Lactones and Sultones

The electrophiles or electrophilic intermediates that are or are postulated to be responsible for the carcinogenic action of chemicals include (i) positively charged carbonium, nitrenium, oxonium and episulfonium ions, (ii) free radicals, (iii) polarized double bonds, (iv) aldehydes, (v) strained rings such as epoxide, aziridine, lactones and sultones, and (vi) quinone/ quinoid/quinoneimine structures. Based on their reactivity (Table I), electrophiles may be graded from "soft" to "hard" similar to the concept of "soft" and "hard" acids and bases (18). In general, soft electrophiles react preferentially with soft nucleophiles whereas hard electrophiles react preferentially with hard nucleophiles. Thus, since the nucleophilic sites in the purine and pyrimidine bases in DNA are moderately hard nucleophiles, moderately hard electrophiles tend to have the greatest likelihood of covalent binding to DNA. Soft electrophiles often deplete the cellular pool of noncritical soft nucleophiles (such as GSH) before they can react with DNA. 

The presence of a sterically strained ring (e.g., epoxide, aziridine, lactones and sultones) in any type of structure. The likelihood of carcinogenicity may increase if the compound contains two or more of these reactive ring structures. 

Title Norbornene-Type Monomers and Polymers Containing Pendent Lactone or Sultone Groups... 

A norbornene terpolymer containing a lactone or sulton substituent has been prepared that is effective in photoresist compositions in the 193 and 157 nm ranges in photolithography. An improvement in etch resistance was also observed. 

Lewis Acid Assisted Nucleophilic Addition of Ketenes (or Sulfenes) to Aldehydes -Lactone and (i-Sultone Synthesis... 

Spontaneous alternating copolymerizations of two cyclic phosphorus compounds, 2-phenyl-l,3,2-dloxaphospholane 11 and 2-phenoxy-1,3,2-dloxaphospholane 20, with several electrophilic monomers were discussed. As the electrophilic monomers, /3-proplolactone 13, 3-hydroxypropanesulfonlc acid lactone (propane-sultone) 15, acrylic acid 16, acrylamide 17, acrylate were sucessfully copolymerized with 11. At temperatures lower than those of copolymerization, the combinations of 11—13, 11—16, 11—-17 and 11—acrylate produced trioxyphosphorane derivatives having spiro-ring structures, which were significant in two... 

Van Durren BL, et al Carcinogenicity of isoesters of epoxides and lactones Aziridine ethanol, propane sultone and related compounds. J Natl Cancer Inst 46 143-149, 1971... 

The same reaction has been also carried out with heterocyclic aminomethyleneketone derivatives of, e.g., 4-pyranones273, chromanones and derivatives and 4-piperidones276 (equation 202). A useful dienophile is dichloroketene, produced from dichloroacetyl chloride and triethylamine. It enables the enaminone oxygen to be incorporated into the functional group of a lactone instead of a sultone (equation 202). 

The basis for exploring heterocycles as inhibitors of HLE came from the discovery that some heterocycles, for example, sultones (12-1, Table 2.12) [174], oxazolinones (12-2) [175], or lactones (12-3) and (12-4) [176], were alternate substrates for serine proteinases. The proteinases reacted with these compounds to (a) cleave the heterocyclic ring, (b) form an intermediate acyl-enzyme and (c) then hydrolyze the acyl-enzyme by the normal catalytic mechanism to release active enzyme and the ring-opened heterocycle. 

Very recently, a similar bifunctional catalyst system (metal triflates and cinchona alkaloid) was successfully applied by Peters and coworkers for the synthesis of (3-sultones (Scheme 4.17) [40] and chiral a,P-unsaturated 8-lactones [41]. 

Dihrornothynwlsulfonephthalein, Bromthymolblue, C27H2805SBr2. This compound was isolated by Orndorff and Cornwell (1. c.) in the colorless form, and was thought by them to be a derivative of the lactone (sultone) form. It forms a colored quinoid hydrate from which the colorless compound is recovered upon heating. The crystalline hydrate contains two molecules of water of crystallization. It is obtained in the form of dark colored crystals which yield a red powder upon being pulverized. 

Sultones are cyclic sulfonic esters. The term sultone arises from sulfonate lactone. Sultones, in particular 1,3-propane sultone, undergo alkylating reactions easily and are potential carcinogens (83-86). 

Sultones are the internal esters of hydroxy sulfonic acids and sulfur analogs of lactones. The biological activities of sultones are concerned with toxicological, skin sensitization, and antiviral properties [13]. In 2009, Majumdar developed a Pd(PPh3)4-catalyzed intramolecular C-H arylation reaction of benzenesulfonic acid 2-bromophenyl esters to afford polycyclic sultones, which are generally synthesized by elimination of the corresponding hydroxyl sulfonic acid derivatives, in up to 90% yield (Scheme 3.3, path a) [14]. TBAB was found to be critical in this reaction, and no reaction occurred in the absence of this additive. An electrophilic palladation mechanism was proposed for this transformation. 

Sultones are the internal esters of hydroxy sulfonic acids and are the sulfur analogs of lactones. Sultones are demanded scaffolds in medicinal chemistry research. Biological studies on sultones are mainly concerned with their toxicological, skin sensitization, and antiviral activities [20]. Sultones are synthetically useful heterocycles which can react with a variety of compounds to introduce the alkylsulfonic acid function and therefore used as sulfoalkylating agents [21]. There have been several new developments for the synthesis of sultones which have also been applied in the total synthesis of natural products. In recent years, the palladium-catalyzed direct arylation of several aromatics via a C-H bond activation using aryl halides has led to successes. An intramolecular version of this reaction has allowed the synthesis of several biaryls via the formation of five- to seven-membered rings. Thus, the sultones should be synthesized by C-H activation via two pathways (Scheme 4.14). 

Merten J, Hennig A, Schwab P, FrohUch R, Tokalov SV, Gut-zeit HO, Metz P. A concise sultone route to highly oxygenated 1,10-seco-eudestnanolides-enantioselective total synthesis of the antileukemic sesquiterpene lactones (—)-eriolanin and (—)-eriolangin. Eur. J. Org. Chem. 2006 12(4) 1144-1161. 

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