Multigram Synthesis of 2-Azabicyclo[2.1.1]hexane-1-Carboxylates (2,4-Methanoprolines) – Promising Bicyclic Proline Analogs

Authors

DOI:

https://doi.org/10.24959/ophcj.24.314843

Keywords:

bicyclic compounds, building blocks, proline analog, bridged pyrrolidine, amino acid

Abstract

An optimized approach towards 4-substituted 2,4-methanoproline derivatives is reported. Careful selection of the starting materials and optimized isolation procedure provided easy access to a key bicyclic building block in a preparative yield of 32% over five laboratory steps of up to 0.7 kg. Further modifications allowed us to obtain a number of useful derivatives, including those containing NH2, COOH, CH2NH2, and CH2F fragments with orthogonally protected functionalities.

Supporting Agency

  • This work was supported by Enamine Ltd. O. O. Grygorenko received additional funding from the Ministry of Education and Science of Ukraine, grant No. 0122U001962 (22BF037-02).

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2024-12-27

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Chernykh, A. V.; Liashuk, O. S.; Hurieva, A. M.; Volochnyuk, D. M.; Grygorenko, O. O. Multigram Synthesis of 2-Azabicyclo[2.1.1]hexane-1-Carboxylates (2,4-Methanoprolines) – Promising Bicyclic Proline Analogs. J. Org. Pharm. Chem. 2024, 22, 24-37.

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Vol. 22 No. 3 (2024)

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Advanced Researches

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