{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:50:51Z","timestamp":1775749851812,"version":"3.50.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22302048"],"award-info":[{"award-number":["22302048"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204231"],"award-info":[{"award-number":["82204231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22502041"],"award-info":[{"award-number":["22502041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Chem"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immunomodulatory imide drugs are widely used in the treatment of multiple myeloma, yet existing production routes are often lengthy and inefficient, underscoring the need for more efficient and broadly applicable synthetic strategies. Herein, we report the synthesis of lenalidomide (63% overall yield) and pomalidomide (62% overall yield) using an integrated continuous flow platform with residence times of 42\u2009minutes and 52\u2009minutes, respectively. Additionally, both continuous flow processes are readily conducted on gram scale. Compared with known methods, our approach improves solvent compatibility across the reaction sequence and enables uninterrupted continuous flow synthesis of both drugs. The products are obtained without the need for column chromatography, and both immunomodulatory imide drugs (IMiDs) can be accessed from a common intermediate through our developed route. Furthermore, we explore the synthesis of CRBN ligand-linkers under continuous flow, affording a series of derivatives with diverse properties in yields exceeding 90%.<\/jats:p>","DOI":"10.1038\/s42004-026-01956-1","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T17:34:42Z","timestamp":1772559282000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accelerated synthesis of immunomodulatory imide drugs and their derivatives via continuous flow chemistry"],"prefix":"10.1038","volume":"9","author":[{"given":"Tianyi","family":"Hou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junrong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1443-3453","authenticated-orcid":false,"given":"Yuxiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8904-5050","authenticated-orcid":false,"given":"Hengzhi","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6734-3388","authenticated-orcid":false,"given":"Fen-Er","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"1956_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/S0140-6736(62)91248-5","volume":"279","author":"AL Speirs","year":"1962","unstructured":"Speirs, A. L. Thalidomide and congenital abnormalities. Lancet 279, 303\u2013305 (1962).","journal-title":"Lancet"},{"key":"1956_CR2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/leu.2009.236","volume":"24","author":"H Quach","year":"2010","unstructured":"Quach, H. et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 24, 22\u201332 (2010).","journal-title":"Leukemia"},{"key":"1956_CR3","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1056\/NEJM199911183412102","volume":"341","author":"S Singhal","year":"1999","unstructured":"Singhal, S., Eddlemon, P. & Dhodapkar, M. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341, 1565\u20131571 (1999).","journal-title":"N. Engl. J. Med."},{"key":"1956_CR4","doi-asserted-by":"publisher","first-page":"4771","DOI":"10.1182\/blood-2011-05-356063","volume":"118","author":"YX Zhu","year":"2011","unstructured":"Zhu, Y. X. et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 118, 4771\u20134779 (2011).","journal-title":"Blood"},{"key":"1956_CR5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","volume":"21","author":"M B\u00e9k\u00e9s","year":"2022","unstructured":"B\u00e9k\u00e9s, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov. 21, 181\u2013200 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1956_CR6","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.chembiol.2015.05.009","volume":"22","author":"J Lu","year":"2015","unstructured":"Lu, J. et al. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem. Biol. 22, 755\u2013763 (2015).","journal-title":"Chem. Biol."},{"key":"1956_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ddtec.2019.01.002","volume":"31","author":"M Pettersson","year":"2019","unstructured":"Pettersson, M. & Crews, C. M. PROteolysis TArgeting Chimeras (PROTACs) \u2014 past, present and future. Drug Discov. Today Technol. 