Alkyllithium Cyclizations in Organic Snythesis
Alkyllithium Cyclizations in Organic Snythesis
批准号:
6879156
负责人:
SCOTT D. RYCHNOVSKY
金额:
$23.15万
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-04-01 至 2007-03-31
中文摘要
描述(由申请人提供):合成化学是一项技术
现代药物开发的基础。人类基因组图谱的成功绘制
是识别新受体和治疗途径的第一步
慢性疾病。从双分子靶点到实现改进的路径
在人类健康中通常需要合成小分子激动剂,
拮抗剂或抑制剂。在本提案中,我们将开发一个潜在的
合成小氮和氧螺环的强大方法。新
像这样的合成方法是一种改进技术
人类健康。
腈的还原裂解是一种很少使用的生成方法
烷基锂试剂。在许多六元环中,该反应是完全的
立体选择性,所得烷基锂将与亲电子试剂偶联
保留配置。我们建议使用这种还原锂化
反应,结合与腈基团相邻的容易的烷基化,
开发螺环的通用和立体选择性合成。这个方法
将开发用于制备螺四氢吡喃环。这些还原性的
环化反应将用于一般合成
反热力学螺缩醛,复杂天然结构中常见的结构
产品。第三个发展领域是综合
螺哌啶,其中底物的修饰将允许
选择性制备螺哌啶的构型。
该提案的合成目标是天然产物和
天然产品本身。丙醛酸片段(海绵抑素)和
将使用逆热力学方法制备氮杂螺酸
螺缩醛。 Histrionicotoxin 和 pinnaic 酸将使用以下方法制备
螺哌啶法。这些化合物对于合成和
药物化学家,有刚性、多环和极性类型
在许多测定中发现结构显示出高生物活性。
英文摘要
DESCRIPTION (provided by applicant): Synthetic chemistry is the technology
underlying modern drug development. The successful mapping of the human genome
was the first step towards identifying new receptors and pathways to treat
chronic diseases. The path from bimolecular targets to realizing improvements
in human health usually requires the synthesis of small molecule agonists,
antagonists, or inhibitors. In this proposal we will develop a potentially
powerful method to synthesize small nitrogen and oxygen spiro rings. New
synthetic methods such as this one are an enabling technology for improving
human health.
The reductive cleavage of nitrile is a rarely used method for generating
alkyllithium reagents. In many six-membered rings this reaction is completely
stereoselective, and the resulting alkyllithium will couple with electrophiles
with retention of configuration. We propose to use this reductive lithiation
reaction, in combination with facile alkylations adjacent to nitrile groups, to
develop a general and stereoselective synthesis of spiro rings. This method
will be developed to prepare the spiro-tetrahydropyran rings. These reductive
cyclization reactions will be used in a general synthesis of
contrathermodynamic spiroacetals, structures commonly found in complex natural
products. The third area of development is in the synthesis of
spiropiperidines, where modification of the substrate will allow either
configuration of the spiropiperidine to be prepared selectively.
The synthetic targets for this proposal are segments of natural products and
natural products themselves. Segments of altohyrtin (spongistatin) and
azaspiracid will be prepared using the approach to contrathermodynamic
spiroacetals. Histrionicotoxin and pinnaic acid will be prepared using the
spiropiperidine method. These compounds are of interest to synthetic and
medicinal chemists, and have the types of rigid, polycyclic and polar
structures found to show high bioactivity in many assays.
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DOI:
10.1021/ol801523r
发表时间:
2008-09-18
期刊:
Organic letters
影响因子:
5.2
作者:
[Bahde RJ, Rychnovsky SD]
通讯作者:
Rychnovsky SD
DOI:
10.1021/jo300161x
发表时间:
2012-04-06
期刊:
The Journal of organic chemistry
影响因子:
--
作者:
[Perry MA, Morin MD, Slafer BW, Rychnovsky SD]
通讯作者:
Rychnovsky SD
Generation and utility of tertiary alpha-aminoorganolithium reagents.
