Synthetic Applications of Formal [3+3] Cycloadditions

形式 [3 3] 环加成的综合应用

• 批准号: 7432490
• 负责人: RICHARD P HSUNG
• 金额: $ 31.01万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432490
• 关键词: Acetylcholinesterase Inhibitors; Ache; Acids; Alkaloids; Amines; Binding; Biological Assay; Biological Factors; Cyclization; Dementia; Development; Family; Goals; In Vitro; Knowledge; Methodology; Methods; Nitrogen; Oxygen; Reaction; Research Personnel; Salts; Variant; amino group; analog; arisugacin; arisugacin A; cycloaddition; hongoquercin A; hyperforin; in vitro Assay; phomactin A; programs

DESCRIPTION (provided by applicant): In the previous proposal, we identified the formal [3 + 3] cycloaddition as a viable approach to arisugacin A, a potent inhibitor of acetylcholinesterase [AChE]. We also recognized the potential of the [3 + 3] reaction as a general methodology for constructing heterocycles including nitrogen heterocycles. We have accomplished those goals. To demonstrate the usefulness of this formal cycloaddition methodology, pursuing its applications in natural product syntheses has become an important focus. Thus, in this competitive renewal, in addition to furthering the medicinal knowledge of arisugacin A for dementias as originally proposed, we intend to pursue syntheses of natural products containing oxygen heterocycles, and to develop a visible program around alkaloid synthesis particularly using the formal aza-[3 + 3] cycloaddition. While we are pursuing several different endeavors, this renewal focuses on selected topics to best illustrate these efforts, and is organized in the following four aims. Specific Aim 1 [Aim 3 in the previous proposal] focuses on synthesis of analogs of arisugacin A using the formal oxa-[3 + 3] cycloaddition and in vitro assay of the analogs to explore binding of arisugacin A to AChE. Specific Aim 2 focuses on applications of formal oxa-[3 + 3] cycloadditions in total syntheses of the natural products hongoquercin A and phomactin A. Specific Aim 3 focuses on employing the oxa-[3 + 3] along with the carbo-[3 + 3] formal cycloaddition toward the synthesis of the hyperforin family of natural products. Specific Aim 4 focuses on applications of formal aza-[3 + 3] cycloadditions toward total syntheses of lepadins and cylindricines, and further development of the intramolecular formal aza-[3 + 3] cycloaddition including its asymmetric variants using chiral Lewis acids and amine salts.

描述（由申请方提供）：在之前的提案中，我们确定了正式的[3 + 3]环加成作为一种可行的方法来制备乙酰胆碱酯酶[AChE]强效抑制剂arisugacin A。我们还认识到[3 + 3]反应作为构建包括氮杂环在内的杂环的一般方法的潜力。我们已经实现了这些目标。 为了证明这种形式的环加成方法的有用性，追求其在天然产物合成中的应用已成为一个重要的焦点。因此，在这个竞争性的更新，除了进一步的药物知识arisugacin A的痴呆症最初提出的，我们打算追求合成的天然产物含有氧杂环，并开发一个可见的程序，生物碱合成，特别是使用正式的氮杂-[3 + 3]环加成。虽然我们正在追求几个不同的努力，这次更新的重点是选定的主题，以最好地说明这些努力，并组织在以下四个目标。 具体目标1 [先前提案中的目标3]侧重于使用正式氧杂-[3 + 3]环加成合成arisugacin A类似物，并对类似物进行体外试验，以探索arisugacin A与AChE的结合。 具体目标2着重于形式氧杂-[3 + 3]环加成在天然产物红栎素A和phomactin A的全合成中的应用。 具体目标3集中于使用氧杂-[3 + 3]沿着碳-[3 + 3]缩甲醛环加成来合成金丝桃素家族的天然产物。 具体目标4侧重于正式氮杂-[3 + 3]环加成对lepadins和cylindricines的全合成的应用，并进一步发展分子内的正式氮杂-[3 + 3]环加成，包括其不对称变体使用手性刘易斯酸和胺盐。

项目成果

A General Approach to the Quinolizidine Alkaloids via an Intramolecular Aza-[3 + 3] Annulation. Synthesis of (±)-2-Deoxy-Lasubine II.

通过分子内 Aza-[3 3] 环化获得喹啉西啶生物碱的一般方法。

• DOI: 10.1055/s-0028-1087661
• 发表时间: 2008
• 期刊: Synlett : accounts and rapid communications in synthetic organic chemistry
• 作者: Zhang,Yu;Gerasyuto,AlekseyI;Long,QuincyA;Hsung,RichardP
• 通讯作者: Hsung,RichardP

Assignment of the C5' relative stereochemistry in (+)-lepadin F and (+)-lepadin G and absolute configuration of (+)-lepadin G.

• DOI: 10.1021/ol9018997
• 发表时间: 2009-10-15
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Li G;Hsung RP
• 通讯作者: Hsung RP

Total syntheses of enantiomerically enriched R-(+)- and S-(-)-deplancheine.

• DOI: 10.1039/b503862f
• 发表时间: 2005-05
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: N. Sydorenko;C. A. Zificsak;A. Gerasyuto;R. Hsung

Stereoselective trans- and cis-dihydroxylations of 2H-pyranyl and dihydropyridinyl heterocycles synthesized from formal [3 + 3]-cycloaddition reactions of alpha,beta-unsaturated iminium ions with 1,3-dicarbonyl equivalents.

由 α,β-不饱和亚胺离子与 1,3-二羰基当量的正式 [3 3]-环加成反应合成的 2H-吡喃基和二氢吡啶基杂环的立体选择性反式和顺式二羟基化。

• DOI: 10.1021/ol010034r
• 发表时间: 2001
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Zehnder,LR;Wei,LL;Hsung,RP;Cole,KP;McLaughlin,MJ;Shen,HC;Sklenicka,HM;Wang,J;Zificsak,CA
• 通讯作者: Zificsak,CA

Total synthesis of (+)-lepadin F.

• DOI: 10.1021/ol802068q
• 发表时间: 2008-11-06
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Li, Gang;Hsung, Richard P.;Slafer, Brian W.;Sagamanova, Irina K.
• 通讯作者: Sagamanova, Irina K.