莨菪碱的化学-酶法合成

doi:10. 3969 / j. issn. 2096-2266. 2026. 04. 004

大理大学学报 ›› 2026, Vol. 11 ›› Issue (4): 21-27.DOI: 10. 3969 / j. issn. 2096-2266. 2026. 04. 004

莨菪碱的化学-酶法合成

王雪倩1，田红畅2，3，段宝忠1，张　磊2，3*

（1.大理大学药学院，云南大理　671000； 2.海军军医大学药学院，上海　200433；
3.教育部真菌感染性疾病医药基础研究创新中心，上海　200433）

收稿日期:2026-02-10 修回日期:2026-02-24 出版日期:2026-04-15 发布日期:2026-05-19
通讯作者: 张磊，教授，博士，E-mail：leizhang100@163.com。
作者简介:王雪倩，硕士研究生，主要从事药品检验与质量控制研究。
基金资助:
国家自然科学基金项目（82504962；82225047；82170274）；教育部真菌感染性疾病医药基础研究创新中心开
放课题（YXX2024-KF02-02）；国家重点研发计划项目（2024YFC3506500；2024YFC3506400）；浙江省自然科
学基金项目（LZ24H280003）

Chemoenzymatic Synthesis of Hyoscyamine

Wang Xueqian¹, Tian Hongchang2,3, Duan Baozhong1, Zhang Lei2,3*

(1. College of Pharmacy, Dali University, Dali, Yunnan 671000, China; 2. School of Pharmacy, Naval Medical University, Shanghai
200433, China; 3. Innovation Center for Basic Medical Research on Fungal Infectious Diseases, Ministry of Education, Shanghai
200433, China)

Received:2026-02-10 Revised:2026-02-24 Online:2026-04-15 Published:2026-05-19

摘要/Abstract

摘要： 目的：建立一种基于化学-酶法策略的莨菪碱高效合成方法。方法：以乙酰基保护的2-苯基-1，3-丙二醇为起始原
料，通过猪胰脂肪酶（PPL）催化去对称化反应构建手性单醇中间体，随后在Fe（NO3）3/KCl 催化体系下氧化生成托品酸片
段；进一步经酰氯化与托品醇酯化反应构建关键酯键，并通过脱乙酰基处理得到目标产物L-莨菪碱。结果：PPL催化的去
对称化反应表现出良好的区域与立体选择性，通过后续氧化和酯化反应能够顺利获得目标产物。该合成路线共包含5个
步骤，总收率为53.6%。结论：所建立的化学-酶法协同合成策略实现了酶催化高选择性与化学转化效率的有效结合，为托
品烷类生物碱的绿色合成提供了新的研究思路。

关键词: 化学-酶法合成, 莨菪碱, 手性构建, 全合成

Abstract: Objective：To establish an efficient synthetic method for hyoscyamine based on a chemoenzymatic strategy. Methods:
Acetyl-protected 2-phenyl-1,3-propanediol was used as the starting material. A chiral monoalcohol intermediate was constructed
through porcine pancreatic lipase (PPL)-catalyzed desymmetrization, followed by oxidation in a Fe(NO₃)₃/KCl catalytic system to generate
the tropic acid fragment. The key ester bond was then formed through acyl chlorination and esterification with tropine, followed by
deacetylation to afford the target product, L-hyoscyamine. Results: The PPL-catalyzed desymmetrization exhibited good regioselectivity
and stereoselectivity. The target product was successfully obtained through subsequent oxidation and esterification reactions. The
synthetic route consisted of five steps with an overall yield of 53.6%. Conclusion: The established chemoenzymatic strategy effectively
integrates the high selectivity of biocatalysis with the efficiency of chemical transformation, providing a new approach for the green syn⁃
thesis of tropane alkaloids.

Key words: chemoenzymatic synthesis, hyoscyamine, chiral construction, total synthesis

中图分类号:

R284.3

王雪倩, 田红畅, 段宝忠, 张　磊, . 莨菪碱的化学-酶法合成[J]. 大理大学学报, 2026, 11(4): 21-27.

Wang Xueqian¹, Tian Hongchang, Duan Baozhong, Zhang Lei, . Chemoenzymatic Synthesis of Hyoscyamine[J]. Journal of Dali University, 2026, 11(4): 21-27.

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莨菪碱的化学-酶法合成

Chemoenzymatic Synthesis of Hyoscyamine

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