Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products
Michael P. Badart, Bill C. Hawkins
Abstract
Abstract The spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products. 1 Introduction 2 Cycloadditions 3 Palladium-Catalysed Coupling Reactions 4 Conjugate Additions 5 Imines, Aminals, and Hemiaminal Ethers 6 Mannich-Type Reactions 7 Oxidative Dearomatisation 8 Alkylation 9 Organometallic Additions 10 Conclusions