Novel Topologically Complex Scaffold Derived from Alkaloid Haemanthamine

Abstract

The generation of natural product-like compound collections has become an important area of research due to low hit rates found with synthetic high-throughput libraries. One method of generating compounds occupying the areas of chemical space not accessible to synthetic planar heterocyclic structures is the utilization of natural products as starting materials. In the current work, using a ring-closing iodoalkoxylation reaction, alkaloid haemanthamine was transformed into a unique structural framework possessing an intricate ring system and a large number of stereocenters. The structure of the new compound was confirmed with an X-ray analysis. A small number of derivatives of this new compound were synthesized as a demonstration of the possibility of generating a large natural product-like compound collection based on the new structural framework.

Keywords

• natural product-like
• diversity-oriented synthesis
• haemanthamine
• haemanthidine
• iodoalkoxylation
• biological activity