60618-90-8

Upstream product

• 13291-74-2 gentamicin A 
• 485-80-3 S-adenosyl-L-methionine 
• 51587-77-0 Acetic acid (2R,3R,4R,5R)-4-(benzyloxycarbonyl-methyl-amino)-2-((1S,2S,3R,4S,6R)-4,6-bis-benzyloxycarbonylamino-2,3-dihydroxy-cyclohexyloxy)-5-hydroxy-5-methyl-tetrahydro-pyran-3-yl ester 

Relevant academic research and scientific papers

Synthesis of Gentamicin Minor Components: Gentamicin B1 and Gentamicin X2

The clinical aminoglycoside antibiotic gentamicin is a mixture of several difficult-to-separate major and minor components. The relative inaccessibility of the minor components in particular complicates efforts to separate antibacterial activity from nephro- and/or ototoxicity and to clarify the origin of the potentially therapeutically important read-through activity. With a view to facilitating such studies, the synthesis of a fully and selectively protected garamine-based acceptor has been developed from readily available sisomicin. Glycosylation of this acceptor with a 6-azido-6,7-dideoxy-d-glycero-d-glucoheptopyranosyl donor affords gentamicin B1 after deprotection, whereas employment of a 2-azido-2-deoxy-d-glucopyranosyl donor under N,N-dimethylformamide-directed glycosylation conditions affords gentamicin X2 after deprotection.

Delineating the biosynthesis of gentamicin X2, the common precursor of the gentamicin C antibiotic complex

Gentamicin C complex is a mixture of aminoglycoside antibiotics used worldwide to treat severe Gram-negative bacterial infections. Despite its clinical importance, the enzymology of its biosynthetic pathway has remained obscure. We report here insights into the four enzyme-catalyzed steps that lead from the first-formed pseudotrisaccharide gentamicin A2 to gentamicin X2, the last common intermediate for all components of the C complex. We have used both targeted mutations of individual genes and reconstitution of portions of the pathway in vitro to show that the secondary alcohol function at C-3″ of A2 is first converted to an amine, catalyzed by the tandem operation of oxidoreductase GenD2 and transaminase GenS2. The amine is then specifically methylated by the S-adenosyl-l-methionine (SAM)-dependent N-methyltransferase GenN to form gentamicin A. Finally, C-methylation at C-4″ to form gentamicin X2 is catalyzed by the radical SAM-dependent and cobalamin-dependent enzyme GenD1.

Bausteine von Oligosacchariden, XXI. Synthesen von Gentamicin X2 und am C-4' und C-3' modifizierter Gentamicine

The garamine derivative 18 can be coupled with the β-chloride 15 of 2-azido-2-deoxy-D-glucose to 20 from which, by deblocking procedure, gentamicin X2 (23) is available.In the same manner the 4'-amino- and 4'-chloro compound 24 and 25, resp., can be obtained.Coupling of 26 with 19 gives the product 27 from which the derivative 28 of gentamicin, modified at C-3', is prepared.

Garamine and derivatives thereof

This disclosure relates to the preparation of garamine, its use as an antibacterial, and its use as an intermediate in the novel processes for preparing novel pseudotrisaccharides containing a garamine moiety, and to the use of the novel pseudotrisaccharides as antimicrobial, anthelmintic, antiprotozoal and antiviral agents.