Citation: Xiaojuan Chen, Yao Zhu, Muhammad Suleman, Ranjit Murmu, Hai-Hua Lu, Zhiyuan Chen. Natural product synthesis facilitated by the deuterium isotope effects (DIE)[J]. Chinese Chemical Letters, ;2026, 37(9): 112510. doi: 10.1016/j.cclet.2026.112510 shu

Natural product synthesis facilitated by the deuterium isotope effects (DIE)

Xiaojuan Chen ^{a, 1} ,
Yao Zhu ^{b, 1} ,
Muhammad Suleman ^a ,
Ranjit Murmu ^b ,
Hai-Hua Lu ^{b, c, *,} ,
Zhiyuan Chen ^{a, *,}

a.
School of Medicine, Hangzhou City University, Hangzhou 310015, China
b.
Zhejiang Key Laboratory of Precise Synthesis of Functional Molecules, Department of Chemistry, and Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China
c.
Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China

luhaihua@westlake.edu.cn

chenzy@hzcu.edu.cn

Received Date: 30 October 2025
Revised Date: 3 February 2026
Accepted Date: 8 February 2026
Available Online: 9 February 2026

Figures(12)

When a deuterium atom (²H or D) replaces a hydrogen atom (¹H) in a reactant molecule, the observed change in the rate (kinetic isotope effect, KIE) or equilibrium (equilibrium isotope effect, EIE) of a chemical reaction is known as a deuterium isotope effect (DIE). Because deuterium is twice as heavy as hydrogen, its zero-point energies (ZPEs), which are the lowest vibrational energies that a bond may have, differ significantly. Due to the obvious advantages of deuterium isotope effects (DIE) in total synthesis and mounting importance of deuterated drugs in pharmaceutical industry, development of synthetic routes to these deuterium-based active drugs via DIE is a challenging and important task. The primary goal of this mini-REVIEW is to demonstrate the novel uses of the DIE effect by placing the D atom at specific locations on drug molecules. This has been shown to serve as a "removable blocking group" to enhance yields and selectivity, while suppressing side reactions in the crucial stages of the complete synthesis of certain drug molecules. This review may be served as a perspective or guide for future study as well as inspire further innovative advancements in the field of total synthesis, and stimulate their applications in the related mechanistic studies.
- Deuterium,
- Isotope effect,
- Natural product,
- DIE,
- Kinetic isotope effect
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