Development of Lipase-Catalyzed, Effective, Asymmetric Synthetic Methods
脂肪酶催化、有效、不对称合成方法的开发
基本信息
- 批准号:11672102
- 负责人:
- 金额:$ 0.64万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Nowadays, lipase-catalyzed asymmetric transesterification of alcohols has been widely employed as one of the most efficient asymmetric synthetic methods. For this kind of reactions, we have recently developed a novel class of acyl donor, 1-ethoxyvinyl esters (EVEs), which are superior to the currently-best acyl donors, vinyl esters (VEs). Their advantages involve solution of the deactivation of lipases by the side-product derived from VEs, high reactivity and enantioselectivity, and easy preparation of EVEs having various acyl moieties. By the use of EVEs, this project aims at developing novel asymmetric synthetic methods that could hardly be attained by the previous methods using VEs. The followings are summary of the results :1. 1-Ethoxyvinyl 2-furoate 1 was developed as a highly effective acyl donor for the lipase-catalyzed desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols. The method using 1 features high reactivity and enantiotopic selectivity, applicability for wid … More e range of the substrates, increase of the optical purity of the products through kinetic amplification, and stability of the products under various conditions. 1 was also found to be effective for the desymmetrization of meso-1,2-cycloalkanediols. This protocol was successfully applied for the construction of the pivotal optically active spiro quaternary carbon center of the antitumor antibiotic, fredericamycin A, and thereby a divergent asymmetric synthesis of both enantiomers of its ABCDE-analog was established.2. A novel lipase-catalyzed tandem asymmetric synthesis has been developed, which involves in situ preparation of a 1-ethoxyvinyl acrylate having an electron-withdrawing substituent at the β-position, lipase-catalyzed kinetic resolution of (2-furyl)carbinols, and intramolecular Diels-Alder reaction of thus introduced acyl moiety. This one-pot procedure provides 7-oxabicyclo[2.2.1]heptenes with up to 99% ee. Unprecedented phenomena of the lipase ; viz., catalysis of the Diels-Alder reaction to amplify the enantioselectivity through kinetic resolution was discovered. Less
脂肪酶催化的醇类不对称酯交换反应是目前应用最广泛的一种不对称合成方法。对于这类反应,我们最近开发了一类新的酰基给体,1-乙氧基乙烯酯(EVEs),它优于目前最好的酰基给体乙烯酯(VEs)。其优点是VEs的副产物可以解决脂肪酶的失活问题,具有较高的反应活性和对映选择性,并且易于制备具有各种酰基部分的es。本项目旨在利用电子束合成技术,开发新的不对称合成方法,这是以往的电子束合成方法难以实现的。结果总结如下:1。研究了脂肪酶催化2,2-二取代1,3-丙二醇脱对称反应的高效酰基给体。采用1的方法具有反应活性高、对映体选择性好、适用范围广、底物范围广、通过动力学放大提高产物光学纯度、在各种条件下产物稳定性好等特点。1也被发现对中1,2-环烷二醇的去对称化有效。该方案成功地应用于抗肿瘤抗生素fredericamycin A的关键旋光性螺环季碳中心的构建,从而建立了其abcde类似物的两个对映体的不对称合成。本文提出了一种新的脂肪酶催化串联不对称合成方法,包括原位制备β位置具有吸电子取代基的1-乙氧基丙烯酸酯,脂肪酶催化(2-呋喃基)甲醇的动力学分解,以及由此引入的酰基片段的分子内Diels-Alder反应。这一锅程序提供7-恶沙比环[2.2.1]庚烯高达99%的ee。脂肪酶的空前现象;即发现了Diels-Alder反应通过动力学分辨放大对映体选择性的催化作用。少
项目成果
期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kita,Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donors, 1-Ethoxyvinyl Ester"Journal of Organic Chemistry. 65. 83-88 (2000)
Kita,Yasuyuki:“使用高反应性、无害的酰基供体 1-乙氧基乙烯基酯,方便地酶促拆分醇”有机化学杂志。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Akai,Shuji: "Lipase-Catalyzed Asymmetric Desymmetrization of Prochiral 2, 2-Disubstituted 1,3-Propanediols Using 1-Ethoxyvinyl Benzoate"Chemical Pharmaceutical Bulletin. 48. 1519-1523 (2000)
Akai,Shuji:“使用 1-乙氧基苯甲酸乙烯基酯进行脂肪酶催化的前手性 2, 2-二取代 1,3-丙二醇的不对称去对称化”化学药物通报。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Akai,Shuji: "1-Ethoxyvinyl 2-furoate, an efficient acyl donor for the lipase-catalyzed enantioselective desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols and meso 1,2-diols"Chemical Communications. 1461-1462 (2000)
Akai,Shuji:“1-乙氧基乙烯基 2-糠酸酯,一种有效的酰基供体,用于脂肪酶催化的前手性 2,2-二取代 1,3-丙二醇和内消旋 1,2-二醇的对映选择性去对称化”化学通讯。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Kita Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donors, 1-Ethoxyvinyl Esters"J. Org. Chem.. 65. 83-88 (2000)
Kita Yasuyuki:“使用高反应性、无害的酰基供体 1-乙氧基乙烯基酯,方便地酶法拆分醇”J。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Akai, Shuji: "Studies on Total Synthesis of Antitumor Antibiotic, Fredericamycin A"Advances in Pharmaceutical Sciences. 15. 21-29 (1999)
赤井修二:“抗肿瘤抗生素 Fredericamycin A 的全合成研究”药物科学进展。
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- 影响因子:0
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AKAI Shuji其他文献
AKAI Shuji的其他文献
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{{ truncateString('AKAI Shuji', 18)}}的其他基金
Synthesis of PEGylated drug candidates for PET imaging
用于 PET 成像的聚乙二醇化候选药物的合成
- 批准号:
24659049 - 财政年份:2012
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Nucleophilic deoxyfluorination of phenol derivatives and its application to drug discovery
苯酚衍生物的亲核脱氧氟化及其在药物发现中的应用
- 批准号:
24390005 - 财政年份:2012
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The development of innovative asy mmetric synthetic methods by the enzyme-metal combo catalysis
酶-金属组合催化创新不对称合成方法的发展
- 批准号:
21390005 - 财政年份:2009
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of regioselective reactions of substituted benzynes and its application to synthesis of polysubstituted fused aromatic compounds
取代苯炔区域选择性反应的进展及其在多取代稠合芳香族化合物合成中的应用
- 批准号:
19590008 - 财政年份:2007
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Construction of Carbon Skeleton via Lipase-Catalyzed Domino-Type Syntheses with Dynamic Kinetic Resolution
通过脂肪酶催化的多米诺骨牌动态分辨率合成碳骨架的构建
- 批准号:
17590006 - 财政年份:2005
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Lipase-Catalyzed Domino-Type Asymmetric Syntheses
脂肪酶催化多米诺骨牌型不对称合成的发展
- 批准号:
15590005 - 财政年份:2003
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of New Method for Construction of Chiral, Non-Racemic Quaternary Carbon Center by Enzymatic Acylation of Alcohols and Application Thereof
醇酶酰化构建手性非外消旋季碳中心新方法的开发及其应用
- 批准号:
13672214 - 财政年份:2001
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)