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

George Pettit, Stephen A. Eastham, Noeleen Melody, Brian Orr, Delbert L. Herald, Jane McGregor, John C. Knight, Dennis L. Doubek, George R. Pettit, Lynnette C. Garner, Joy A. Bell

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 μg/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.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalJournal of Natural Products
Volume69
Issue number1
DOIs
StatePublished - Jan 2006

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Cell growth
Amines
amines
Lactams
cell growth
Hymenocallis
Biological Products
lactams
Lymphoid Leukemia
hydrides
Neoplasms
lymphocytic leukemia
Esters
lithium
Crystal structure
Cells
Alcohols
structure-activity relationships
Structure-Activity Relationship
Growth

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine. / Pettit, George; Eastham, Stephen A.; Melody, Noeleen; Orr, Brian; Herald, Delbert L.; McGregor, Jane; Knight, John C.; Doubek, Dennis L.; Pettit, George R.; Garner, Lynnette C.; Bell, Joy A.

In: Journal of Natural Products, Vol. 69, No. 1, 01.2006, p. 7-13.

Research output: Contribution to journalArticle

Pettit, G, Eastham, SA, Melody, N, Orr, B, Herald, DL, McGregor, J, Knight, JC, Doubek, DL, Pettit, GR, Garner, LC & Bell, JA 2006, 'Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine', Journal of Natural Products, vol. 69, no. 1, pp. 7-13. https://doi.org/10.1021/np058068l
Pettit, George ; Eastham, Stephen A. ; Melody, Noeleen ; Orr, Brian ; Herald, Delbert L. ; McGregor, Jane ; Knight, John C. ; Doubek, Dennis L. ; Pettit, George R. ; Garner, Lynnette C. ; Bell, Joy A. / Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine. In: Journal of Natural Products. 2006 ; Vol. 69, No. 1. pp. 7-13.
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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 μg/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.",
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T1 - Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine

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AU - Melody, Noeleen

AU - Orr, Brian

AU - Herald, Delbert L.

AU - McGregor, Jane

AU - Knight, John C.

AU - Doubek, Dennis L.

AU - Pettit, George R.

AU - Garner, Lynnette C.

AU - Bell, Joy A.

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