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Synthesis 2022; 54(24): 5540-5550
DOI: 10.1055/s-0042-1751361
paper

Protecting-Group-Free Synthesis of Novel Cannabinoid-Like 2,5-Dihydrobenzoxepines

Gia-Nam Nguyen 
a   Technical Biochemistry, Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany
b   MINDbioscience GmbH, Emil-Figge-Strasse 76a, 44227 Dortmund, Germany
,
Erin Noel Jordan
a   Technical Biochemistry, Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany
,
Oliver Kayser  ∗
a   Technical Biochemistry, Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany
› Author AffiliationsWe acknowledge the financial support from the German Federal Ministry of Education and Research in the program VIPplus for the project CannaCell (03VP06370).
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Abstract

An efficient synthesis of 2,5-dihydrobenzoxepine analogues was developed without using protecting groups. Regioselective allylation was optimized through a recent method utilizing magnesium dicarboxylates. Grubbs catalysts were applied to investigate ring-closing metathesis. The scope of the present route was extended to produce four analogues, which provided novel cannabinoid-like 2,5-dihydrobenzoxepines in sufficient quantities to permit in vitro assays on recombinant CB1/CB2 receptors. In vitro assays related to CB1/CB2 receptors did not indicate any activity.

Key words

2,5-dihydrobenzoxepine - radulanin A - benzoxepin cannabinoids - regioselective allylation - ring-closing metathesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751361.
  • Supporting Information


Publication History

Received: 27 June 2022

Accepted after revision: 21 July 2022

Article published online:
13 September 2022

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