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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

25卷

期数:

2019年04期

页码:

313-315319

栏目:

基础医学

出版日期:

2019-07-20

文章信息/Info

Title:

Optimizating synthesis line of Ion-31a-a hand-type Ionone alkaloid derivative

文章编号:

1006-8147(2019)04-0313-03

作者:

樊 晔¹; 吴潇然¹; 聂江平¹; 秦 楠¹; 2; 段宏泉¹; 2

（1.天津医科大学药学院生药学教研室，天津市临床药物关键技术重点实验室，天津 300070；2.天津医科大学基础医学研究中心，天津 300070）

Author(s):

FAN Ye¹;  WU Xiao-ran¹;  NIE Jiang-ping¹;  QIN Nan¹; 2;  DUAN Hong-quan¹; 2

(1. Department of Pharmaceutical Teaching and Research, School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologics Enabling Development of Clinical Therapeutics and Dignostics(Theranostics), Tianjin 300070, China; 2.Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China)

关键词:

手性紫罗兰酮生物碱; 抗肿瘤转移; Ion-31a; 酶促拆分; 工艺优化

Keywords:

Chiral ionone alkaloid;  anti-tumor metastasis;  Ion-31a;  enzymatic resolution;  process optimization

分类号:

R93

DOI:

-

文献标志码:

A

摘要:

目的：新型手性紫罗兰酮生物碱衍生物Ion-31a对MDA-MB-231乳腺癌细胞具有抗转移作用，原有文献报道该化合物的产率很低。该文旨在对Ion-31a合成路线进行优化，以提高产率为深入进行新药研究提供大量化合物。方法：以洋葱假单胞菌中获取的脂肪酶为酶促拆分剂，通过酶-化学拆分法代替原路线的结晶拆分法获得光学纯中间体8，通过优化α-β不饱和酰胺的还原方法提高关键中间体11收率。通过优化反应条件减少最后一步副产物的生成提高Ion-31a的产率。结果：用酶促拆分法代替结晶拆分法使中间体8的光学纯度和产率显著提高；中间体11经雷尼镍催化氢化和四氢铝锂两步还原产率明显提高，最后一步制备Ion-31a时通过减少副产物提高其产率。结论：通过建立新的合成路线提高了中间体8和11的产率，结合优化后的反应条件将抗肿瘤转移先导化合物Ion-31a的合成工艺进行了优化，其收率大幅提高。

Abstract:

Objective: Ion-31a is anovel chiral ionone alkaloid derivative with anti-metastatic effects against MDA-MB-231 breast cancer cells. The yield of Ion-31a was very low in most studies. The synthetic route of Ion-31a wasoptimized in this paper to further increase its yield for further research. Methods: The lipase obtained from Pseudomonas cepacia was used as an enzymatic resolving agent. The enzyme-chemical resolution method replaced the crystallization resolution in the original study. The aim was to obtain an optically purity intermediate 8. The yield of key intermediate 11 was increased by optimizing the reduction process for α-β unsaturated amide. Optimizing the reaction conditions reduced the formation of by-products in the last step. Results: The yield of intermediate 8 was significantly improved by using enzymatic resolution. Toincrease the yield of intermediates 11, amide reduction with catalytic hydrogenation with Raney nickel was used followed by lithium tetrahydrogen aluminum. The preparation of Ion-31a was enhanced by reducing by-products in the final step. Conclusion: This paper has showed a newsynthetic route to obtain key intermediates 8 and 11. The total yield of Ion-31a has been greatly improved.

参考文献/References:

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相似文献/References:

[1]陈家浩,方海军,秦 楠,等.紫罗兰酮酰胺衍生物的合成与抗肿瘤转移活性研究[J].天津医科大学学报,2016,22(03):191.
　CHEN Jia-hao,FANG Hai-jun,QIN Nan,et al.?Study on the ionone amide derivatives synthesis and anti-metastatic effect[J].Journal of Tianjin Medical University,2016,22(04):191.

备注/Memo

备注/Memo:

基金项目 国家自然科学基金面上项目基金资助（81373297）
作者简介 樊晔（1993-），女，硕士在读，研究方向：天然产物结构改造；通信作者：段宏泉，E-mail:duanhq@tijmu.edu.cn。

常用功能

更新日期/Last Update: 2019-08-28