Selective Synthesis of <i>cis</i>- and <i>trans</i>-2-(Methyl/phenyl)-3-(trifluoromethyl)aziridines and Their Regio- and Stereospecific Ring Opening

A convenient and stereoselective approach toward <i>cis</i>- and <i>trans</i>-1-alkyl-2-(methyl/phenyl)-3-(tri­fluoro­methyl)­aziridines was developed starting from the corresponding α,α,α-trifluoroketones via imination, α-chlorination, and hydride-induced ring closure. The reactivity of these newly synthesized nonactivated α-CF₃-aziridines was evaluated by applying <i>N</i>-protonation or <i>N</i>-alkylation to effect regio- and stereospecific aziridine ring opening by oxygen, halogen, sulfur, and nitrogen nucleophiles. Furthermore, nonactivated α-CF₃-aziridines were easily transformed into their activated analogues by replacing the <i>N</i>-benzyl protecting group with a <i>N</i>-tosyl group, rendering these α-CF₃-aziridines much more susceptible to nucleophilic ring opening

Chemical and Enzymatic Synthesis of 2-(2-Carbamoylethyl)- and 2-(2-Carboxyethyl)aziridines and Their Conversion into δ-Lactams and γ-Lactones

Treatment of 1-arylmethyl-2-(2-cyanoethyl)aziridines with a nitrile hydratase afforded the corresponding 2-(2-carbamoylethyl)aziridines, which underwent rearrangement into 5-hydroxypiperidin-2-ones upon heating under microwave irradiation. In addition, treatment of 2-(2-cyanoethyl)aziridines with a nitrilase selectively afforded 5-hydroxypiperidin-2-ones in good yields. On the other hand, chemical hydrolysis of 2-(2-cyanoethyl)aziridines using KOH in EtOH/H₂O furnished the corresponding potassium 3-(aziridin-2-yl)propanoates, which, upon acidification with acetic acid, smoothly rearranged into 4-(aminomethyl)butyrolactones

Design, Synthesis, and Antiviral Evaluation of Purine-β-lactam and Purine-aminopropanol Hybrids

Purine-β-lactam chimera were prepared as a novel class of hybrid systems through <i>N</i>-alkylation of 6-benzylamino- or 6-benzyloxypurine with (ω-haloalkyl)-β-lactams, followed by reductive ring opening of the β-lactam ring by LiEt₃BH to provide an entry into the class of purine-aminopropanol hybrids. Both new types of hybrid systems were assessed for their antiviral activity and cytotoxicity, resulting in the identification of eight purine-β-lactam hybrids and two purine-aminopropanol hybrids as promising lead structures

Solvent-Controlled Selective Transformation of 2-Bromomethyl-2-methylaziridines to Functionalized Aziridines and Azetidines

The reactivity of 2-bromomethyl-2-methylaziridines toward oxygen, sulfur, and carbon nucleophiles in different solvent systems was investigated. Remarkably, the choice of the solvent has a profound influence on the reaction outcome, enabling the selective formation of either functionalized aziridines in dimethylformamide (through direct bromide displacement) or azetidines in acetonitrile (through rearrangement via a bicyclic aziridinium intermediate). In addition, the experimentally observed solvent-dependent behavior of 2-bromomethyl-2-methylaziridines was further supported by means of DFT calculations