STUDY ON THE EFFECTIVE APPEARANCE OF ENZYMATIC FUNCTION DIRECTED TOWARD THE ORGANIC SYNTHESIS

为了使水不溶性底物在有机溶剂中顺利进行酶促反应，研制了一种新型固定化酶——脂脂酶聚合体。为了制备不同种类的脂-脂酶聚集体，新合成了27种二烷基醚型磷脂类似物，并将其用于脂肪酶聚集体的制备。由此得到的脂-脂酶聚合体有效地催化了水不溶性（<正-负>）- α -乙酰氧基酯在水饱和异丙醚中的不对称水解，生成(S)- α -乙酰氧基酯，这是药物活性盐酸地尔硫卓的关键中间体，比用合成预聚物（ENTP-400）固定的脂肪酶在水饱和异丙醚中的效率要高得多。也就是说，反应时间大大缩短（完成时间从21天缩短到2到3天），并且发现反应产物的化学收率和光学收率都很高。通过x射线衍射分析，认为超声处理得到的醚连接脂质-脂肪酶聚集体在结晶相中具有堆积的双层脂质结构。此外，为了利用脂肪酶合成手性合子，实现了一种简单的化学酶法合成具有光学活性的4,5-二取代- 2e -己酸酯衍生物

For the purpose of carrying out smoothly enzymatic reaction of water-insoluble substrates in organic solvents, a new type of immobilized enzyme, a lipid-lipase aggregate, was developed. In order to prepare various kinds of lipid-lipase aggregates, 27 kinds of dialkyl ether-type phospholipid analogues were newly synthesized and used for the preparation of aggregates with lipase. Thus obtained lipid-lipase aggregates catalyzed effectively an asymmetric hydrolysis of water-insoluble (<plus-minus>)-alpha-acyloxy ester in water-saturated isopropyl ether producing (S)-alpha-acyloxy ester, a key intermediate for medicinally active diltiazem hydrochloride, much more efficiently than lipase immobilized with synthetic prepolymer (ENTP-400) in water-saturated isopropyl ether. Namely, the reaction time became much shorter (2 to 3d for completion as compared with 21d) and the chemical and optical yields of the reaction products were found to be high. An ether-linked lipid-lipase aggregate obtained by sonication treatment was considered to have stacked bilayr structure of the lipid in the crystalline phase based on X-ray diffraction analysis. In addition, for the purpose of the synthesis of chiral synthon using lipase, a facile chemoenzymatic route to optically active 4,5-disubstituted-2E-hexenoate derivatives was achieve