Asymmetric Synthesis of (–)-Colchicine and Its Natural Analog (–)-N-Acetylcolchicine Methyl Ether

doi:10.6023/cjoc202206034

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (1): 313-319.DOI: 10.6023/cjoc202206034 Previous Articles Next Articles

秋水仙碱及其天然类似物(–)-N-乙酰秋水酚甲醚的不对称合成

濮留洋^†^,^a^,^b^,^c, 李芷悦^†^,^b^,^c, 李利民^b^,^c, 马玉翠^b^,^c, 马民^a^,^*(), 胡胜全^b^,^c^,^*(), 吴正治^b^,^c^,^*()

a 暨南大学中西医结合博士后流动站广州 510632
b 深圳市转化医学研究院深圳市第二人民医院深圳大学第一附属医院广东深圳 518035
c 深圳市老年医学研究所广东深圳 518035

收稿日期:2022-06-20 修回日期:2022-07-26 发布日期:2022-09-01
通讯作者: 马民, 胡胜全, 吴正治
作者简介:
^† 共同第一作者
基金资助:
深圳市科技计划(JSGG20210901145539016); 深圳市科技计划(JCYJ20190812171005713); 深圳市科技计划(JCYJ20210324121611032); 深圳市宝安中医药发展基金会(2020KJCX-KTYJ-215); 深圳市优秀科技创新人才培养-博士启动(RCBS20210706092212002); 广东省基础与应用基础研究基金(2020A1515011427); 广东省基础与应用基础研究基金(2022A1515011777)

Asymmetric Synthesis of (–)-Colchicine and Its Natural Analog (–)-N-Acetylcolchicine Methyl Ether

Liu-Yang Pu^†^,^a^,^b^,^c, Zhiyue Li^†^,^b^,^c, Limin Li^b^,^c, Yucui Ma^b^,^c, Min Ma^a(), Shengquan Hu^b^,^c(), Zhengzhi Wu^b^,^c()

a Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632
b Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035
c Shenzhen Institute of Geriatrics, Shenzhen, Guangdong 518035

Received:2022-06-20 Revised:2022-07-26 Published:2022-09-01
Contact: Min Ma, Shengquan Hu, Zhengzhi Wu
About author:
^† These authors contributed equally to this work.
Supported by:
Shenzhen Science and Technology Innovation Commission(JSGG20210901145539016); Shenzhen Science and Technology Innovation Commission(JCYJ20190812171005713); Shenzhen Science and Technology Innovation Commission(JCYJ20210324121611032); Shenzhen Baoan Chinese Medicine Development Foundation(2020KJCX-KTYJ-215); Shenzhen Excellent Scientific and Technological Innovation Talents Training Project-PhD Initiation Program(RCBS20210706092212002); Guangdong Basic and Applied Basic Research Foundation(2020A1515011427); Guangdong Basic and Applied Basic Research Foundation(2022A1515011777)

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Abstract

(–)-Colchicine and its natural analogue (–)-N-acetylcolchinol methyl ether have been synthesized in a com- paratively conciser asymmetric synthetic approach. Firstly, the carbon framework was constructed by Aldol condensation of simple aldehydes and ketones, and then the chiral amine intermediates were synthesized economically and efficiently through asymmetric reductive amination with chiral tert-butanesulfinamide. The 3-rings skeleton of colchicine and related alkaloids was then constructed by oxidation with hypervalent iodine reagent. Our strategy provides an efficient method for the convenient and economical synthesis of these alkaloids.

Key words: colchicine, (–)-N-acetylcolchinol methyl ether, tert-butanesulfinamide, asymmetric synthesis

Cite this article

Liu-Yang Pu, Zhiyue Li, Limin Li, Yucui Ma, Min Ma, Shengquan Hu, Zhengzhi Wu. Asymmetric Synthesis of (–)-Colchicine and Its Natural Analog (–)-N-Acetylcolchicine Methyl Ether[J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 313-319.

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Fig. & Tab. 4

Figure 1. Molecular structures of colchicine 1 and natural allocolchicinoids 2 and 3

Scheme 1. Retrosynthetic analysis of (–)-colchicine

Scheme 2. Formal total synthesis of (–)-colchicine

Scheme 3. Formal total synthesis of (–)-N-acetylcolchinol methyl ether (NCME)

References 16

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秋水仙碱及其天然类似物(–)-N-乙酰秋水酚甲醚的不对称合成

Asymmetric Synthesis of (–)-Colchicine and Its Natural Analog (–)-N-Acetylcolchicine Methyl Ether

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