Total synthesis and structure confirmation of the annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin a, and 5(R)-uvarigrandin a (narumicin I?).
A synthesis of the bistetrahydrofuran Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin A through application of a previously disclosed four-component modular approach is described in which extended core segments are coupled to a C4- or C5-hydroxy butenolide terminus. The butenolide termini segments were prepared from (S)- or (R)-malic acid. Spectral properties of synthetic 30(S)-hydroxybullatacin and uvarigrandin A, as well as their Mosher ester derivatives, were in close agreement to the reported values for the natural substances. The synthetic 5(R)-uvarigrandin A is possibly identical to narumicin I, but subtle differences in the reported NMR spectra prevented an unambiguous assessment of this point.
Marshall
James A
JA
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, USA.
Piettre
Arnaud
A
Paige
Mikell A
MA
Valeriote
Frederick
F
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003110:Colonic Neoplasms; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
C475946:30(S)-hydroxybullatacin; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007202:Indicators and Reagents; D007783:Lactones; C437401:uvarigrandin A; D015107:4-Butyrolactone