Enantiodivergent, Catalytic Asymmetric Synthesis of γ‐Amino Vinyl Sulfones.

Picó, Anna; Moyano, Albert; Pericàs, Miquel À.

doi:10.1002/chin.200342091

Cited by 3 publications

(5 citation statements)

References 1 publication

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“…IR: ν̅ (cm –1 ) = 3334, 3062, 1733, 1584, 1447, 1245, 1145, 1079, 788, 695, ESI-MS: m / z = 410.2 (100, [M + Na] + , calcd 439.2). The analytical data are consistent with those reported in the literature …”

Section: Experimental Sectionsupporting

confidence: 91%

“…The analytical data are consistent with those reported in the literature. 61 Benzyl [(1E)-4-Phenyl-1-(phenylsulfonyl)prop-1-en-2-yl]carbamate (4b). This compound was prepared according to the general procedure using Cbz-L-phenylalanine (1b, a) 134 mg, 0.9 mmol, b) 4.50 g, 15 mmol, 3.00 equiv) and trans-1,2-bis-(phenylsulfonyl)ethylene ((a) 93 mg, 0.3 mmol, (b) 1.50 g, 5 mmol, 1.00 equiv).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Kammer¹,

Lipp²,

Opatz³

2018

J. Org. Chem.

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The synthesis of vinyl sulfones and (α,β-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777.

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Section: Experimental Sectionsupporting

confidence: 91%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Kammer¹,

Lipp²,

Opatz³

2018

J. Org. Chem.

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“…20 Sharpless asymmetric epox- idation of 9 using (−)-diethyl D-tartrate under standard conditions provided epoxide 10 in excellent yield. 21 Regioselective opening of epoxide with TMSN 3 and Ti(O-i Pr) 4 in benzene at 80 °C for 2 h afforded azidodiol 11 in 55% yield. 22 This was treated with 2-acetoxyisobutyryl chloride in chloroform to form the corresponding chloroacetate which was reacted with sodium methoxide to provide epoxide 12 in excellent yield.…”

Section: ■ Chemistrymentioning

confidence: 99%

“…Reaction of commercially available butadiene monoxide 8 with 3-benzyloxyphenylmagnesium bromide in the presence of a catalytic amount of CuCN provided ( E )-allylic alcohol 9 . Sharpless asymmetric epoxidation of 9 using (−)-diethyl d -tartrate under standard conditions provided epoxide 10 in excellent yield . Regioselective opening of epoxide with TMSN 3 and Ti(O- i Pr) 4 in benzene at 80 °C for 2 h afforded azidodiol 11 in 55% yield .…”

Section: Chemistrymentioning

confidence: 99%

Structure-Based Design of Potent HIV-1 Protease Inhibitors with Modified P1-Biphenyl Ligands: Synthesis, Biological Evaluation, and Enzyme–Inhibitor X-ray Structural Studies

Ghosh

Osswald

et al. 2015

J. Med. Chem.

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We report the design, synthesis, X-ray structural studies, and biological evaluation of a novel series of HIV-1 protease inhibitors. We designed a variety of functionalized biphenyl derivatives to make enhanced van der Waals interactions in the S1 subsite of HIV-1 protease. These biphenyl derivatives were conveniently synthesized using a Suzuki-Miyaura cross-coupling reaction as the key step. We examined the potential of these functionalized biphenyl-derived P1 ligands in combination with 3-(S)-tetrahydrofuranyl urethane and bis-tetrahydrofuranyl urethane as the P2 ligands. Inhibitor 21e, with a 2-methoxy-1, 1’-biphenyl derivative as P1 ligand and bis-THF as the P2 ligand, displayed the most potent enzyme inhibitory and antiviral activity. This inhibitor also exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray crystal structure of related Boc-derivative 17a-bound HIV-1 protease provided important molecular insight into the ligand-binding site interactions of the biphenyl core in the S1 subsite of HIV-1 protease.

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“…We further extended the above mentioned synthetic strategy to synthesize γ-phenyl-γ-amino vinyl sulfone 6 . So far, there is only one synthetic procedure reported in the literature for the synthesis of γ-phenyl-γ-amino vinyl sulfone 6 in eight steps by Picó et al employing sharpless asymmetric epoxidation of cinnamyl alcohol . We synthesized γ-phenyl-γ-amino vinyl sulfone 6 in four steps starting from commercially available (±)-2-phenylglycinol 14 .…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Synthesis of γ-Phenyl-γ-amino Vinyl Phosphonates and Sulfones and Their Application to the Synthesis of Novel Highly Potent Antimalarials

et al. 2020

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Racemic and enantioselective syntheses of γ-phenyl-γ-amino vinyl phosphonates and sulfones have been achieved using Horner–Wadsworth–Emmons olefination of trityl protected α-phenyl-α-amino aldehydes with tetraethyl methylenediphosphonate and diethyl ((phenylsulfonyl)methyl)phosphonate, respectively, without any racemization. The present strategy has also been successfully applied to the synthesis of peptidyl vinyl phosphonate and peptidyl vinyl sulfone derivatives as potential cysteine protease inhibitors of Chagas disease, K11002, with 100% de. The developed synthetic protocol was further utilized to synthesize hybrid molecules consisting of artemisinin as an inhibitor of major cysteine protease falcipain-2 present in the food vacuole of the malarial parasite. The synthesized artemisinin–dipeptidyl vinyl sulfone hybrid compounds showed effective in vitro inhibition of falcipain-2 and potent parasiticidal efficacies against Plasmodium falciparum in nanomolar ranges. Overall, the developed synthetic protocol could be effectively utilized to design cysteine protease inhibitors not only as novel antimalarial compounds but also to be involved in other life-threatening diseases.

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Enantiodivergent, Catalytic Asymmetric Synthesis of γ‐Amino Vinyl Sulfones.

Cited by 3 publications

References 1 publication

Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Structure-Based Design of Potent HIV-1 Protease Inhibitors with Modified P1-Biphenyl Ligands: Synthesis, Biological Evaluation, and Enzyme–Inhibitor X-ray Structural Studies

Enantioselective Synthesis of γ-Phenyl-γ-amino Vinyl Phosphonates and Sulfones and Their Application to the Synthesis of Novel Highly Potent Antimalarials

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