氘标记联苯双酯的制备研究

Deuteration of Dimethyl 4,4'-Dimethoxy-5,6,5',6'- Dimethylenedioxybiphenyl-2,2'-Dicarboxylate (BDD): A Remedy for Chronic Hepatitis

采用均相催化氘化法,由联苯双酯和氘水在氯亚铂酸钠催化下直接制备,方法新颖,得率高,一次交换反应所得产品的同位素丰度大于85％,满足药物代谢动力学的研究需要(≥50％)。

A new antihepatitic drug, BDD (Ⅰ), which is very active and powerful especially in lowering elevated SGPT levels, has been previously discovered during the systematic study of Schisandra chinensis. In order to study the metabolism of this new antihepatitic drug, deuterated BDD was prepared according to the following method.BDD 1g, sodium chloroplatinate 193mg, deuterium oxide 16ml, acetic anhydride 30ml, and acetyl chloride 0.4ml were well mixed in a sealed ampoule and heated to 120-130℃ for 12h. T'ae mixture was then poured into water. The precipitate (0.86g) contained the deuterated acid (Ⅱa, Ⅱb) of BDD.After esterification with methanol, a mixture (m.p. 150-153℃)of mono-and di-deu-terated BDD was obtained. Molecular clustering, as determined by GC/MS, showed that the product consisted of mono-deutero-BDD (Ⅲa) (m/e419) and dideutero-BDD (Ⅲb) (m/e420) in the ratio of 1:1.3.