Synthesis,XRD analysis and anti-tumor activity of novel compounds containing tetrahydronaphthalen-2-ol

SUN Nannan; LIU Jia; ZHENG Canhui; ZHOU Youjun

doi:10.3969/j.issn.1006-0111.2014.03.007

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Objective To synthesize the enantiomers of (E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-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-tubulin and anti-tumor assay. Results The structure of the target compounds were determined by ¹H NMR,¹³C NMR,MS,and XRD analysis.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=0.14 μmol/L) and inhibition of tubulin polymerization (IC₅₀=0.41 μmol/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.

Synthesis,XRD analysis and anti-tumor activity of novel compounds containing tetrahydronaphthalen-2-ol

Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2014-03-25

Rev Recd Date: 2014-04-11

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Abstract: Objective To synthesize the enantiomers of (E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-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-tubulin and anti-tumor assay. Results The structure of the target compounds were determined by ¹H NMR,¹³C NMR,MS,and XRD analysis.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=0.14 μmol/L) and inhibition of tubulin polymerization (IC₅₀=0.41 μmol/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.

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Reference (8)

[1]	刘嘉,周有骏.基于微管蛋白的小分子肿瘤血管阻断剂的设计、合成及抗肿瘤活性研究[D].第二军医大学博士论文,2012.
[2]	Jordan MA,Wilson L. Microtubules as a target for anticancer drugs[J]. Nat Rev Cancer,2004,4(4):253-265.
[3]	Zhou J,Giannakakou P. Targeting microtubules for cancer chemotherapy[J].Curr Med Chem Anticancer Agents,2005,5(1):65-71.
[4]	Liu J,Zheng CH,Zhou YJ,et al. Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen-2-one as a new class of microtubule-targeting agents[J].J Med Chem,2012,55(12):5720-5733.
[5]	Yao B,Ji H,Cao Y. Synthesis and antifungal activities of novel 2-aminotetralin derivatives[J].J Med Chem,2007,50(22):5293-5300.
[6]	Sun L,Tran N,Tang F. Synthesis and biological evaluations of 3-substituted indolin-2-ones:a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases[J].J Med Chem,1998,41(14):2588-2603.
[7]	Corey EJ,Azimioara M,Sarshar S. X-ray crystal structure of a chiral oxazaborolidine catalyst for enantioselective carbonyl reduction[J].Tetrahedron Lett,1992,33(24):3429-3430.
[8]	Hamel E. Evaluation of antimitotic agents by quantitative comparisons of their effects on the polymerization of purified tubulin[J].Cell Biochem Biophys,2003,38(1):1-21.

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Synthesis,XRD analysis and anti-tumor activity of novel compounds containing tetrahydronaphthalen-2-ol

doi: 10.3969/j.issn.1006-0111.2014.03.007

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通讯作者: 陈斌, [email protected]

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