Synthesis of Bioactive Natural Products and Unnatural Congeners
生物活性天然产物和非天然同系物的合成
基本信息
- 批准号:10714398
- 负责人:
- 金额:$ 36.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AlkaloidsAreaBreathingChemicalsChemistryComplexDevelopmentDiaminesEconomicsHallucinogensIndolesLaboratoriesLysergic Acid DiethylamideMedicineMental DepressionModificationNatural ProductsOxidation-ReductionParkinson DiseasePatternPost-Traumatic Stress DisordersResearchRouteTherapeuticaddictionanalogbioactive natural productsimprovedinnovationmarineneuropsychiatric disordernoveloxidationscaffoldsmall molecule
项目摘要
Project Summary/Abstract
Alkaloid natural products have had an immense impact on the field of therapeutic medicine,
and hold promise for the discovery of new neuropharmacological treatments. One area of
proposed research in the Smith Lab concerns the development of new psychoplastogenic
compounds based on the psychedelic lysergic acid diethylamide (LSD). Although derivatives of
LSD have been explored previously over many decades, derivatives bearing various substitutions
on the indole ring of the ergoline scaffold have never been explored. All of these derivatives are
currently only accessible through total synthesis, and potentially can serve as therapeutic leads
for various neuropsychiatric diseases including Parkinson's disease, PTSD, severe depression,
and addiction. Our concise synthetic approach to the scaffold of LSD hinges on the utilization
and chemical modification of widely available heterocyclic aromatic precursors. This strategy
allows for the exploration of chemical space that would otherwise be inaccessible, however
therapeutically enabling.
Synthetic inspiration drawn from our route to these LSD analogs has led us to investigate the
synthesis of marine macrocyclic diamine alkaloids such as the halicyclamines and the sarains.
None of these targets have been synthesized previously. Our modular, yet redox-economic
platform for assembling these structurally complex compounds hinges on employing heterocyclic
starting materials at higher oxidation levels to efficiently access their congeners with lower redox
levels. Innovation in this research direction is mainly strategic, demanding a navigation of
synthetic assembly that has not been traversed previously. This will also demand tactical
advances in chemistry that will undoubtedly shed light on novel reactivity patterns that will be
broadly important within the realm of heterocyclic chemistry.
项目总结/摘要
生物碱天然产物对治疗医学领域产生了巨大的影响,
并有望发现新的神经药理学治疗方法。的一个区域
史密斯实验室提出的研究涉及新的心理致塑性的发展,
基于迷幻剂麦角酸二乙基酰胺(LSD)的化合物。虽然衍生物
迷幻药已经探索了几十年,衍生物轴承各种取代
在麦角林支架的吲哚环上的作用从未被探索过。所有这些衍生物都是
目前只能通过全合成获得,并可能作为治疗线索
治疗各种神经精神疾病,包括帕金森氏病,创伤后应激障碍,严重抑郁症,
和上瘾。我们对LSD支架的简洁合成方法取决于
和广泛可得的杂环芳族前体的化学改性。这一战略
允许探索化学空间,否则将无法进入,然而,
治疗使能。
从我们获得这些LSD类似物的途径中获得的合成灵感使我们研究了
海洋大环二胺生物碱如盐环胺和sarains的合成。
这些目标以前都没有合成过。我们的模块化,但氧化还原经济
组装这些结构复杂的化合物的平台取决于采用杂环
以更高的氧化水平起始材料,以更低的氧化还原有效地获得它们的同系物
程度.这一研究方向的创新主要是战略性的,需要导航,
以前没有遍历过的合成组件。这也将要求战术
化学的进步,无疑将揭示新的反应模式,
在杂环化学领域中非常重要。
项目成果
期刊论文数量(0)
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