桦木醇二酸酯衍生物的合成及溶解性能比较

为了增强桦木醇的极性，以其为母体，合成了桦木醇丁二酸酯和桦木醇戊二酸酯，采用红外光谱、核磁共振和质谱对产物进行了结构表征。选用平衡法测定了桦木醇、桦木醇丁二酸酯和桦木醇戊二酸酯在丙酮、无水乙醇、水和磷酸盐缓冲溶液(pH=7.4)中的溶解度。结果表明:在丙酮和无水乙醇中，桦木醇丁二酸酯的溶解度是桦木醇的10.6和12.0倍；桦木醇戊二酸酯的溶解度是桦木醇的33.5和22.6倍；在水中，桦木醇戊二酸酯的溶解度为桦木醇丁二酸酯的7倍；在PBS(pH=7.4)中，桦木醇戊二酸酯的溶解度约为桦木醇丁二酸酯的4倍，目标产物的亲水性有了显著的改善。采用MTT法评价了桦木醇丁二酸酯和桦木醇戊二酸酯对SMMC7721、TCA8113、MCF-7、SGC和B16这5种癌细胞株的生长抑制活性。结果表明:桦木醇二酸酯衍生物具有潜在的体外细胞毒活性。 

Synthesis and solubility comparison of 3.28-Di-O-acylated betulin derivatives

In order to enhance the polarity of betulin, 3,28-Di-O-acylated betulin derivatives were synthesized from betulin and an appropriate anhydride. The structures of the products were identified by FT-IR, 1 H NMR and MS spectra. The solubility data of betulin and its derivatives in acetone, anhydrous ethanol, water and PBS (pH=7.4) were determined by equilibrium method. The results showed that in acetone and anhydrous ethanol, the solubility of 3,28-Di-O-succinyl-betulin was 10.6 and 12.0 times of that of betulin; and the solubility of 3,28-Di-O-glutaryl-betulin was 33.5 and 22.6 times of that of betulin. In water, the solubility of 3,28-Di-O-glutaryl-betulin was 7 times of that of 3,28-Di-O-succinyl-betulin; and in PBS (pH=7.4), the solubility of 3, 28-Di-O-glutaryl-betulin was 4 times of that of 3, 28-Di-O-succinyl-betulin. Their hydrophilicity had a significant increase. Antitumor activity of the target compounds in vitro against SMMC7721, TCA8113, MCF-7, SGC and B16 cell lines was evaluated by MTr assay via the respective IC_50 values. The bioactive assay shows that 3,28-Di-O-acylated betulin derivatives display potential cytotoxicity against the tested cancer cell lines.