A new and improved method for deglycosidation of glycopeptide antibiotics exemplified with vancomycin, ristocetin, and ramoplanin

Wanner, Jutta; Tang, Datong; McComas, Casey C.; Crowley, Brendan M.; Jiang, Wanlong; Moss, Jason A.; Boger, Dale L.

doi:10.1016/s0960-894x(03)00051-9

Cited by 28 publications

(18 citation statements)

References 35 publications

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“…High-yield synthesis of aglycovancomycin (1) and aglycoristocetin (2) ( Fig. 1) was performed as originally described by Wanner et al (2003) and consisted of deglycosidation of the parent antibiotics with hydrogen fluoride in anisole at neutral pH ( Fig. 2) (Sztaricskai et al, 2006).…”

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confidence: 99%

Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

et al. 2009

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Previous studies have demonstrated that glycopeptide compounds carrying hydrophobic substituents can have favorable pharmacological (i.e. antibacterial and antiviral) properties. We here report on the in vitro anti-influenza virus activity of aglycoristocetin derivatives containing hydrophobic side chain-substituted cyclobutenedione. The lead compound 8e displayed an antivirally effective concentration of 0.4 microM, which was consistent amongst influenza A/H1N1, A/H3N2 and B viruses, and a selectivity index > or =50. Structural analogues derived from aglycovancomycin were found to be inactive. The hydrophobic side chain was shown to be an important determinant of activity. The narrow structure-activity relationship and broad activity against several human influenza viruses suggest a highly conserved interaction site, which is presumably related to the influenza virus entry process. Compound 8e proved to be inactive against several unrelated RNA and DNA viruses, except for varicella-zoster virus, against which a favorable activity was noted.

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confidence: 99%

Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

et al. 2009

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“…For comparison, the authentic ramoplanin A1 and A3 aglycons were obtained from the natural ramoplanin complex by deglycosidation (HF) followed by HPLC purification (26). The 1 H NMR spectroscopic data of the synthetic ramoplanin A1 and A3 aglycons (9a͞9b) were in complete agreement with the authentic compounds.…”

Section: Resultsmentioning

confidence: 91%

Total synthesis and structure of the ramoplanin A1 and A3 aglycons: Two minor components of the ramoplanin complex

Shin

Rew

Boger

2004

Proc. Natl. Acad. Sci. U.S.A.

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Ramoplanin is a potent antibiotic, first disclosed in 1984, that acts by inhibiting bacterial cell-wall biosynthesis. The original ramoplanin complex was shown to consist of a mixture of three closely related compounds, ramoplanin A1-A3, of which ramoplanin A2 is the most abundant. The structure of ramoplanin A2 was unambiguously established first through a series of extensive spectroscopic studies, allowing complete stereochemical assignments and subsequently providing a minor reassignment of the side-chain double-bond stereochemistry and, most recently, through total synthesis of authentic material. Here we report the total syntheses of the aglycons of the minor components of the ramoplanin complex, A1 and A3, which unambiguously establish their structure and provide an expected structural revision for the lipid side-chain double-bond stereochemistry. Ramoplanin is a lipoglycodepsipeptide with potent antibacterial activity that was isolated from the fermentation broth of Actinoplanes sp. ATCC 33076 as a mixture of three closely related compounds, 1-3, of which 2 is the most abundant ( Fig. 1) (1, 2). Although less extensively studied, the enduracidins represent closely related antibiotics (3, 4), and the uncharacterized antibiotic janiemycin has been reported to bear an amino acid composition and biological properties that suggest it represents an additional member of this class of natural products (5). The ramoplanin complex is 2-10 times more active than vancomycin against Gram-positive bacteria (6) and exhibits a distinct mode of action (7-12), and the ramoplanin A2 aglycon is equally or slightly more potent than the corresponding natural product in antimicrobial assays (13). Ramoplanin has been shown to inhibit bacterial cell-wall biosynthesis by binding and sequestering lipid intermediates I and II (II Ͼ I), thereby preventing the intracellular glycosyltransferase (MurG) and the more accessible extracellular transglycosylase-catalyzed steps of the peptidoglycan assemblage. As a consequence of its unique mechanism of action, cross-resistance with existing antibiotics including vancomycin or the ␤-lactams has not been observed. Ramoplanin is currently in phase III clinical trials for the oral treatment of intestinal vancomycin-resistant Enterococcus faecium and in phase II trials for nasal methicillin-resistant Staphylococcus aureus.Five years after the report of its isolation, the initial structure of ramoplanin was disclosed in 1989. It was established that compounds 1-3 differ only in the acyl group attached to the Asn-1 N terminus (14-17), and the stereochemistry of the two double bonds in the three different acyl groups was assigned as cis-cis (14). In 1991, the structure of a closely related natural product, ramoplanose (4), was disclosed by Williams and coworkers (18), whose composition was identical to ramoplanin A2 with the exception of the branched mannose trisaccharide attached at Hpg 11 and the stereochemistry of the lipid side chain (cis,trans-vs. cis,cis-7-methyloctadi-2,4-enoic acid). Soon t...

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“…Before attempting the one‐pot glycosylation method (described below; Scheme 1) the GtfE reaction was investigated and optimized. Vancomycin aglycon, prepared by HF‐mediated cleavage of the disaccharide,42 was glycosylated enzymatically with GtfE by using UDP–glucose as the glycosyl donor (Figure 3 a). Previous work has shown that GtfE has optimal activity at 37 °C 43.…”

Section: Resultsmentioning

confidence: 99%

“…1 : The one‐pot enzymatic reaction mixtures at pH 9.0 contained the following: tricine (50 m m) , MgCl 2 (1 m m) , glycerol (10 % v / v ), tris‐(2‐carboxyethyl)phosphine (2 m m) , BSA (0.2 mg mL −1 ), UTP (0.25 m m) , Glc‐1‐P (2.5 m m) , phosphoenolpyruvate (PEP; 2.5 m m) , vancomycin aglycon (2 m m) ,42 inorganic pyrophosphatase (4 U mL −1 ), Ep (50 n m) , GtfE (500 n m) , pyruvate kinase (4 U mL −1 ). Reaction mixtures of up to 20 mL were incubated at 37 °C and monitored by RP‐HPLC.…”

Section: Methodsmentioning

confidence: 99%

Vancomycin Analogues Containing Monosaccharides Exhibit Improved Antibiotic Activity: A Combined One‐Pot Enzymatic Glycosylation and Chemical Diversification Strategy

Thayer

Wong

2006

Chemistry An Asian Journal

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Many natural products contain carbohydrate moieties that contribute to their biological activity. Manipulation of the carbohydrate domain of natural products through multiple glycosylations to identify new derivatives with novel biological activities has been a difficult and impractical process. We report a practical one-pot enzymatic approach with regeneration of cosubstrates to synthesize analogues of vancomycin that contain an N-alkyl glucosamine, which exhibited marked improvement in antibiotic activity against a vancomycin-resistant strain of Enterococcus.

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A new and improved method for deglycosidation of glycopeptide antibiotics exemplified with vancomycin, ristocetin, and ramoplanin

Cited by 28 publications

References 35 publications

Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

Total synthesis and structure of the ramoplanin A1 and A3 aglycons: Two minor components of the ramoplanin complex

Vancomycin Analogues Containing Monosaccharides Exhibit Improved Antibiotic Activity: A Combined One‐Pot Enzymatic Glycosylation and Chemical Diversification Strategy

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