Research Progress in Synthesis of Indole Alkaloid Catharanthine

doi:10.6023/cjoc202509026

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (3): 725-742.DOI: 10.6023/cjoc202509026 Previous Articles Next Articles

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吲哚生物碱Catharanthine合成研究进展

王雪倩^a^,^b, 段宝忠^b^,^*(), 田红畅^a^,^*(), 张磊^a^,^*()

^a 海军军医大学药学院教育部真菌感染性疾病医药基础研究创新中心教育部真菌感染性疾病医药基础研究创新中心上海 200433
^b 大理大学药学院云南大理 671000

收稿日期:2025-09-22 修回日期:2025-10-24 发布日期:2025-12-09
通讯作者: 段宝忠, 田红畅, 张磊
基金资助:
国家自然科学基金(82504962); 国家自然科学基金(82225047); 国家自然科学基金(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(2024YFC3506500); 国家重点研发计划(2024YFC3506400); 浙江省自然科学基金(LZ24H280003)

Research Progress in Synthesis of Indole Alkaloid Catharanthine

Xueqian Wang^a^,^b, Baozhong Duan^b^,^*(), Hongchang Tian^a^,^*(), Lei Zhang^a^,^*()

^a The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Naval Medical University, Shanghai 200433
^b College of Pharmaceutical Science, Dali University, Dali, Yunnan 671000

Received:2025-09-22 Revised:2025-10-24 Published:2025-12-09
Contact: Baozhong Duan, Hongchang Tian, Lei Zhang
Supported by:
National Natural Science Foundation of China(82504962); National Natural Science Foundation of China(82225047); National Natural Science Foundation of China(82170274); Open Research Project of the Ministry of Education Innovation Center for Basic Medical Research on Fungal Infectious Diseases(YXX2024-KF02-02); National Key Research and Development Program of China(2024YFC3506500); National Key Research and Development Program of China(2024YFC3506400); Zhejiang Provincial Natural Science Foundation(LZ24H280003)

Catharanthine, an iboga-type indole alkaloid isolated from Catharanthus roseus, features a pentacyclic framework with three stereocenters. As a key structural fragment of the anticancer drugs vinblastine and its analogue vincristine, its complex and unique chemical architecture has made it a hotspot in synthetic studies. In recent years, its complete biosynthetic pathway has been elucidated and functionally reconstructed in heterologous systems, such as yeast and Nicotiana benthamiana. Since 1969, 18 research groups have reported chemical syntheses of catharanthine, encompassing racemic, asymmetric, and biomimetic syntheses, as well as various transition-metal-catalyzed approaches. This review chronologically summarizes the advances in both the biosynthesis and chemical synthesis of catharanthine and offers perspectives on future research directions.

Key words: catharanthine, indole alkaloid, biosynthesis, total synthesis

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Xueqian Wang, Baozhong Duan, Hongchang Tian, Lei Zhang. Research Progress in Synthesis of Indole Alkaloid Catharanthine[J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 725-742.

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Fig. & Tab. 23

Figure 1. Structures of catharanthine

Scheme 1. Biosynthesis route of CatharanthineGES, Geraniol synthase; G8H, Geraniol 8-hydroxylase; CPR, Cytochrome P450 reductase; GOR, 8-Hydroxygeraniol oxidoreductase; ISY, Isopiperitenone synthase; MLPL, Monoterpenyl phosphate phosphatase; IO, Iridoid oxidase; CYPADH2, Cytochrome P450-dependent alcohol dehydrogenase 2; 7DLGT, 7-Deoxyloganic acid glucosyltransferase; LAMT, Loganic acid O-methyl-transferase; SLS, Secologanin synthase; TDC, Tryptophan decarboxylase; STR, Strictosidine synthase; SGD, Strictosidine β-D-glucosidase; GS, Geissoschizine synthase; GO, Geissoschizine oxidase; Redox 1, Redoxase 1; Redox 2, Redoxase 2; SAT, Coronaridine-O-acetyltransferase; PAS, precondylocarpine acetate synthase; DPAS, Dihydroprecondylocarpine synthase; CS, Catharanthine synthase.

