Episulfonium

Scheme 6 depicts a typical penicillin sulfoxide rearrangement (69JA1401). The mechanism probably involves an initial thermal formation of a sulfenic acid which is trapped by the acetic anhydride as the mixed sulfenic-acetic anhydride. Nucleophilic attack by the double bond on the sulfur leads to an episulfonium ion which, depending on the site of acetate attack, can afford either the penam (19) or the cepham (20). Product ratios are dependent on reaction conditions. For example, in another related study acetic anhydride gave predominantly the penam product, while chloroacetic anhydride gave the cepham product (7lJCS(O3540). The rearrangement can also be effected by acid in this case the principal products are the cepham (21) and the cephem (22 Scheme 7). Since these early studies a wide variety of reagents have been found to catalyze the conversion of a penicillin sulfoxide to the cepham/cephem ring system (e.g. 77JOC2887).

When the reaction was run in CH3CN, migration of the EtS group to the 2-position was observed. This is attributed to episulfonium salt formation, with the resultant addition of acetate at the anomeric position. ... 

In the presence of TMSOTf 20 the olefin 1266 adds methyl benzene sulfenate to give the episulfonium triflate 1267, which cyclizes in 97% yield to give a ca 1 1 mixture of epimers of 1268 [57] (Scheme 8.23). 

A large number of DNA-alkylating agents are known and we will not attempt a comprehensive survey here. A number of excellent reviews provide an overview of this area. " Here we will review DNA alkylation by three types of reactive intermediates that are important in medicinal chemistry and toxicology— episulfonium ions, aziridinium ions, and carbocations. 

Toremifene also undergoes oxidative metabolism to form a QM.59 The 4-hydro-xytoremifene QM has a half-life of lh at physiological pH and temperature (Table 10.2), while its half-life in the presence of GSH is approximately 6 min.59 The 4-hydroxytoremifene QM reacts with two molecules of GSH and loses chlorine to yield the corresponding di-GSH conjugate (Scheme 10.9). This reaction mechanism likely involves an electrophilic episulfonium ion intermediate, which could contribute to the potential cytotoxicity of toremifene. 

The product of an episulfonium ion-mediated cyclotrimerisation previously reported as a 15-membered ring trilactam has now been shown to be a 1,3,5-triazine <060BC3120>. The tautomerism of 2,4-di(benzyloxy)-l,3,5-triazin-6(5A)-one has been studied <06MI561>. 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

This approach allows one to functionalize the j3-C atom of AN. For this purpose, AN are initially subjected to double silylation to prepare BENAs, which are then coupled with various stabilized carbocations (512, 513), as well as with sulfenyl and episulfonium cations (514). Molecules containing good leaving groups (e.g., arenesulfenyl chlorides (514)) are used as sources (or precursors) of... 

Substitution of fi-nitro sulfides.2 (3-Nitro sulfides in the presence of a Lewis acid undergo displacement reactions with either allyl- or cyanotrimethylsilane. The reaction is considered to involve an episulfonium intermediate, which is then substituted at the more positive carbon (equation I). The reaction proceeds with retention of configuration, and anti (J-nitro sulfides react much more rapidly than... 

Sulfenoetherification. The reagent in combination with trifluoromethane-sulfonic acid converts suitably unsaturated alcohols into five- to seven-membered cyclic ethers. The cyclization is considered to involve an intermediate episulfonium ion. 

FIGURE 7.17 Conjugation of dibromoethane with glutathione (GSH) ultimately leads to a more reactive episulfonium ion. 

Terminal alkenes, containing tu-OH or (U-COOH functionalities, may undergo cyclization [129] with different orientation of the intramolecular attack of the nucleophilic end of the molecule on the intermediate episulfonium ion (Eq. 16). 

Usually, 5- and 6-membered Markovni-kov-type products are formed in other cases the process results in various open-chain products. The formation of an anti-Markovnikov adduct from 2-cyclohex-1-enyl-ethanol was explained by the cyclization of an episulfonium intermediate... 

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