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Yang et al. Chem Synth 2023;3:7 Chemical Synthesis
DOI: 10.20517/cs.2022.38

Review Open Access

Recent advances in organocatalytic cascade

reactions for enantioselective synthesis of chiral
spirolactone skeletons

1,*
2
2
1,3
Jun Yang , Bo-Wen Pan , Lin Chen , Ying Zhou , Xiong-Li Liu 1,*
1
National & Local Joint Engineering Research Center for the Exploition of Homology Resources of Southwest Medicine and Food,
Guizhou University, Guiyang 550025, Guizhou, China.
2
College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou, China.
3
Department of Pharmacy, Zunyi Medical And Pharmaceutical College, Zunyi 563006, Guizhou, China.
*Correspondence to: Prof. Lin Chen, National & Local Joint Engineering Research Center for the Exploition of Homology
Resources of Southwest Medicine and Food, Guizhou University, Jiaxiu South Road, Guiyang 550025, Guizhou, China. E-mail:
lchen5@gzu.edu.cn; Prof. Xiong-Li Liu, National & Local Joint Engineering Research Center for the Exploition of Homology
Resources of Southwest Medicine and Food, Guizhou University, Jiaxiu South Road, Guiyang 550025, Guizhou, China. E-mail:
xlliu1@gzu.edu.cn
How to cite this article: Yang J, Pan BW, Chen L, Zhou Y, Liu XL. Recent advances in organocatalytic cascade reactions for
enantioselective synthesis of chiral spirolactone skeletons. Chem Synth 2023;3:7. https://dx.doi.org/10.20517/cs.2022.38
Received: 4 Dec 2022 First Decision: 4 Jan 2023 Revised: 14 Jan 2023 Accepted: 29 Jan 2023 Published: 8 Feb 2023

Academic Editor: Feng Shi Copy Editor: Ke-Cui Yang Production Editor: Ke-Cui Yang

Abstract
Chiral spirolactones, including spiropropyllactones, spirobutyrolactones, and spirovalerolactones, are important
heterocyclic frameworks that attracted the attention of organic and medicinal chemists because these motifs
constitute the core structure of several natural products and bioactive molecules. The absolute configuration and
the substituents on the fully substituted spirocyclic stereocenter of the lactone can potentially enhance specificity
for ligand-protein binding and enhance bioavailability, potency, and metabolic stability. So, intensive attention from
chemists has been paid to the synthetic methods leading to such prominent structural motifs. The synthetic
methods can be divided into two main classes. The first approach takes advantage of the presence of the existing
lactone structure and focuses on its functionalization. The second approach is the lactone framework constructed
from various precursors in a direct spirolactonization reaction. In this review, for convenience in reading, the recent
advances in the synthesis of spirolactones are summarized and discussed according to the two major
organocatalytic asymmetric synthetic routes: (i) using the lactone-related frameworks as building blocks; and (ii)
direct spirolactonization reaction using various reagents. This review also describes both the mechanisms and
related transformations, and gives some insights into challenging issues in this research field, which will enlighten
the future development of this field.

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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