Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors
<p dir="ltr">We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double C-C/C-O arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal...
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2025
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| _version_ | 1864513552164847616 |
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| author | Raed M. Al-Zoubi (2037490) |
| author2 | Walid K. Al-Jammal (8345346) Mohanad Shkoor (3768385) Abdulilah D. Bani-Yaseen (17917721) Abbas Khan (5141000) Abdelali Agouni (181926) Robert McDonald (1228902) |
| author2_role | author author author author author author |
| author_facet | Raed M. Al-Zoubi (2037490) Walid K. Al-Jammal (8345346) Mohanad Shkoor (3768385) Abdulilah D. Bani-Yaseen (17917721) Abbas Khan (5141000) Abdelali Agouni (181926) Robert McDonald (1228902) |
| author_role | author |
| dc.creator.none.fl_str_mv | Raed M. Al-Zoubi (2037490) Walid K. Al-Jammal (8345346) Mohanad Shkoor (3768385) Abdulilah D. Bani-Yaseen (17917721) Abbas Khan (5141000) Abdelali Agouni (181926) Robert McDonald (1228902) |
| dc.date.none.fl_str_mv | 2025-01-21T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.jorganchem.2025.123526 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Regioselective_Domino_C_C_C_O_Arylation_of_1_2_3-Triiodobenzenes_and_1_3-Diketones_Synthesis_and_In_Silico_Evaluation_of_7-Iodobenzo_i_b_i_furan_as_Potential_ALK_Inhibitors/28254236 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Chemical sciences Organic chemistry benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |
| dc.title.none.fl_str_mv | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double C-C/C-O arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most reactive and least sterically hindered. The O-arylation reactions were selectively performed with the more reactive carbonyl group. This domino process demonstrated excellent substrate tolerance. Under optimized conditions, the reaction of electron-deficient 1,2,3-triiodoarenes with dicarbonyl compounds afforded the highest isolated yields. Furthermore, the designed novel compounds were screened against ALK, revealing that among the 17 tested, ALK-9p, ALK-9b, ALK-9n, and ALK-9m exhibited the best docking scores using the extra-precision docking method. Molecular simulations of these compounds with ALK confirmed their stable binding behavior, compact topology, and minimal residue flexibility. Finally, binding free energy calculations using MM/PBSA and MM/GBSA methods further validated the pharmacological potential of these shortlisted hits as ALK inhibitors. These results demand prompt experimental validation to determine the promising clinical applications of these compounds in the management of cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Organometallic Chemistry<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jorganchem.2025.123526" target="_blank">https://dx.doi.org/10.1016/j.jorganchem.2025.123526</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_f9a657bd776443218d4e78553d10194b |
| identifier_str_mv | 10.1016/j.jorganchem.2025.123526 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/28254236 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK InhibitorsRaed M. Al-Zoubi (2037490)Walid K. Al-Jammal (8345346)Mohanad Shkoor (3768385)Abdulilah D. Bani-Yaseen (17917721)Abbas Khan (5141000)Abdelali Agouni (181926)Robert McDonald (1228902)Biomedical and clinical sciencesPharmacology and pharmaceutical sciencesChemical sciencesOrganic chemistrybenzofuranIodinationArylationC-C couplingC-O couplingSubstituent effectRegioselectivity<p dir="ltr">We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double C-C/C-O arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most reactive and least sterically hindered. The O-arylation reactions were selectively performed with the more reactive carbonyl group. This domino process demonstrated excellent substrate tolerance. Under optimized conditions, the reaction of electron-deficient 1,2,3-triiodoarenes with dicarbonyl compounds afforded the highest isolated yields. Furthermore, the designed novel compounds were screened against ALK, revealing that among the 17 tested, ALK-9p, ALK-9b, ALK-9n, and ALK-9m exhibited the best docking scores using the extra-precision docking method. Molecular simulations of these compounds with ALK confirmed their stable binding behavior, compact topology, and minimal residue flexibility. Finally, binding free energy calculations using MM/PBSA and MM/GBSA methods further validated the pharmacological potential of these shortlisted hits as ALK inhibitors. These results demand prompt experimental validation to determine the promising clinical applications of these compounds in the management of cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Organometallic Chemistry<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jorganchem.2025.123526" target="_blank">https://dx.doi.org/10.1016/j.jorganchem.2025.123526</a></p>2025-01-21T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.jorganchem.2025.123526https://figshare.com/articles/journal_contribution/Regioselective_Domino_C_C_C_O_Arylation_of_1_2_3-Triiodobenzenes_and_1_3-Diketones_Synthesis_and_In_Silico_Evaluation_of_7-Iodobenzo_i_b_i_furan_as_Potential_ALK_Inhibitors/28254236CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/282542362025-01-21T06:00:00Z |
| spellingShingle | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors Raed M. Al-Zoubi (2037490) Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Chemical sciences Organic chemistry benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |
| status_str | publishedVersion |
| title | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| title_full | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| title_fullStr | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| title_full_unstemmed | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| title_short | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| title_sort | Regioselective Domino C–C/C–O Arylation of 1,2,3-Triiodobenzenes and 1,3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo[<i>b</i>]furan as Potential ALK Inhibitors |
| topic | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Chemical sciences Organic chemistry benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |