Natural Product Scaffolds of Value in Medicinal Chemistry
The utility of privileged natural product structures as “starting points” for medicinal chemistry syntheses is demonstrated using as models the arabinose-containing nucleosides that has led to the massive armamentarium of antiviral and antitumor agents now in use as human drugs. This example is then followed by discussions of alkaloids of varying structural classes, demonstrating how base molecules can be modified, plus more recent work that demonstrates how relatively complex tricyclic structures can be used to derive scaffolds that have utility as both pharmacological leads and as probes. This chapter continues with examples of simple, but frequently unrecognized “bioactive building blocks”, the diketopiperazines, that can lead to syntheses of very complicated drugs. Finally, a discussion of the ansamycins and the rapamycins is used to show the interplay between biosynthesis and chemical syntheses in the search for novel antitumor agents from these naturally occurring structures.