Skip to content
DraconiticResearch
Search Sources API
186,123 studies31 sourcesUpdated 10 min ago
PreprintCC BYChemRxiv

Multigram Synthesis of Heterabicyclo[4.1.1]octanes: Conformationally Restricted Azepane Analogs for Drug Discovery

  • Ivan V. Mazurenko1,2
  • Yevhen M. Ivon1,3
  • Nataliia Y. Slyvka2
  • Olena D. Semoshkina3,4
  • Oleksandr S. Liashuk3,4
  • Dmytro Lesyk1,3
  • Petro Borysko1,5
  • Viktor Yakubovskyi1,3
  • Svetlana V. Shishkina6
  • Oleksandr O. Grygorenko1,3,4
6 affiliations
  1. 1Enamine Ltd., Winston Churchill Street 78, Kyїv, Ukraine, 02094
  2. 2Lesya Ukrainka Volyn National University, Voli Avenue 13, Lutsk, Ukraine, 43025
  3. 3Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyїv, Ukraine, 01601
  4. 4Enamine Scientific Research Institute, Winston Churchill Street 67, Kyїv, Ukraine, 02094
  5. 5V. P. Kukhar Institute of Bioorganic Chemistry & Petrochemistry, National Academy of Sciences of Ukraine, Akademik Kukhar Street 1, Kyїv, Ukraine, 02066
  6. 6Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Akademik Kukhar Street 5, Kyїv, Ukraine, 02066
Open at sourcePDFDOICite

Abstract

A convenient and scalable synthetic approach enabling multigram access to three heterabicyclo[4.1.1]octane families – 2-azabicyclo[4.1.1]octane, 2,5-diazabicyclo[4.1.1]octane, and 2-oxa-5-azabicyclo[4.1.1]octane – is described. Starting f rom readily available cis -1,3-disubstituted cyclobutanes, the target scaf folds were obtained by the common lactamization – amide reduction strategy, providing access to the (mono)protected (di)amines as ready-to-use building blocks. Representative members were characterized by single-crystal X-ray diffraction studies, and basicity (p K a ) and lipophilicity (Log P ) were determined for selected compounds. These rigid f rameworks can be considered as saturated analogs of the azepane, 1,4-diazepane, and 1,4-oxazepane rings.

Related

  1. Design and synthesis of conformationally constrained Tn antigen mimics
    Tetrahedron lettersPeer-reviewedCC BY-NC-NDFull textOrganic chemistryEurope PMC
  2. Aryne-Enabled Synthesis of 1,8-Disubstituted Thioxanthones for Conformationally Gated Metal-Ion Sensing
    Riku Arakaki, Mayu Kawada, Suguru Yoshida
    ChemRxivPreprintCC BYFull textPhysical chemistryChemRxiv
  3. Conformationally locked planar-chiral single- and double-bridged perylene diimides with highly twisted structures: topology-controlled synthesis and chiroptical properties
    Taiga Suzuki, Sara Arikawa, Natsuhiko Sugimura +2
    Chemical sciencePeer-reviewedCC BYFull textOrganic chemistryEurope PMCEurope PMCPMC
  4. Multigram Copper-Catalyzed Azidodeboronation of Alkenyl Boronates
    Maksym Kovalenko, Yevhen M. Ivon, Yaroslava Kovalchuk +6
    ChemRxivPreprintCC BYFull textOrganic chemistryChemRxiv
  5. Information-Dense Synthesis for Molecular Discovery
    Kasper K. Jakobsen, Eli N. Weinstein
    arXivPreprintCC BY 4.0Full textBiophysicsPhysical chemistryarXiv

Cite

BibTeXRIS
BibTeX
@misc{mazurenko2026multigram,
  title = {{Multigram Synthesis of Heterabicyclo[4.1.1]octanes: Conformationally Restricted Azepane Analogs for Drug Discovery}},
  author = {Ivan V. Mazurenko and Yevhen M. Ivon and Nataliia Y. Slyvka and Olena D. Semoshkina and Oleksandr S. Liashuk and Dmytro Lesyk and Petro Borysko and Viktor Yakubovskyi and Svetlana V. Shishkina and Oleksandr O. Grygorenko},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15008479/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008479/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Multigram Synthesis of Heterabicyclo[4.1.1]octanes: Conformationally Restricted Azepane Analogs for Drug Discovery
AU  - Ivan V. Mazurenko
AU  - Yevhen M. Ivon
AU  - Nataliia Y. Slyvka
AU  - Olena D. Semoshkina
AU  - Oleksandr S. Liashuk
AU  - Dmytro Lesyk
AU  - Petro Borysko
AU  - Viktor Yakubovskyi
AU  - Svetlana V. Shishkina
AU  - Oleksandr O. Grygorenko
PY  - 2026
DA  - 2026/09/08
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008479/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008479/v1
AB  - A convenient and scalable synthetic approach enabling multigram access to three heterabicyclo[4.1.1]octane families – 2-azabicyclo[4.1.1]octane, 2,5-diazabicyclo[4.1.1]octane, and 2-oxa-5-azabicyclo[4.1.1]octane – is described. Starting f rom readily available cis -1,3-disubstituted cyclobutanes, the target scaf folds were obtained by the common lactamization – amide reduction strategy, providing access to the (mono)protected (di)amines as ready-to-use building blocks. Representative members were characterized by single-crystal X-ray diffraction studies, and basicity (p K a ) and lipophilicity (Log P ) were determined for selected compounds. These rigid f rameworks can be considered as saturated analogs of the azepane, 1,4-diazepane, and 1,4-oxazepane rings.
ER  -