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Synthesis of new functionalized aziridine-2- and azetidine-3-carboxylic acid derivatives of potential interest for biological and foldameric applications

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Abstract

A short synthesis of alkyl 2-(bromomethyl)aziridine-2-carboxylates and alkyl 3-bromoazetidine-3-carboxylates was developed involving amination, bromination, and base-induced cyclization of alkyl 2-(bromomethyl)acrylates. The aziridines are the kinetically favored cyclization products and could be transformed into 3-bromoazetidine-3-carboxylic acid derivatives via thermal isomerization. The new small-membered azaheterocyclic α- and β-amino acid derivatives contain a bromo-substituted carbon center as a useful moiety for functionalization. Transformation of these functionalized azaheterocycles via nucleophilic substitution with carbon, sulfur, oxygen, and nitrogen nucleophiles and via elaboration of the amino and carboxyl group provided a broad range of new conformationally constrained aziridine-2- and azetidine-3-carboxylic acid derivatives, which are of interest from a biological point-of-view as well as for applications in the field of foldamers.

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Acknowledgments

The authors are indebted to the Research Foundation—Flanders (FWO—Flanders) and Ghent University (BOF) for financial support.

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Correspondence to Norbert De Kimpe.

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Sven Mangelinckx is the Postdoctoral Fellow of the Research Foundation-Flanders (FWO).

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Žukauskaitė, A., Mangelinckx, S., Buinauskaitė, V. et al. Synthesis of new functionalized aziridine-2- and azetidine-3-carboxylic acid derivatives of potential interest for biological and foldameric applications. Amino Acids 41, 541–558 (2011). https://doi.org/10.1007/s00726-011-0879-1

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