Synthesis of pregnane 3-carboxylic acids via Pd-catalyzed alkoxycarbonylation and their effect on NMDA receptor activity

2011 ◽  
Vol 76 (9) ◽  
pp. 1141-1161 ◽  
Author(s):  
Eva Šťastná ◽  
Hana Chodounská ◽  
Vladimír Pouzar ◽  
Jiřina Borovská ◽  
Ladislav Vyklický
Keyword(s):  
Nmda Receptor ◽  
Carboxylic Acid ◽  
Voltage Clamp ◽  
Carboxylic Acids ◽  
Substitution Reaction ◽  
Hippocampal Neurons ◽  
Receptor Activity ◽  
Induced Responses ◽  
Palladium Catalyzed ◽  
Leaving Groups

We have prepared 20-oxo-5α- and 20-oxo-5β-pregnane-3-carboxylic acids by palladium catalyzed alkoxycarbonylation using triflate and nonaflate as the leaving groups in this substitution reaction. The activity of the synthesized compounds was studied in cultured rat hippocampal neurons under voltage-clamp conditions. The 5β-carboxylic acid derivatives were found to diminish NMDA-induced responses, whereas the 5α-derivative potentiated the response.

ChemInform Abstract: Synthesis of Pregnane 3-Carboxylic Acids via Pd-Catalyzed Alkoxycarbonylation and Their Effect on NMDA Receptor Activity.

ChemInform ◽  
2011 ◽  
Vol 43 (1) ◽  
pp. no-no
Author(s):  
Eva Stastna ◽  
Hana Chodounska ◽  
Vladimir Pouzar ◽  
Jirina Borovska ◽  
Ladislav Jr. Vyklicky
Keyword(s):  
Nmda Receptor ◽  
Carboxylic Acids ◽  
Receptor Activity

scholarly journals Stereoselective Palladium-Catalyzed C(sp3)–H Mono-Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group

2021 ◽  
Author(s):  
Amalia-Sofia Piticari ◽  
Daniele Antermite ◽  
Joe I. Higham ◽  
J. Harry Moore ◽  
Matthew P. Webster ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Functional Groups ◽  
One Pot ◽  
Palladium Catalyzed ◽  
Directing Group

A selective Pd-catalyzed C(3)–H cis-functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)–H functionalization reactions, which is facilitated by a DoE optimization. A one-pot C–H functionalization-epimerization procedure provides the trans-3,4-disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall fragment compounds suitable for screening are generated in 3–4 steps from readily-available heterocyclic carboxylic acids.

scholarly journals Direct β- and γ-C(sp3)–H Alkynylation of Free Carboxylic Acids

2020 ◽  
Author(s):  
Francesca Ghiringhelli ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Synthetic Methods ◽  
Broad Scope ◽  
Palladium Catalyzed ◽  
Directing Group

In this study we report the identification of a novel class of ligands for palladium-catalyzed C(sp3)–H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α-quaternary and challenging α-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal γ-position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

scholarly journals Direct β- and γ-C(sp3)–H Alkynylation of Free Carboxylic Acids

2020 ◽  
Author(s):  
Francesca Ghiringhelli ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Synthetic Methods ◽  
Broad Scope ◽  
Palladium Catalyzed ◽  
Directing Group

In this study we report the identification of a novel class of ligands for palladium-catalyzed C(sp3)–H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α-quaternary and challenging α-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal γ-position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

scholarly journals Spontaneous neurotransmission signals through store-driven Ca2+ transients to maintain synaptic homeostasis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Austin L Reese ◽  
Ege T Kavalali
Keyword(s):  
Nmda Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Critical Role ◽  
Elongation Factor ◽  
Protein Translation ◽  
Receptor Activity ◽  
Synaptic Homeostasis ◽  
Group I

