青蒿素及相关天然产物的非酶生物合成机制：量子化学研究。

IF 5.3 2区化学 Q1 CHEMISTRY, MEDICINAL

Journal of Chemical Information and Modeling Pub Date : 2025-04-13 DOI:10.1021/acs.jcim.5c00034

Maocai Yan,Xinfa Ding,Likun Zhao,Xudong Lü,Hai-Yan He,Shuai Fan,Zhaoyong Yang

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引用次数: 0

摘要

青蒿素是一种重要的抗疟天然药物，其倍半萜结构中含有独特的内过氧化物桥。青蒿素生物合成的最后阶段涉及双氢青蒿酸（DHAA）转化为青蒿素，其具体机制尚不清楚。本工作在前人实验研究的基础上，探讨了DHAA非酶转化为青蒿素的可能机制，并利用量子化学计算确定了化学上最合理的反应途径。该途径的速率决定步骤是酸催化烯醇被三重态O2氧化，总自由能垒为22.5 kcal/mol。该途径还产生副产物二氢青蒿素B和二氢表青蒿素B。此外，本文还讨论了青蒿中21种天然产物的非酶促形成机制。这些结果为青蒿素及其相关天然产物的生物合成过程提供了基础知识，也为青蒿素的半合成和结构修饰研究提供了重要参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Mechanistic Insights into the Nonenzymatic Biosynthesis of Artemisinin and Related Natural Products: A Quantum Chemical Study.

Artemisinin (Qinghaosu) is an important antimalaria natural medicine containing a unique endoperoxide bridge in its sesquiterpene structure. The last phase of artemisinin biosynthesis involves conversion of dihydroartemisinic acid (DHAA) to artemisinin, and the detailed mechanism remains unclear. Based on previous experimental studies, this work investigated the possible mechanism of nonenzymatic conversion of DHAA to artemisinin and identified the most chemically plausible reaction pathway using quantum chemical computations. The rate-determining step in this pathway is acid-catalyzed oxidation of the enol by triplet O2, with an overall free energy barrier of 22.5 kcal/mol. This pathway also gives byproducts dihydroarteannuin B and dihydro-epi-arteannuin B. In addition, the nonenzymatic formation mechanism of 21 natural products from Artemisia annua was discussed in this work. These results provide fundamental knowledge of the biosynthetic processes of artemisinin and related natural products, as well as important references for semisynthesis and structural modification studies of artemisinin.

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来源期刊

Journal of Chemical Information and Modeling 化学-化学综合

CiteScore

9.80

自引率

10.70%

发文量

529

审稿时长

1.4 months

期刊介绍： The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery. Astute chemists, computer scientists, and information specialists look to this monthly’s insightful research studies, programming innovations, and software reviews to keep current with advances in this integral, multidisciplinary field. As a subscriber you’ll stay abreast of database search systems, use of graph theory in chemical problems, substructure search systems, pattern recognition and clustering, analysis of chemical and physical data, molecular modeling, graphics and natural language interfaces, bibliometric and citation analysis, and synthesis design and reactions databases.