Stereodivergent Total Synthesis of Tacaman Alkaloids
Xiangtao Chen
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorHuijing Wang
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorJie Zeng
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorQiuhong Li
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorTonghui Zhang
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorQiaoyun Yang
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorCorresponding Author
Pei Tang
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorCorresponding Author
Fen-Er Chen
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433 China
Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433 China
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022 China
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorXiangtao Chen
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorHuijing Wang
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorJie Zeng
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorQiuhong Li
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorTonghui Zhang
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorQiaoyun Yang
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorCorresponding Author
Pei Tang
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Search for more papers by this authorCorresponding Author
Fen-Er Chen
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433 China
Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433 China
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022 China
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan, 430205 China
Search for more papers by this authorAbstract
This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer–Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet–Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet–Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.
Conflict of Interests
The authors declare no competing financial interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
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