Efficient Preparation of Optically Active Highly Strained Azirines and Synthesis of Natural and Unnatural Amines and Amino Acids

光学活性高应变氮丙啶的高效制备以及天然和非天然胺和氨基酸的合成

• 批准号: 12450366
• 负责人: SAKAI Takashi
• 金额: $ 8.38万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12450366/
• 关键词: azirine; optically active; lipase; asymmetric synthesis; enzyme; amino acid; low-temperature reaction; aziridine; 固定化酵素; アミノアルコール; 架橋剤

Stereoselective reactions starting from azirines have been developed. In the hydrogenation of aziridine, which was synthesized by the reaction of azirine with AlMe_3, the ring-opening reaction took place at the 3-position specifically to give only β-amino alcohol. Whether the stereochemistry at the 3-position was retained or inverted depended on the solvent used. An interesting correlation was found between the dielectric constants of the solvents and the diastereomeric excess values (% de). We also succeeded in the synthesis of new azirine carboxylic acid ester. Β-Keto ester was reacted with hydroxyl amine to give the corresponding oxime. Treatment with tosyl chloride and triethylamine afforded the new azirine carboxylic acid ester.Although the reaction rate of the lipase-catalyzed kinetic resolution of azirine at -40 ℃ was improved by using lipase immobilized to porous ceramics support, the enantioselectivily was decreased as compared to that obtained with the lipase on Celite. Vario … More us acylating agents were examined to improve the enantioselectivity. Using vinyl butyrate, the E value was increased up to 96, and the catalytic turnover number was improved by more than 10-fold.We have previously found in the lipase-catalyzed kinetic resolution that lowering the reaction temperature results in an increase in enantioselectiviry. In this study, we found that the enantioselectivity is increased according to a thermodynamic equation, but below a critical temperature, the enantioselectivity is decreased according to another equation. We call this temperature "the inversion temperature". In the kinetic resolution of azirine, the change of solvent resulted in the change of the inversion temperature. Furthermore, the change of lipase also resulted in the shift of the inversion temperature. The correlation between the inversion temperatures and various parameters of the solvents was investigated. To investigate the salvation mode for azirine, low-temperature NMR spectra were measured. As a result, complicated factors that are affected by the kinds of lipase and substrate seemed to be responsible for the inversion temperature. Less

从氮杂环开始的立体选择性反应已经被开发出来。在氮杂环丙烷与AlMe_3反应合成的氮杂环丙烷的加氢反应中，开环反应发生在3-位，仅生成β-氨基醇。3-位的立体化学是保留还是颠倒取决于所用的溶剂。在溶剂的介电常数和非对映异构体的超额值(%de)之间发现了一个有趣的相关性。我们还成功地合成了新的氮杂环羧酸酯。将Β-酮酯与羟胺反应生成相应的肟类化合物。用对甲苯磺酰氯和三乙胺处理得到了新的氮杂羧酸酯，固载在多孔陶瓷载体上的脂肪酶虽然在-40℃处提高了脂肪酶催化动力学拆分氮杂环丙烷的反应速度，但与脂肪酶在硅藻土上的反应相比，对映体选择性降低了。Vario…为了提高对映体的选择性，考察了更多的美国酰化剂。使用丁酸乙烯酯，E值提高到96，催化转化率提高了10倍以上。我们以前在脂肪酶催化的动力学拆分中发现，降低反应温度会增加对映体选择性。在本研究中，我们发现对映体选择性按热力学方程增加，但在临界温度以下，对映体选择性按另一方程降低。我们称这个温度为“反转温度”。在动力学拆分中，溶剂的变化导致了转化温度的变化。此外，脂肪酶的变化也导致了转化温度的变化。考察了反转温度与溶剂各参数之间的关系。测定了氮杂环丙烷的低温核磁共振谱，研究了氮杂环丙烷的拯救模式。因此，受脂肪酶种类和底物影响的复杂因素似乎是导致转化温度的原因。较少

项目成果

Tadashi Ema: "High Enantioselectivity and Broad Substrate Specificity of a Carbonyl Reductase : Toward a Versatile Biocatalyst"The Journal of Organic Chemistry. 66巻25号. 8682-8684 (2001)

Tadashi Ema：“羰基还原酶的高对映选择性和广泛的底物特异性：走向多功能生物催化剂”有机化学杂志，第 66 卷，第 25 期。8682-8684 (2001)