新雌激素衍生物的合成及抗辐射升白生物活性

Synthesis of Novel Estrogen Derivatives & Biological Activities of Anti-radiation Promotion White Blood Cells

以17α-炔雌二醇和17β-雌二醇为原料,分别与烯丙基溴、溴代异戊烯反应,通过一步反应合成了4个新雌激素衍生物,分别是17α-炔雌二醇-3-烯丙基醚(ES-1),17β-雌二醇-3-烯丙基醚(ES-2),17α-炔雌二醇-3-异戊烯基醚(ES-3)和17β-雌二醇-3-异戊烯基醚(ES-4),产率分别为92.2%,73.7%,65.9%和67.6%.化合物通过1HNMR,13CNMR,IR,MS及元素分析确证了结构,4个化合物均未见文献报道.初步的抗辐射升白生物活性研究表明,4个化合物对137Csγ-射线引起的小鼠白细胞低下及造血系统功能损伤有一定的保护作用.其中ES-3的升白作用最佳,经统计学处理,3个给药剂量组与对照组比,升白作用均有非常显著性差异(P<0.001).

Four novel estrogen derivatives were synthesized by a one-step reaction with 17α-ethynylestradiol and 17β-estradiol as the initial materials,reacted with allyl bromide and isopentenyl bromide,respectively,obtained 17α-ethynylestradiol-3-allyl ether （ES-1）,17β-estradiol-3-allyl ether （ES-2）,17α-ethyny-lestradiol-3-isopentenyl ether （ES-3） and 17β-estradiol-3-isopentenyl ether （ES-4）,in yields of 92.2%,73.7%,65.9% and 67.6%. And the structures of products were conformed by 1H NMR,13C NMR,MS,IR techniques and elemental analysis. The four compounds are novel estrogens without paper reported. The initial research of biological activities on anti-radiation promotion white blood cells （WBC） was carried out,and the results suggested that the four compounds possess certain protective effects to 6.5Gy 137Cs γ-rays damages on lowered WBC and haematogenesis system function,promotion WBC effect of ES-3 with obvious preponderance was best in the four products. The effect of promotion WBC for three dosages of ES-3 administered mice,treated by statistics with very obvious difference （P0.001） vs. control mice.