Scheme 2. Synthetic route to (±)-Catharanthine from the Büchi group

Scheme 3. Synthetic route to (±)-Catharanthine from the Kutney group

Scheme 4. Synthetic route to (±)-Catharanthine from the Trost group

Scheme 5. Formal synthetic route to (±)-Catharanthine from the Beisler group

Scheme 6. Synthetic route to (±)-Catharanthine from the Tmanishi group

Scheme 7. Biomimetic synthesis of (±)-Catharanthine by the Das group

Scheme 8. Total synthesis of (±)-Catharanthine by the Raucher group

Scheme 9. Synthesis of (±)-Catharanthine by the Kuehne group in 1986

Scheme 10. Selective synthesis of (±)-Catharanthine by the Kuehne group in 2008

Scheme 11. Asymmetric synthesis of (＋)-Catharanthine by the Szántay group

Scheme 12. Stereocontrolled total synthesis of (±)-Catharanthine by the Fukuyam group

Scheme 13. Formal synthesis of (＋)-Catharanthine by the Doris group

Scheme 14. Asymmetric synthesis of (－)-Catharanthine by the Oguri group

Scheme 15. Formal synthesis of (－)-Catharanthine by the Ishihara group in 2014

Scheme 16. Asymmetric synthesis of (＋)-Catharanthine by the Ishihara group in 2025

Scheme 17. Formal synthesis of (＋)-Catharanthine by the Tuopin Luo group

Scheme 18. Total synthesis of (＋)-Catharanthine by the Batey Group

Scheme 19. Asymmetric synthesis of (＋)-Catharanthine by the Nemoto group

Scheme 20. Synthesis of (±)-Catharanthine by the Dixon group

Scheme 21. Enantioselective synthesis of (－)-Catharanthine by the Gröger group

Entry	Research group	Year	(±/＋/－)-Catharanthine	Steps	Yield/%	Reference
1	Büchiʼ group	1969	(±)-Catharanthine	17	1.4	[19]
2	Kutneyʼ group	1975	(±)-Catharanthine	12	<1	[20]
3	Trostʼ group	1979	(±)-Catharanthine	12	13	[22]
4	Beislerʼ group	1980	(±)-Catharanthine	14	<1	[23]
5	Tmanishiʼ group	1980	(±)-Catharanthine	19	<1	[26]
6	Dasʼ group	1981	(±)-Catharanthine	10	1.4	[27]
7	Raucherʼ group	1985	(±)-Catharanthine	10	13	[29]
8	Kuehneʼ group	1986	(±)-Catharanthine	9	11	[30a]
9	Kuehneʼ group	2008	(±)-Catharanthine	12	2.6	[30b]
10	Szántayʼ group	1990	(＋)-Catharanthine	9	6.3	[31]
11	Fukuyamaʼ group	1999	(±)-Catharanthine	13	12.4	[32a]
12	Dorisʼ group	2006	(＋)-Catharanthine	24	<1	[33]
13	Oguriʼ group	2013	(－)-Catharanthine	10	3.2	[34]
14	Ishiharaʼ group	2014	(－)-Catharanthine	17	<1	[35]
15	Ishiharaʼ group	2015	(＋)-Catharanthine	19	<1	[36]
16	Tuoping Luoʼ group	2016	(＋)-Catharanthine	13	<1	[37]
17	Bateyʼ group	2018	(＋)-Catharanthine	15	<1	[39]
18	Nemotoʼ group	2019	(＋)-Catharanthine	27	<1	[40]
19	Dixonʼ group	2021	(±)-Catharanthine	5	2.1	[42]
20	Grögerʼ group	2023	(－)-Catharanthine	22	<1	[43]

Table 1. Summary of total synthesis of Catharanthine

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吲哚生物碱Catharanthine合成研究进展

Research Progress in Synthesis of Indole Alkaloid Catharanthine

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