Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products

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

Key words

spiro compounds - total synthesis - cycloaddition - Michael addition - palladium - natural products

Publication History

Received: 15 December 2020

Accepted after revision: 01 February 2021

Accepted Manuscript online:
01 February 2021

Article published online:
24 February 2021

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