Syntheses of Combretastatin A-4 and Related Stilbenes by Using Aqueous Conditions

Barnes, Natalie G.; Ahmed Mal Ullah, Amjed A.; Ragazzon, Patricia A.; Charafi, Nadia; Hadfield, John A.

doi:10.1002/slct.202101960

Syntheses of Combretastatin A-4 and Related Stilbenes by Using Aqueous Conditions

Barnes, Natalie G.; Ahmed Mal Ullah, Amjed A.; Ragazzon, Patricia A.; Charafi, Nadia; Hadfield, John A.

Authors

Natalie G. Barnes

Amjed A. Ahmed Mal Ullah

Patricia Ragazzon p.ragazzon@keele.ac.uk

Nadia Charafi

John A. Hadfield

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.

Journal Article Type	Article
Acceptance Date	Jul 19, 2021
Online Publication Date	Jul 26, 2021
Publication Date	Jul 27, 2021
Publicly Available Date	May 30, 2023
Journal	ChemistrySelect
Print ISSN	2365-6549
Publisher	Wiley
Volume	6
Issue	28
Pages	7082 - 7086
DOI	https://doi.org/10.1002/slct.202101960
Keywords	General Chemistry
Publisher URL	https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/slct.202101960