高异三尖杉酯碱的合成及其立体异构体的分离鉴定

2-氧代-6-甲基庚酰基三尖杉碱(3)与0-(1-甲氧基异丙基)羟基乙酸甲酯(4)在强碱性试剂二异丙胺锂(LDA)存在下,起亲核加成反应,反应中间体5在室温用酸性丙酮水解,得到一种新的三尖杉酯类生物碱一一高异三尖杉酯碱(6c)及其立体异构体(6a、6b、6d)的混合物,产率56%、通过制备薄层层析分得这四个立体异构体,它们的1H NMR和异三尖杉酯碱及其立体异构体的1H NMR类似,推定了它们的绝对构型。初步药理试验表明,高异三尖杉酯碱及其立体异构体的混合物对白血病L7712的DNA合成有明显的抑制作用。

Synthesis of homoisoharringtonine and separation of its stereomers

Cephalotaxine ester of 2-oxo-6-methylheptanoic acid was treated with lithium diisopropylamide and Me O-(1-methoxyisopropyl)glycolate to give a mixture of homoisoharringtonine (I) and its stereoisomers with 56% yield. The four stereoisomers separated by TLC showed identical mass spectra and almost superimposed IR but with different 1H NMR spectra. The configuration of the 2'-C and 3'-C of the four isomers were postulated based upon their 1H NMR spectra as compared with the 1H NMR spectra of isoharringtonine and its stereoisomers. The mixture of four stereoisomers exhibited antitumor activity against Leukemia L-7712 by inhibiting the synthesis of DNA.