2-Oxabicyclo[2.1.1]hexanes: Synthesis, Properties, and Validation as Bioisosteres of ortho- and meta-Benzenes

Vadym V Levterov; Yaroslav Panasiuk; Oleh Shablykin; Oleksandr Stashkevych; Kateryna Sahun; Artur Rassokhin; Iryna Sadkova; Dmytro Lesyk; Anna Anisiforova; Yuliia Holota; Petro Borysko; Iryna Bodenchuk; Nataliya M Voloshchuk; Pavel K Mykhailiuk

doi:10.1002/anie.202319831

2-Oxabicyclo[2.1.1]hexanes: Synthesis, Properties, and Validation as Bioisosteres of ortho- and meta-Benzenes

Angew Chem Int Ed Engl. 2024 May 6;63(19):e202319831. doi: 10.1002/anie.202319831. Epub 2024 Apr 3.

Authors

Affiliations

¹ Enamine Ltd, Winston Churchill Str. 78, 02094, Kyiv, Ukraine.
² V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry NAS of Ukraine, Academician Kukhar Str. 1, 02094, Kyiv, Ukraine.
³ Taras Shevchenko National University of Kyiv, Chemistry Department, Volodymyrska Str. 64, 01601, Kyiv, Ukraine.
⁴ Bienta, Winston Churchill Str. 78, 02094, Kyiv, Ukraine.
⁵ National University of Life and Environmental Sciences of Ukraine, V. F. Peresypkin Department of Phytopathology, Heroyiv Oborony Str. 15, 03041, Kyiv, Ukraine.

PMID: 38465464
DOI: 10.1002/anie.202319831

Abstract

We have developed a general and practical approach towards 2-oxabicyclo[2.1.1]hexanes with two and three exit vectors via an iodocyclization reaction. The obtained compounds have been easily converted into the corresponding building blocks for use in medicinal chemistry. 2-Oxabicyclo[2.1.1]hexanes have been incorporated into the structure of five drugs and three agrochemicals, and validated biologically as bioisosteres of ortho- and meta-benzenes.

Keywords: 2-oxabicyclo[2.1.1]hexane; agrochemistry; bioisostere; cyclobutane; medicinal chemistry.

Grants and funding

101000893/H2020 European Research Council