Multigram Synthesis of 3‐Azabicyclo[3.1.1]heptane Derivatives Including Bicyclic Thalidomide Analogs
Abstract An efficient approach to the multigram synthesis of 3‐azabicyclo[3.1.1]heptanes is described. The method relied on the intramolecular imide formation in the properly 1,3‐functionalized cyclobutane derivative. In turn, the latter compound was obtained via the diastereoselective Strecker reaction of readily accessible 3‐oxocyclobutanecarboxylate. The resulting synthetic intermediate – 1‐amino‐3‐azabicyclo[3.1.1]heptane‐2,4‐dione – was used to synthesize several monoprotected bicyclic diamines valuable as building blocks for medicinal chemistry, as well as a series of bridged analogs of Thalidomide, a known anticancer drug and a component of proteolysis‐targeting chimeras (PROTACs).
Authors
- В. С. Броварец (ORCID: https://orcid.org/0000-0001-6668-3412)
- Kostiantyn Nazarenko (ORCID: https://orcid.org/0000-0002-1037-6381)
- Alexander Kostyuk (ORCID: https://orcid.org/0000-0001-8502-0008)
- Oleksandr O. Grygorenko (ORCID: https://orcid.org/0000-0002-6036-5859)
- Oleh Shyshlyk (ORCID: https://orcid.org/0009-0009-2785-1079)
- A. V. Golovchenko (ORCID: https://orcid.org/0000-0001-7756-6019)
- Viacheslav Lysenko (ORCID: https://orcid.org/0000-0001-5177-7678)
- Anton Portiankin
- Т. И. Савченко
Institutions
- National Academy of Sciences of Ukraine (UA)
- Taras Shevchenko National University of Kyiv (UA)
- Institute of Bioorganic Chemistry and Petrochemistry V.P. Kukhar (UA)
- Institute of Organic Chemistry (UA)
- Enamine (Ukraine) (UA)
Publication Details
- Journal
- European Journal of Organic Chemistry
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1002/ejoc.202400938
- Citations
- 1
- Primary Topic
- Plant-based Medicinal Research
- Type
- article
- Field-Weighted Citation Impact
- 0.47