Asymmetric synthesis of nature inspired drug scaffolds: Applications of pluripotent building blocks

Natural products encompass a wealth of structural diversity within defined, nonplanar scaffolds; however, there are well-documented hurdles to their use in screening campaigns because of their limited availability relative to the quantities needed for structure activity relationship (SAR) development and clinical trials.¹ Thus, the recent decade has witnessed an upsurge in the development of privileged strategies for the de novo construction of nature-inspired compounds.² One such strategy represents the use of a single pluripotent functional group that can be decorated through reactions with variety of reagents, thereby empowering the synthesis of skeletally diverse compound collections with high 3D-content.³ On the other side, multicomponent reactions (MCRs) hold a privileged position in diversity oriented synthesis (DOS), allowing the formation of many new bonds and bringing together more than two reactants in one-step. A particularly attractive DOS strategy, is a reaction that combines both strategies in one. Such a strategy should produce a large set of stereochemically diverse molecular scaffolds, not achievable by either strategy alone. In fact, the design and synthesis of a quality compound library containing a skeletally diverse scaffolds, whose members rapidly deliver new chemical probes active against multiple phenotypes, is paramount in drug discovery. In this context, within our group, we have developed several starting material- and MCR-based DOS approaches utilizing few pluripotent building blocks. Gratifyingly, the developed libraries offered potential biological activities on different disease states.

Author(s): Vunnam Srinivasulu

Abstract | PDF

Share This Article