CAJ | 학술논문

(-)-(1R,4S)-N-(叔丁氧羰基)-2-氮杂双环[2.2.1]庚-5-烯-3-酮是抗艾滋病药物阿巴卡韦的重要中间体。今以2-氮杂双环[2.2.1]庚-5-烯-3-酮为原料，先与(Boc)2O反应生成外消旋体(±)-N-(叔丁氧羰基)-2-氮杂双环[2.2.1]庚-5-烯-3-酮，再以固定化脂肪酶作为拆分试剂选择性拆分制得。试验中分别使用了三种酶，三种酶均表现出较好的反应活性和较高的反应收率，其中固定化酶Lipozyme RM IM的反应活性最高，对其催化的酶促反应进行了优化，得到最佳的反应条件：以异丙醚为反应溶剂，酶与底物质量投料比为1.5/2.0，反应温度为30℃，收率46.5%，对映体过量大于99%。结构经1H-NMR确证。该方法成本低，酶的选择性、催化活性和反应收率高。
(-)-(1R,4S)-N-(숙정양탄기)-2-담잡쌍배[2.2.1]경-5-희-3-동시항애자병약물아파잡위적중요중간체。금이2-담잡쌍배[2.2.1]경-5-희-3-동위원료，선여(Boc)2O반응생성외소선체(±)-N-(숙정양탄기)-2-담잡쌍배[2.2.1]경-5-희-3-동，재이고정화지방매작위탁분시제선택성탁분제득。시험중분별사용료삼충매，삼충매균표현출교호적반응활성화교고적반응수솔，기중고정화매Lipozyme RM IM적반응활성최고，대기최화적매촉반응진행료우화，득도최가적반응조건：이이병미위반응용제，매여저물질량투료비위1.5/2.0，반응온도위30℃，수솔46.5%，대영체과량대우99%。결구경1H-NMR학증。해방법성본저，매적선택성、최화활성화반응수솔고。
(?)-(1R,4S)-N-(tert-Butoxycarbonyl)-2-azabicyclo[2.2.1]hept-5-en-3-one is an important intermediate of abacavir which is widely used in AIDS treatment. This chemical was prepared with 2-azabicyclo-[2.2.1]hept-5-en-3-one(2) as the starting material in this study. The starting material(2) was first reacted with (Boc)2O to give the raceme (±)-N-(tert-Butoxycarbonyl)-2-azabicyclo[2.2.1]hept-5-en-3-one(3) via amidation. The key intermediate was preparedvia a prominent turnover from the raceme(3) with immobilized lipases, and its structure was identified by1H-NMR. The optimum conditions of the enzymatic reaction were as follows: Lipozyme RM IM andisopropyl elther were used as the enzyme reaction catalyst, and reaction solvent separatively, the mass ratio of enzyme: substrate 1.5/2.0 and the reaction temperature of 30℃. The yield can reach to 46.5% under these optimal conditions with enantiomeric excess up to 99%. This synthetic process is suitable for large-scale manufacture due to the cheap available material and higher catalytic activity and selectivity of the lipase.