2,4-二苄氧基-5-异丙烯基苯甲酸的合成工艺研究

摘要以2，4-二羟基苯甲酸甲酯为原料，经过"一锅法"的Friedel-Crafts反应和Fries重排、亲核取代反应、Wittig反应和酯水解4步操作，合成了非安莎霉素（AT13387）的重要中间体2，4-二苄氧基-5-异丙烯基苯甲酸（1）。其结构经¹H NMR、¹³C NMR和MS确证。探讨了反应体系、投料比、反应温度和溶剂对化合物1合成过程中各步得率的影响，确定了化合物1合成的最适宜工艺条件，其总收率为65.8%。

	Service

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	Email Alert
	RSS
	作者相关文章
	冯文艳
	辛红兴
	闫红

关键词： AT13387中间体 2 4-二苄氧基-5-异丙烯基苯甲酸合成工艺优化

Abstract： An important intermediate of non-ansamycin (AT13387), 2,4-dibenzyloxy-5-isopropenyl benzoic acid(1), was prepared via one-pot of Friedel-Crafts reaction and Fries rearrangement, nucleophilic substitution, Wittig reaction and hydrolysis of ester using the 2,4-dihydroxy-benzoic acid methyl ester as starting material. The structure of compound 1 was confirmed by ¹H NMR,¹³C NMR and MS. The comprehensive investigations on the optimization of reaction system, the rate of ingredients, reaction temperature and solvent on the yield of compound 1 were conducted. The overall yield was 65.8%.

Keywords： AT13387 intermediate； 2,4-dibenzyloxy-5-isopropenyl benzoic acid； optimization of synthesis process

Received 2018-01-09;

Fund:2015年北京市自然科学基金重点项目（KZ201510005007）。

Corresponding Authors: 闫红,E-mail:hongyan@bjut.edu.cn。 Email: hongyan@bjut.edu.cn

About author: 冯文艳(1991-),女,硕士研究生,现从事抗肿瘤药物合成方面的研究。

引用本文:

冯文艳, 辛红兴, 闫红.2,4-二苄氧基-5-异丙烯基苯甲酸的合成工艺研究[J]. 化学工业与工程, 2019,36(4): 1-6

Feng Wenyan, Xin Hongxing, Yan Hong.Synthetic Technology of 2,4-Dibenzyloxy-5-isopropenyl Benzoic Acid[J]. Chemcial Industry and Engineering, 2019,36(4): 1-6

[1] 卞传才. 苯安莎霉素类天然产物的全合成探索(Ⅰ)[D]. 北京:北京协和医学院, 2014 Bian Chuancai. Study on the total synthesis of benzo-ansamycin natural products(I)[D]. Beijing:Peking Union Medical College, 2014(in Chinese)
[2] 严睿. 苯醌安莎霉素类天然产物的全合成探索(Ⅱ)[D]. 北京:北京协和医学院, 2014 Yan Rui. Study on the synthesis of natural products of benzoquinone ansamycin(Ⅱ)[D]. Beijing:Peking Union Medical College, 2014(in Chinese)
[3] Patel B H, Barrett A G M. Total synthesis of resorcinol amide hsp 90 inhibitor AT13387[J]. The Journal of Organic Chemistry, 2012, 77(24):11296-11301
[4] Stuart C M, Helen F L, Martyn F, et al. Preparation of N-benzoylisoindoline derivatives and analogs as analgesics:UK, WO 2008/044027A2[P]. 2008-04-17
[5] Liang C, Gu L, Yang Y, et al. Alternate synthesis of HSP₉₀ inhibitor AT13387[J]. Synthetic Communications, 2014, 44(16):2416-2425
[6] Martyn F, Francis L J, Thomas T N, et al. Hydrobenzamide derivatives as inhibitors of Hsp90:UK, WO 2008/044034A1[P].2008-04-17
[7] Alexander R D, Sanjeev R, Rajashree J. Pharmaceutical formulation comprising AT13387:JP, WO 2015/140624A1[P]. 2015-09-24
[8] Jiang F, Wang H, Jin Y, et al. Novel tetrahydropyrido[4,3-d] pyrimidines as potent inhibitors of chaperone heat shock protein 90[J]. Journal of Medicinal Chemistry, 2016, 59(23):10498-10519
[9] 郭冠群, 杨明仙. 从分子中正电荷分数探讨常用溶剂的极性顺序[J]. 色谱, 1996, 14(4):267-270 Guo Guanqun, Yang Mingxian. Evaluation of polar order of common solvents from fraction of positive charge in molecules[J]. Chinese Journal of Chromatography, 1996, 14(4):267-270(in Chinese)