Wu K, Tong Z S, Dai C S, Li L, Zheng S X
Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing.
Yao Xue Xue Bao. 1993;28(4):266-72.
4-Methyl-7-hydroxy-6 or 8-allylcoumarin, a new type of radioprotectors, has poor solubility in water and in oil, which influences markedly its absorption in body and effectiveness of peroral administration. For improving its solubility, 14 coumarin derivatives were synthesized on the basis of increasing its hydro- or lipophilicity, and studied preliminarily on their toxicities, radioprotective activities, and relations between their hydro- or lipophilicity and activities. It is found that both compounds (5a, 6a), can be dissolved in ethyl oleate and the latter in water partially as well, retain the radioprotective activities basically, and improve the survival of 65% (P < 0.01) of mice exposed to 9.0 Gy 60Co gamma-ray when administered before irradiation. In synthesis, von Pechmann reaction was improved; 6-allyl intermediate was synthesized by the method of blocking the 8-position by iodine, and the process was studied. Mannich base was synthesized under high pressure by using CH2Cl2 as C1 synthon.
4-甲基-7-羟基-6或8-烯丙基香豆素是一种新型辐射防护剂，其在水和油中的溶解度较差，这显著影响其在体内的吸收及口服给药的效果。为提高其溶解度，在增加其亲水性或亲脂性的基础上合成了14种香豆素衍生物，并对其毒性、辐射防护活性以及亲水性或亲脂性与活性之间的关系进行了初步研究。发现两种化合物（5a、6a）均可溶于油酸乙酯，后者也能部分溶于水，基本保留了辐射防护活性，在照射前给药时可使受9.0 Gy 60Coγ射线照射的小鼠存活率提高65%（P<0.01）。合成过程中，改进了冯·佩希曼反应；采用碘封端8位的方法合成了6-烯丙基中间体，并对该过程进行了研究。以CH2Cl2作为C1合成子在高压下合成了曼尼希碱。