Spontaneous glutamate release-driven NMDA receptor activity exerts a strong influence on synaptic homeostasis. However, the properties of Ca2+ signals that mediate this effect remain unclear. Here, using hippocampal neurons labeled with the fluorescent Ca2+ probes Fluo-4 or GCAMP5, we visualized action potential-independent Ca2+ transients in dendritic regions adjacent to fluorescently labeled presynaptic boutons in physiological levels of extracellular Mg2+. These Ca2+ transients required NMDA receptor activity, and their propensity correlated with acute or genetically induced changes in spontaneous neurotransmitter release. In contrast, they were insensitive to blockers of AMPA receptors, L-type voltage-gated Ca2+ channels, or group I mGluRs. However, inhibition of Ca2+-induced Ca2+ release suppressed these transients and elicited synaptic scaling, a process which required protein translation and eukaryotic elongation factor-2 kinase activity. These results support a critical role for Ca2+-induced Ca2+ release in amplifying NMDA receptor-driven Ca2+ signals at rest for the maintenance of synaptic homeostasis.

The Direct Pd-Catalyzed β-C(sp3)–H Activation of Carboxylic Acids

Synlett ◽  
2018 ◽  
Vol 29 (15) ◽  
pp. 1937-1943 ◽  
Author(s):  
Manuel van Gemmeren ◽  
Alexander Uttry
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Bond Activation ◽  
State Of The Art ◽  
Acid Moiety ◽  
Straightforward Manner ◽  
Aliphatic Acids ◽  
Tremendous Progress ◽  
Palladium Catalyzed ◽  
Directing Group

The carboxylic acid moiety is one of the most versatile and abundant functional groups. However, despite of tremendous progress in the field of C–H functionalization reactions its use as a directing group for C(sp3)–H activation has remained limited. In this Synpact article we present the challenges associated with the carboxylic acid moiety as a native directing group and report on the newest developments in this field, including our recent study in which we developed a generally applicable protocol for the direct palladium catalyzed β-C(sp3)–H arylation of propionic acid and related α-branched aliphatic acids giving access to hydrocinnamic acids derivatives in a highly straightforward manner.1 Introduction2 Challenges in the C(sp3)–H Bond Activation of Carboxylic Acids3 History/State of the Art4 Studies towards a General β-C(sp3)–H Functionalization of ­Aliphatic Acids5 Conclusion

scholarly journals Palladium catalyzed oxidative aminations and oxylations: where are we?

2016 ◽  
Vol 88 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Mélanie M. Lorion ◽  
Julie Oble ◽  
Giovanni Poli
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Product Formation ◽  
Sigmatropic Rearrangement ◽  
Reaction Pathways ◽  
Reaction Conditions ◽  
Initial Substrate ◽  
Palladium Catalyzed ◽  
Oxidative Acetoxylation

AbstractSelective product formation in the Pd-catalyzed cyclization of unsaturated amide and carboxylic acid derivatives is an intriguing and challenging task. We recently discovered that the oxidative intramolecular Pd(II)-catalyzed amination or oxylation of unsaturated N-sulfonyl carbamates, N-sulfonyl carboxamides and carboxylic acids takes place through the involvement of cyclic (usually, 5- or 6-membered) aminopalladated (AmPIs) or oxypalladated (OxPI) intermediates. Such cyclic intermediates can undergo a variety of transformations such as distocyclic β-H elimination, oxidative acetoxylation or intramolecular carbopalladation, depending upon the substrate and/or the reaction conditions. In the absence of appropriate reaction pathways, the cyclic nucleopalladated intermediates (NuPIs) simply engage in an inconsequential equilibrium with the initial substrate and other transformations occur such as allylic C–H activation or, in the particular case of allyl carbamates, [3,3]-sigmatropic rearrangement.

Ligand-Enabled γ-C(sp3)–H Olefination of Free Carboxylic Acids

2020 ◽  
Author(s):  
Kiron Kumar Ghosh ◽  
Alexander Uttry ◽  
Francesca Ghiringhelli ◽  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Reaction Mechanism ◽  
Carboxylic Acids ◽  
Michael Addition ◽  
Kinetic Studies ◽  
Wide Range ◽  
Palladium Catalyzed

We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.<br>

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