2.50
Hdl Handle:
http://hdl.handle.net/10541/85532
Title:
Novel syntheses of cis and trans isomers of combretastatin A-4.
Authors:
Gaukroger, Keira; Hadfield, John A; Hepworth, Lucy A; Lawrence, Nicholas J; McGown, Alan T
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.
Affiliation:
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.
Citation:
Novel syntheses of cis and trans isomers of combretastatin A-4. 2001, 66 (24):8135-8 J. Org. Chem.
Journal:
The Journal of Organic Chemistry
Issue Date:
30-Nov-2001
URI:
http://hdl.handle.net/10541/85532
DOI:
10.1021/jo015959z
PubMed ID:
11722216
Type:
Article
Language:
en
ISSN:
0022-3263
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGaukroger, Keiraen
dc.contributor.authorHadfield, John Aen
dc.contributor.authorHepworth, Lucy Aen
dc.contributor.authorLawrence, Nicholas Jen
dc.contributor.authorMcGown, Alan Ten
dc.date.accessioned2009-11-06T11:34:34Z-
dc.date.available2009-11-06T11:34:34Z-
dc.date.issued2001-11-30-
dc.identifier.citationNovel syntheses of cis and trans isomers of combretastatin A-4. 2001, 66 (24):8135-8 J. Org. Chem.en
dc.identifier.issn0022-3263-
dc.identifier.pmid11722216-
dc.identifier.doi10.1021/jo015959z-
dc.identifier.urihttp://hdl.handle.net/10541/85532-
dc.description.abstractA 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.en
dc.language.isoenen
dc.subject.meshAntineoplastic Agents, Phytogenic-
dc.subject.meshStereoisomerism-
dc.subject.meshStilbenes-
dc.subject.meshStructure-Activity Relationship-
dc.titleNovel syntheses of cis and trans isomers of combretastatin A-4.en
dc.typeArticleen
dc.contributor.departmentCRC 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.journalThe Journal of Organic Chemistryen

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