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Download fileA Modular Synthesis of Annonaceous Acetogenins
journal contribution
posted on 2003-02-08, 00:00 authored by James A. Marshall, Arnaud Piettre, Mikell A. Paige, Frederick ValerioteA 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 μM range. The IC90 activities were ca. 10-3 μM for asimicin and asimin but
only 0.1−1 μM for bullanin and asiminocin.
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diastereoselective additionsAnnonaceous Acetogeninstin reagentsAnnonaceous acetogeninscolon cancer cellsasiminaliphatic terminusasimicinasiminocinenantiopure allylic indiumIC 50 valuesapproachspacer subunitcore aldehyde segmentbutenolide terminuscore aldehyde unitACDBCEtermini subunitsE segmentsC 4butenolide terminiBCD intermediatesbullaninModular SynthesisIC 90 activities