The most dramatic example of the power of DOS to
generate novel chemical diversity is the recent report by
Morton et al. of the synthesis of a 96-membered library based
on 84 distinct molecular scaffolds.184 Astonishingly, 65% of
the scaffolds in this library are novel. When the skeletal
diversity of the library was assessed by Waldmann’s
hierarchical scheme,170,171 the resulting scaffold tree was very
similar to Waldmann’s analysis of natural products. Morton
et al. report no biological data for the library, but the “natural
product-likeness” should allow access to large regions of
biologically relevant chemical space