Synthesis of the AB Ring System of Daphniphyllum Alkaloid Daphniglaucin C

doi:10.6023/cjoc202411005

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (3): 925-932.DOI: 10.6023/cjoc202411005 Previous Articles Next Articles

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虎皮楠生物碱Daphniglaucin C的AB环系合成

张晓锋^a^,^b, Aggeliki Roumana^b, 毛海康^a^,^b^,^*(), 徐晶^b^,^*()

a 哈尔滨工业大学化学与化工学院哈尔滨 150001
b 南方科技大学化学系深圳格拉布斯研究院广东省催化化学重点实验室深圳市小分子药物发现与合成重点实验室广东深圳 518055

收稿日期:2024-11-05 修回日期:2024-12-04 发布日期:2025-01-10
通讯作者: 毛海康, 徐晶
基金资助:
国家自然科学基金(22271136); 国家自然科学基金(22471117)

Synthesis of the AB Ring System of Daphniphyllum Alkaloid Daphniglaucin C

Xiaofeng Zhang^a^,^b, Aggeliki Roumana^b, Haikang Mao^a^,^b(), Jing Xu^b()

a School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001
b Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangdong Provincial Key Laboratory of Catalysis, Shenzhen Grubbs Institute, Department of Chemistry, Southern University of Science and Technology, Shenzhen, Guangdong 518055

Received:2024-11-05 Revised:2024-12-04 Published:2025-01-10
Contact: Haikang Mao, Jing Xu
Supported by:
National Natural Science Foundation of China(22271136); National Natural Science Foundation of China(22471117)

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Abstract

The AB ring system of Daphniphyllum alkaloid Daphniglaucin C was concisely synthesized from readily available starting materials through rhodium-catalyzed cyclization and Heck coupling. The formation of C-ring using Huang’s amide- activation-annulation was also investigated. This efficient strategy lays the foundation for the synthesis of Daphniglaucin C-type Daphniphyllum alkaloids.

Key words: Daphniphyllum alkaloid, Daphniglaucin C, Rh-catalyzed cycloaddition, Heck coupling, total synthesis

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Xiaofeng Zhang, Aggeliki Roumana, Haikang Mao, Jing Xu. Synthesis of the AB Ring System of Daphniphyllum Alkaloid Daphniglaucin C[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 925-932.

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Fig. & Tab. 5

Figure 1. Representative daphniglaucin C-type and daphnezomine L-type daphniphyllum alkaloids

Scheme 1. Summary of synthetic studies towards daphniglaucin C-type Daphniphyllum alkaloids

Scheme 2. Retrosynthetic analysis of daphniglaucin C-type alkaloids

Scheme 3. Synthesis of the AB bicyclic core of the daphniglaucin C-type alkaloids and studies of the amide-activation-annulation

Entry	Catalyst	Ligand	Base	Solvent	Yield/%
1	Pd(OAc)₂	PPh₃	Et₃N	DMF	30^a
2	Pd(OAc)₂	P(o-tol)₃	DBU	PhMe	Trace
3	Pd(PPh₃)₄	—	Et₃N	DMF	52^b
4	Pd(OAc)₂	PPh₃	K₂CO₃	DMF	78
5^c	Pd(OAc)₂	PPh₃	K₂CO₃	DMF	71

Table 1. Optimization of Heck reaction

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虎皮楠生物碱Daphniglaucin C的AB环系合成

Synthesis of the AB Ring System of Daphniphyllum Alkaloid Daphniglaucin C

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