CAJ | 학술논문

目的：合成（E）-6-甲氧基-1-（3，4，5-三甲氧基苯亚甲基）-1，2，3，4-四氢-2-萘醇及其对映异构体，测定其晶体结构，并考察其生物活性。方法以2，6-二甲氧基萘为起始原料，经还原及Knoevenael 缩合制得中间体萘酮，再以CBS不对称催化还原分别制得R、S构型的目标化合物。采用单晶X-衍射测定其晶体结构，并测试其微管蛋白的抑制活性及体外抗肿瘤活性。结果目标化合物结构经MS、NMR及X-单晶衍射等确证。目标化合物的不对称还原反应收率达90．3％，e．e．％达99．04％，体外药理活性数据显示，S-构型目标化合物对微管蛋白聚合、HCT116和CCRF-CEM肿瘤细胞的抑制活性优于R-构型异构体及先导化合物22b，其IC50分别达到0．41、0．14和0．001μmol/L。结论采用CBS不对称催化还原的方法是一条制备高光学纯度的手性目标化合物的合成方法；高活性的S构型异构体具有进一步研究的价值。
목적：합성（E）-6-갑양기-1-（3，4，5-삼갑양기분아갑기）-1，2，3，4-사경-2-내순급기대영이구체，측정기정체결구，병고찰기생물활성。방법이2，6-이갑양기내위기시원료，경환원급Knoevenael 축합제득중간체내동，재이CBS불대칭최화환원분별제득R、S구형적목표화합물。채용단정X-연사측정기정체결구，병측시기미관단백적억제활성급체외항종류활성。결과목표화합물결구경MS、NMR급X-단정연사등학증。목표화합물적불대칭환원반응수솔체90．3％，e．e．％체99．04％，체외약리활성수거현시，S-구형목표화합물대미관단백취합、HCT116화CCRF-CEM종류세포적억제활성우우R-구형이구체급선도화합물22b，기IC50분별체도0．41、0．14화0．001μmol/L。결론채용CBS불대칭최화환원적방법시일조제비고광학순도적수성목표화합물적합성방법；고활성적S구형이구체구유진일보연구적개치。
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 .