31, 15\u201327 (2019).","journal-title":"Drug Discov. Today Technol."},{"key":"1956_CR8","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1158\/1535-7163.MCT-23-0747","volume":"23","author":"KA Rutherford","year":"2024","unstructured":"Rutherford, K. A. & McManus, K. J. PROTACs: current and future potential as a precision medicine strategy to combat cancer. Mol. Cancer Ther. 23, 454\u2013463 (2024).","journal-title":"Mol. Cancer Ther."},{"key":"1956_CR9","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1126\/science.aab1433","volume":"348","author":"GE Winter","year":"2015","unstructured":"Winter, G. E. et al. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 1376\u20131381 (2015).","journal-title":"Science"},{"key":"1956_CR10","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1126\/science.1177319","volume":"327","author":"T Ito","year":"2010","unstructured":"Ito, T. et al. Identification of a primary target of thalidomide teratogenicity. Science 327, 1345\u20131350 (2010).","journal-title":"Science"},{"key":"1956_CR11","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1126\/science.1244917","volume":"343","author":"G Lu","year":"2014","unstructured":"Lu, G. et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343, 305\u2013309 (2014).","journal-title":"Science"},{"key":"1956_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nature13527","volume":"512","author":"ES Fischer","year":"2014","unstructured":"Fischer, E. S. et al. Structure of the DDB1\u2013CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49\u201353 (2014).","journal-title":"Nature"},{"key":"1956_CR13","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1021\/acsmedchemlett.9b00425","volume":"10","author":"PP Chamberlain","year":"2019","unstructured":"Chamberlain, P. P. et al. Evolution of cereblon-mediated protein degradation as a therapeutic modality. ACS Med. Chem. Lett. 10, 1592\u20131602 (2019).","journal-title":"ACS Med. Chem. Lett."},{"key":"1956_CR14","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1021\/acschembio.7b00485","volume":"12","author":"P Ottis","year":"2017","unstructured":"Ottis, P. et al. Assessing different E3 ligases for small molecule lnduced protein ubiquitination and degradation. ACS Chem. Biol. 12, 2570\u20132578 (2017).","journal-title":"ACS Chem. Biol."},{"key":"1956_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52604-y","volume":"15","author":"Q Wang","year":"2024","unstructured":"Wang, Q. et al. Prodrug activation by 4,4\u2019-bipyridine-mediated aromatic nitro reduction. Nat. Commun. 15, 8643 (2024).","journal-title":"Nat. Commun."},{"key":"1956_CR16","doi-asserted-by":"publisher","first-page":"153152","DOI":"10.1016\/j.tetlet.2021.153152","volume":"74","author":"H Wang","year":"2021","unstructured":"Wang, H. et al. One-pot method to construct isoindolinones and its application to the synthesis of DWP205109 and intermediate of Lenalidomide. Tetrahedron Lett 74, 153152 (2021).","journal-title":"Tetrahedron Lett"},{"key":"1956_CR17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s11164-022-04869-5","volume":"49","author":"L Ouni","year":"2023","unstructured":"Ouni, L., Ramazani, A. & Aghahosseini, H. Experimental design optimization for the synthesis of lenalidomide nitro precursor. Res. Chem. Intermed. 49, 329\u2013339 (2023).","journal-title":"Res. Chem. Intermed."},{"key":"1956_CR18","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1080\/00397911.2016.1189574","volume":"46","author":"D Huang","year":"2016","unstructured":"Huang, D. et al. New synthesis route for the preparation of pomalidomide. Synth. Commun. 46, 1343\u20131348 (2016).","journal-title":"Synth. Commun."},{"key":"1956_CR19","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s41981-022-00223-3","volume":"12","author":"M Ivanova","year":"2022","unstructured":"Ivanova, M., Legros, J., Poisson, T. & Jubault, P. A multi-step continuous flow synthesis of pomalidomide. J. Flow Chem. 12, 383\u2013387 (2022).","journal-title":"J. Flow Chem."},{"key":"1956_CR20","doi-asserted-by":"publisher","first-page":"5382","DOI":"10.1039\/D3OB00328K","volume":"21","author":"R Qi","year":"2023","unstructured":"Qi, R. et al. Solvent-promoted photochemical carbonylation of benzylic C\u2013H bonds under iron catalysis. Org. Biomol. Chem. 21, 5382\u20135386 (2023).","journal-title":"Org. Biomol. Chem."