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Updated: Mar 29, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
A novel C,D-spirodioxene taxoid synthesized through an unexpected Pd-mediated ring cyclization
Shao-Rong Wang1, Pedro A Sánchez-Murcia2, Federico Gago2
1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Road, Beijing 100050, China. wfang@imm.ac.cn.
Abstract:
A novel C,D-spirodioxene taxoid (6) was prepared from paclitaxel (1a), with the key steps including an unexpected Pd-mediated ring cyclization. The anti-tubulin activity of 6 was decreased relative to that of 1a and a previously reported C,D-spirolactone taxane (5). These observations could be rationalized on the basis of molecular modeling results. To the best of our knowledge, this is the first example indicating that 1,4-dioxenes can be synthesized from a mono-allyl vicinal diol through a Wacker-type cyclization. This strategy may be applicable to the synthesis of other C,D-spiro taxoids.
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The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.

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