摘要
从D0甘露醇出发，经NaIO。氧化、Reformasty反应、脱去异丙叉基保护基团、自身成环合成了吉西他宾关键中间体3，5-双-O-苯甲酰基-2-脱氧-2，2-二氟-1-氧代-D-呋喃核糖。对二氟五元核糖糖环结构中二氟的引入和3-位羟基手性的控制关键反应条件进行了优化。结果表明，将未活化的锌粉加入三烷基氯硅烷、未经重结晶的2，3-O-异丙亚基-》甘油醛直接参与反应，反应温度45℃，顺反产物的选择性提高到1：13，关键中间体3R，3S-2，2-二氟-3-羟基-3-（2，2-二甲基-1，3-二氧戊环-4-基）戊酸乙酯的合成时间从4d缩短到3～12h，目标产物质量总收率76．4％。产物结构经IR与1HNMR确证。
Starting from D-mannital, the key intermediate of gemcitabine, 3, 5-di-O-benzoyl-2-deoxy-2 and 2-difluoro-l-oxo-ribofuranose, was synthesized through sodium periodate oxidation, Reformasty reaction, separating the protective moieties of iso-propyl-benzyliden and cyclization. The introduction of difluoro in the saccharide ring of difluoro-pentahydric-ribose and the control of 3-hydroxyl chirality were optimized. Under the following optimized conditions, i. e. , directly adding inactive zinc powder into trialkyl-phosphine-chlorosilane, using un-reerystallized G2 and reaction temperature 45 ℃, the selectivity of cis-trans products was increased to 1 ： 13 and the time required for the synthesis of G3 was shortened from 4 d to 3 -12 h, with the total yield reaching to 76.4%. The structure of the product was characterized by IR and 1H NMR.
出处
《精细石油化工》
CAS
CSCD
北大核心
2009年第3期1-4,共4页
Speciality Petrochemicals
基金
河南省教育厅自然科学研究资助计划项目(2009C150004)
