手性环氧醇及其磷酸酯化物的合成及抗肿瘤活性筛选

Synthesis and antitumor activity evaluation of chiral glycidyl alcohols and their phosphoester derivatives

目的寻找基于Sharpless不对称环氧化反应的手性环氧醇及其磷酸酯化物合成的优化条件。方法以烯丙基醇为起始原料,合成炔基、苯基和烷基(3b~8b)取代的手性环氧醇。再用氯磷酸二苯酯处理上述产物,得到相应的磷酸酯化物(3c~5c,8c)。采用1H NMR,13C NMR,31P NMR和MS表征化合物结构,手性HPLC测定产物的对映异构过量(ee)值,并对所得化合物的抗肿瘤活性进行初筛。结果合成了10种不同取代的手性环氧醇及其磷酸酯化物,活性实验结果显示部分化合物对Hela细胞、231细胞和HepG2细胞增殖有一定的抑制作用。结论建立了优化的Sharpless不对称环氧化反应条件及手性环氧醇的磷酸酯化反应条件,对拓展Sharpless法的应用有重要参考意义。

Objective To study the optimization conditions for Sharpless asymmetric epoxidation-based synthesis of chiral glyc⁃idyl alcohols and their phosphoester compounds.Methods With allyl alcohol as the starting material,we synthesized alkynyl,phenyl,and alkyl(3b~8b)substituted chiral glycidyl alcohols,followed by treatment with diphenyl chlorophosphate for corresponding phos⁃phoester derivatives(3c~5c,8c).We characterized the structures of the compounds by 1H nuclear magnetic resonance(NMR),13C NMR,31P NMR,and mass spectrometry,measured their enantiomeric excess(ee)values by chiral high-performance liquid chroma⁃tography,and preliminarily evaluated their antitumor activities.Results Ten chiral glycidyl alcohols with different substitutions and their phosphoester derivatives were synthesized.Antitumor activity tests showed that some of the compounds had inhibitory effects on the proliferation of HeLa cells,231 cells,and HepG2 cells.Conclusion We established optimization conditions for Sharpless asym⁃metric epoxidation and chiral glycidyl alcohol phosphoesterification,providing a reference for expanding the application of the Sharp⁃less method.