},{"key":"1956_CR21","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1007\/s11094-013-0868-7","volume":"46","author":"AN Balaev","year":"2013","unstructured":"Balaev, A. N., Okhmanovich, K. A. & Fedorov, V. E. Alternative synthesis of lenalidomide. Pharm. Chem. J. 46, 676\u2013678 (2013).","journal-title":"Pharm. Chem. J."},{"key":"1956_CR22","doi-asserted-by":"publisher","first-page":"4075","DOI":"10.1016\/j.bmcl.2017.07.046","volume":"27","author":"S Hu","year":"2017","unstructured":"Hu, S., Yuan, L., Yan, H. & Li, Z. Design, synthesis and biological evaluation of Lenalidomide derivatives as tumor angiogenesis inhibitor. Bioorg. Med. Chem. Lett. 27, 4075\u20134081 (2017).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"1956_CR23","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s10593-015-1670-0","volume":"51","author":"Y Ponomaryov","year":"2015","unstructured":"Ponomaryov, Y. et al. Scalable and green process for the synthesis of anticancer drug lenalidomide. Chem. Heterocycl. Compd. 51, 133\u2013138 (2015).","journal-title":"Chem. Heterocycl. Compd."},{"key":"1956_CR24","doi-asserted-by":"publisher","first-page":"8042","DOI":"10.1021\/acs.jmedchem.1c00482","volume":"64","author":"TA Bemis","year":"2021","unstructured":"Bemis, T. A., La Clair, J. J. & Burkart, M. D. Unraveling the role of linker design in proteolysis targeting chimeras: miniperspective. J. Med. Chem. 64, 8042\u20138052 (2021).","journal-title":"J. Med. Chem."},{"key":"1956_CR25","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.1039\/D2CS00148A","volume":"51","author":"I Sosi\u010d","year":"2022","unstructured":"Sosi\u010d, I., Bricelj, A. & Steinebach, C. E3 ligase ligand chemistries: from building blocks to protein degraders. Chem. Soc. Rev. 51, 3487\u20133534 (2022).","journal-title":"Chem. Soc. Rev."},{"key":"1956_CR26","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/j.bmcl.2019.04.030","volume":"29","author":"SD Edmondson","year":"2019","unstructured":"Edmondson, S. D., Yang, B. & Fallan, C. Proteolysis targeting chimeras (PROTACs) in \u2018beyond rule-of-five\u2019 chemical space: recent progress and future challenges. Bioorg. Med. Chem. Lett. 29, 1555\u20131564 (2019).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"1956_CR27","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.3390\/biom12091257","volume":"12","author":"M Xiao","year":"2022","unstructured":"Xiao, M., Zhao, J., Wang, Q., Liu, J. & Ma, L. Recent advances of degradation technologies based on PROTAC mechanism. Biomolecules 12, 1257 (2022).","journal-title":"Biomolecules"},{"key":"1956_CR28","doi-asserted-by":"publisher","first-page":"4838","DOI":"10.1039\/D3CS01127E","volume":"53","author":"R Stevens","year":"2024","unstructured":"Stevens, R. et al. Innovative, combinatorial and high-throughput approaches to degrader synthesis. Chem. Soc. Rev. 53, 4838\u20134861 (2024).","journal-title":"Chem. Soc. Rev."},{"key":"1956_CR29","doi-asserted-by":"publisher","first-page":"3838","DOI":"10.1021\/acs.orglett.9b01326","volume":"21","author":"X Qiu","year":"2019","unstructured":"Qiu, X. et al. Chemoselective synthesis of lenalidomide-based PROTAC library using alkylation reaction. Org. Lett. 21, 3838\u20133841 (2019).","journal-title":"Org. Lett."},{"key":"1956_CR30","doi-asserted-by":"publisher","first-page":"115228","DOI":"10.1016\/j.bmc.2019.115228","volume":"28","author":"F Zhang","year":"2020","unstructured":"Zhang, F. et al. Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide\/pomalidomide. Bioorg. Med. Chem. 28, 115228 (2020).","journal-title":"Bioorg. Med. Chem."},{"key":"1956_CR31","doi-asserted-by":"publisher","first-page":"4519","DOI":"10.1039\/D0SC05442A","volume":"12","author":"DK Brownsey","year":"2021","unstructured":"Brownsey, D. K., Rowley, B. C., Gorobets, E., Gelfand, B. S. & Derksen, D. J. Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries. Chem. Sci. 12, 4519\u20134525 (2021).","journal-title":"Chem. Sci."},{"key":"1956_CR32","doi-asserted-by":"publisher","first-page":"5814","DOI":"10.1039\/D5CC00611B","volume":"61","author":"Y Jiang","year":"2025","unstructured":"Jiang, Y. et al. Rapid synthesis of pomalidomide-conjugates in minutes via temperature elevation and delayed feeding. Chem. Commun. 