Diastereoselective Synthesis of Camptothecin‐like Scaffolds: Construction of a New Class of Pseudo‐natural Products

Abstract

The discovery of novel small molecules endowed with high 3Dcontent remains a powerful tool for interrogating underrepresented biological space. To this end, the pseudo-natural products (pseudo-NP) strategy has become one of the most important tools to deliver biologically significant chemical probes. In this article, we describe the development of a new class of pseudo-NP collection, through connecting tryptamines with a furanose derivative followed by subjecting the product from this operation to a ring distortion strategy that led to diastereoselective synthesis of camptothecin-like compounds. This process is driven by a cascade that unites Pictet-Spengler reaction with Michael addition reaction, followed by oxidativering enlargement and subsequent transannular aldol cyclization delivering camptothecin-like architectures. The obtained diastereoselectivity was verified using density functional theory (DFT) calculations.