Sulfinate‐Organocatalyzed (3+2) Annulation Reaction of Propargyl or Allenyl Sulfones with Activated Imines

Martzel, Thomas; Lohier, Jean‐François; Gaumont, Annie‐Claude; Brière, Jean‐François; Perrio, Stéphane

doi:10.1002/ejoc.201800749

Cited by 11 publications

(4 citation statements)

References 64 publications

(19 reference statements)

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“…Here, amine 2 was coupled with freshly prepared sulfenyl chloride to give sulfenamide 3. The activation of 3,5-dichlorothiophenol was performed with sulfuryl chloride and acetic acid, as described by Martzel et al 18 The aim was to form the respective sulfinyl chloride and after the reaction with 2 the respective sulfinamide. Surprisingly, the only product found in this reaction was sulfenamide 3.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues

Purder,

Meyners,

Sugiarto

et al. 2023

JACS Au

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Sulfonamides are one of the most important pharmacophores in medicinal chemistry, and sulfonamide analogues have gained substantial interest in recent years. However, the protein interactions of sulfonamides and especially of their analogues are underexplored. Using FKBP12 as a model system, we describe the synthesis of optically pure sulfenamide, sulfinamide, and sulfonimidamide analogues of a well characterized sulfonamide ligand. This allowed us to precisely determine the binding contributions of each sulfonamide oxygen atom and the consequences of nitrogen replacements. We also present high-resolution cocrystal structures of sulfonamide analogues buried in the pocket of a protein target. This revealed intimate contacts with the protein including an unprecedented hydrogen bond acceptor of sulfonimidamides. The use of sulfonamide analogues enabled new exit vectors that allowed remodeling of a subpocket in FKBP12. Our results illuminate the protein interaction potential of sulfonamides/sulfonamide analogues and will aid in their rational design.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues

Purder,

Meyners,

Sugiarto

et al. 2023

JACS Au

View full text Add to dashboard Cite

show abstract

“…Here, amine 2 was coupled with a freshly prepared sulfenyl chloride to give sulfenamide 3. The activation of 3,5-dichlorothiophenol was performed with sulfuryl chloride and acetic acid, as described by MARTZEL et al 18 The aim was to form the respective sulfinyl chloride and after reaction with 2 the respective sulfinamide. Surprisingly, the only product found in this reaction was sulfenamide 3.…”

Section: Resultsmentioning

confidence: 99%

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs

Purder

Meyners

Sugiarto

et al. 2023

Preprint

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Sulfonamides are one of the most important pharmacophores in medicinal chemistry and sulfonamide analogs have gained substantial interest in recent years. However, the protein interactions of sulfonamides and especially of their analogs are underexplored. Using FKBP12 as a model system, we describe the synthesis of optically pure sulfenamide, sulfinamide and sulfonimidamide analogs of a well characterized sulfonamide ligand. This allowed us to precisely determine the binding contributions of each sulfonamide oxygen atom and the consequence of nitrogen replacements. We also present high resolu-tion cocrystal structures of sulfonamide analogs buried in the pocket of a protein target. This revealed intimate contacts with the protein, including an unprecedented hydrogen bond acceptor of sulfonimidamides. The use of sulfonamide analogs ena-bled new exit vectors that allowed to remodel a subpocket in FKBP12. Our results illuminate the protein interaction potential of sulfonamides/sulfonamide analogs and will aid in their rational design.

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“…2306760-67-6) was prepared via a modified version of a previously described procedure. 30 Compound 2-propynyl p -tolyl sulfide 31 (0.36 g, 1.1 equiv, 2.2 mmol) was dissolved in diisopropylamine (4 mL, 0.5 M). Then iodobenzene (0.22 mL, 1 equiv, 2 mmol), PdCl 2 Ph 3 (28 mg, 2 mol %), and CuI (7.6 mg, 2 mol %) were sequentially added.…”

Section: Methodsmentioning

confidence: 99%

From Propargylic Alcohols to Substituted Thiochromenes: gem-Disubstituent Effect in Intramolecular Alkyne Iodo/hydroarylation

et al. 2021

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This work describes the 6- endo - dig cyclization of S -aryl propargyl sulfides to afford 2 H -thiochromenes. The substitution at the propargylic position plays a crucial role in allowing intramolecular silver-catalyzed alkyne hydroarylation and N -iodosuccinimide-promoted iodoarylation. Additionally, a PTSA-catalyzed thiolation reaction of propargylic alcohols was developed to synthesize the required tertiary S -aryl propargyl ethers. The applicability of merging these two methods is demonstrated by synthesizing the retinoic acid receptor antagonist AGN194310.

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Sulfinate‐Organocatalyzed (3+2) Annulation Reaction of Propargyl or Allenyl Sulfones with Activated Imines

Cited by 11 publications

References 64 publications

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues

Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs

From Propargylic Alcohols to Substituted Thiochromenes: gem-Disubstituent Effect in Intramolecular Alkyne Iodo/hydroarylation

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