Improved Scalable Syntheses of Mono- and Bis-Urethane Derivatives of Ornithine.

Wiejak, Stanisław; Masiukiewicz, Ełżbieta; Rzeszotarska, Barbara

doi:10.1248/cpb.49.1189

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…The reduction with Zn in formic acid was more convenient and gave similar results. Preparation of the next higher homolog, 2-amino-5-(benzimidazol-1-yl)pentanoic acid (bishomo-BZI-Ala) (4c), was similar, but started with readily available L-ornithine, which was converted to N a -Cbz-N d -Boc-L-ornithine, as described by Wiejak et al [22]. Removal of the t-butyloxycarbonyl group gave N a -Cbz-L-ornithine (1c), which was then converted to the benzimidazole under the conditions shown in Scheme 2.…”

Section: Resultsmentioning

confidence: 99%

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

Harris

Phillips

2013

The FEBS Journal

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Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from L-tryptophan (L-Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. b-(Benzimidazol-1-yl)-L-alanine (BZI-Ala), 2-amino-4-(benzimidazol-1-yl)butyric acid (homo-BZI-Ala) and 2-amino-5-(benzimidazol-1-yl)pentanoic acid (bishomo-BZI-Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI-Ala is a good substrate of TIL, with K m = 300 lM, k cat = 5.6 s À1 and k cat /K m = 1.9 9 10 4 , similar to L-Trp. BZI-Ala is also a good substrate for H463F mutant TIL, which has very low activity with L-Trp. In contrast, homo-BZI-Ala was found to be a potent competitive inhibitor of TIL, with a K i of 13.4 lM. However, the higher homolog, bishomo-BZI-Ala, was inactive as an inhibitor of TIL at a concentration of 600 lM, and is thus a much weaker inhibitor. The reaction of TIL with BZI-Ala was too fast to be observed in the stopped-flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo-BZI-Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem-diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo-BZI-Ala may be due to it being a 'bi-product' analog of the indole-a-aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.

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Section: Resultsmentioning

confidence: 99%

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

Harris

Phillips

2013

The FEBS Journal

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“…Protected acid 37 was prepared by the reaction of 35 (10.2 g; 19.4 mmol) and 8-quinolinol (7.3 g; 50.4 mmol), using the method described previously [56][57][58][59]…”

Section: -(Tert-butoxycarbonylamino)-2-(s)-aminopentanoic Acid 37mentioning

confidence: 99%

“…The strategy of orthogonal functional group protection [56][57][58][59] of L-ornithine and L-lysine is usually used for the synthesis of their azido derivatives.…”

Section: Introductionmentioning

confidence: 99%

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

Pícha

Budêšínský

Macháčková

et al. 2017

Journal of Peptide Science

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The rise of CuI‐catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in‐house preparation of a set of five Fmoc azido amino acids: β‐azido l‐alanine and d‐alanine, γ‐azido l‐homoalanine, δ‐azido l‐ornithine and ω‐azido l‐lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user‐friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2‐(1H‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses.Experimental procedures and/or analytical data for compounds 3–5, 20, 25, 26, 30 and 43–47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

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“…This workup protocol allowed the facile isolation of heterocyclic asymmetric allylation products via distillation (eq 18). 14 Allylation products that could be sensitive to mildly basic or oxidative conditions (e.g., α-Cl allylation products, 15 1,4-dienyl compounds, 16 and electron-rich heterocycles 17 ) were accessed using the 8-hydroxyquinoline workup (eqs [19][20][21]. The ease of the workup method also enabled the asymmetric allylation of the aldehyde derived from acetal 5, a process done on multigram scale toward the syntheses of the latrunculin macrolides (eq 22).…”

Section: Applications In Boron Allylation and Crotylationmentioning

confidence: 99%

“…Following substitution, 8-hydroxyquinoline ligation will reveal the free amino acid. This protocol has been utilized in selective alkoxycarbonylations of a number of derivatives of both lysine 19 and 20 Acylations have also been demonstrated in eq 26. 21 The process has also been employed as a selective protection method for the hydroxyl group of serine, although the yields were somewhat diminished (eq 27 Boron Abstraction from Boroxazolidones.…”

Section: Applications In Boron Allylation and Crotylationmentioning

confidence: 99%

8-Hydroxyquinoline

Ferreira¹

2013

Encyclopedia of Reagents for Organic Synthesis

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Improved Scalable Syntheses of Mono- and Bis-Urethane Derivatives of Ornithine.

Cited by 18 publications

References 23 publications

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

8-Hydroxyquinoline

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