Synthesis of the Antimalarial Drug FR900098 Utilizing the Nitroso-Ene Reaction

Fokin, Andrey A.; Yurchenko, A. G.; Rodionov, V. N.; Gunchenko, Pavel A.; Yurchenko, R. I.; Reichenberg, Armin; Wiesner, Jochen; Hintz, Martin; Jomaa, Hassan; Schreiner, Peter R.

doi:10.1021/ol702082k

Cited by 29 publications

(15 citation statements)

References 40 publications

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“…All fosmidomycin derivatives were synthesised as previously described [9][10][11][12][13] (see Supplementary Fig. 1 for an overview of the structures).…”

Section: Antimicrobial Agentsmentioning

confidence: 99%

Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives

Messiaen

Verbrugghen

Declerck

et al. 2011

International Journal of Antimicrobial Agents

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The Burkholderia cepacia complex (BCC) is a group of 17 closely related opportunistic pathogens that are able to infect the respiratory tract of cystic fibrosis patients. BCC bacteria are intrinsically resistant to many antibiotics and are therefore difficult to eradicate. Fosmidomycin could be a new therapeutic agent to treat BCC infections as it inhibits 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in the non-mevalonate pathway essential in BCC bacteria for isoprenoid synthesis. In this study, the antimicrobial activity of fosmidomycin and eight fosmidomycin derivatives towards 40 BCC strains was investigated. All BCC strains were resistant to fosmidomycin, although addition of glucose-6-phosphate reduced the minimum inhibitory concentration values of FR900098, the fosmidomycin acetyl derivative, from 512 mg/L to 64 mg/L for Burkholderia multivorans and B. cepacia. This enhanced activity was linked to increased expression of the genes involved in glycerol-3-phosphate transport, which appears to be the only route for fosmidomycin import in BCC bacteria. Furthermore, upregulation of a fosmidomycin resistance gene (fsr) encoding an efflux pump was observed during fosmidomycin and FR900098 treatment. These results strongly suggest that the observed resistance in BCC bacteria is due to insufficient uptake accompanied by fosmidomycin and FR900098 efflux.

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“…All fosmidomycin derivatives were synthesised as previously described [9][10][11][12][13] (see Supplementary Fig. 1 for an overview of the structures).…”

Section: Antimicrobial Agentsmentioning

confidence: 99%

Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives

Messiaen

Verbrugghen

Declerck

et al. 2011

International Journal of Antimicrobial Agents

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“…大大拓展了亚硝基−烯反应在复杂底物中的应用和对敏感官能团的容忍性. 对于抗疟药 FR900098 (94)的合成, 若引入亚硝基− 烯反应 , 则仅需 5 步便可以 64% 的总产率获得 [66] (Scheme 28). 其中乙酰基亚硝基中间体是通过逆 DielsAlder 得到的.…”

Section: α 卤代亚硝基底物unclassified

Research Progress on Nitroso-ene Reaction

黄莎华¹,

霍华兴²,

李文华³

et al. 2012

Chin. J. Org. Chem.

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“…A series of conformationally restricted cyclopropyl analogs 108 of fosmidomycin has been synthesized starting from methylphosphonate carbanion [227]. Recently, a new approach to fosmidomycin was developed involving, as the key step, the nitrosoene reaction of commercially available diethyl allylphosphonate with in situ prepared nitrosocarbonyl methane [228].…”

Section: Synthesis Of G-aminophosphonates and Higher Homologs J219mentioning

confidence: 99%

Chemistry of Aminophosphonic Acids and Phosphonopeptides

Kukhar

Romanenko

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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Aminophosphonic (and aminophosphinic) acids occupy a prominent position in the understanding of bioprocesses in living organisms and in the construction of new bioregulators -pharmaceuticals and agrochemicals. The so-called phosphorus analogs of the amino acids, aminophosphonic and aminophosphinic acids, are amino acid mimetics in which the carboxylic group is substituted by a phosphonic acid residue P(O)(OH) 2 or phosphinic acid group P(O)(OH)R. The replacement of the carboxylic group by a phosphonic or related moiety results in a number of important consequences: the central atom of a phosphonic acid function consists of an additional substituent that has a tetrahedral configuration in contrast to the planar carbonyl atom of carboxylic group. There are also significant differences in the acidity and steric bulk of these residues. The tetrahedral configuration of the pentavalent phosphorus atom mimics the transition state of the peptide bond cleavage reaction in some enzyme-substrate interactions that is used in the synthesis of new inhibitors. The hydrolytic stability of CÀP bonds is often used in order to prepare stable analogs of bioactive phosphates OÀP(O)(OH) 2 . In addition, aminophosphonic acids and their derivatives are important as metal-complexing agents, which have diagnostic and therapeutic applications, and as industrial chemicals in water treatment, metal extraction, or pollution control.Synthesis, and the chemical, physical, and biological properties of aminophosphonic acids and some directions for their practical application are presented in a number of reviews and book chapters. The most comprehensive account of the chemistry and biology of aminophosphonates and aminophosphinate which covers literature up to 2000 is presented in Kukhar and Hudson ([1] and references therein). Readers are referred to this reference for more detailed information concerning specific aspects of the chemistry and biological activity of aminophosphonic acid derivatives. The purpose of this chapter is to give an updated report on aminophosphonic acids as analogs of amino acids. Numerous heterocyclic compounds that contain both phosphonic and amino groups will not be covered in this report.

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Synthesis of the Antimalarial Drug FR900098 Utilizing the Nitroso-Ene Reaction

Cited by 29 publications

References 40 publications

Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives

Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives

Research Progress on Nitroso-ene Reaction

Chemistry of Aminophosphonic Acids and Phosphonopeptides

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