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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2010-4-30
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pubmed:abstractText |
A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (approximately 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (approximately 100 nM).
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1520-6904
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
7
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2820-35
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:20392070-Antineoplastic Agents,
pubmed-meshheading:20392070-Benzoquinones,
pubmed-meshheading:20392070-Cell Line, Tumor,
pubmed-meshheading:20392070-HSP90 Heat-Shock Proteins,
pubmed-meshheading:20392070-Humans,
pubmed-meshheading:20392070-Lactams, Macrocyclic,
pubmed-meshheading:20392070-Molecular Structure,
pubmed-meshheading:20392070-Phenols,
pubmed-meshheading:20392070-Quinones,
pubmed-meshheading:20392070-Structure-Activity Relationship
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pubmed:year |
2010
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