Aza-Heck/C-C cleavage/cross coupling cascades of pinene derivatives for the synthesis of zoanthamine alkaloids
蒎烯衍生物的 Aza-Heck/C-C 裂解/交叉偶联级联用于合成佐安胺生物碱
基本信息
- 批准号:10328890
- 负责人:
- 金额:$ 6.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AlkaloidsAlkynesArchitectureBiologicalCatalysisCollagen ReceptorsComplexCouplingCyclizationDevelopmentDiseaseLaboratoriesLigandsMediatingMethodologyMethodsNatural ProductsNitrogenOsteoporosisOsteoporoticOximesPharmaceutical ChemistryPharmacologyPlatelet aggregationPreparationProcessPropertyReactionReportingResearch ProposalsRouteSchemeStructureStructure-Activity RelationshipTransition Elementsadductanalogantagonistbasecatalystcitronellaldrug synthesisinterestmetal complexnorzoanthaminerapid techniquescaffoldsmall moleculezoanthenol
项目摘要
PROJECT SUMMARY/ABSTRACT
Nitrogen-containing heterocycles are of considerable interest in medicinal chemistry, often responsible for key
non-bonding interactions that contribute to a molecule’s overall pharmacological activity. The zoanthamine
alkaloids are an example of natural products that display a variety of biological activities mostly attributed to the
heterocyclic portion of their structures. Notable examples include norzoanthamine with potent anti-osteoporotic
properties, and zoanthenol, which is a selective collagen receptor antagonist for inhibiting platelet aggregation.
The difficulties in synthesizing these architecturally complex alkaloids are apparent in the relative dearth of total
syntheses: since their initial isolation in 1984, only two total syntheses have been reported for norzoanthamine
and one for zoanthenol, all of which are considerably lengthy (40+ steps). This project proposes a total synthesis
for zoanthenol using an aza-Heck/C–C cleavage/cross coupling cascade process to provide an overall
convergent approach to the natural product.
The proposed methodology builds upon precedent established by the Sarpong group in utilizing C–C
cleavage/cross coupling as a strategy for rapidly generating complexity from simple, hydroxylated pinenes. The
addition of an aza-Heck reaction to this overall sequence should provide an avenue for introducing N-
heterocycles onto natural product-like structures. Specific Aim I outlines key considerations for introducing an
aza-Heck reaction to the C–C cleavage/cross coupling sequence, and identifying O-acyl oximes as a versatile
precursor for N-heterocycle formation using transition metal catalysis. Specific Aim II then details a total synthesis
of the natural product zoanthenol using the cascade process developed in Specific Aim I as the key coupling
step. This approach should also enable preparations of related derivatives for potential structure-activity
relationship (SAR) studies to fully elucidate the unique bioactivities displayed by the zoanthamine alkaloids.
项目总结/摘要
含氮杂环化合物在药物化学中具有相当大的意义,通常是药物化学中的关键组成部分。
非键相互作用,有助于分子的整体药理活性。Zoanthamine
生物碱是显示出多种生物活性的天然产物的一个例子,
其结构杂环部分。值得注意的例子包括去甲虫胺,
和zoanthenol,其是用于抑制血小板聚集的选择性胶原受体拮抗剂。
合成这些结构复杂的生物碱的困难明显表现在总生物碱的相对缺乏。
合成:自1984年首次分离以来,仅报道了2个去甲虫胺的总合成
和一个zoanthenol,所有这些都是相当长的(40+步骤)。该项目提出了一个全面的综合
对于zoanthenol,使用氮杂-Heck/C-C裂解/交叉偶联级联方法,以提供总体的
对天然产物的收敛方法。
拟议的方法建立在Sarpong集团在利用C-C方面建立的先例基础上
裂解/交叉偶联作为从简单的羟基化的蒎烯快速产生复杂性的策略。的
将氮杂-Heck反应添加到该总序列中应该提供引入N-
杂环化合物到天然产物样结构上。具体目标一概述了引入
aza-Heck反应的C-C裂解/交叉偶联序列,并确定O-酰基肟作为一个通用的
使用过渡金属催化形成N-杂环的前体。具体目标二,然后详细介绍了一个全面的综合
使用特定目标I中开发的级联过程作为关键偶联,
步这种方法也应该使相关衍生物的潜在结构活性的准备工作
相关性(SAR)研究,以充分阐明zoanthamine生物碱显示的独特生物活性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Christina Grace Na', 18)}}的其他基金
Aza-Heck/C-C cleavage/cross coupling cascades of pinene derivatives for the synthesis of zoanthamine alkaloids
蒎烯衍生物的 Aza-Heck/C-C 裂解/交叉偶联级联用于合成佐安胺生物碱
- 批准号:
10540775 - 财政年份:2021
- 资助金额:
$ 6.72万 - 项目类别:
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