A modular synthesis of annonaceous acetogenins
| Autor: | Mikell Paige, James A. Marshall, Frederick Valeriote, Arnaud Piettre |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Allylic rearrangement
Stereochemistry Diol Sonogashira coupling Aldehyde Chemical synthesis Catalysis chemistry.chemical_compound Lactones X-Ray Diffraction Tumor Cells Cultured Humans Furans Nuclear Magnetic Resonance Biomolecular Butenolide chemistry.chemical_classification Molecular Structure Chemistry Organic Chemistry Stereoisomerism Antineoplastic Agents Phytogenic Enantiopure drug Acetogenin Colonic Neoplasms Indicators and Reagents Drug Screening Assays Antitumor |
| Zdroj: | The Journal of organic chemistry. 68(5) |
| ISSN: | 0022-3263 |
| Popis: | A synthesis of four Annonaceous acetogenins, asiminocin, asimicin, asimin, and bullanin, by a modular approach from seven fundamental subunits, A-G, is described. The approach employs a central core aldehyde segment, C, to which are appended an aliphatic terminus, A or B, a spacer subunit, D or E, and a butenolide terminus, F or G. Coupling of the A, B, D, and E segments to the core aldehyde unit is effected by highly diastereoselective additions of enantiopure allylic indium or tin reagents. The butenolide termini are attached to the ACD, BCE, or BCD intermediates by means of a Sonogashira coupling. The design of the core, spacer, and termini subunits is such that any of the C30, C10, or C4 natural acetogenins or stereoisomers thereof could be prepared. IC50 values for the four aforementioned acetogenins against H-116 human colon cancer cells were found to be in the 10(-3) to 10(-4) microM range. The IC90 activities were ca. 10(-3) microM for asimicin and asimin but only 0.1-1 microM for bullanin and asiminocin. |
| Databáze: | OpenAIRE |
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