Conformational Design Principles in Total Synthesis

Abstract

Conformation is one of the most fundamental concepts in organic chemistry for chemists to visualize a molecule as a three-dimensional object in addition to its constitution and configuration. Conformational factors significantly affect the physical properties, chemical reactivities, and biological activities of a molecule. The significance of conformational design has been generally recognized since its successful application in the total synthesis of complex natural products, such as vitamin B12 and erythronolide. Conformational analysis, especially intentional control of conformational preferences by conformational design, could play a critical role in the synthesis of complex organic molecules by guiding the formation of bonds, stereocenters, or rings. This Minireview highlights selected examples of conformational design in natural-product synthesis, with particular emphasis on the applications and new insights advanced in the last 20 years. The examples discussed herein are divided into three categories by structural features of the substrates: open-chain type, cyclohexane type, and medium- and large-ring type.

Keywords: C−H functionalization; conformational design; ring formation; stereochemistry; total synthesis.