61, 5814\u20135817 (2025).","journal-title":"Chem. Commun."},{"key":"1956_CR33","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.eng.2023.01.016","volume":"32","author":"M Jiang","year":"2024","unstructured":"Jiang, M., Liu, M., Li, W., Xia, Y. & Chen, F.-E. An eight-step continuous-flow total synthesis of vitamin B1. Engineering 32, 226\u2013232 (2024).","journal-title":"Engineering"},{"key":"1956_CR34","first-page":"243","volume":"3","author":"L Wan","year":"2022","unstructured":"Wan, L. et al. Flow chemistry in the multi-step synthesis of natural products. Green Synth. Catal. 3, 243\u2013258 (2022).","journal-title":"Green Synth. Catal."},{"key":"1956_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56371-2","volume":"16","author":"Y Zhang","year":"2025","unstructured":"Zhang, Y. et al. Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach. Nat. Commun. 16, 1064 (2025).","journal-title":"Nat. Commun."},{"key":"1956_CR36","doi-asserted-by":"publisher","first-page":"107782","DOI":"10.1016\/j.cclet.2022.107782","volume":"34","author":"H Luo","year":"2023","unstructured":"Luo, H. et al. Recent advances in chemical fixation of CO2 based on flow chemistry. Chinese Chem. Lett. 34, 107782 (2023).","journal-title":"Chinese Chem. Lett."},{"key":"1956_CR37","first-page":"272","volume":"3","author":"XQ Ng","year":"2022","unstructured":"Ng, X. Q. et al. A green access to supported cinchona alkaloid amide catalysts for heterogeneous enantioselective allylsilylation of aldehydes and process intensity evaluation in batch and flow. Green Synth. Catal. 3, 272\u2013277 (2022).","journal-title":"Green Synth. Catal."},{"key":"1956_CR38","doi-asserted-by":"publisher","first-page":"107694","DOI":"10.1016\/j.cclet.2022.07.037","volume":"34","author":"J Ren","year":"2023","unstructured":"Ren, J. et al. Highly efficient synthesis and application of aryl diazonium salts via femtosecond laser-tailored 3D flow microfluidic chips. Chinese Chem. Lett. 34, 107694 (2023).","journal-title":"Chinese Chem. Lett."},{"key":"1956_CR39","doi-asserted-by":"publisher","first-page":"e161","DOI":"10.1055\/s-0043-1772252","volume":"05","author":"J-L Chen","year":"2023","unstructured":"Chen, J.-L. et al. Multistep synthesis of paracetamol in continuous flow. Pharmaceutical Fronts 05, e161\u2013e167 (2023).","journal-title":"Pharmaceutical Fronts"},{"key":"1956_CR40","doi-asserted-by":"publisher","first-page":"4230","DOI":"10.1039\/D3SC00992K","volume":"14","author":"L Capaldo","year":"2023","unstructured":"Capaldo, L., Wen, Z. & No\u00ebl, T. A field guide to flow chemistry for synthetic organic chemists. Chem. Sci. 14, 4230\u20134247 (2023).","journal-title":"Chem. Sci."},{"key":"1956_CR41","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s43586-025-00414-x","volume":"5","author":"SE Raby-Buck","year":"2025","unstructured":"Raby-Buck, S. E. et al. Continuous flow chemistry for molecular synthesis. Nat. Rev. Methods Primers 5, 44 (2025).","journal-title":"Nat. Rev. Methods Primers"},{"key":"1956_CR42","doi-asserted-by":"publisher","first-page":"4618","DOI":"10.1039\/D3SC06808K","volume":"15","author":"AI Alfano","year":"2024","unstructured":"Alfano, A. I., Garc\u00eda-Lacuna, J., Griffiths, O. M., Ley, S. V. & Baumann, M. Continuous flow synthesis enabling reaction discovery. Chem. Sci. 15, 4618\u20134630 (2024).","journal-title":"Chem. Sci."},{"key":"1956_CR43","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1039\/D0GC03883K","volume":"23","author":"AI Alfano","year":"2021","unstructured":"Alfano, A. I., Brindisi, M. & Lange, H. Flow synthesis approaches to privileged scaffolds \u2013 recent routes reviewed for green and sustainable aspects. Green Chem. 23, 2233\u20132292 (2021).","journal-title":"Green Chem."},{"key":"1956_CR44","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1080\/00102202.2025.2453901","volume":"198","author":"K Wang","year":"2026","unstructured":"Wang, K., Gao, W. & Jiang, H. Thermal decomposition and explosion characteristics of benzoyl peroxide: an experimental and kinetic modeling study. Combust. Sci. Technol. 198, 405\u2013423 (2026).","journal-title":"Combust. Sci. Technol."