Natural products in combinatorial chemistry: an andrographolide-based library

Abstract

The generation of a natural-product-based library starting from andrographolide is described. Utilizing andrographolide itself in parallel solution-phase synthesis leads to a 360-membered library. The initial transformation of the starting material via ozonolysis is followed by the conversion into a suitable template by introduction of a thiazole moiety. Subsequent decoration at two points of diversity yields the desired natural product derivatives. The selection of actually synthesized compounds is based on a virtually generated library and the assessment of its members with respect to physicochemical parameters, thus ensuring pharmacological relevance of the compounds.