Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-trans-Dihydronarciclasine,1
| Autor: | George R. Pettit, Stephen A. Eastham, Noeleen Melody, Brian Orr, Delbert L. Herald, Jane McGregor, John C. Knight, Dennis L. Doubek, Lynnette C. Garner, Joy A. Bell |
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| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
Silylation Chemistry Stereochemistry Organic Chemistry Narciclasine Pharmaceutical Science Stereoisomerism Pancratistatin Chemical synthesis Analytical Chemistry chemistry.chemical_compound Complementary and alternative medicine Drug Discovery Lactam Molecular Medicine Amine gas treating Triol |
| Zdroj: | Journal of Natural Products. 69:7-13 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/np058068l |
| Popis: | As an extension of structure-activity relationship studies of pancratistatin (1), various techniques were first evaluated for separating the mixtures of 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a) isolated from Hymenocallis littoralis. An efficient solution for that otherwise difficult separation then allowed the lactam carbonyl group of protected (4c and 5c) alcohols 2b and 3a to be reduced employing lithium aluminum hydride. Cleavage (TBAF followed by H2SO4) of the silyl ester/acetonide protected 6a gave amine 8. X-ray crystal structure determinations were employed to confirm the structures of 3,4-acetonide-5-aza-6-deoxynarciclasine (6b), 5-aza-6-deoxynarciclasine (8a), and 5-aza-6-deoxy-trans-dihydronarciclasine (9a, 9b). Against the murine P388 lymphocytic leukemia and a panel of human cancer cell lines, the parent natural products, 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a), were found to generally be more cancer cell growth inhibitory (GI50 0.1 to |
| Databáze: | OpenAIRE |
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