Cyclic peptides containing a δ-sugar amino acid—synthesis and evaluation as artificial receptors

Billing, Johan; Nilsson, Ulf J.

doi:10.1016/j.tet.2004.11.024

Cited by 44 publications

(25 citation statements)

References 27 publications

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“…This general approach has shown value in the preparation of 2-acetamido-1,2-dideoxynojirimycin-lysine hybrids [41] and other iminosugars. [42] Starting from the readily accessible hydrochloride 3, available in three steps from d-glucosamine hydrochloride, [43] the azido group was introduced to protect the amine moiety using an azido-transfer reagent [44] to give the triol 4 [45] (Scheme 2). With triol 4 in hand, a one-pot activation at O-6, using a tosylate group followed by displacement of the tosylate with sodium iodide and in situ acetylation gave the iodide 5 in excellent yield.…”

Section: Resultsmentioning

confidence: 99%

The Development of Selective Inhibitors of NagZ: Increased Susceptibility of Gram‐Negative Bacteria to β‐Lactams

et al. 2013

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The increasing incidence of inducible chromosomal AmpC β-lactamases within the clinic is a growing concern because these enzymes deactivate a broad range of even the most recently developed β-lactam antibiotics. As a result, new strategies are needed to block the action of this antibiotic resistance enzyme. Presented here is a strategy to combat the action of inducible AmpC by inhibiting the β-glucosaminidase NagZ, which is an enzyme involved in regulating the induction of AmpC expression. A divergent route facilitating the rapid synthesis of a series of N-acyl analogues of 2-acetamido-2-deoxynojirimycin is reported here. Among these compounds are potent NagZ inhibitors that are selective against functionally related human enzymes. These compounds reduce minimum inhibitory concentration values for β-lactams against a clinically relevant Gram-negative bacterium bearing inducible chromosomal AmpC β-lactamase, Pseudomonas aeruginosa. The structure of a NagZ–inhibitor complex provides insight into the molecular basis for inhibition by these compounds.

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Section: Resultsmentioning

confidence: 99%

The Development of Selective Inhibitors of NagZ: Increased Susceptibility of Gram‐Negative Bacteria to β‐Lactams

et al. 2013

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“…Boc-L-tyrosine 5 was conjugated with either L-glycine or alanine to give dipeptide intermediates [27]. The precursors could be obtained from 6a (or 6b ) via alkylation with ethylene glycol ditosylate.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of 18F labeled FET prodrugs for tumor imaging

Wang¹,

Lieberman²,

Plöessl³

et al. 2014

Nuclear Medicine and Biology

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Introduction O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O-(2-[18F]fluoroethyl)-L-tyrosyl-L-glycine (FET-Gly, [18F]2), O-(2-[18F]fluoroethyl)-L-tyrosyl-L-alanine (FET-Ala, [18F]3) and N-acetyl O-(2-[18F]fluoroethyl)-L-tyrosine (AcFET, [18F]4), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([18F]1). Methods Three new [18F]FET derivatives, 2 – 4, were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors. Results New FET prodrugs were prepared with 3 – 28 % decay corrected radiochemical yields, good enantiomeric purity (> 95 %) and high radiochemical purity (> 95 %). FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) exhibited negligible uptake in comparison to the high uptake of FET ([18F]1) in 9L cells. Metabolism studies of FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) in rat and human blood showed that FET-Ala ([18F]3) was hydrolyzed to FET ([18F]1) faster than FET-Gly ([18F]2) or AcFET ([18F]4). Most of the FET-Ala (79 %) was converted to FET ([18F]1) within 5 min in blood in vivo. Biodistribution studies demonstrated that FET-Ala ([18F]3) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([18F]3) and FET ([18F]1) were comparable and appeared to be better than those of FET-Gly ([18F]2) and AcFET ([18F]4). PET imaging studies showed that both FET ([18F]1) and FET-Ala ([18F]3) could visualize tumors effectively, and that they share similar imaging characteristics. Conclusions FET-Ala ([18F]3) demonstrated promising properties as a prodrug of FET ([18F]1), which could be used in PET imaging of tumor amino acid metabolism.

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“…115 Compound 191 was obtained by chemo-, regio-, and stereoselective [4 + 2]-cycloaddition between the glucal derivative 190 and an aspartic acid derivative (189) generated in situ from the precursor 188. 123 Scheme 38. 117 In particular, the highly reactive 189 was trapped "in situ" by glycal derivative 190, providing the hetero Diels-Alder product 191 as single isomer, 116 which was converted further into the target compound 192 (Scheme 34).…”

Section: Cyclic Peptides Containing Amino Sugar Unitsmentioning

confidence: 99%