Syntheses of Combretastatin A‐4 and related stilbenes by using aqueous conditions

Barnes, NG; Ahmed Mal Ullah, AA; Ragazzon, PA; Charafi, N; Hadfield, JA

Abstract

Combretastatin A‐4 (CA4) is a potent anti‐mitotic and vascular disrupting agent. Organic chemists have been working to optimize the synthesis of CA4 for the past 3 decades, with methods requiring hazardous solvents and harsh reaction conditions. Here, we report the synthesis of CA4 and a variety of stilbenes in an aqueous Wittig system. Potassium carbonate or lithium hydroxide were used as base in this Wittig reaction to give excellent yields of mixtures of E‐ and Z‐stilbenes. The synthesis of CA4 was achieved using tetrahydropyran (THP) or silyl protected phenolic aldehydes. The THP groups were removed using dilute acid whilst the silyl groups fortuitously fell off during work up.

Citation

Barnes, N., Ahmed Mal Ullah, A., Ragazzon, P., Charafi, N., & Hadfield, J. (2021). Syntheses of Combretastatin A‐4 and related stilbenes by using aqueous conditions. ChemistrySelect, 6(28), 7082-7086. https://doi.org/10.1002/slct.202101960

• Journal Article Type: Article
• Acceptance Date: Jul 19, 2021
• Publication Date: Jul 26, 2021
• Deposit Date: Jul 27, 2021
• Publicly Available Date: Jul 27, 2021
• Journal: ChemistrySelect
• Print ISSN: 2365-6549
• Publisher: Wiley
• Volume: 6
• Issue: 28
• Pages: 7082-7086
• DOI: https://doi.org/10.1002/slct.202101960
• Publisher URL: https://doi.org/10.1002/slct.202101960
• Related Public URLs: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2365-6549
• Additional Information: Additional Information : ** Article version: VoR ** From Wiley via Jisc Publications Router ** Licence for VoR version of this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: issn 2365-6549 **Article IDs: publisher-id: slct202101960 **History: published 27-07-2021; published 26-07-2021; accepted 19-07-2021; submitted 02-06-2021; Funders : Engineering and Physical Sciences Research Council (EPSRC);Kidscan Children's Cancer Research, UK; Grant Number: 1817912; Grant Number: KGR14