Synthesis of Complex Terpenes From Simple Precursors
Synthesis of Complex Terpenes From Simple Precursors
批准号:
10387530
负责人:
Thomas John Maimone
金额:
$7.0万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-04-01 至 2025-03-31
关键词:
ArchitectureAwardBiologicalBreathingChemicalsComplexCouplingCyclizationFamilyIsopreneLaboratoriesMedicineMethodologyMethodsNatural ProductsPaclitaxelParentsPathway interactionsProcessPropertyProteinsProteomicsResearchRouteStructureStudentsSynthesis ChemistryTechniquesTerpenesTherapeutic AgentsTrainingTriterpenesWorkanti-cancerartesunatebasechemical synthesiscytotoxicdrug discoveryexhaustionfascinatehuman diseasemembernovelnovel therapeuticsprogramssmall moleculesuccess
中文摘要
家长奖撮要(R01GM116952)
英文摘要
Summary of Parent Award (R01GM116952)
From Taxol® to artesunate to retapamulin, complex terpenes have had a profound impact on both the
treatment and understanding of human disease. Despite their enormous medicinal relevance, however,
most complex terpene architectures are not optimal starting points for exhaustive medicinal and
chemical biological studies, and unlike many small molecule drug discovery programs, it is difficult to
easily mix- and-match structural fragments. The proposed research program seeks to discover and
develop simple, modular synthetic pathways to access complex, medicinally relevant terpenoid natural
products and determine their protein targets. At the core of this proposal is the desire to greatly simplify
terpene synthesis by using simple isoprene-derived units and chiral pool materials in concert with novel
methodologies and synthetic strategies. The targets chosen for this program represent both state-of-
the-art challenges for complex molecule synthesis as well as potential next-generation therapeutics
ideal for in-depth chemical biological studies. Owing to their potent cytotoxic properties, complex
quassinoid triterpenes have remained attractive targets for decades, yet synthetic routes to these
molecules are lengthy and many members have yet to succumb to syntheses at all. Using novel cross-
coupling methodology we have developed a blueprint for facile access to this family. Cyclized, marine
cembranoids represent a structurally fascinating class of terpene targets with intriguing, yet poorly
understood, cytotoxic activities. Despite much work from numerous laboratories, many flagship
members have eluded practitioners of chemical synthesis for decades. Using a chiral pool building block-
based approach and various radical cyclization strategies, we believe many such targets can be accesses
efficiently allowing for their protein targets to be interrogated using cutting-edge proteomics
techniques. Overall this program seeks to use advances in synthetic chemistry to construct rare,
biologically active terpenes with high efficiency allowing interrogation of their anti-cancer properties
and protein targets. In the process of this work, students will be provided with rigorous and
intellectually stimulating training in synthetic chemistry.
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会议论文
Chemical Synthesis and Biology of Complex Alkaloids
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批准号:10598537
-
项目类别:
-
资助金额:$46.09万
-
财政年份:2020
-
负责人:Thomas John Maimone
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依托单位:
Chemical Synthesis and Biology of Complex Alkaloids
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批准号:10372050
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项目类别:
-
资助金额:$46.09万
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财政年份:2020
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负责人:Thomas John Maimone
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依托单位:
Chemical Synthesis and Biology of Complex Alkaloids
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批准号:10593719
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项目类别:
-
资助金额:$2.71万
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财政年份:2020
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负责人:Thomas John Maimone
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依托单位:
Harnessing E3 Ligases for Cancer Therapy
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批准号:10442517
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项目类别:
-
资助金额:$45.4万
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财政年份:2019
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负责人:Thomas John Maimone
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依托单位:
Harnessing E3 Ligases for Cancer Therapy
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批准号:10204971
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项目类别:
-
资助金额:$47.94万
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财政年份:2019
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负责人:Thomas John Maimone
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依托单位:
Harnessing E3 Ligases for Cancer Therapy
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批准号:10656333
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项目类别:
-
资助金额:$43.78万
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财政年份:2019
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负责人:Thomas John Maimone
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依托单位:
Synthesis of Complex Terpenes From Simple Precursors: Renewal
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批准号:10366008
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项目类别:
-
资助金额:$28.51万
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财政年份:2016
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负责人:Thomas John Maimone
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依托单位:
Synthesis of Complex Terpenes From Simple Precursors
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批准号:9705683
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项目类别:
-
资助金额:$10.0万
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财政年份:2016
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负责人:Thomas John Maimone
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依托单位:
Synthesis of Complex Terpenes From Simple Precursors: Renewal
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批准号:10595552
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项目类别:
-
资助金额:$28.51万
-
财政年份:2016
-
负责人:Thomas John Maimone
-
依托单位:
Synthesis of Complex Terpenes From Simple Precursors: Renewal
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批准号:10208395
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项目类别:
-
资助金额:$28.46万
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财政年份:2016
-
负责人:Thomas John Maimone
-
依托单位:
Synthesis of Complex Terpenes From Simple Precursors
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批准号:9458213
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项目类别:
-
资助金额:$27.89万
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财政年份:2016
-
负责人:Thomas John Maimone
-
依托单位:
Synthesis of Complex Terpenes From Simple Precursors
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批准号:9901555
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项目类别:
-
资助金额:$27.75万
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财政年份:2016
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负责人:Thomas John Maimone
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依托单位:
Shape Shifting Phosphines in Transition Metal Catalysis
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批准号:8011297
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项目类别:
-
资助金额:$4.43万
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财政年份:2009
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负责人:Thomas John Maimone
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依托单位:
Shape Shifting Phosphines in Transition Metal Catalysis
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批准号:7744107
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项目类别:
-
资助金额:$4.52万
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财政年份:2009
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负责人:Thomas John Maimone
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依托单位:
Shape Shifting Phosphines in Transition Metal Catalysis
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批准号:8206131
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项目类别:
-
资助金额:$1.2万
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财政年份:2009
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负责人:Thomas John Maimone
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依托单位:
Shape Shifting Phosphines in Transition Metal Catalysis
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批准号:8264337
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项目类别:
-
资助金额:$2.83万
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财政年份:2009
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负责人:Thomas John Maimone
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依托单位:
海外基金