Synthesis of Novel Anticancer Agents

新型抗癌药物的合成

• 批准号: 7228801
• 负责人: Marisa C Kozlowski
• 金额: $ 19.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-20 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7228801
• 关键词: 3-hydroxybutanal; 9,10-anthraquinone; Accounting; Acids; Anthracenes; Anthraquinones; Antineoplastic Agents; Applications Grants; Area; Biological; Biological Factors; Cellulose; Characteristics; Chemicals; Class; Complex; Copper; Coupled; Coupling; Cues; Cyclization; Development; Diamines; Elements; Family; Flavones; Foundations; Goals; Grant; Hypericin; Hypericum perforatum; Methodology; Methods; Modeling; Molecular; Naphthols; Nature; Object Attachment; Oxidants; Parents; Pathway interactions; Polymers; Positioning Attribute; Process; Property; Reaction; Research; Route; Science; Solid; Source; Staging; Structure; Structure-Activity Relationship; System; United States National Institutes of Health; analog; anthracene; calphostin D; cancer therapy; catalyst; cercosporin; decalin; design; diketone; enol; flavone; hypocrellin A; innovation; interest; novel; programs

DESCRIPTION (provided by applicant): The potential for photodynamic cancer therapy with the perylenequinone and hypericin structural types is especially noteworthy given recent developments in this area. The proposed program focuses on synthesis of such complex natural products and their analogs by mimicking biological oxidative systems. Methods to form C-C bonds via oxidative C-H bond activation while establishing axial chirality will be developed using chiral oxidative catalysts. The possibility of selectivity in these transformations with respect to complex substrates is of significant synthetic potential. If such goals are realized, novel and unique synthetic strategies for the assembly of natural products can be envisioned. Routes to symmetric and dissymmetric chiral binaphthyl, perylenequinone, bisnaphthopyrone, bisanthraquinone, hypericin, and bisflavone natural products are presented.

描述（由申请人提供）：鉴于这一领域的最新发展，用苝醌和金丝桃素结构类型进行光动力癌症治疗的潜力尤其值得注意。该计划的重点是通过模拟生物氧化系统合成这种复杂的天然产物及其类似物。通过氧化C-H键活化形成C-C键同时建立轴向手性的方法将使用手性氧化催化剂开发。在这些转换中相对于复杂的底物的选择性的可能性是显着的合成潜力。如果这些目标得以实现，就可以设想用于组装天然产物的新颖而独特的合成策略。介绍了对称和不对称手性联萘、苝醌、双萘并吡喃酮、双蒽醌、金丝桃素和双黄酮等天然产物的合成路线。

项目成果

Perylenequinone natural products: evolution of the total synthesis of cercosporin.

• DOI: 10.1021/jo9013854
• 发表时间: 2010-01-01
• 期刊: The Journal of organic chemistry
• 作者: Morgan BJ;Mulrooney CA;Kozlowski MC
• 通讯作者: Kozlowski MC

Correction to Aerobic Copper-Catalyzed Organic Reactions.

有氧铜催化有机反应的修正。

• DOI: 10.1021/cr400583n
• 发表时间: 2014
• 期刊: Chemical reviews
• 影响因子: 62.1

Mild aromatic palladium-catalyzed protodecarboxylation: kinetic assessment of the decarboxylative palladation and the protodepalladation steps.

• DOI: 10.1021/jo400222c
• 发表时间: 2013-05-17
• 期刊: The Journal of organic chemistry
• 作者: Dickstein JS;Curto JM;Gutierrez O;Mulrooney CA;Kozlowski MC
• 通讯作者: Kozlowski MC

Perylenequinone natural products: total syntheses of the diastereomers (+)-phleichrome and (+)-calphostin D by assembly of centrochiral and axial chiral fragments.

• DOI: 10.1021/jo901384h
• 发表时间: 2010-01-01
• 期刊: The Journal of organic chemistry
• 作者: Morgan BJ;Mulrooney CA;O'Brien EM;Kozlowski MC
• 通讯作者: Kozlowski MC

Design, synthesis, and investigation of protein kinase C inhibitors: total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones.

• DOI: 10.1021/ja902324j
• 发表时间: 2009-07-08
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Morgan BJ;Dey S;Johnson SW;Kozlowski MC
• 通讯作者: Kozlowski MC