从L-丝氨酸合成新型旋光活性环状磷脂的替加氟(Tegafur)和尿苷缀合物

从Ｌ－丝氨酸出发，经酯化、环磷酰化、磷酰化、加硫等步骤得到替加氟、尿苷硫代环磷酰胺酯缀合物２、３．Ｌ－丝氨酸酯经Ｎ－烷基化，然后再与磷酰二氯关环，进一步与替加氟乙醇反应得到环磷脂缀合物４．考察了两种环磷酰化反应中碳手性中心对磷原子的不对称诱导效果，并用硅胶柱层析分离了产物２、３、４ 的非对映异构体．基于ＮＭＲ数据，对它们的构型进行了讨论和初步的确定，它们的抗癌活性正在测试当中．

SYNTHESIS OF NOVEL OPTICALLY ACTIVE CYCLIC PHOSPHOLIPID CONJUGATES OF TEGAFUR AND URIDINE STARTING FROM L-SERINE

Starting from L serine, cyclic thiophosphoramidate conjugates (2 and 3) of Tegafur and uridine were synthesized via a multiple step procedure, e.g. esterification, cyclic phosphorylation, phosphorylation and sulfurization, etc. L serinoate was N alkylated, then cyclized with phosphorus oxychloride, and further reacted with N 3 (2 hydroxyethyl)Tegafur to afford cyclic phospholipid conjugate 4. The resultants (2,3 and 4) were successfully separated in the form of pure diastereomer by column chromatography on silica gel. Their configurations are discussed and assigned according to their NMR spectra. The bioassay on their antitumor activities is under investigation in our laboratory. The asymmetric induction effects of the carbon based chiral center on the diastereomer preference were also observed in these two synthetic phosphorylation cyclizations.