Browsing by Author "Keyes, Robert F."

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    The biosynthesis of ravidomycin
    Keyes, Robert F. (Virginia Tech, 1989-07-01)
    Ravidomycin is a yellow antitumor antibiotic produced by Streptomyces ravidus. Ravidomycin shows strong antitumor activity against P388 lymphocytic leukemia, the colon 38 tumor, and the CD8Fl mammary tumor. It is also very active against Gram positive bacteria. Biosynthetic studies have shown that the aglycone unit comes from the folding of a polyketide chain with the vinyl unit arising from propionic acid. Since this vinyl functionality is believed to playa role in the antitumor activity of the antibiotic, it is of interest to elucidate the stereochemical selectivity in its formation from propionic acid. The synthesis of (R) and (S)-L2-²H₁ j propionate, incorporation of the labelled material, and chemical analysis of the resulting antibiotic was be used to determine the stereochemistry of formation of the vinyl side chain. It was found that propionate was incorporated with ravidomycin with stereospecific loss of the 2-(pro-R)-proton.
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    Structure elucidation and studies relating to the synthesis of plasmalopentaene-12
    Keyes, Robert F. (Virginia Tech, 1992-11-20)
    The glycerol enol ether, fecapentaene-12, is a direct acting fecal mutagen that is formed in the lower portion of the gastrointestional tract by anaerobic bacteria. The biological precursor to fecapentaene-12 is a natural product of mammalian origin whose role in the etiology of colon cancer is unknown. Preliminary evidence indicated that the precursor may be a plasmalogen with an intact pentaenol ether moiety. Further structural studies by means of degradative methods and chromatographic techniques enabled the structure of the precursor to be elucidated. Based on the structure of the precursor, the name plasmalopentaene-12 was coined. Synthetic methodology was developed for obtaining synthetic plasmalopentaene12. This was necessary in order to confirm the structure and to determine the precursor's biological role. The synthetic methodology proceeded through a novel "acyl migration" which enables the highly labile pentaenol ether to be generated late in the synthesis. Model studies indicated that this was a feasible pathway. It was also determined that this methodology may be highly adaptable to the synthesis of other plasmalogens and may also provide a new synthetic route to fecapentaene-12.