De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

Richard T. Desmond; Anniefer N. Magpusao; Chris Lorenc; Jeremy B. Alverson; Nigel Priestley; Mark W. Peczuh

doi:10.3762/bjoc.10.229

De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

Richard T. Desmond, Anniefer N. Magpusao, Chris Lorenc, Jeremy B. Alverson, Nigel Priestley, Mark W. Peczuh

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Natural product-like macrocycles were designed as potential antibacterial compounds. The macrocycles featured a D-glucose unit fused into a 12- or 13-member macrolactone. The rings are connected via the C6' and anomeric (C1') positions of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules. Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds.

Original language	English
Pages (from-to)	2215-2221
Number of pages	7
Journal	Beilstein Journal of Organic Chemistry
Volume	10
DOIs	https://doi.org/10.3762/bjoc.10.229
State	Published - Sep 17 2014

Keywords

Antibiotic
Carbohydrate
Exo-anomeric effect
Macrolide
Structure
Synthesis

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10.3762/bjoc.10.229

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title = "De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles",

abstract = "Natural product-like macrocycles were designed as potential antibacterial compounds. The macrocycles featured a D-glucose unit fused into a 12- or 13-member macrolactone. The rings are connected via the C6' and anomeric (C1') positions of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules. Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds.",

keywords = "Antibiotic, Carbohydrate, Exo-anomeric effect, Macrolide, Structure, Synthesis",

author = "Desmond, \{Richard T.\} and Magpusao, \{Anniefer N.\} and Chris Lorenc and Alverson, \{Jeremy B.\} and Nigel Priestley and Peczuh, \{Mark W.\}",

note = "Publisher Copyright: {\textcopyright} 2014 Desmond et al; licensee Beilstein-Institut.",

year = "2014",

month = sep,

day = "17",

doi = "10.3762/bjoc.10.229",

language = "English",

volume = "10",

pages = "2215--2221",

journal = "Beilstein Journal of Organic Chemistry",

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T1 - De novo macrolide-glycolipid macrolactone hybrids

T2 - Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

AU - Desmond, Richard T.

AU - Magpusao, Anniefer N.

AU - Lorenc, Chris

AU - Alverson, Jeremy B.

AU - Priestley, Nigel

AU - Peczuh, Mark W.

PY - 2014/9/17

Y1 - 2014/9/17

N2 - Natural product-like macrocycles were designed as potential antibacterial compounds. The macrocycles featured a D-glucose unit fused into a 12- or 13-member macrolactone. The rings are connected via the C6' and anomeric (C1') positions of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules. Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds.

AB - Natural product-like macrocycles were designed as potential antibacterial compounds. The macrocycles featured a D-glucose unit fused into a 12- or 13-member macrolactone. The rings are connected via the C6' and anomeric (C1') positions of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules. Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds.

KW - Antibiotic

KW - Carbohydrate

KW - Exo-anomeric effect

KW - Macrolide

KW - Structure

KW - Synthesis

UR - https://www.scopus.com/pages/publications/84910095341

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DO - 10.3762/bjoc.10.229

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SN - 1860-5397

VL - 10

SP - 2215

EP - 2221

JO - Beilstein Journal of Organic Chemistry

JF - Beilstein Journal of Organic Chemistry

ER -

De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

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Keywords

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