Toward Computing Relative Configurations: 16-epi-Latrunculin B, a New Stereoisomer of the Actin Polymerization Inhibitor Latrunculin B

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• 作者：Thomas R. Hoye ; Seif-Eldin N. Ayyad ; Brian M. Eklov ; Nadia E. Hashish ; W. Thomas Shier ; Khalid A. El Sayed ; and Mark T. Hamann
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：June 26, 2002
• 年：2002
• 卷：124
• 期：25
• 页码：7405 - 7410
• 全文大小：93K
• 年卷期：v.124,no.25(June 26, 2002)
• ISSN：1520-5126

文摘

The title compound, 16-epi-latrunculin B (3), has been isolated from the sponge Negombatamagnifica collected from the Red Sea near Hurghada, Egypt. This new natural product was determined tobe an epimer of latrunculin B (1), which was found in the same sponge collection. The structure of 3 wasinitially deduced from proton and carbon NMR chemical shift trends and proton-proton nuclear Overhausereffect experiments. The cytotoxicity (murine tumor and normal cell lines) and antiviral (HSV-1) propertiesof 3 and 1 were determined. A computational study applicable to this class of stereochemical problemswas then investigated. Specifically, the complete set of vicinal and allylic coupling constants was calculatedfor each of the four diastereomers whose configurations differed at C(8) and C(16). These computed J'swere then compared with the experimental J values (28 in number) determined for 1 and 3. This analysisresulted in the same assignment of relative configuration for compound 3 reached using the more classicalmethods. The validity of the method is established by the fact that the 28 computed coupling constants for(known) 1 and (newly determined) 3 varied from the experimental J values with an average of just 0.57and 0.53 Hz, respectively. This strategy represents a general, powerful, and readily adoptable tool fordetermining the relative configuration of complex molecules.