叔α-氨基有机锂试剂的产生和应用。
DOI:
10.1021/ol049039p
发表时间:
2004
期刊:
Organic letters.
影响因子:
--
作者:
[Wolckenhauer,ScottA, Rychnovsky,ScottD]
通讯作者:
Rychnovsky,ScottD
DOI:
10.1021/ol050567q
发表时间:
2005-04
期刊:
Organic letters
影响因子:
5.2
作者:
[Matthew D. Morin;S. Rychnovsky]
通讯作者:
Matthew D. Morin;S. Rychnovsky
DOI:
10.1021/ja104250b
发表时间:
2010-07-21
期刊:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子:
15
作者:
[Perry, Matthew A., Morin, Matthew D., Slafer, Brian W., Wolckenhauer, Scott A., Rychnovsky, Scott D.]
通讯作者:
Rychnovsky, Scott D.
共 6 条
ACQUISITION OF A 500 MHZ NMR SPECTROMETER: CHEMISTRY
-
批准号:6973228
-
项目类别:
-
资助金额:$26.05万
-
财政年份:2004
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Acquisition of a 500 MHz NMR Spectrometer
-
批准号:6733320
-
项目类别:
-
资助金额:$26.05万
-
财政年份:2004
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Alkyllithium Cyclizations in Organic Snythesis
-
批准号:6460197
-
项目类别:
-
资助金额:$22.58万
-
财政年份:2002
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Alkyllithium Cyclizations in Organic Snythesis
-
批准号:6722807
-
项目类别:
-
资助金额:$23.21万
-
财政年份:2002
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Alkyllithium Cyclizations in Organic Snythesis
-
批准号:6623001
-
项目类别:
-
资助金额:$23.27万
-
财政年份:2002
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of Anticancer Agents Using Prins Cyclizations
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批准号:6522261
-
项目类别:
-
资助金额:$23.69万
-
财政年份:2001
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of Anticancer Agents Using Prins Cyclizations
-
批准号:6400176
-
项目类别:
-
资助金额:$23.69万
-
财政年份:2001
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of Anticancer Agents Using Prins Cyclizations
-
批准号:6619600
-
项目类别:
-
资助金额:$23.69万
-
财政年份:2001
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
NEW METHODS FOR THE SYNTHESIS OF PHORBOXAZOLE
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批准号:2859180
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项目类别:
-
资助金额:$18.15万
-
财政年份:1998
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负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
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批准号:6865345
-
项目类别:
-
资助金额:$24.77万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
-
批准号:6952461
-
项目类别:
-
资助金额:$26.02万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
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批准号:7263420
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项目类别:
-
资助金额:$7.26万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
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批准号:7114997
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项目类别:
-
资助金额:$25.31万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
NEW METHODS FOR THE SYNTHESIS OF PHORBOXAZOLE
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批准号:2896795
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项目类别:
-
资助金额:$16.41万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
-
批准号:7256896
-
项目类别:
-
资助金额:$24.47万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
NEW METHODS FOR THE SYNTHESIS OF PHORBOXAZOLE
-
批准号:6173848
-
项目类别:
-
资助金额:$16.65万
-
财政年份:1998
-
负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
Synthesis of anticancer agents using Prins cyclization
-
批准号:7448842
-
项目类别:
-
资助金额:$7.45万
-
财政年份:1998
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负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
NEW ION CHANNEL FORMING AMPHOPHILES
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批准号:2518796
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项目类别:
-
资助金额:$6.18万
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财政年份:1993
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负责人:SCOTT D. RYCHNOVSKY
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依托单位:
NEW ION CHANNEL FORMING AMPHOPHILES
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批准号:2165992
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项目类别:
-
资助金额:$6.91万
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财政年份:1993
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负责人:SCOTT D. RYCHNOVSKY
-
依托单位:
NEW ION CHANNEL FORMING AMPHOPHILES
-
批准号:2165993
-
项目类别:
-
资助金额:$6.18万
-
财政年份:1993
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负责人:SCOTT D. RYCHNOVSKY
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依托单位:
海外基金