Aziridinium ion

Homochiral thiiranium and aziridinium ion intermediates formed by Lewis acid-induced rearrangement of l-hetero-2, 3-epoxides 97SL11. 

Alkylating agent, a reactive chemical that forms a covalent bond with chemical moieties on the biological target (usually a protein). For instance, p-haloalkylamines generate an aziridinium ion in aqueous base that inserts into -SH, -CHOH, or other chemical structures in peptides. Once inserted, the effects of the alkylating agent are irreversible. 

Scheme 12.24 Generation of aziridinium ions from epoxides.

Scheme 12.25 Nucleophilic opening of aziridinium ions with azide.

Taken together, the broad scope of these reactions and the easy access to the starting materials from the corresponding epoxides makes aziridinium ions ideal click intermediates. 

Aziridinium ion-based click chemistry provides convenient access to pyrazolo[l,2-ajpyrazoles, active inhibitors of penicillin-binding proteins [58, 59]. Ring-opening of aziridinium ions 32 at the benzylic position with hydrazine, followed by intramolecular cyclization, gave pyrazolidin-3-ones 37 in excellent yields (Scheme 12.27). Heating of the hydrazides 37 with aromatic aldehydes at reflux in absolute... 

The chemistry of functionalized aziridines is still in full swing. There is no doubt that many new applications will be found, especially when optimal use is made of the stereogenic centers in these small-ring heterocycles. In addition, the chemistry of aziridinium ions [71,72] will add much to the flavor of this area of chemistry. 

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. 

Nitrogen mustards such as 23 decompose to yield aziridinium ions 24 (Scheme 8.14). " As in the case of sulfur mustards, the reaction involves rate-limiting intramolecular displacement of p-chlorine by nitrogen. The resulting aziridinium ions... 

It was synthesized from p-iodoanisole (65) by copper-catalyzed coupling with p-trifluoromethyliodobenzene (66) to give the expected statistical mixture from which unsymmetrical product 67 could be separated. Ether cleavage with HBr and HOAc gave 68 this was then alkylated with the aziridinium ion derived from N-(2-chloroethyl)pyrrolidine, using NaH as base, to complete the synthesis of boxidine (69). 

Although geneologically related to indoles, the dihydroindoles behave chemically rather like alkyl anilines. When diphenylamine reacts with chloro-propionyl chloride, amide 40 results this in turn readily cyclizes to oxindole 41. Sodium hydride followed by 2-chloroethyldimethylamine alkylates the 3-position (possibly through an intermediate aziridinium ion) partial demethylation is accomplished by refluxing with ethylchiorocarbonate, followed by hydrolysis of the intermediate carbamate to give indolinone 42, the antidepressant amedalin Repetition of this sequence on the chloropropyl homologue, followed by reduction of the appropriate indolinone produces dihydroindole 43, daledalin, which also has antidepressant activity. ... 

Scheme 1.30. Cationic cyclization/aziridinium ion formation/nucleophilic ring-opening procedure for the synthesis of pyrrolidines.

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