Novel syntheses of cis and trans isomers of combretastatin A-4.
| dc.contributor.author | Gaukroger, Keira | |
| dc.contributor.author | Hadfield, John A | |
| dc.contributor.author | Hepworth, Lucy A | |
| dc.contributor.author | Lawrence, Nicholas J | |
| dc.contributor.author | McGown, Alan T | |
| dc.date.accessioned | 2009-11-06T11:34:34Z | |
| dc.date.available | 2009-11-06T11:34:34Z | |
| dc.date.issued | 2001-11-30 | |
| dc.identifier.citation | Novel syntheses of cis and trans isomers of combretastatin A-4. 2001, 66 (24):8135-8 J. Org. Chem. | en |
| dc.identifier.issn | 0022-3263 | |
| dc.identifier.pmid | 11722216 | |
| dc.identifier.doi | 10.1021/jo015959z | |
| dc.identifier.uri | http://hdl.handle.net/10541/85532 | |
| dc.description.abstract | A high-yielding, two-step stereoselective synthesis of the anticancer drug (Z)-combretastatin A-4 (1) has been devised. The method uses the Perkin condensation of 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxybenzaldehyde followed by decarboxylation of the cinnamic acid intermediate using copper and quinoline. The iodine-catalyzed isomerization of the Z isomer 1 results in complete conversion to the E isomer. The Suzuki cross-coupling of an aryl boronic acid and vinyl bromide has also been successfully employed to produce both Z and E isomers of combretastatin A-4 stereoselectively. Both methods are far superior to the current five-step Wittig synthesis in which both isomers are produced nonstereoselectively. | |
| dc.language.iso | en | en |
| dc.subject.mesh | Antineoplastic Agents, Phytogenic | |
| dc.subject.mesh | Stereoisomerism | |
| dc.subject.mesh | Stilbenes | |
| dc.subject.mesh | Structure-Activity Relationship | |
| dc.title | Novel syntheses of cis and trans isomers of combretastatin A-4. | en |
| dc.type | Article | en |
| dc.contributor.department | CRC Drug Development Group and CRC Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, U.K. | en |
| dc.identifier.journal | The Journal of Organic Chemistry | en |
| html.description.abstract | A high-yielding, two-step stereoselective synthesis of the anticancer drug (Z)-combretastatin A-4 (1) has been devised. The method uses the Perkin condensation of 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxybenzaldehyde followed by decarboxylation of the cinnamic acid intermediate using copper and quinoline. The iodine-catalyzed isomerization of the Z isomer 1 results in complete conversion to the E isomer. The Suzuki cross-coupling of an aryl boronic acid and vinyl bromide has also been successfully employed to produce both Z and E isomers of combretastatin A-4 stereoselectively. Both methods are far superior to the current five-step Wittig synthesis in which both isomers are produced nonstereoselectively. |