SYNTHESIS AND BIO-ACTIVITY OF COUMARIN DERIVATIVES AND STUDIES ON ITS RELATIONSHIPS BETWEEN ACTIVITY AND LIPOPHILICITY

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 ⁶⁰Coγ-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.