Stereochemical elucidation and total synthesis of dihydropacidamycin D, a semisynthetic pacidamycin. |
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Authors: | C G Boojamra R C Lemoine J C Lee R Léger K A Stein N G Vernier A Magon O Lomovskaya P K Martin S Chamberland M D Lee S J Hecker V J Lee |
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Institution: | Microcide Pharmaceuticals, Inc., 850 Maude Avenue, Mountain View, California 94043, USA. |
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Abstract: | Hydrogenation of the C(4') exocyclic olefin of the pacidamycins has been shown to produce a series of semisynthetic compounds, the dihydropacidamycins, with antimicrobial activity similar to that of the natural products. Elucidation of stereochemistry in the pacidamycins has been completed through a campaign of natural product degradation experiments in combination with the total synthesis of the lowest-molecular weight dihydropacidamycin, dihydropacidamycin D. The stereochemical identities of the tryptophan and two alanine residues contained in pacidamycin D have been shown to be of the natural (S) configuration, and the unique 3-methylamino-2-aminobutyric acid contained in this series of antibiotics has been shown to be of the (2S,3S) configuration. Finally, the stereochemistry obtained by hydrogenation of the C(4')-C(5') exocyclic olefin has been shown to be (R) at the C(4') nucleoside site. |
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