Synthesis of C6-Substituted Purine Nucleoside Analogues via Late-Stage Photoredox/Nickel Dual Catalytic Cross-Coupling

Enantioselective Synthesis of Azamerone

10.26434/chemrxiv.7369844.v1 ◽

2018 ◽

Author(s):

Matthew L. Landry ◽

Grace McKenna ◽

Noah Burns

Keyword(s):

Late Stage ◽

Cross Coupling ◽

Enantioselective Synthesis ◽

Selective Synthesis

A concise and selective synthesis of the dichlorinated meroterpenoid azamerone is described. The paucity of tactics for the synthesis of chiral organochlorides motivated the development of unique strategies for accessing these motifs in enantioenriched forms. The route features a novel enantioselective chloroetherification reaction, a Pd-catalyzed cross-coupling between a quinone diazide and a boronic hemiester, and a late-stage tetrazine [4+2]-cycloaddition/oxidation cascade.

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Enantioselective Synthesis of Azamerone

10.26434/chemrxiv.7369844 ◽

2018 ◽

Author(s):

Matthew L. Landry ◽

Grace McKenna ◽

Noah Burns

Keyword(s):

Late Stage ◽

Cross Coupling ◽

Enantioselective Synthesis ◽

Selective Synthesis

A concise and selective synthesis of the dichlorinated meroterpenoid azamerone is described. The paucity of tactics for the synthesis of chiral organochlorides motivated the development of unique strategies for accessing these motifs in enantioenriched forms. The route features a novel enantioselective chloroetherification reaction, a Pd-catalyzed cross-coupling between a quinone diazide and a boronic hemiester, and a late-stage tetrazine [4+2]-cycloaddition/oxidation cascade.

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

10.26434/chemrxiv.7553444.v1 ◽

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

In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-trans-Δ8-THC derivatives, which can be used to modulate the pharmacologically important CB1 and CB2 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 Δ8-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. 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.

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The Total Synthesis of Rhabdastrellic Acid A

10.26434/chemrxiv.7479944 ◽

2018 ◽

Author(s):

Yaroslav Boyko ◽

Christopher Huck ◽

David Sarlah

Keyword(s):

Total Synthesis ◽

Late Stage ◽

Cross Coupling ◽

Side Chains ◽

General Strategy ◽

Modular Approach ◽

Linear Sequence ◽

Generating Sequence ◽

First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained trans-syn-trans-perhydrobenz[e]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a p-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

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Synthesis of novel racemic carbocyclic nucleoside analogues derived from 4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol and 4-oxatricyclo[4.3.1.03,7]decane-10-methanol, compounds with activity against Coxsackie viruses

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc2008193 ◽

2009 ◽

Vol 74 (3) ◽

pp. 469-485 ◽

Cited By ~ 7

Author(s):

Hubert Hřebabecký ◽

Martin Dračínský ◽

Armando M. De Palma ◽

Johan Neyts ◽

Antonín Holý

Keyword(s):

Alder Reaction ◽

Diels Alder ◽

Purine Nucleoside ◽

Nucleoside Analogues ◽

Lithium Aluminium Hydride ◽

Subsequent Reduction ◽

Lithium Aluminium ◽

Diels Alder Reaction ◽

Carbocyclic Nucleoside ◽

Carbocyclic Nucleoside Analogues

(1R*,2R*,3R*,4S*)-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol (10) and (1R*,2R*,3R*,4S*)-bicyclo[2.2.2]oct-5-ene-2,3-dimethanol (14), which were prepared by the Diels–Alder reaction and subsequent reduction with lithium aluminium hydride, were treated with benzyl azidoformate to give benzylN-[(1R*,2R*,3S*,6S*,7S*,9S*)-9-(hydroxymethyl)-4,8-dioxatricyclo[4.2.1.03,7]nonan-2-yl]carbamate (11) and benzylN-[(1R*,2R*,3R*,6R*,7S*,10S*)-10-(hydroxymethyl)-4-oxatricyclo[4.3.1.03,7]decan-2-yl]carbamate (15). Hydrogenolysis of carbamates11or15afforded (1R*,2R*,3S*,6S*,7S*,9S*)-2-amino-4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol (12) or (1R*,2R*,3R*,6R*,7S*,10S*)-2-amino-4-oxatricyclo[4.3.1.03,7]decane-10-methanol (16). The amines12and16were transformed to thymine and purine nucleoside analogues. The target compounds were tested for the activity againstCoxsackievirus.

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