Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine

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...

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Bibliographic Details
Published in:	Journal of natural products (Washington, D.C.) Vol. 69; no. 1; pp. 7 - 13
Main Authors:	Pettit, G.R, Eastham, S.A, Melody, N, Orr, B, Herald, D.L, McGregor, J, Knight, J.C, Doubek, D.L, Pettit, G.R. III, Garner, L.C
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society of Pharmacognosy 2006 Glendale, AZ American Chemical Society
Subjects:	7-deoxy-trans-dihydronarciclasine 7-deoxynarciclasine Amaryllidaceae Alkaloids Animals Antineoplastic agents Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - isolation & purification Antineoplastic Agents, Phytogenic - pharmacology Biological and medical sciences chemical structure crystal structure Crystallography, X-Ray Drug Screening Assays, Antitumor General aspects General pharmacology Humans Hymenocallis Hymenocallis littoralis isoquinolines Isoquinolines - chemistry Isoquinolines - isolation & purification Isoquinolines - pharmacology Leukemia P388 Medical sciences medicinal plants Mice Molecular Structure Narcissus - chemistry Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Plants, Medicinal - chemistry Stereoisomerism Structure-Activity Relationship structure-activity relationships traditional medicine Antineoplastic agent Monocotyledones Lactam P388-Leukemia Cytotoxicity Medicinal plant Alkaloid Structure activity relation Angiospermae Aromatic compound Secondary alcohol Chemical synthesis Tumor cell Oxygen nitrogen heterocycle Human Pharmacognosy Rodentia Tetracyclic compound X ray diffraction In vitro Vertebrata Mammalia Cell line Mouse Animal Plant origin Isolation Spermatophyta Amaryllidaceae Triol Structural analysis Crystalline structure
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Summary:	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 microg/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.
Bibliography:	http://pubs.acs.org/journals/jnprdf/index.html ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0163-3864 1520-6025
DOI:	10.1021/np058068l