摘要
针对4-氨基-8-去氮杂四氢叶酸二乙酯现有合成方法中化合物极性大、溶解度差、收率低的缺点,采用在2,4位氨基引入保护基的方法进行改进。以6-乙酰氧基-2,4-二氯吡啶并[3,2-d]嘧啶为原料,在2,4-位引入苄基后与对氨基苯甲酰谷氨酸二乙酯连接,经硼氢化钠和氯化镍还原后再脱保护,生成叶酸类抑制剂关键中间体4-氨基-8-去氮杂四氢叶酸二乙酯。此方法所需时间短,收率较高,操作及后处理方便。并对6-乙酰氧基-2,4-二氯吡啶并[3,2-d]嘧啶苄基化的选择性、硼氢化钠和氯化镍还原方法进行了讨论。此方法对于四氢叶酸类化合物的合成有重要参考意义。
To conquer disadvantages in existing synthetic routes of diethyl 4-amino-8-deazatetrafolate,just as high polarity and poor solubility of some intermediates as well as unsatisfying overall yield,a novel synthesis method with protecting groups introduced for 2,4-diamino groups was reported.Starting from 6-acetoxymethyl-2,4-dichloropyridopyrimidine,diethyl 4-amino-8-deazatetrafolate as a key intermediate of anti-folate inhibitors was obtained by a series of successive reactions including protection,condensation,reduction and debenzylation.Relatively shorter reaction time,higher yield and convenient work-up were achieved using this method.The regioselectivity of benzylation and reduction method of pyridine ring were also investigated.This novel synthesis route is of significance for synthesis of tetrahedronfolate analogues.
出处
《化学通报》
CAS
CSCD
北大核心
2012年第10期897-902,共6页
Chemistry
基金
国家自然科学基金项目(2097201
2067208)
国家博士点基金项目(20070001742)资助
