53176-87-7

Basic information

• Product Name: 2′,3′-di-O-benzoyl-L-erythronolactone
• Synonyms: 2′,3′-di-O-benzoyl-L-erythronolactone
• CAS NO: 53176-87-7
• Molecular Weight: 326.306
• Mol File: 53176-87-7.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 2′,3′-di-O-benzoyl-L-erythronolactone(CAS DataBase Reference)
• NIST Chemistry Reference: 2′,3′-di-O-benzoyl-L-erythronolactone(53176-87-7)
• EPA Substance Registry System: 2′,3′-di-O-benzoyl-L-erythronolactone(53176-87-7)

Safety Data

• Hazardous Substances Data: 53176-87-7(Hazardous Substances Data)

Upstream product

• 488-16-4 threonic acid 
• 98-88-4 benzoyl chloride 
• 13092-55-2 DL-threonic acid-4-lactone 
• 15667-21-7 D-erythronolactone 
• 23732-40-3 L-erythrono-1,4-lactone 
• 89-65-6 isoascorbic acid 

Relevant articles and documents

Apralogs: Apramycin 5- O-Glycosides and Ethers with Improved Antibacterial Activity and Ribosomal Selectivity and Reduced Susceptibility to the Aminoacyltranserferase (3)-IV Resistance Determinant

Apramycin is a structurally unique member of the 2-deoxystreptamine class of aminoglycoside antibiotics characterized by a monosubstituted 2-deoxystreptamine ring that carries an unusual bicyclic eight-carbon dialdose moiety. Because of its unusual structure, apramycin is not susceptible to the most prevalent mechanisms of aminoglycoside resistance including the aminoglycoside-modifying enzymes and the ribosomal methyltransferases whose widespread presence severely compromises all aminoglycosides in current clinical practice. These attributes coupled with minimal ototoxocity in animal models combine to make apramycin an excellent starting point for the development of next-generation aminoglycoside antibiotics for the treatment of multidrug-resistant bacterial infections, particularly the ESKAPE pathogens. With this in mind, we describe the design, synthesis, and evaluation of three series of apramycin derivatives, all functionalized at the 5-position, with the goals of increasing the antibacterial potency without sacrificing selectivity between bacterial and eukaryotic ribosomes and of overcoming the rare aminoglycoside acetyltransferase (3)-IV class of aminoglycoside-modifying enzymes that constitutes the only documented mechanism of antimicrobial resistance to apramycin. We show that several apramycin-5-O-β-d-ribofuranosides, 5-O-β-d-eryrthofuranosides, and even simple 5-O-aminoalkyl ethers are effective in this respect through the use of cell-free translation assays with wild-type bacterial and humanized bacterial ribosomes and of extensive antibacterial assays with wild-type and resistant Gram negative bacteria carrying either single or multiple resistance determinants. Ex vivo studies with mouse cochlear explants confirm the low levels of ototoxicity predicted on the basis of selectivity at the target level, while the mouse thigh infection model was used to demonstrate the superiority of an apramycin-5-O-glycoside in reducing the bacterial burden in vivo.

APRAMYCIN DERIVATIVES

The invention relates to derivatives of apramycin-based aminoglycoside antibacterial drugs modified in positions C5 and/or C6 and O5 and/or O6. The modifications impart favourable properties regarding increased selectivity and retention of activity in the presence of resistance determinants of the AAC(3) class. The invention further relates to said compounds for use in the therapy of bacterial infection by systemic administration, especially in instances where the infection is caused by a pathogen comprising a resistance determinant of the AAC(3) class, in particular AAC(3)-IV.