铀促排药物研究Ⅵ:2,3-二羟基-4-甲氧羰基苄基胺羧酰胺螯合剂的合成

铀化合物在国防工业和国民经济建设中有十分重要的地位,但其通过各种途径(主要是吸入)进入人体后对人体造成的危害却十分严重。陈文致、徐美忠等曾对几种新的膦酸类和含邻苯二酚残基的化合物进行研究,发现它们对铀的促排效果比钛铁试剂更好。为进一步探讨含邻苯二酚残基的螯合剂对铀促排的构效关系,我们合成了12种2,3-二羟基-4-甲氧羰基苄基胺羧酰胺类化合物(Ⅳ),并进行了多种金属的解毒试验。以生产香料香兰素的副产物邻香兰素(o-vanillin)为起始原料,经八步反应得到目标化合物(Scheme 1)。

STUDIES ON URANIUM MOBILIZATION AGENTS VI: SYNTHESIS OF 2,3-DIHYDROXY-4-CARBOMETHOXYBENZYL AMINOCARBOXYLIC ACID AMIDES CHELATING AGENTS

In searching for new chelation therapy drugs against uranium intoxication, a series of N-carboxymethyl-N- (substituted carbamoylmethyl)- 2, 3- dihydroxy- 4- carbomethoxybenzylamine was synthesized starting with o-vanillin. The effect on detoxieation of UO_2 (NO_3)_2, CuSO_4 and NiCl_2 in mice was tested. Some of them (IVa, IVd, IVf and IVg) were shown to be good antidotes for acute uranium intoxication, but all were less effective for Cu~(2+) and Ni~(2+).