Chemical modification of some gentamicins and sisomicin at the 3"-position.

Nagabhushan, Tattanahalli L.; Wright, John J.; Cooper, A. B.; Turner, W. N.; Miller, George H.

doi:10.7164/antibiotics.31.43

Cited by 18 publications

(3 citation statements)

References 13 publications

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“…In addition to a few sugars highlighted in the previous paragraph found appended at C-6 of aminoglycoside core aglycons ( 2 , 4 , 8 , 10 , 12 ), 54,62,63 additional sugar diversity has been found at C-6 including: α-D-glucose ( 18 ); 64 3′-amino-3′-deoxy-α-D-xylose 21 (gentamicins and sisomicins) 37,65 and its C-4′-methyl branched 19 (prevalent in a range of aminoglycosides); 51,66,67 C-4′-methyl branched 3′-amino-3′-deoxy-α-D-galactose 20 (combimicins); 56 3′-amino-3′-deoxy-β-L-arabinose ( 22 , gentamicins and related compounds); 37,65 2′-amino-2′-deoxy-α-D-xylose 24 and its corresponding 2′,3′-diamino-2′,3′-dideoxy analog 23 (seldomycins); 58,68 as well as 3′-amino-3′-deoxy-β-D-mannose ( 42 ) and the diasaccharide I [comprised of the uniquely C-6′ oxidized mannose 43 and 2′-amino-2′-deoxy-α-D-xylose ( 24 ) in boholmycin]. 50 Other C-6′-appended sugars include L-streptose ( 28 ), 5′-hydroxy-L-streptose ( 30 ) and the corresponding reduced forms 29 and 31 have been found among streptomycins 69–71 wherein further C-2′ glycosylation of the streptose moiety with 2′-amino-2′-deoxy-α-L-glucose ( 32 ) has been observed.…”

Section: Aminoglycosides and Related Secondary Metabolitesmentioning

confidence: 99%

“…While a diverse range of aglycon glycosylation patterns exist among aminoglycosides, glycosylation at C-4 and C-6 are among the most prevalent. Sugars employed the context of C-4 glycosylation of core aglycons include: the highly deoxygenated diaminosugar 1 and its C-5′ branched 3 and 4 (gentamicins) 39,51 as well as the corresponding C-4′/C-5′-unsaturated variants 2 (sisomycin), 52 15 and 16 (verdamicins); 53 2′-amino-2′-deoxy-α- d -glucose ( 5 ), its C-5′-methyl branched analog 6 (gentamicins) 37 or its 2′-deoxy 14 (nebramycin); 54 6′-amino-6′-deoxy-α- d -glucose ( 7 , gentamicins and combimicins) 37,55 its corresponding 3′-deoxy 9 (combimicins) 56 or its C-5′-methyl branched 11 (gentamicins); 37 2′,6′-diamino-2′,6′-dideoxy-α- d -glucose 10 (combimicins) 55 and its corresponding 3′-deoxy 8 (nebramine and tobramycin); 57 3′-amino-3′-deoxy-α- d -glucose ( 12 , nebramycins) 54 and 2′,6′-diamino-4′-deoxy 13 (seldomycins). 58 The novel 2′,4′-diamino-2′,3′,4′,6′-tetradeoxyhexose 41 comprised the C-4 attachment in minosaminomycin and C-1 in kasugamycin (Fig.…”

Section: Aminoglycosides and Related Secondary Metabolitesmentioning

confidence: 99%

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A comprehensive review of glycosylated bacterial natural products

et al. 2015

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A systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature up through early 2013 is presented. This comprehensive analysis of 15 940 bacterial natural products revealed 3426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts.

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Section: Aminoglycosides and Related Secondary Metabolitesmentioning

confidence: 99%

Section: Aminoglycosides and Related Secondary Metabolitesmentioning

confidence: 99%

A comprehensive review of glycosylated bacterial natural products

et al. 2015

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“…Our synthetic approach for amikacin hapten 14 followed that of the parent drug from kanamycin A (14,15). The order of reactivity for acylation of amino groups in kanamycin A, 5, has been determined as C-6' > C-1 > C-3 > C-3", which makes its direct transformation to 14 by reaction with 10 less attractive.…”

Section: Amikacin Haptenmentioning

confidence: 99%

Controlled coupling of aminoglycoside antibiotics to proteins for use in homogeneous enzyme immunoassays

Singh¹,

Pirio²,

Leung³

et al. 1984

Can. J. Chem.

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Selective N-acylation of aminoglycoside antibiotics with the N-hydroxysuccinimide ester of methyldithioacetic acid, followed by reaction with methanethiol or dithioerythritol, gives sulfhydryl labeled antibiotics. Alternatively, the nucleophilic sulfhydryl group is incorporated into an antibiotic by treatment with N-acetyl-d,l-homocysteine thiolactone. These derivatives couple readily with proteins that have previously been modified with bromoacetylglycyl groups to provide conjugates for use in the development of homogeneous enzyme immunoassays.

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Aminoglycosides

Mcgregor

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Aminoglycosides are members of the class of antibacterial antibiotics, the structures of which are derived from D ‐streptamine, D ‐2‐deoxystreptamine, or closely related compounds. The term aminocyclitol is sometimes used to identify this group of compounds. In 1991, the most widely used aminoglycosides in medical practice were gentamicin, tobramycin, amikacin, and netilmicin. In general, the aminoglycosides are useful for the treatment of serious infections involving aerobic or facultative gram‐negative bacilli. The most common resistance mechanism involves the inactivation of the aminoglycoside by reactions catalyzed by plasmid‐borne enzymes. Less common resistance mechanisms include decreased affinity for the antibiotic by the bacterial ribosome and decreased rate of transport into the bacterial cytoplasm. The aminoglycosides are administered primarily by intravenous infusion or intramuscular injection. Most of the administered dose is eliminated unmetabolized in the urine. Potential toxicity is a primary limiting factor in the clinical use of aminoglycosides. The most important toxicities are nephrotoxicity, ototoxicity, and to a lesser extent, neuromuscular blockade. All the aminoglycosides in medical practice are capable of causing these adverse events. The effect of this potential is to prevent the use of significantly increased doses to cover difficult infections. The bactericidal mechanisms employed by aminoglycosides are incompletely understood. In the cytoplasm, ribosomal binding leads to misreading of the genetic code and production of abnormal proteins and protein synthesis inhibition. The cause of cell death is uncertain. A large amount of research has been conducted aimed at reducing the limitations in the areas of toxicity and susceptibility to bacterial resistance mechanisms while maintaining the advantages by modification of the aminoglycoside molecular structure. Overall, structural modification has been successful in reducing susceptibility to bacterial inactivation. It has not been possible, however, to substantially dissociate the toxicity potential from the antibacterial activity.

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Chemical modification of some gentamicins and sisomicin at the 3"-position.

Cited by 18 publications

References 13 publications

A comprehensive review of glycosylated bacterial natural products

A comprehensive review of glycosylated bacterial natural products

Controlled coupling of aminoglycoside antibiotics to proteins for use in homogeneous enzyme immunoassays

Aminoglycosides

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