Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity.

Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Research Abstract Details 

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Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Abstract Text:

Yosup Rew,Dongwoo Shin,Inkyu Hwang,Dale L Boger,

The total synthesis and evaluation of three key ramoplanin aglycon analogues are detailed. The first (5a) represents replacement of the labile depsipeptide ester with a stable amide (HAsn2 --> Dap2) with removal of the HAsn pendant carboxamide, and it was found to be slightly more potent than the natural aglycon in antimicrobial assays providing a new lead structure with an improved profile and a more stable and accessible macrocyclic template on which to conduct structure-function studies. In contrast, a second amide analogue 5b which contains a single additional methylene relative to 5a (HAsn2 --> Dab2) was found to be inactive in antimicrobial assays (>100-fold loss in activity). The third key analogue 5c in which the Asn1 lipid side chain was replaced with an acetyl group revealed that it contributes significantly to the antimicrobial activity (16-fold) of the ramoplanins, but is not essential.

Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Publishing Authors By Initials

Y Rew,D Shin,I Hwang,DL Boger,

For similar bacteria: gram-positive bacteria: gram-positive cocci: staphylococcaceae: staphylococcus: staphylococcus aureus research abstracts see: bacteria: gram-positive bacteria: gram-positive cocci: staphylococcaceae: staphylococcus: staphylococcus aureus research

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Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 126

Page Numbers: 1041-3

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 4

MONTH: Feb

YEAR: 2004

Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Keywords Mesh Terms:

KEYWORDS: Staphylococcus aureus

MESH TERMS: drug effects

Chemical & Substance for Abstract: Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Information

Substance Name: ramoplanin

Registry Number: 76168-82-6

Grant and Affiliation Information for Total synthesis and examination of three key analogues of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity.

AFFILIATION: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA41101

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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