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

以氮丙啶为原料的立体选择性反应已被开发出来，在氮丙啶与AlMe_3反应合成的氮丙啶中，开环反应专门发生在3位，仅产生β-氨基醇。根据所使用的溶剂，3-位的保留或反转，发现溶剂的介电常数和非对映异构体过量值之间存在有趣的相关性（％）。 de)还成功合成了新的氮丙啶羧酸酯，与羟胺反应得到相应的肟，用甲苯磺酰氯和三乙胺处理得到了新的氮丙啶羧酸酯。通过将脂肪酶固定在多孔陶瓷载体上，提高了-40 ℃下脂肪酶催化氮丙啶的动力学拆分，与使用硅藻土上的脂肪酶获得的结果相比，对映选择性有所降低……我们检查了酰化剂以提高对映选择性，使用丁酸乙烯酯，E 值增加至 96，并且催化周转数提高了 10% 以上。 10倍。我们之前在脂肪酶催化的动力学拆分中发现，降低反应温度会导致对映选择性的增加。在这项研究中，我们发现：根据热力学方程，对映选择性增加，但低于临界温度，根据另一个方程，对映选择性降低，我们将这个温度称为“转化温度”。在氮丙啶的动力学拆分中，溶剂的变化导致了变化。此外，脂肪酶的变化也导致了转化温度的变化，研究了转化温度与溶剂的各种参数之间的相关性。低温核磁共振谱的测量结果表明，受脂肪酶和底物种类影响的复杂因素似乎是造成转化温度的原因。

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)