Apramycin, a unique aminocyclitol antibiotic

O'Connor, S. C.; Lam, Luke K. T.; Jones, Noel D.; Chaney, Michael O.

doi:10.1021/jo00874a003

Cited by 110 publications

(83 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As the starting material, the readily available 2',3'-isopropylidene-3-methyluridine (6) (23) was chosen. This compound could be prepared from 2',3'-0-isopropylideneuridine in large quantities more easily by methylation with N,Ndimethylformamide dimethyl acetal.…”

Section: Resultsmentioning

confidence: 99%

“…( 6 ) A suspension of 2',3'-0-isopropylideneuridine (35) (7.1 g, 20 mmol) and N,N-dimethylformamide dimethyl acetal (9.5 g, 80 mmol) in chloroform (80 mL) was heated at reflux temperature with vigorous stirring. The mixture became homogeneous within 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…(and a-L-ta1o)-octofuranosyl]-3-methyluracil (24) Hydrolysis of 23 (0.18 g, 0.33 mmol) was performed as described above for 14 and afforded, after preparative tlc (toluene-acetone, 2:3 (vlv)), 24 as a glass (0.13 g, 75%) having R, 0.36 (solvent A); ir (film) v,,,: 3410, 1710, 1670, 1630, 1360, 1 1 8 0~m -~; uv h,,, (EtOH): 227 (E 13 000), 259 (12 000) nm; 'Hmr 6: 1.66-2.01 (4H, m, 2(H-5')'s, 2(H-6')s), 2.46 (3H, s, PhMe), 3.29 (3H,s,NMe),[2][3][4][5][6][7][8]'s, 2OH's), 5.64(1H, d, J 1 * , 2 3 = 3.5 HZ, H-l'), 5.82(1H,d,J5,6= 8.OHz,7.27 (lH,d,m,aromatic H's).…”

Section: -[8-o-aceryl-56-dideoxy-7-0-ptolylsulfonyl-p-~allomentioning

confidence: 99%

“…The product was isolated by the procedure which was used for 14 to give 28 as a syrup (0.75 g, 94%). An analytical sample was obtained by preparative tlc using toluene-acetone, 2:l (vlv) as eluent; ir (film) v, , : 1710, 1670, 1630, 1360, 1180cm-I; uv [2][3][4][5][6][7][8])'s, 2 allylic H's, 2 terminal vinylic H's), m,vinylic H),5.54 (lH,d,J1',2'= 2.0Hz,5.68(1H,d,J5,6= 8 . 0 H~,aromatic H's,.…”

Section: -[8-0-allyl-56-dideoxy-23-o-isopropylidene-7-o-p-mentioning

confidence: 99%

“…Deblocking of the isopropylidene groups of 28 (0.7g, 1.2 mmol) was performed as described above for 14 and afforded, after column chromatography (toluene-acetone, 7:3 (vlv)), 29 as a colorless syrup (0.58g, 89%) having Rf 0.17 (solvent C); ir (film) v,,,: 3430, 1710, 1660, 1355, 1180 cm-I; uv A , , , (EtOH): 227 (E 15 500), 259 (13 500) nm; 'Hmr 6: 1.69-2.02 (4H, m, 2(H-5')'s, 2(H-6')'s), 2.44 (3H, s, PhMe), 3.30 (3H,s,NMe),[2][3][4][5][6][7][8])'s, 2 allylic H's, 2 terminal vinylic H's), 5.62 (IH,d,J1',2' = 3.5 Hz),m,vinylic H),5.76 (IH,d,J5,6= 8.0 Hz,5 aromatic H's). 4 mmol, 50% oil dispersion) at room temperature for 8 h. The reaction mixture was poured into ice-water (40 mL) and the mixture was exhaustively extracted with dichloromethane.…”

Section: -[8-0-allyi-5gdideoxy-7-o-prolylsulfonyl-p -~A L L O (And mentioning

confidence: 99%

See 4 more Smart Citations

Synthesis of 3′,7′-anhydrooctose nucleosides related to the ezomycins and the octosyl acids

Kim¹,

Szarek²

1981

Can. J. Chem.

View full text Add to dashboard Cite

Several novel 3′,7′-anhydrooctose nucleosides, including a 3′,7′-anhydroocturonic acid nucleoside, namely l-(3,7-anhydro-5,6-dideoxy-β-D-allo-octofuranosyluronic acid)-3-methyluracil (40), have been synthesized. The synthetic sequence leading to 40 consists of three key steps: preparation of an octose nucleoside by a chain extension of an uridine derivative using a Wittig reaction, conversion of the octose nucleoside into a bicyclic-octose nucleoside by an intramolecular cyclization, and elaboration of a carboxylic acid function at the C-8′ position of the bicyclic-octose nucleoside. The structures of the 3′,7′-anhydrooctose nucleosides have been established by their uv, 1Hmr, 13Cmr, and mass spectral data.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: -[8-o-aceryl-56-dideoxy-7-0-ptolylsulfonyl-p-~allomentioning

confidence: 99%

Section: -[8-0-allyl-56-dideoxy-23-o-isopropylidene-7-o-p-mentioning

confidence: 99%

Section: -[8-0-allyi-5gdideoxy-7-o-prolylsulfonyl-p -~A L L O (And mentioning

confidence: 99%

See 3 more Smart Citations

Synthesis of 3′,7′-anhydrooctose nucleosides related to the ezomycins and the octosyl acids

Kim¹,

Szarek²

1981

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

Aminoglycosides

Mcgregor

2000

Kirk-Othmer Encyclopedia of Chemical Technology

View full text Add to dashboard Cite

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.

show abstract