Synthesis 2017; 49(11): 2361-2373
DOI: 10.1055/s-0036-1588783
short review
© Georg Thieme Verlag Stuttgart · New York

Transition-Metal-Catalyzed Synthesis of Spirolactones

Yelena Mostinski, David Lankri, Dmitry Tsvelikhovsky*
  • Institute for Drug Research, Division of Medicinal Chemistry, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel   Email: dmitryt@ekmd.huji.ac.il
Further Information

Publication History

Received: 08 March 2017

Accepted: 17 March 2017

Publication Date:
18 April 2017 (eFirst)

Abstract

Spiranoid lactone structures can frequently be observed as scaffold segments of various biochemical compounds and drugs of natural origin. Examples of these structures have been identified among terpenoids, alkaloids, steroids, carbohydrates, and many other natural products. Such a broad natural diversity and biological activity allows a wide spectrum of these systems to be attractive targets for synthetic and medicinal chemists. Covering a broad spectrum of recognized approaches toward the design of spirolactones established over the past several decades, this review focuses on transition-metal-catalyzed synthesis, which is the most prominent methodology reported to date.

1 Introduction

2 Patterned Approaches

2.1 Cyclocarbonylation

2.2 Hydroalkylation/Arylation of Hydroxy α,β-Acetylenic Esters

2.3 [2+2+2]-Cyclotrimerization: Rapid Access to Spirobenzofuranone Scaffolds

2.4 Cyclization of Allenoic Acids/Allenoates

2.5 Cycloisomerization–Oxidation of Homopropargyl Alcohols

2.6 Hydroalkoxylation of Alkynoic or Alkenoic Acids

2.7 C–H Carbonylation: Access to Spirobenzofuranone and Spiroisochromanone Derivatives

2.8 Alkylative Spirolactonization of α,β-Unsaturated Esters

2.9 Olefin Ring-Closing Metathesis

2.10 Reductive Opening of Epoxides

2.11 Intramolecular C–H Insertion

3 Nonpatterned Approaches

3.1 Azomethine Ylide Cycloaddition

3.2 Hydrohydroxyalkylation of Vicinal Diols

3.3 Photoredox Catalysis: C-Alkylation of Alcohols

3.4 Carbonylative Spirolactonization of Hydroxycyclopropanols

3.5 Copper-Catalyzed Alkylation of β-Keto Esters

4 Conclusion