Examples of Natural Products or Analogs as Drugs

The initial hit isolated from the biomass, irrespective of source, is not necessarily the lead required for further development into a drug. It may be too insoluble, not potent enough, or be broadly rather than specifically active. Once the structure has been determined, then synthetic chemistry, involving both conventional and combinatorial methods, may be used in order to generate derivatives/analogs that have the more desirable characteristics of a potential drug. Several examples of these types of processes are shown in Section IV. 

Detailed analyses of active natural product skeletons have led to the identification of relatively simple key precursor molecules which form the building blocks for use in combinatorial synthetic schemes that have produced numbers of potent molecules, thereby enabling structure activity relationships to be probed. Thus, in the study of the structure-activity relationships of the epothilones, solid-phase synthesis of combinatorial libraries was used to probe regions of the molecule important to retention or improvement of activity.  

The use of an active natural product as the central scaffold in the combinatorial approach can also be applied to the generation of large numbers of analogs for structure-activity studies, the so-called parallel synthetic approach. This is embodied in the concept of privileged structures, originally proposed by Evans et and then advanced further by Nicolaou et and the Waldmann 

Angiotensin-converting enzyme inhibitors [captopril and derivatives) 

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