Metal-Free Traceless Directing Group-Assisted Cascade Cyclisation of 2-Alkynylquinazolinones for the Synthesis of Enpyrroloquinazolinones and Their Anticancer Activity
Abstract
Pyrroloquinazolinones, representing the pharmacological scaffold of the natural product Luotonin A, exhibit significant biological activities. Distinguishing from metal-catalysed methodologies, this study delineates a metal-and photocatalystfree strategy for the synthesis of enpyrroloquinazolinone derivatives via a cascade Michael addition-cyclisation-denitrative aromatisation, involving 2-alkynyl quinazolinones and nitroalkenes, which renders the nitro group into a traceless directing group. The resultant enpyrroloquinazolinone analogues underwent systematic evaluation for their anticancer efficacy and potential to activate caspases 3/7 against A549 (NSCLC) and SW480 (colorectal) cancer cell lines. Furthermore, molecular modelling indicates that these enpyrroloquinazolinones possess substantial potential as effective inhibitors of topoisomerase I, providing a promising foundation for the continued development of topoisomerase I inhibitors for therapeutic interventions.
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BibTeX
@misc{wu2026metalfree,
title = {{Metal-Free Traceless Directing Group-Assisted Cascade Cyclisation of 2-Alkynylquinazolinones for the Synthesis of Enpyrroloquinazolinones and Their Anticancer Activity}},
author = {Han-Kui Wu and Ling Wang and Anjana Patel and William Midgley and Mustapha Musa and Ehmke Pohl and Steven Shnyder and Na Wu},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009983/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009983/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Metal-Free Traceless Directing Group-Assisted Cascade Cyclisation of 2-Alkynylquinazolinones for the Synthesis of Enpyrroloquinazolinones and Their Anticancer Activity
AU - Han-Kui Wu
AU - Ling Wang
AU - Anjana Patel
AU - William Midgley
AU - Mustapha Musa
AU - Ehmke Pohl
AU - Steven Shnyder
AU - Na Wu
PY - 2026
DA - 2026/10/06
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009983/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009983/v1
AB - Pyrroloquinazolinones, representing the pharmacological scaffold of the natural product Luotonin A, exhibit significant biological activities. Distinguishing from metal-catalysed methodologies, this study delineates a metal-and photocatalystfree strategy for the synthesis of enpyrroloquinazolinone derivatives via a cascade Michael addition-cyclisation-denitrative aromatisation, involving 2-alkynyl quinazolinones and nitroalkenes, which renders the nitro group into a traceless directing group. The resultant enpyrroloquinazolinone analogues underwent systematic evaluation for their anticancer efficacy and potential to activate caspases 3/7 against A549 (NSCLC) and SW480 (colorectal) cancer cell lines. Furthermore, molecular modelling indicates that these enpyrroloquinazolinones possess substantial potential as effective inhibitors of topoisomerase I, providing a promising foundation for the continued development of topoisomerase I inhibitors for therapeutic interventions.
ER -