ChemInform Abstract: Ammonium Formate Catalytic Transfer Hydrogenation: A Convenient Method for Removal of Halogenated Benzyloxycarbonyl and Benzyl Protecting Groups in Peptide Synthesis.

Gowda, D. Channe; Rajesh, B.; Gowda, Shankare

doi:10.1002/chin.200107166

Cited by 4 publications

(5 citation statements)

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“…However, the starting compound was recovered intact. Instead, catalytic transfer hydrogenation using dry ammonium formate and 10% Pd/C afforded the amino intermediate 41 in very good yield (89%). Further attachment of 41 , through the formation of amide bonds, to the tripodal ( 3 ) or tetrapodal ( 23 ) central scaffolds afforded intermediates 13 (85%) and 27 (75%), respectively.…”

Section: Resultsmentioning

confidence: 99%

Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors

et al. 2019

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Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection for which no antiviral therapies are available. We describe here the discovery of potent entry dual inhibitors of HIV and EV71. These compounds contain in their structure three or four tryptophan (Trp) residues linked to a central scaffold. Critical for anti-HIV/EV71 activity is the presence of extra phenyl rings, bearing one or two carboxylates, at the C2 position of the indole ring of each Trp residue. The most potent derivatives, 22 and 30, inhibit early steps of the replicative cycles of HIV-1 and EV-A71 by interacting with their respective viral surfaces (glycoprotein gp120 of HIV and the fivefold axis of the EV-A71 capsid). The high potency, low toxicity, facile chemical synthesis, and great opportunities for chemical optimization make them useful prototypes for future medicinal chemistry studies.

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Section: Resultsmentioning

confidence: 99%

Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors

et al. 2019

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“…As previously described for l -Trp, the mild reaction conditions allowed the stereochemical integrity of the Trp unit to be preserved [ 22 ]. Subsequent carboxybenzyl (Cbz) deprotection through catalytic transfer hydrogenolysis [ 26 ] afforded the amino intermediate 3 in good yield (83%). Next, HATU-mediated coupling of 3 with the tetrapodal amino scaffold 4 [ 27 ] afforded intermediate 5 (74%).…”

Section: Resultsmentioning

confidence: 99%

“…First, commercially available benzyl (2-aminoethyl)carbamate 36 was reacted with dimethyl 5-isocyanatoisophthalate to afford urea 37 in 54% yield. Subsequent carboxybenzyl (Cbz) deprotection through catalytic transfer hydrogenolysis, using dry ammonium formate and 10% Pd/C [ 26 ], afforded the amino intermediate 38 . Subsequent coupling to the tetrapodal central scaffold 4 [ 27 ] gave intermediate 39 in 34% yield.…”

Section: Resultsmentioning

confidence: 99%

Insertion of an Amphipathic Linker in a Tetrapodal Tryptophan Derivative Leads to a Novel and Highly Potent Entry Inhibitor of Enterovirus A71 Clinical Isolates

Martí-Marí

Abdelnabi

Schols

et al. 2023

IJMS

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AL-471, the leading exponent of a class of potent HIV and enterovirus A71 (EV-A71) entry inhibitors discovered in our research group, contains four l-tryptophan (Trp) units bearing an aromatic isophthalic acid directly attached to the C2 position of each indole ring. Starting from AL-471, we (i) replaced l-Trp with d-Trp, (ii) inserted a flexible linker between C2 and the isophthalic acid, and (iii) substituted a nonaromatic carboxylic acid for the terminal isophthalic acid. Truncated analogues lacking the Trp motif were also synthesized. Our findings indicate that the antiviral activity seems to be largely independent of the stereochemistry (l- or d-) of the Trp fragment and also that both the Trp unit and the distal isophthalic moiety are essential for antiviral activity. The most potent derivative, 23 (AL-534), with the C2 shortest alkyl urea linkage (three methylenes), showed subnanomolar potency against different EV-71 clinical isolates. This finding was only observed before with the early dendrimer prototype AL-385 (12 l-Trp units) but remained unprecedented for the reduced-size prototype AL-471. Molecular modeling showed the feasibility of high-affinity binding of the novel l-Trp-decorated branches of 23 (AL-534) to an alternative site on the VP1 protein that harbors significant sequence variation among EV-71 strains.

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“…In addition, the side chain γ-amino group in the Dab residue at position 10 was protected with the benzyloxy-carbonyl (Z) group to prevent any potential side reaction between the side chain amino group and the C-terminal thioester during the cyclization step. This group could be removed easily after cyclization using a catalytic hydrogenation reaction …”

Section: Resultsmentioning

confidence: 99%

Chemical Synthesis of a Potent Antimicrobial Peptide Murepavadin Using a Tandem Native Chemical Ligation/Desulfurization Reaction

et al. 2021

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Classical approaches for the backbone cyclization of polypeptides require conditions that may compromise the chirality of the C-terminal residue during the activation step of the cyclization reaction. Here, we describe an efficient epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation in combination with a concomitant desulfurization reaction. Using this approach, bioactive murepavadin was produced in a good yield in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.

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ChemInform Abstract: Ammonium Formate Catalytic Transfer Hydrogenation: A Convenient Method for Removal of Halogenated Benzyloxycarbonyl and Benzyl Protecting Groups in Peptide Synthesis.

Cited by 4 publications

References 0 publications

Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors

Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors

Insertion of an Amphipathic Linker in a Tetrapodal Tryptophan Derivative Leads to a Novel and Highly Potent Entry Inhibitor of Enterovirus A71 Clinical Isolates

Chemical Synthesis of a Potent Antimicrobial Peptide Murepavadin Using a Tandem Native Chemical Ligation/Desulfurization Reaction

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