Structure Diversification of Vancomycin through Peptide-Catalyzed, Site-Selective Lipidation: A Catalysis-Based Approach To Combat Glycopeptide-Resistant Pathogens

Yoganathan, Sabesan; Miller, Scott J.

doi:10.1021/jm501872s

Cited by 62 publications

(40 citation statements)

References 60 publications

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“…18 Toward this goal, we sought to better understand the reactivity of vancomycin’s 6 c -Cl position absent the competing, more favorable, reaction at 2 c -Cl under SM coupling conditions. We identified 2 as a suitable substrate for such studies, and a modified method based on that of Harris et al .…”

mentioning

confidence: 99%

A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin ‘in-chloride’

Wadzinski

Gea

Miller

2016

Bioorganic & Medicinal Chemistry Letters

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In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6c-Cl (the “in-chloride”) position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6c-Cl group were found that ensure high conversion with minimal product decomposition. A set of 2c-dechloro-6c-functionalized vancomycin derivatives was prepared, and antibiotic activities of the compounds were evaluated against a panel of vancomycin-resistant and vancomycin-susceptible strains. Results from biological testing further underscore the steric sensitivity of vancomycin’s binding pocket.

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mentioning

confidence: 99%

A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin ‘in-chloride’

Wadzinski

Gea

Miller

2016

Bioorganic & Medicinal Chemistry Letters

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“…124 Due to the observation that lipophilic antibiotics are more active against bacteria, potentially due to their increased membrane permeability, lipidation is a useful technique to functionalize to natural products and pharmaceuticals. 125–129 …”

Section: Group Transfer To Hydroxyl Groupsmentioning

confidence: 99%

“…(B) Numerous lipidated analogues of vancomycin display heightened biological activity, especially important against VanA and VanB, which are vancomycin resistant. 124 …”

Section: Figurementioning

confidence: 99%

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

2017

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The application of small molecules as catalysts for the diversification of natural product scaffolds is reviewed. Specifically, principles that relate to the selectivity challenges intrinsic to complex molecular scaffolds are summarized. The synthesis of analogs of natural products by this approach is then described as a quintessential “late-stage functionalization” exercise wherein natural products serve as the lead scaffolds. Given the historical application of enzymatic catalysts to the site-selective alteration of complex molecules, the focus of this review is on the recent studies of non-enzymatic catalysts. Reactions involving hydroxyl group derivatization with a variety of electrophilic reagents are discussed. C–H bond functionalizations that lead to oxidations, aminations, and halogenations are also presented. Several examples of site-selective olefin functionalizations and C–C bond formations are also included. Numerous classes of natural products have been subjected to these studies of site-selective alteration including polyketides, glycopeptides, terpenoids, macrolides, alkaloids, carbohydrates and others. What emerges is a platform for chemical remodeling of naturally occurring scaffolds that targets virtually all known chemical functionalities and microenvironments. However, challenges for the design of very broad classes of catalysts, with even broader selectivity demands (e.g., stereoselectivity, functional group selectivity, and site-selectivity) persist. Yet, a significant spectrum of powerful, catalytic alterations of complex natural products now exists such that expansion of scope seems inevitable. Several instances of biological activity assays of remodeled natural product derivatives are also presented. These reports may foreshadow further interdisciplinary impacts for catalytic remodeling of natural products, including contributions to SAR development, mode of action studies, and eventually medicinal chemistry.

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“…4, 5 As such, novel antibiotics that inhibit a panel of multidrug-resistant bacteria is in an urgent need. 6–8 …”

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confidence: 99%

Novel bis-cyclic guanidines as potent membrane-active antibacterial agents with therapeutic potential

Teng

Nimmagadda

et al. 2017

Chem. Commun.

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Structure Diversification of Vancomycin through Peptide-Catalyzed, Site-Selective Lipidation: A Catalysis-Based Approach To Combat Glycopeptide-Resistant Pathogens

Cited by 62 publications

References 60 publications

A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin ‘in-chloride’

A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin ‘in-chloride’

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

Novel bis-cyclic guanidines as potent membrane-active antibacterial agents with therapeutic potential

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