Sulfonic acids thioesters

An important drug in the present context is the mineralocorticoid receptor antagonist spironolactone (7.74, Fig. 7.12). Among its many metabolic reactions, spironolactone is readily hydrolyzed at the thioester bond (Fig. 7.12, Reaction a) to form deacetyl-spironolactone (7.75, Fig. 7.12), a metabolite found in a variety of tissues [155 -157]. This thiol compound, which is also a potent mineralocorticoid antagonist, promotes the mechanism-based inactivation of hepatic, adrenal, and testicular cytochrome P450 isozymes. There is now good evidence to indicate that this behavior is the result of microsomal 5-oxidation (see Chapt. 7 in [7]). When spironolactone was incubated with liver microsomes from rats pretreated with dexamethasone (an inducer of CYP3A), the sulfinic and sulfonic acid derivatives were characterized [158]. Perhaps the importance of the 5-deacetylation of spironolactone... 

Apart from aryl esters and amides of carboxylic acids, aryl carbonates, and carbamates, other types of organic compound have been reported to undergo PFR. They include oxalates, formiates, sulfonates, sulfonamides, thioesters, selenoesters, and telluroesters. 

Substituents attached to a heterocyclic ring through a sulfur atom exist in wider variety than those through oxygen. Besides the simple thio analogues—the thiols (mercaptans), thioethers, thioesters and the like—they include compounds of various higher oxidation states of sulfur, including sulfoxides, sulfones, sulfinic and sulfonic acids and their derivatives. 

Unithiol (see Fig. 4 for structure) is the sodium salt of the sulfonic acid derivative of BAL. The compound is thus more soluble in water and is a crystalline solid at room temperature. It has its two thiol groups separated by 2 carbon atoms and thus if it forms a bisthioester with chromate, it would contain a 5-membered ring, and if the oxidation of such a thioester proceded intramolecularly, the disulfide bond formed would be contained in a 4-membered ring. 

The chemical shift assignments for the various products were further supported by model reactions utilizing methyl 3-mercaptoproplonate (9). Reaction of 9 with DCC-prepared azlactone 2 in the presence of ethane-sulfonic acid led to the clean production of Michael adduct 10 (Scheme 7 and Figure 3). Alternatively, repetition of this reaction in the presence of triethylamine produced a product mixture on which the thioester... 

As has been indicated in a number of studies, sulfur-containing compounds give a synergic effect with amines and phenols in the stabilization of high-molecular compounds [89, 279]. The following have been proposed and are used as stabilizers of polyvinyl chloride mercaptides of antimony [280, 281], condensation products of aldehydes or ketones with mercaptans [63], thioesters [282], salts of thioacids [283], aromatic esters of aliphatic sulfonic acids [284], esters of xanthic acids [285] the use of the polysulfide of the composition... 

Thioesters have been shown to decompose several moles of hydroperoxide per mole of stabilizer [7]. The hydroperoxide is typically reduced to an alcohol and the thioester is transformed into a variety of oxidized sulfur products including sulfenic and sulfonic acids. S5uiergistic combinations with phenolic antioxidants are often used to enhanced thermal stability in polyolefins at elevated temperatures (>100°C). 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

Peptide thioesters (Section 15.1.10) are generally prepared by coupling protected amino acids or peptides with thiols and are used for enzymatic hydrolysis. Peptide dithioesters, used to study the structures of endothiopeptides (Section 15.1.11), may be prepared by the reaction of peptide nitriles with thiols followed by thiolysis (Pinner reaction). Peptide vinyl sulfones (Section 15.1.12), inhibitors of various cysteine proteases, are prepared from N-protected C-terminal aldehydes with sulfonylphosphonates. Peptide nitriles (Section 15.1.13) prepared by dehydration of peptide amides, acylation of a-amino nitriles, or the reaction of Mannich adducts with alkali cyanides, are relatively weak inhibitors of serine proteases. 

Another cinchona alkaloid-catalysed Mannich reaction was reported by Barbas et al, occurring between a thioester and an a-amido sulfone, leading in the presence of KOH to the unti-Mannich product in 79% yield, with both moderate diastereo- and enantioselectivity of 64% de and 45% ee, respectively. Finally, Akiyama et al. have developed a new method for the enantioselec-tive synthesis of y-butenolide derivatives, which involved the vinylogous Mannich-type reaction catalysed by a novel chiral phosphoric acid bearing iodine groups at the 6,6 -positions. Aliphatic as well as aromatic aldimines... 

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