Synthesis, reactions and structure–activity relationships of 1-hydroxyspiro[2.5]cyclooct-4-en-3-ones: Illudin analogs with in vitro cytotoxic activity

1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones—analogs of natural illudines—were prepared in good yields by cyclization of 1,3-dicarbonyl dianions or 1,3-bis-silyl enol ethers (‘masked dianions’) with 1,1-diacylcyclopropanes. Several spirocyclopropanes showed a significant antiproliferative activity agains...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2006-07, Vol.14 (14), p.4694-4703
Main Authors: Bose, Gopal, Bracht, Karin, Bednarski, Patrick J., Lalk, Michael, Langer, Peter
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Proliferation - drug effects
Cyclopropanes
Cytotoxicity
General aspects
HL-60 Cells
Humans
Illudins
In Vitro Techniques
Medical sciences
Pharmacology. Drug treatments
Sesquiterpenes - chemistry
Sesquiterpenes - pharmacology
Spiro compounds
Spiro Compounds - chemical synthesis
Spiro Compounds - chemistry
Spiro Compounds - pharmacology
Structure-Activity Relationship
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Summary:1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones—analogs of natural illudines—were prepared in good yields by cyclization of 1,3-dicarbonyl dianions or 1,3-bis-silyl enol ethers (‘masked dianions’) with 1,1-diacylcyclopropanes. Several spirocyclopropanes showed a significant antiproliferative activity against human leukemia HL60 cells in vitro. 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones represent highly reactive precursors of unstable spiro[5.2]cycloocta-4,7-dien-6-ones and reactions with a number of nucleophiles were studied.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2006.03.037