},{"key":"1956_CR45","doi-asserted-by":"publisher","first-page":"12355","DOI":"10.1007\/s10973-025-14485-1","volume":"150","author":"Q Ma","year":"2025","unstructured":"Ma, Q. et al. Experimental and kinetic studies on the thermal decomposition and explosion of azobisisobutyronitrile. J. Therm. Anal. Calorim. 150, 12355\u201312368 (2025).","journal-title":"J. Therm. Anal. Calorim."},{"key":"1956_CR46","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1021\/acs.chemrev.1c00332","volume":"122","author":"L Buglioni","year":"2022","unstructured":"Buglioni, L., Raymenants, F., Slattery, A., Zondag, S. D. A. & No\u00ebl, T. Technological lnnovations in photochemistry for organic synthesis: flow chemistry, high-throughput experimentation, scale-up, and photoelectrochemistry. Chem. Rev. 122, 2752\u20132906 (2022).","journal-title":"Chem. Rev."},{"key":"1956_CR47","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.trechm.2019.09.003","volume":"2","author":"C Sambiagio","year":"2020","unstructured":"Sambiagio, C. & No\u00ebl, T. Flow photochemistry: shine some light on those tubes!. Trends Chem. 2, 92\u2013106 (2020).","journal-title":"Trends Chem."},{"key":"1956_CR48","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1021\/acs.oprd.1c00240","volume":"26","author":"C Bottecchia","year":"2022","unstructured":"Bottecchia, C. et al. Manufacturing process development for belzutifan, part 2: a continuous flow visible-light-Induced benzylic bromination. Org. Process Res. Dev. 26, 516\u2013524 (2022).","journal-title":"Org. Process Res. Dev."},{"key":"1956_CR49","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1021\/jo402409k","volume":"79","author":"D Cantillo","year":"2014","unstructured":"Cantillo, D., De Frutos, O., Rincon, J. A., Mateos, C. & Kappe, C. O. A scalable procedure for light-Induced benzylic brominations in continuous flow. J. Org. Chem. 79, 223\u2013229 (2014).","journal-title":"J. Org. Chem."},{"key":"1956_CR50","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1021\/acs.oprd.3c00348","volume":"28","author":"C Pratley","year":"2024","unstructured":"Pratley, C. et al. Development of a horizontal dynamically mixed flow reactor for laboratory scale-up of photochemical Wohl\u2013Ziegler bromination. Org. Process Res. Dev. 28, 1725\u20131733 (2024).","journal-title":"Org. Process Res. Dev."},{"key":"1956_CR51","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s42004-024-01363-4","volume":"7","author":"P Xu","year":"2024","unstructured":"Xu, P. & Ma, C. Scalable deoxygenative alkynylation of alcohols via flow photochemistry. Commun. Chem. 7, 276 (2024).","journal-title":"Commun. Chem."},{"key":"1956_CR52","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.5012\/bkcs.2014.35.5.1337","volume":"35","author":"G Sun","year":"2014","unstructured":"Sun, G., Liu, X., Zhou, H., Liu, Z. & Mao, Z. Synthesis of hydroxylactams and esters derived from thalidomide and their antitumor activities. Bull. Korean Chem. Soc. 35, 1337\u20131342 (2014).","journal-title":"Bull. Korean Chem. Soc."},{"key":"1956_CR53","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41392-023-01647-6","volume":"8","author":"Z-Q Wang","year":"2023","unstructured":"Wang, Z.-Q. et al. Bromodomain and extraterminal (BET) proteins: biological functions, diseases and targeted therapy. Signal Transduct. Target. Ther. 8, 420 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"1956_CR54","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41401-023-01164-w","volume":"45","author":"C-Y Chiang","year":"2024","unstructured":"Chiang, C.-Y. et al. A novel selective ERK1\/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer. Acta Pharmacol. Sin. 45, 422\u2013435 (2024).","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Communications Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42004-026-01956-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42004-026-01956-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42004-026-01956-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:02:46Z","timestamp":1775746966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42004-026-01956-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1956"],"URL":"https:\/\/doi.org\/10.1038\/s42004-026-01956-1","relation":{},"ISSN":["2399-3669"],"issn-type":[{"value":"2399-3669","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"assertion":[{"value":"26 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"154"}}