Journal of Natural Products 2003-01-01

Antineoplastic agents 500. Narcistatin.

George R Pettit, Noeleen Melody, Michael Simpson, Michael Thompson, Delbert L Herald, John C Knight

Index: J. Nat. Prod. 66(1) , 92-6, (2003)

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Abstract

An efficient procedure was found for synthetic conversion of the sparingly soluble anticancer isocarbostyril narciclasine (1), a component of various Narcissus species, to a cyclic phosphate designated narcistatin (3b). The reaction between narciclasine, tetrabutylammonium dihydrogen phosphate, and p-toluenesulfonic acid in pyridine afforded pyridinium narcistatin (3a) in reasonable yields. Transformation of narcistatin (3a) to, for example, the water-soluble prodrug sodium narcistatin (3d) was easily achieved by cation exchange chromatography. Narcistatin (3b) and 15 salt derivatives were evaluated against a panel of human cancer cell lines, and the range (0.1-0.01) of GI(50) values in micro g/mL was found to parallel that shown by the parent narciclasine.