{"id":8226,"date":"2025-03-03T13:38:07","date_gmt":"2025-03-03T12:38:07","guid":{"rendered":"https:\/\/www.iadchem.uam.es\/?p=8226"},"modified":"2025-03-03T16:47:22","modified_gmt":"2025-03-03T15:47:22","slug":"enantioselective-photocatalytic-synthesis-of-bicyclo2-1-1hexanes-as-ortho-disubstituted-benzene-bioisosteres-with-improved-biological-activity","status":"publish","type":"post","link":"https:\/\/www.iadchem.uam.es\/?p=8226","title":{"rendered":"Enantioselective Photocatalytic Synthesis of Bicyclo[2.1.1]hexanes as Ortho-disubstituted Benzene Bioisosteres with improved Biological Activity"},"content":{"rendered":"

\"\"<\/a><\/p>\n

Title:<\/strong> Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity
\nAuthors:<\/strong> Pablo Garrido-Garc\u00eda, Irene Quir\u00f3s, Paula Mil\u00e1n-Rois, Silvia Ortega-Guti\u00e9rrez, Mar Mart\u00edn-Fontecha, Luis A. Campos, \u00c1lvaro Somoza, Israel Fern\u00e1ndez, Thomas Rigotti and Mariola Tortosa
\nJournal:<\/strong> Nature Chemistry
\nYear:<\/strong> 2025
\nDOI:<\/strong> 10.1038\/s41557-025-01746-7<\/a><\/p>\n

1<\/span>,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 because they are saturated bioisosteres of ortho-substituted phenyl rings. Here we have developed a Lewis-acid-catalysed [2\u2009+\u20092] photocycloaddition to obtain these motifs as enantioenriched scaffolds, providing an efficient approach for their incorporation in a variety of drug analogues. Retention of the biological activity of the bicyclo[2.1.1]hexane-containing analogues in the specific proteins targeted by the original drugs has confirmed the suitability of this moiety to serve as a bioisostere of ortho-substituted phenyl rings. Moreover, we have studied the potential of the different enantiomers of the drug analogues to selectively induce cytotoxicity in a panel of tumour cell lines, observing markedly differential effects for the two enantiomers and a substantial improvement over the corresponding sp2-based drugs. This showcases that the control of the absolute configuration and tridimensionality of the drug analogue has a large impact on its biological properties.<\/p>\n","protected":false},"excerpt":{"rendered":"

Title: Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity Authors: Pablo Garrido-Garc\u00eda, Irene Quir\u00f3s, Paula Mil\u00e1n-Rois, Silvia Ortega-Guti\u00e9rrez, Mar Mart\u00edn-Fontecha, Luis A. Campos, \u00c1lvaro Somoza, Israel Fern\u00e1ndez, Thomas Rigotti and Mariola Tortosa Journal: Nature Chemistry Year: 2025 DOI: 10.1038\/s41557-025-01746-7 1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are…<\/p>\n","protected":false},"author":3,"featured_media":8241,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,5],"tags":[254,275,276],"class_list":["post-8226","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-articles","category-research-highlights","tag-biological-activity","tag-enantioselective","tag-photocatalytic-synthesis","entry"],"yoast_head":"\nEnantioselective Photocatalytic Synthesis of Bicyclo[2.1.1]hexanes as Ortho-disubstituted Benzene Bioisosteres with improved Biological Activity - IAdChem - Institute for Advanced Research in Chemical Sciences<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.iadchem.uam.es\/?p=8226\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Enantioselective Photocatalytic Synthesis of Bicyclo[2.1.1]hexanes as Ortho-disubstituted Benzene Bioisosteres with improved Biological Activity - IAdChem - Institute for Advanced Research in Chemical Sciences\" \/>\n<meta property=\"og:description\" content=\"Title: Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity Authors: Pablo Garrido-Garc\u00eda, Irene Quir\u00f3s, Paula Mil\u00e1n-Rois, Silvia Ortega-Guti\u00e9rrez, Mar Mart\u00edn-Fontecha, Luis A. Campos, \u00c1lvaro Somoza, Israel Fern\u00e1ndez, Thomas Rigotti and Mariola Tortosa Journal: Nature Chemistry Year: 2025 DOI: 10.1038\/s41557-025-01746-7 1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are…\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.iadchem.uam.es\/?p=8226\" \/>\n<meta property=\"og:site_name\" content=\"IAdChem - Institute for Advanced Research in Chemical Sciences\" \/>\n<meta property=\"article:published_time\" content=\"2025-03-03T12:38:07+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-03-03T15:47:22+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.iadchem.uam.es\/wp-content\/uploads\/2025\/02\/Graphical-abstract-Garrido-Garcia-et-al.-2025-840x450-1.png\" \/>\n\t<meta property=\"og:image:width\" content=\"840\" \/>\n\t<meta property=\"og:image:height\" content=\"450\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"IADCHEM Editor\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"IADCHEM Editor\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226\"},\"author\":{\"name\":\"IADCHEM Editor\",\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/#\\\/schema\\\/person\\\/acff178c6fdfa63f2a2f3082da68abf2\"},\"headline\":\"Enantioselective Photocatalytic Synthesis of Bicyclo[2.1.1]hexanes as Ortho-disubstituted Benzene Bioisosteres with improved Biological Activity\",\"datePublished\":\"2025-03-03T12:38:07+00:00\",\"dateModified\":\"2025-03-03T15:47:22+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226\"},\"wordCount\":224,\"image\":{\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.iadchem.uam.es\\\/wp-content\\\/uploads\\\/2025\\\/02\\\/Graphical-abstract-Garrido-Garcia-et-al.-2025-840x450-1.png\",\"keywords\":[\"Biological activity\",\"Enantioselective\",\"Photocatalytic synthesis\"],\"articleSection\":[\"Articles\",\"Research Highlights\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226\",\"url\":\"https:\\\/\\\/www.iadchem.uam.es\\\/?p=8226\",\"name\":\"Enantioselective Photocatalytic Synthesis of Bicyclo[2.1.1]hexanes as Ortho-disubstituted Benzene Bioisosteres with improved Biological Activity - 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