MOVING BEYOND NATURAL PRODUCTS

MANY PROGRAMS IN PLACE IN industry and academia make compounds based on natural products or designed to be like natural products. They utilize three ways to go beyond natural products: building around natural product scaffolds with combinatorial chemistry techniques, assembling natural-product-like compounds through diversity-oriented synthetic routes, and creating new natural product derivatives based on paths made accessible by target-oriented synthesis. All can advance drug discovery. Combinatorial libraries based on natural product scaffolds—core structures around which analogs and derivatives are produced—are not new. For example, combinatorial chemistry around scaffolds of tubulin inhibitors is paving the way for new anticancer drugs. Libraries of paclitaxel analogs have yielded four second-generation drug candidates in clinical trials. Those of curacin A have brought out viable candidates for drug development. And in the anti-infectives area, compounds active against vancomycin-resistant bacteria h...