Total Synthesis of Tetracyclic Homoproaporphine Alkaloids (+)-Crociflorinone and (+)-6a-epi-Crociflorinone

doi:10.6023/cjoc202409026

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (3): 969-976.DOI: 10.6023/cjoc202409026 Previous Articles Next Articles

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四环高原阿朴啡碱(+)-Crociflorinone及(+)-6a-epi-Crociflorinone的不对称全合成

杨帆^a, 濮留洋^b^,^*(), 谢建华^a^,^*(), 周其林^a

a 南开大学化学学院元素有机化学国家重点实验室有机新物质创造前沿科学中心天津 300071
b 南华大学化学化工学院湖南衡阳 421001

收稿日期:2024-09-20 修回日期:2024-10-29 发布日期:2024-12-05
基金资助:
国家自然科学基金(92256303); 国家自然科学基金(22221002); 国家自然科学基金(22188101)

Total Synthesis of Tetracyclic Homoproaporphine Alkaloids (+)-Crociflorinone and (+)-6a-epi-Crociflorinone

Fan Yang^a, Liuyang Pu^b(), Jianhua Xie^a(), Qilin Zhou^a

a Frontiers Science Center for New Organic Matter, State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
b School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan 421001

Received:2024-09-20 Revised:2024-10-29 Published:2024-12-05
Contact: * E-mail: puly@usc.edu.cn; jhxie@nankai.edu.cn
Supported by:
National Natural Science Foundation of China(92256303); National Natural Science Foundation of China(22221002); National Natural Science Foundation of China(22188101)

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Abstract

Tetracyclic homoproaporphine alkaloids are a subset of isoquinoline alkaloids bearing a tetrahydroisoquinoline- fused spiro skeleton. Building on the successful enantioselective total synthesis of pentacyclic homoproaporphine alkaloids, this study utilizes chiral tricyclic cyclohexanone (–)-5 containing a quaternary carbon center as the starting material and develops a strategy involving Wittig reaction and Pictet-Spengler cyclization as the key steps to construct the chiral penta- cyclic skeleton containing a spiro structure and a quaternary carbon center. Subsequently, through late-stage functionalization including a tandem retro-oxa-Michael reaction/methylation, the first asymmetric total synthesis of tetracyclic homoproapor- phine alkaloid (+)-crociflorinone alongside its C6a epimer (+)-6a-epi-crociflorinone was achieved, thereby confirming their absolute configurations.

Key words: tetracyclic homoproaporphine alkaloids, asymmetric total synthesis, crociflorinone, Pictet-Spengler cyclization, isoquinoline alkaloids

Cite this article

Fan Yang, Liuyang Pu, Jianhua Xie, Qilin Zhou. Total Synthesis of Tetracyclic Homoproaporphine Alkaloids (+)-Crociflorinone and (+)-6a-epi-Crociflorinone[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 969-976.

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Fig. & Tab. 5

Figure 1. Tetracyclic skeleton and representative examples of homoproaporphine alkaloids

Figure 2. Our previous research and this work

Figure 3. Retrosynthetic analysis of asymmetric synthesis of homoproaporphine alkaloids

Scheme 1. Synthesis of intermediate (–)-4

Scheme 2. Total synthesis of homoproaporphine alkaloids

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四环高原阿朴啡碱(+)-Crociflorinone及(+)-6a-epi-Crociflorinone的不对称全合成

Total Synthesis of Tetracyclic Homoproaporphine Alkaloids (+)-Crociflorinone and (+)-6a-epi-Crociflorinone

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