Asymmetric Synthesis with Chiral Nucleophilc Catalysts

手性亲核催化剂的不对称合成

• 批准号: 11470468
• 负责人: KAWABATA Takeo
• 金额: $ 7.23万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470468/
• 关键词: nucleophilic catalyst; kinetic resolution; hydrogen bonding; substrate-specificity; acceleration; π-π interaction; meso-diol; proline; 求核触媒; ペプチド; ラクトン化; induced fit; プロリン; ヒドロキシプロリン; アミノアルコール; PPY; DMAP

A chiral nucleophilic catalyst, 4-pyrrolidinopyridine (PPY) analogue, has been developed which could effectively catalyze the acylative kinetic resolution racemic amino alcohol derivatives with selectivity factors of 10 to 54. Kinetic studies of acylation indicated that the observed high enantioselectivity of the acylation promoted by the catalyst is due to the rate acceleration of acylation of one enantiomer rather than the rate deceleration of the other. The origin of the acceleration was revealed to be due to the transition state-hydrogen bonding between a substrate and the catalyst.Chiral PPY analogues were also readily prepared from L-proline. Although these catalysts do not possess chiral elements near the catalytically active pyridine-nitrogen, they promote kinetic resolution of racemic alcohols highly selectively. Contrary to the mechanism of enantioselective acylation by the previously PPY analogue, π-π interaction between an aromatic ring and pyridinium π-system is critical in the chiral nucleophilic catalysts derived from L-proline. A new generation of chiral nucleophilic catalysts with dual functional side chains was successfully prepared from 4-hydroxy-L-proline. These catalysts showed superior chemo- and enantioselectivity in asymmetric desymmetrization of meso-diols.

合成了一种手性亲核催化剂4-吡咯烷并吡啶（PPY）类似物，该催化剂能有效地催化外消旋氨基醇衍生物的酰化动力学拆分，选择性因子为10 ~ 54。酰化反应的动力学研究表明，所观察到的高对映选择性的催化剂促进的酰化是由于一个对映异构体的酰化速率加速，而不是速率减速的其他。研究表明，这种加速反应是由底物与催化剂之间的过渡态氢键作用引起的。虽然这些催化剂在催化活性的吡啶氮附近不具有手性元素，但它们高度选择性地促进外消旋醇的动力学拆分。与PPY类似物的不对称酰化反应机理相反，在L-脯氨酸衍生的手性亲核催化剂中，芳香环与吡啶π-体系之间的π-π相互作用是关键。以4-羟基-L-脯氨酸为原料，成功地合成了新一代具有双功能侧链的手性亲核催化剂。这些催化剂在meso-二醇的不对称去对称化反应中表现出了上级的化学选择性和对映选择性。

项目成果

川端猛夫: "エナンチオマーを分別する人工酵素"Bio Review. 18・8. 16-24 (2001)

川端武夫：“分离对映体的人工酶”18・8（2001）。

Trusar D.Bagul: "Total Synthesis of Spirotryprostatin B via Asymmetric Nitroolefination"Org. Lett.. 4・2. 249-251 (2002)

Trusar D. Bagul：“通过不对称硝基烯化全合成 Spirotryprostatin B”Org. 249-251 (2002)

Takeo Kawabata: "Kinetic resolution of amino alcohol derivatives with a chiral nucleophilic catalyst : access to enantiopure cyclic cis-amino alcohols"Chem. Commun.. 2700-2701 (2001)

Takeo Kawabata：“使用手性亲核催化剂动力学拆分氨基醇衍生物：获得对映体纯的环状顺式氨基醇”Chem.

川端猛夫: "最新酵素利用技術と応用展開"シーエムシー. 71-81 (2001)

川端武雄：《最新酶利用技术及应用开发》CMC 71-81（2001）。

川端猛夫: "最新酵素利用技術と応用展開"シーエムシー. 11 (2001)

川端武雄：《最新酶利用技术及应用开发》CMC 11（2001）。