Preparation of Erythromycin Analogs Having Functional Groups at C-15

Ashley, Gary W.; Burlingame, Mark A.; Desai, Ruchir P.; Fu, Huimin; Leaf, Tim; Licari, Peter; Tran, Chau Q.; Abbanat, Darren; Bush, Karen; Macielag, Mark J.

doi:10.1038/ja.2006.56

Cited by 22 publications

(15 citation statements)

References 14 publications

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“…Later, a series of C9‐oximes ether ketolides bearing N‐aryl–alkyl acetamides were also synthesized, where the length of the alkyl group differed by up to five atoms (Iwaki et al ., ; Nomura et al ., ; Nomura et al ., ). Other structure modifications included the following: modified 5‐ O ‐desosamine ketolides (Chen et al ., ), fluorination at the C2‐ and/or C12 positions (Denis and Bonnefoy, ; Krokidis et al ., ), variation of the cyclic carbonate and hydrazono‐carbamate at 11,12 positions (Hunziker et al ., ; Andreotti et al ., ; Zhu et al ., ) or variation of the aglycon ring (Shaw et al ., ; Ashley et al ., ; Sugimoto and Tanikawa, ). Lastly, modifications also included replacement of desosamine with different sugars (Liang et al ., ; Romero et al ., ; Chen et al ., ).…”

Section: Antimicrobial Activity and Chemical Derivatizationmentioning

confidence: 97%

The macrolide antibiotic renaissance

Dinos

2017

British J Pharmacology

326

221

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Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases.

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Section: Antimicrobial Activity and Chemical Derivatizationmentioning

confidence: 97%

The macrolide antibiotic renaissance

Dinos

2017

British J Pharmacology

326

221

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“…A KS1 null strain of DEBS has been used to diversify starter units in addition to modifying other positions in erythromycin [60]. This mutasynthesis approach has afforded analogues modified with various non-natural alkyl substituents, in addition to fluoro, azido, and alkynl derivatives [4,43]. More recently, this approach was applied in E. coli and coupled with a colony bioassay and resulted in the identification of 15-propargyl erythromycin A [51].…”

Section: Promiscuity and Engineering Of Pks/nrps Assembly Linesmentioning

confidence: 99%

Harnessing natural product assembly lines: structure, promiscuity, and engineering

Ladner

Williams

2016

Journal of Industrial Microbiology and Biotechnology

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Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies have been developed that enable the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and nonribosomal peptide analogues.

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“…These aglycones are then converted to the corresponding erythromycin derivatives using mutant Sa. erythraea strains with disrupted polyketide synthase systems (Ward et al 2007;Desai et al 2004;Ashley et al 2006). 15-Fluoroerythromycin A was found to possess similar activity but lower lipophilicity than erythromycin A.…”

Section: Precursor-directed Biosynthesis and Mutasynthesismentioning

confidence: 99%

Metabolism of fluoroorganic compounds in microorganisms: impacts for the environment and the production of fine chemicals

Murphy

Clark

Amadio

2009

Appl Microbiol Biotechnol

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Publication information Applied Microbiology and Biotechnology, 84 (4): 617-629Publisher Springer Item record/more information http://hdl.handle.net/10197/5314 Publisher's statementThe final publication is available at www.springerlink.com can lead to the generation of toxic compounds that are of environmental concern, yet similar biotransformations can yield difficult-to-synthesise products and intermediates, in particular derivatives of biologically active secondary metabolites. In this paper we review the historical and recent developments of organofluorine biotransformation in microorganisms, and highlight the possibility of using microbes as models of fluorinated drug metabolism in mammals.3

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Preparation of Erythromycin Analogs Having Functional Groups at C-15

Cited by 22 publications

References 14 publications

The macrolide antibiotic renaissance

The macrolide antibiotic renaissance

Harnessing natural product assembly lines: structure, promiscuity, and engineering

Metabolism of fluoroorganic compounds in microorganisms: impacts for the environment and the production of fine chemicals

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