No abstract

The pyridoacridine natural products represent a large and growing class and serve here to illustrate the wealth of information that can be extracted by comparing natural products on the basis of structure and occurrence.

An extremely rapid, low cost, and environmentally friendly entry into the pyridoacridine family of alkaloids has been devised, as demonstrated here by the first total synthesis of styelsamine B (3) and its oxidation to the quinoneimine cystodytin J (4). The known reaction of cystodytin J with methanethiol makes this a formal synthesis of diplamine. [reaction: see text]

Five synthetic combinatorial libraries of 2,080 components each were screened as mixtures for inhibition of DNA binding to two transcription factors. Rapid, solution-phase synthesis coupled to a gel-shift assay led to the identification of two compounds active at a 5-to 10-M concentration level. The likely mode of inhibition is intercalation between DNA base pairs. The efficient deconvolution through sublibrary synthesis augurs well for the use of large mixtures of small, nonpeptide molecules in biological screens.