? Skeletal diveristy is one of the key descriptors in determining structural diversity of small molecules. Generating skeletal diversity by combinatorics, however, is not straight forward. The goal of this proposed research is to develope a modular approach with which complex and skeletally distinct molecules can be combinatorially assembled from different structural modules in a common reaction theme. Small molecule libraries will be constructed to test the viability of this approach. Specifically, a structural module composed of different dipolarophiles will be coupled with another structural module built of a variety of structurally distinct isomunchnones by [3+2] cycloadditions. Application of additional diversity-generating processes will further expand library diversity. The assembly of this library will showcase the viability of this modular approach in generating skeletal diversity and provide additional small molecule entities that help to achieve the goal of chemical genomics. ? ?
