Synthesis, XRD analysis and anti-tumor activity of novel compounds containing tetrahydronaphthalen-2-ol
10.3969/j.issn.1006-0111.2014.03.007
- VernacularTitle:新型四氢-2-萘醇类化合物的合成、晶体结构及抗肿瘤活性
- Author:
Nannan SUN
1
;
Jia LIU
;
Canhui ZHENG
;
Youjun ZHOU
Author Information
1. 第二军医大学药学院药物化学教研室
- Keywords:
asymmetric synthesis;
anti-tumor activity;
microtubulin
- From:
Journal of Pharmaceutical Practice
2014;(3):191-194
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize the enantiomers of ( E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene )-1,2,3,4-tetra-hydronaphthalen-2-ol,determine their structures by XRD and evaluate their anti-tumor activity in vitro.Methods The target compounds were prepared from 2,6-Dimethoxybenzoyl chloride.The key intermediate,(E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-2-one,was obtained through Cornforth reduction and Knoevenael reaction ,and the final R,S compounds were got by CBS asymmetric reduction .The structure of the target compounds were determined by XRD .The target compounds were rested by anti-tu-bulin and anti-tumor assay.Results The structure of the target compounds were determined by 1 H NMR,13 C NMR,MS,and XRD analy-sis.The yield of asymmetric reduction reaction was 90.3%,e.e.%was 99.04%,in vitro anti-tumor assay showed all of the S isomer had stronger anticancer activity than the R isomer ,especially on CCRF-CEM cell(IC50 =1 nmol/L),HCT-116 cell(IC50 =0.14μmol/L) and inhibition of tubulin polymerization ( IC50 =0.41μmol/L) .Conclusion The CBS asymmetric reduction was a good way to get high-yield and high optical purity compound .The S isomer with outstanding anticancer activity was worth further research .
