Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-trans-Dihydronarciclasine Export

@article{citeulike:3475032, abstract = {Abstract: 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 <0.01 g/mL) than the compounds with structural modifications such as amine 8 by a factor of 10 or more. The trans ring juncture of isocarbostyril 3a proved to be an important modification of narciclasine (2a) for improving cancer cell growth inhibition in this series.}, address = {Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404}, author = {Pettit, G. R. and Eastham, S. A. and Melody, N. and Orr, B. and Herald, D. L. and Mcgregor, J. and Knight, J. C. and Doubek, D. L. and Pettit, G. R. and Garner, L. C. and Bell, J. A.}, citeulike-article-id = {3475032}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/np058068l}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/np058068l}, day = {27}, doi = {10.1021/np058068l}, journal = {J. Nat. Prod.}, keywords = {isocarbostyril, narciclasine}, month = {January}, number = {1}, pages = {7--13}, posted-at = {2008-11-03 14:03:52}, priority = {2}, title = {Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-trans-Dihydronarciclasine}, url = {http://dx.doi.org/10.1021/np058068l}, volume = {69}, year = {2006} }

TY - JOUR ID - citeulike:3475032 L3 - citeulike-article-id:3475032 N2 - Abstract: 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 <0.01 g/mL) than the compounds with structural modifications such as amine 8 by a factor of 10 or more. The trans ring juncture of isocarbostyril 3a proved to be an important modification of narciclasine (2a) for improving cancer cell growth inhibition in this series. IS - 1 JF - J. Nat. Prod. AD - Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404 EP - 13 TI - Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-trans-Dihydronarciclasine VL - 69 SP - 7 KW - isocarbostyril KW - narciclasine AU - Pettit, GR AU - Eastham, SA AU - Melody, N AU - Orr, B AU - Herald, DL AU - Mcgregor, J AU - Knight, JC AU - Doubek, DL AU - Pettit, GR AU - Garner, LC AU - Bell, JA PY - 2006/01/27/ UR - http://dx.doi.org/10.1021/np058068l ER -