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

• Published in: Journal of the American Chemical Society 2002-06, Vol.124 (25), p.7405-7410
• Main Authors: HOYE, Thomas R., AYYAD, Seif-Eldin N., EKLOV, Brian M., HASHISH, Nadia E., SHIER, W. Thomas, EL SAYED, Khalid A., HAMANN, Mark T.
• Format: Article
• Language: English
• Subjects: Actins - antagonists & inhibitors; Actins - metabolism; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Bridged Bicyclo Compounds, Heterocyclic - isolation & purification; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Chemistry; Exact sciences and technology; Herpesvirus 1, Human - drug effects; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Medical sciences; Mice; Molecular Conformation; Nuclear Magnetic Resonance, Biomolecular - methods; Organic chemistry; Pharmacology. Drug treatments; Porifera - chemistry; Preparations and properties; Stereoisomerism; Thiazoles - chemistry; Thiazoles - isolation & purification; Thiazoles - pharmacology; Thiazolidines; Tumor Cells, Cultured
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja025734l

The title compound, 16-epi-latrunculin B (3), has been isolated from the sponge Negombata magnifica collected from the Red Sea near Hurghada, Egypt. This new natural product was determined to be an epimer of latrunculin B (1), which was found in the same sponge collection. The structure of 3 was initially deduced from proton and carbon NMR chemical shift trends and proton-proton nuclear Overhauser effect experiments. The cytotoxicity (murine tumor and normal cell lines) and antiviral (HSV-1) properties of 3 and 1 were determined. A computational study applicable to this class of stereochemical problems was then investigated. Specifically, the complete set of vicinal and allylic coupling constants was calculated for each of the four diastereomers whose configurations differed at C(8) and C(16). These computed J's were then compared with the experimental J values (28 in number) determined for 1 and 3. This analysis resulted in the same assignment of relative configuration for compound 3 reached using the more classical methods. 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 0.57 and 0.53 Hz, respectively. This strategy represents a general, powerful, and readily adoptable tool for determining the relative configuration of complex molecules.