Chapter 16 - Ring Transformations

Abstract

Noncyclic molecules can be cyclized, attached to, or included in ring systems. In medicinal chemistry three kinds of approaches are currently used. The first approach, the analogical approach, consists of ring-chain transformations, ring contractions or expansions, and various other ring transformations. The second strategy, called the disjunctive approach, aims at the progressive simplification of the original active principle (which is often a natural compound). The objective is to extract information about the minimal structure that is required for activity. Finally, the conjunctive approach is based on the creation or addition of supplementary rings. The objective is to constrain an originally flexible compound and to impose precise conformations and configurations. The preparation of such molecules is of prime importance in the exploration of ligand–receptor interaction and for molecular modeling studies. Molecular variations involving the study of homologous series or the application of the vinylogy concept induce relatively minor changes of the pharmacological profile and result in optimizing the potency. Modifying ring systems—ring-chain transformation, ring contractions and expansions, and reorganization of cyclic systems—represents a highly productive approach in the design of new drug analogs and in the exploration of the drug–receptor interactions.