Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine

McCabe, Stephanie R.; Wipf, Peter

doi:10.1055/s-0037-1610395

Cited by 18 publications

(13 citation statements)

References 25 publications

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“… Dirhodium(II,II) complexes containing O , O '‐bridging ligands with structural motive OOCCHHetR; Het=nitrogen, R=tertiary substituent: V1 , [230] V2 , [231] V3 , [231] V4 , [239] V5 , [239] V6 , [240] V7 , [241] V8 , [236] V9 , [242] V10 , [243] V11 , [239] V12 , [244] V13 , [245] V14 , [246] V15 , [239] V16 , [227] V17 , [231] V18 , [235] V19 , [247] V20 , [247] V21 , [247] V22 , [229] V23 , [229] V24 , [248] V25 , [249] V26 [248] …”

Section: Overview Of Rh2a4 Paddlewheel Complexesmentioning

confidence: 99%

Dirhodium(II,II) Paddlewheel Complexes

Hrdina

2021

Eur J Inorg Chem

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This minireview summarizes synthetic approaches towards homoleptic dirhodium(II,II) paddlewheel complexes with the general formula Rh2A4. These complexes have found numerous applications in a wide range of chemical research and industry as catalysts, detectors, enzymatic inhibitors or building blocks for molecular scaffolds. In organic synthesis they are commonly used to transfer electron‐deficient species, they act as Lewis acids to activate unsaturated bonds, serve as hydrogenation catalysts and participate in oxidation/reduction processes. Dirhodium paddlewheel complexes are composed of the Rh‐Rh backbone and four bridging anions, which surround the core. According to the application, the electrochemical potential of the Rh atom can be modulated, as can the geometry and physical and chemical properties of the metal complex. Dirhodium complexes can be prepared in one step from basic inorganic precursors or by post‐functionalization of the paddlewheel structures.

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Section: Overview Of Rh2a4 Paddlewheel Complexesmentioning

confidence: 99%

Dirhodium(II,II) Paddlewheel Complexes

Hrdina

2021

Eur J Inorg Chem

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“…Methylenecyclopropanes (MCPs) are readily accessible four-carbon synthons for the synthesis of natural products as well as medical intermediates. − As the smallest carbocycle with an exomethylene moiety, MCPs have a unique character and display diverse and valuable reactivity under transition-metal catalysis . In recent years, Shi’s group together with other research groups have worked toward significantly broadening the reaction patterns of MCPs under homogeneous gold catalysis.…”

Section: Gold-catalyzed Conversion Of Methylenecyclopropanes (Mcps)mentioning

confidence: 99%

Gold-Catalyzed Conversion of Highly Strained Compounds

et al. 2020

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The past decade has witnessed the golden age of homogeneous gold-catalyzed reactions, especially those that involve the transformation of highly strained molecules into complex molecular architectures. Gold catalysts, with unique electronic properties and catalytic abilities, have elevated versatile reaction modes through π-interaction induced activation. On the basis of increasing research interest in this topic, together with the significant development of various ligands, including phosphine ligands and azacyclic or noncyclic carbene ligands, the understanding of the catalytic function of gold catalysts has become much deeper and more comprehensive. Different reaction needs thus could be adapted by a novel gold catalyst with a diversified ligand selection. Furthermore, the whole evolution of the gold catalysis on synthetic methodologies has realized and expanded its application into natural product synthesis as well as the potentiality of drug discovery, which endows this ancient metal with a magnificent renaissance. The reactivity of strained small ring molecules with high tension has always been an important research topic in organic chemistry. When the highly strained small ring is linked with a π-electron rich moiety or contains a heteroatom, the gold activation of the π-system or coordination with the heteroatom can initiate a cascade reaction, usually followed by ring opening or expansion. These processes can result in the rapid construction of complex and distinct molecular structures, many of which feature in biologically important molecules. In this review, we will mainly summarize the advances on diverse reaction types and molecular constructions accomplished by homogeneous gold catalysis using highly strained substrates, including methylenecyclopropanes (MCPs), vinylidenecyclopropanes (VDCPs), cyclopropenes as well as aziridine- and epoxide-containing molecules, focusing on the last 10 years. For functionalized alkynyl cyclopropanes, several early inspiring and elegant examples will be described in this review for systematically understanding these transformations.

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“…2−4 In comparison to investigations of lysergic acid amides, the therapeutic potential of many other ergot alkaloids has remained underutilized, in spite of their frequently more selective dopamine and serotonin receptor binding profiles. 5,6 For example, (+)-and (−)-cycloclavine were found to show increased selectivity for dopamine D 3 and serotonin 5-HT 1A and 5-HT 2A central nervous system (CNS) receptors, 7,8 and indole fluorination of (+)-lysergol enhanced selectivity among 5-HT receptors compared to D-LSD. 9 Selective agonism at 5-HT 1−7 receptors is a target profile for the treatment of neuropsychiatric conditions, with the potential to yield new classes of therapeutics.…”

mentioning

confidence: 99%

“…Recent clinical results have renewed the interest in d -lysergic acid diethylamide ( d -LSD), first marketed as Delysid by Sandoz Ltd. in 1947, as a medication for depression, anxiety, neurodegeneration, and substance abuse disorders . However, given the strong hallucinogenicity and adverse side effects associated with d -LSD, establishing effective dosing regimens in a controlled clinical environment has remained a challenge. − In comparison to investigations of lysergic acid amides, the therapeutic potential of many other ergot alkaloids has remained underutilized, in spite of their frequently more selective dopamine and serotonin receptor binding profiles. , For example, (+)- and (−)-cycloclavine were found to show increased selectivity for dopamine D 3 and serotonin 5-HT 1A and 5-HT 2A central nervous system (CNS) receptors, , and indole fluorination of (+)-lysergol enhanced selectivity among 5-HT receptors compared to d -LSD . Selective agonism at 5-HT 1–7 receptors is a target profile for the treatment of neuropsychiatric conditions, with the potential to yield new classes of therapeutics. , Furthermore, structural modifications of ergot alkaloids may deliver more effective therapeutic agents compared to the available portfolio of natural products and lysergate amides and avoid ergotism, a disease causing convulsions and gangrene.…”

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confidence: 99%

A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT_1/2 Receptor Selectivity of Lysergols and Isolysergols

Tasker

Wipf

2022

Org. Lett.

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Key transformations in a four-step synthesis of the ergot alkaloid scaffold include a novel cesium carbonate-mediated hydrogen autotransfer alkylation to generate the C(3)–C(4) bond and an intramolecular Heck reaction that directly establishes the C(9)–C(10) alkene of methyl lysergate. An ester reduction and a streamlined experimental procedure establish a readily scalable, expedient total synthesis of all four stereoisomers of lysergol and isolysergol, including the previously unknown (−)-lysergol, for pharmacological evaluation at 5-HT1A and 5HT2A,B,C receptors. A bicyclic scaffold is also characterized for the first time in the intramolecular Heck coupling.

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Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine

Cited by 18 publications

References 25 publications

Dirhodium(II,II) Paddlewheel Complexes

Dirhodium(II,II) Paddlewheel Complexes

Gold-Catalyzed Conversion of Highly Strained Compounds

A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT_1/2 Receptor Selectivity of Lysergols and Isolysergols

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Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine

Cited by 18 publications

References 25 publications

Dirhodium(II,II) Paddlewheel Complexes

Dirhodium(II,II) Paddlewheel Complexes

Gold-Catalyzed Conversion of Highly Strained Compounds

A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT1/2 Receptor Selectivity of Lysergols and Isolysergols

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A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT_1/2 Receptor Selectivity of Lysergols and Isolysergols