核苷类药物中间体2-脱氧-α-D-核糖-1-磷酸的合成

Synthesis of a intermediate of nucleosides: 2-deoxy-α-D-ribosyl-1-phosphate

2-脱氧-α-D-核糖-1-磷酸是酶法合成核苷类药物的重要中间体,以往的化学合成法立体选择性不高,笔者以α/β混合构型的1-氯-3′,5′-二(O-对氯苯甲酰基)-2-脱氧-D-核糖为原料,采用结晶诱导不对称转化技术,合成了单一构型的2-脱氧-α-D-核糖-1-磷酸盐,HPLC测定其α构型含量为96.8%,总收率82.14%.考察了反应物投料比,反应时间,反应温度等因素的影响,得到了较佳工艺条件为:投料摩尔比为1∶3,-5～0℃下结晶诱导反应23h然后在含有3%环己胺的甲醇溶液中,45℃下反应36h脱除保护基.该工艺反应条件温和、操作简单、产物立体选择性好且收率高,是经济价值较高的合成路线.

2-deoxy-α-D-ribosybl-phosphate is a important intermediate for synthesizing nucleosides. 2- deoxy-α-D-ribosyl-l-phosphate was synthesized from 1-chloro-3 ＇ 5 ＇-di-（4-chlorobenzoyl）-2-deoxy- D-ribose by crystallization-induce asymmetric transformation, The yield of the product was 82.14% with 96. 8 percent of a configuration by HPLC. The influence factors of raw ratio, reaction time and reaction temperature were investigated. The optimum reaction conditions were determined as follows ：The molar ratio of raw ratio was 1.3, reaction temperature was -5 0 ℃, the reaction time was 23 h. The protect group was released with weak-base solution, reacted at 45 ℃ for 36 h in methanol with 3% cyclohexane. The process is mild reaction condition, good stereoseleetivity, convenient to operate with low cost and high yield. This application is proved to be a technique with a higher economic value.