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Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene

Aminoglycosides (AGs) represent a large group of pseudoglycoside natural products, in which several different sugar moieties are harnessed to an aminocyclitol core. AGs constitute a major class of antibiotics that target the prokaryotic ribosome of many problematic pathogens. Hundreds of AGs have be...

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Autores principales: Ungarean, Chad N., Galer, Petra, Zhang, Yu, Lee, Ken S., Ngai, Justin M., Lee, Sungjong, Liu, Peng, Sarlah, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536474/
https://www.ncbi.nlm.nih.gov/pubmed/36213185
http://dx.doi.org/10.1038/s44160-022-00080-x
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author Ungarean, Chad N.
Galer, Petra
Zhang, Yu
Lee, Ken S.
Ngai, Justin M.
Lee, Sungjong
Liu, Peng
Sarlah, David
author_facet Ungarean, Chad N.
Galer, Petra
Zhang, Yu
Lee, Ken S.
Ngai, Justin M.
Lee, Sungjong
Liu, Peng
Sarlah, David
author_sort Ungarean, Chad N.
collection PubMed
description Aminoglycosides (AGs) represent a large group of pseudoglycoside natural products, in which several different sugar moieties are harnessed to an aminocyclitol core. AGs constitute a major class of antibiotics that target the prokaryotic ribosome of many problematic pathogens. Hundreds of AGs have been isolated to date, with 1,3-diaminocyclohexanetriol, known as 2-deoxystreptamine (2-DOS), being the most abundant aglycon core. However, owning to their diverse and complex architecture, all AG-based drugs are either natural substances or analogues prepared by late-stage modifications. Synthetic approaches to AGs are rare and lengthy; most studies involve semi-synthetic reunion of modified fragments. Here we report a bottom-up chemical synthesis of the 2-DOS-based AG antibiotic ribostamycin, which proceeds in ten linear operations from benzene. A key enabling transformation involves a Cu-catalyzed, enantioselective, dearomative hydroamination, which set the stage for the rapid and selective introduction of the remaining 2-DOS heteroatom functionality. This work demonstrates how the combination of a tailored, dearomative logic and strategic use of subsequent olefin functionalizations can provide practical and concise access to the AG class of compounds.
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spelling pubmed-95364742022-11-26 Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene Ungarean, Chad N. Galer, Petra Zhang, Yu Lee, Ken S. Ngai, Justin M. Lee, Sungjong Liu, Peng Sarlah, David Nat Synth Article Aminoglycosides (AGs) represent a large group of pseudoglycoside natural products, in which several different sugar moieties are harnessed to an aminocyclitol core. AGs constitute a major class of antibiotics that target the prokaryotic ribosome of many problematic pathogens. Hundreds of AGs have been isolated to date, with 1,3-diaminocyclohexanetriol, known as 2-deoxystreptamine (2-DOS), being the most abundant aglycon core. However, owning to their diverse and complex architecture, all AG-based drugs are either natural substances or analogues prepared by late-stage modifications. Synthetic approaches to AGs are rare and lengthy; most studies involve semi-synthetic reunion of modified fragments. Here we report a bottom-up chemical synthesis of the 2-DOS-based AG antibiotic ribostamycin, which proceeds in ten linear operations from benzene. A key enabling transformation involves a Cu-catalyzed, enantioselective, dearomative hydroamination, which set the stage for the rapid and selective introduction of the remaining 2-DOS heteroatom functionality. This work demonstrates how the combination of a tailored, dearomative logic and strategic use of subsequent olefin functionalizations can provide practical and concise access to the AG class of compounds. 2022-07 2022-05-26 /pmc/articles/PMC9536474/ /pubmed/36213185 http://dx.doi.org/10.1038/s44160-022-00080-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Ungarean, Chad N.
Galer, Petra
Zhang, Yu
Lee, Ken S.
Ngai, Justin M.
Lee, Sungjong
Liu, Peng
Sarlah, David
Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title_full Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title_fullStr Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title_full_unstemmed Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title_short Synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
title_sort synthesis of (+)-ribostamycin by catalytic, enantioselective hydroamination of benzene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536474/
https://www.ncbi.nlm.nih.gov/pubmed/36213185
http://dx.doi.org/10.1038/s44160-022-00080-x
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