The objective of this project is to construct two fully synthetic active sites (1.1') designed to catalyze bond formation. Each active site, which is an organic molecule with a molecular weight greater than 1,000, contains substrate binding sites and a catalytic unit and is intended to exhibit catalysis, selectivity and turnover. The two active sites will employ transition state stabilization to achieve their catalytic activity. The synthesis of 1/1: which takes advantage of the commercial availability of large subunits, should afford 1/1' by a highly convergent route in which the longest synthetic sequence is only about ten steps. The proposal outlines the strategies reflected in the design of 1/1' and details how individual elements in the concept of 1/1' (including substrate binding, transition state stabilization, proton transfer, flexibility vs rigidity, product release, turnover and selectively) will be incorporated, measured and optimized.
