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

有机合成酶促功能有效发挥的研究

• 批准号: 06672115
• 负责人: AKITA Hiroyuki
• 金额: $ 1.15万
• 依托单位: Toho University, School of Pharmaceutical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672115/
• 关键词: lipid-lipase aggregate; water-insoluble substrate; enantioselective hydrolysis; X-ray diffraction; immobilized enzyme; lipase; 4,5-disubstituted-2E-hexenoate; X線回折; エポキシエステル

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

为了对有机溶剂中水不溶的底物进行平滑的酶促反应，开发了一种新型的固定酶，一种脂质脂肪酶骨料。为了制备各种脂质 - 脂肪酶聚集体，新合成了27种二烷基醚型磷脂类似物，并用于用脂肪酶制备聚集体。因此获得的脂质 - 脂肪酶聚集了有效催化水的不对称水解（<plus-minus>） - 水中饱和的异丙基醚产生（S） - α-囊肿 - α-囊肿酯的α-乙乙醚中的α-酰基酯酯，与药物含量高的diltiazem hydrosy hydrosy hydrodey hydrodeymy hydroide，更高效果，高于α-囊肿。水饱和异丙基醚中的合成前聚合物（ENTP-400）。也就是说，反应时间变短了（与21d相比，完成为2至3D），并且发现反应产物的化学和光学产量很高。根据X射线衍射分析，通过超声处理处理获得的醚连接的脂质脂肪酶聚集物被认为在结晶相中堆叠了脂质的Bilayr结构。此外，为了使用脂肪酶合成手性合成，可以实现一种轻松的化学酶途径，以进行光学活性4,5-二苯二酚2e-己酸盐衍生物

项目成果

Hiroyuki Akita,Isao Umezawa,Hiroko Matsukura,Takeshi Oishi: "A Lipid-Lipase Aggregate as a New Type of Immobilized Enzyme" Chem.Pharm.Bull.39. 1632-1633 (1991)

Hiroyuki Akita、Isao Umezawa、Hiroko Matsukura、Takeshi Oishi：“脂质-脂肪酶聚集体作为新型固定化酶”Chem.Pharm.Bull.39。

Shinji Nagumo,Isao Umezawa,Junko Akiyama and Hiroyuki Akita: "Formal Syntheses of N-Trifluoroacetyl-L-acosamine and N-Trifluoroacetyl-L-daunosamine from an Achiral Precursor, Methyl Sorbate" Chem.Pharm.Bull.43. 171-173 (1995)

Shinji Nagumo、Isao Umezawa、Junko Akiyama 和 Hiroyuki Akita：“从非手性前体山梨酸甲酯正式合成 N-三氟乙酰基-L-阿糖胺和 N-三氟乙酰基-L-道诺胺”Chem.Pharm.Bull.43。

Hiroyuki Akita, Isao Umezawa, Michika Takano and Takeshi Oishi: "A Facile Chemoenzymatic Route to Optically Active 4,5-Disubstituted -2E-hexenoate Derivatives. II" Chem.Pharm.Bull.41. 680-684 (1993)

Hiroyuki Akita、Isao Umezawa、Michika Takano 和 Takeshi Oishi：“光学活性 4,5-二取代 -2E-己烯酸酯衍生物的简便化学酶途径。II”Chem.Pharm.Bull.41。

Hiroyuki Akita,Isao Umezawa,Djadjat Tisnadjaja,Hiroko Matsukura and Takeshi Oishi: "Enantioselective Acetylation of an α-Hydroxy Ester by Using Ether-Linked Lipid-Lipase Aggregates in Oraganic Solvents" Chem.Pharm.Bull.41. 16-20 (1993)

Hiroyuki Akita、Isao Umezawa、Djadjat Tisnadjaja、Hiroko Matsukura 和 Takeshi Oishi：“在有机溶剂中使用醚连接的脂质-脂肪酶聚集体对 α-羟基酯进行对映选择性乙酰化”Chem.Pharm.Bull.41（1993 年） ）

Hiroyuki Akita,Isao Umezawa,Djadjat Tisnadjaja Hiroko Matsukura,Takeshi Oishi: "Enantioselective Acetylation of an α-Hydroxy Ester by Using Ether-Linked Lipid Lipase Aggregatesin Organic Solvents" Chem.Pharm.Bull.41. 16-20 (1993)

Hiroyuki Akita、Isao Umezawa、Djadjat Tisnadjaja Hiroko Matsukura、Takeshi Oishi：“使用醚连接的脂质脂肪酶聚集体在有机溶剂中对 α-羟基酯进行对映选择性乙酰化”Chem.Pharm.Bull.41 (1993)。