A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
One Pot ◽  
Biologically Relevant ◽  
Cross Coupling Reactions ◽  
Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
One Pot ◽  
Biologically Relevant ◽  
Cross Coupling Reactions ◽  
Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

scholarly journals A Revised Modular Approach to (-)-trans -Δ8 -THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Vol 2019 (12) ◽  
pp. 2289-2296 ◽  
Author(s):  
Victor R. L. J. Bloemendal ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
Thomas J. Boltje ◽  
Jan. C. M. van Hest ◽  
...  
Keyword(s):  
Late Stage ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
Cross Coupling Reactions

scholarly journals Convenient Access to Functionalized Non-Symmetrical Atropisomeric 4,4′-Bipyridines

Compounds ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 58-74
Author(s):  
Emmanuel Aubert ◽  
Emmanuel Wenger ◽  
Paola Peluso ◽  
Victor Mamane
Keyword(s):  
Solid State ◽  
Intermolecular Interactions ◽  
Medicinal Chemistry ◽  
Crystal Packing ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Halogen Bonds ◽  
Cross Coupling Reactions ◽  
Cyano Groups ◽  
Post Functionalization

Non-symmetrical chiral 4,4′-bipyridines have recently found interest in organocatalysis and medicinal chemistry. In this regard, the development of efficient methods for their synthesis is highly desirable. Herein, a series of non-symmetrical atropisomeric polyhalogenated 4,4′-bipyridines were prepared and further functionalized by using cross-coupling reactions. The desymmetrization step is based on the N-oxidation of one of the two pyridine rings of the 4,4′-bipyridine skeleton. The main advantage of this methodology is the possible post-functionalization of the pyridine N-oxide, allowing selective introduction of chlorine, bromine or cyano groups in 2- and 2′-postions of the chiral atropisomeric 4,4′-bipyridines. The crystal packing in the solid state of some newly prepared derivatives was analyzed and revealed the importance of halogen bonds in intermolecular interactions.

scholarly journals Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes via one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions

2020 ◽  
Vol 11 (37) ◽  
pp. 10236-10242
Author(s):  
Yukun Cheng ◽  
Channing K. Klein ◽  
Ian A. Tonks
Keyword(s):  
Small Molecule ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
One Pot ◽  
Cross Coupling Reactions

Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly-substituted pyrrole cores remains challenging.

Pd-Catalyzed one-pot sequential cross-coupling reactions of tetrabromothiophene

2017 ◽  
Vol 15 (48) ◽  
pp. 10289-10298 ◽  
Author(s):  
Kapil Mohan Saini ◽  
Rakesh K. Saunthwal ◽  
Akhilesh K. Verma
Keyword(s):  
Palladium Catalyst ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Arylboronic Acid ◽  
One Pot ◽  
Cross Coupling Reactions ◽  
Sterically Hindered

Unsymmetrical one-pot sequential cross-coupling reactions of sterically hindered tetrabromothiophene with arylboronic acid and an alkyne/alkene to afford selective bi-, tri-, and tetrasubstituted aryl/alkynyl-thiophenes with the aid of a palladium catalyst were described.

ChemInform Abstract: One-Pot Synthesis of Arylated 1-Methyl-1H-indoles by Suzuki-Miyaura Cross-Coupling Reactions of 2,3-Dibromo-1-methyl-1H-indole and 2,3,6-Tribromo-1-methyl-1H-indole.

ChemInform ◽  
2013 ◽  
Vol 44 (52) ◽  
pp. no-no
Author(s):  
Muhammad Farooq Ibad ◽  
Dhafer Saber Zinad ◽  
Munawar Hussain ◽  
Asad Ali ◽  
Alexander Villinger ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Coupling Reactions ◽  
One Pot ◽  
One Pot Synthesis ◽  
Cross Coupling Reactions
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