抗脑卒中新药匹诺塞林两种代谢产物的合成  

Synthesis of two metabolites of pinocembrin

作　　者：王冬梅[1] 刘海涛[1] 童元峰[1] 吴松[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室&卫生部天然药物生物合成重点实验室,北京100050

出　　处：《中国新药杂志》2013年第10期1130-1132,1165,共4页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2012ZX09301002-001)

摘　　要：目的:合成匹诺塞林的两种体内代谢产物5-羟基-黄烷酮-7-O-磺酸钠及5-羟基-黄烷酮-7-O-β-D-葡糖糖醛酸。方法:以匹诺塞林为原料,吡啶作为溶剂和催化剂,与氯磺酸进行磺酸化反应后再成盐得到5-羟基-黄烷酮-7-O-磺酸钠。5-羟基-黄烷酮-7-O-β-D-葡糖糖醛酸的合成同样以匹诺塞林为原料,经过乙酰化保护羟基,再选择性脱去保护基,然后与三-O-乙酰基-α-D-溴代葡糖糖醛酸甲酯进行糖苷化,再水解脱去保护基团得到目标化合物。结果:两个目标化合物的结构经1H-NMR、MS得到确证,纯度经HPLC检测均达到98%以上。结论:本文首次合成了5-羟基-黄烷酮-7-O-磺酸钠和5-羟基-黄烷酮-7-O-β-D-葡糖糖醛酸两种代谢产物,可作为新药匹诺塞林体内代谢研究的对照品。Objective： To synthesize two metabolites of pinocembrin, 5-hydroxy-flavanone-7-O-sodium sul- phonate and 5-hydroxy-flavanone-7-O-β-D-glucuronic acid none-7-O-sodium sulphonate was synthesized by sulfonating Methods ： Starting from pinocembrin, 5-hydroxy-flava- with chlorosulfonic acid using pyridine as the solvent and catalyst. 5-Hydroxy-flavanone-7-O-β-D-glucuronic acid was also synthesized from pinocembrin by acetyl pro- tection, selective deprotection, glycosidation with methyl （tri-O-acetyl-α-D-gluco-pyranosyl bromide ） -urinate and removal of the protection groups. Results： The structures of the two objective compounds were confirmed by 1H-NMR and MS, and their purities were over 98% as determined by HPLC. Conclusion： Two metabolites of pi- nocembrin, 5-hydroxy-flavanone-7-O-β-D-glucuronic acid and 5-hydroxy-flavanone-7-O-sodium sulphonate, were synthesized for the first time, and they can be used as the reference substances in the metabolic studies of pinocem- brin in vivo.

关 键 词：抗脑卒中药物 匹诺塞林 代谢产物 合成 

分 类 号：R914.5[医药卫生—药物化学]