Potential anticancer agents XXXI. N-demethylation of fagaronine.

Abstract

Fusion of fagaronine (1) afforded N-demethyl fagaronine (2) and two minor desmethyl products. Through examination of spectral properties and derivatization, the structures were deduced to be 3, a tetramethoxy derivative, and 5, a derivative bearing a hydroxy (rather than a methoxy) group at position-8. Acetylation of 2 afforded a monoacetate derivative (4), and similarly, a diacetate (6) was produced from 5. Compounds 2-6 were substantially less cytotoxic than 1, as judged by KB or P-388 cell culture assays, supporting the functional importance of the quaternary nitrogen atom. The results obtained to date for fagaronine in tumor panel-testing are also presented, and the marginal cytotoxic activity demonstrated by compounds 5 and 6 against cultured P-388 cells is discussed in terms of mechanisms of action of the parent compound.

• Authors: M Arisawa, J M Pezzuto, C Bevelle, G A Cordell
• Journal: Journal of natural products (J Nat Prod) 1984 May-Jun Vol. 47 Issue 3 Pg. 453-8 ISSN: 0163-3864 [Print] United States
• PMID: 6481359 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Alkaloids
• Antineoplastic Agents, Phytogenic
• Benzophenanthridines
• Phenanthridines
• fagaronine

Topics

• Alkaloids
• Animals
• Antineoplastic Agents, Phytogenic (chemical synthesis)
• Benzophenanthridines
• Chemical Phenomena
• Chemistry
• Dealkylation
• Leukemia P388 (drug therapy)
• Magnetic Resonance Spectroscopy
• Mice
• Phenanthridines