines—silyla-tion [145,146], coupling with carboxylic acids [22,146], and condensation with aldehydes [22,147] (iii) hydroxyl groups—reactions with anhydrides [148,149], isocyanates [150], epichlorohydrin [151], and chlorosilanes [152] (iv) carboxylic acids—formation of acyl chlorides [153], mixed anhydrides [154], and activated esters [148,155] (v) carboxylic esters—reduction and hydrolysis [156] (vi) thiols and sulfides—oxidation to generate disulfides [157-159] and sulfoxides [160] and (vii) aldehydes—condensation with active amines [161], Nucleophilic... 

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