Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as orthodisubstituted benzene bioisosteres with improved biological activity

03 October 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are becoming increasingly popular building blocks in medicinal chemistry since they are saturated bioisosteres of orthosubstituted phenyl rings. Here we have developed the first enantioselective catalytic strategy based on a Lewis acid-catalyzed [2+2] photocycloaddition to obtain these motifs as enantioenriched scaffolds, providing an efficient approach for their incorporation in a variety of drug analogues. The bioisostere-containing drugs have been evaluated in cancer cell viability studies, observing that in some cases the biological activity of the two enantiomers is highly different. This showcases that the control of the absolute configuration and tridimensionality of the drug analogue has a large impact on its bioactivity, highlighting the need for stereoselective methods towards the construction of the bicyclo[2.1.1]hexane core.


asymmetric catalysis


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.