ChemInform Abstract: O‐BENZOTRIAZOLYL‐N,N,N′,N′‐TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE AS COUPLING REAGENT FOR THE SYNTHESIS OF PEPTIDES OF BIOLOGICAL INTEREST

Dourtoglou, Vassilis; Gross, B.; Lambropoulou, Vassiliki; Zioudrou, Christine

doi:10.1002/chin.198449296

Cited by 12 publications

(46 citation statements)

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“…The esters 65 and 66 were synthesized by treating the benzylated carboxylic acid derivatives with the corresponding alcohol in the presence of triphenylphosphine and diethyl azodicarboxylate. 22 The amide analogues 69 and 76-79 were obtained via reaction of the succinimidyl-activated ester 7a with primary amines in two steps or the in situ formation of the benzotriazolylactivated ester 7c (Scheme 2) in one step in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) as an activating agent 23,24 (Table 2).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, Physicochemical Properties, and Evaluation ofN-Substituted-2-alkyl-3-hydroxy-4(1H)-pyridinones

et al. 1998

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The synthesis of a range of 3-hydroxy-4(1H)-pyridinones with potential for the chelation of iron(III) is described. The pKa values of respective ligands and the stability constants of their iron(III) complexes are presented. The distribution coefficient values of a range of 48 hydroxypyridinones and their corresponding iron(III) complexes between 1-octanol and MOPS buffer (pH 7.4) are reported. The range of log Dcomplex values covers 7 orders of magnitude. The results suggest the existence of a biphasic relationship between the distribution coefficient values of the chelator and the corresponding iron(III) complexes. For ligands with a log Dligand = -1, a linear relationship exists with a value of the slope 2.53, whereas with ligands with a log Dligand < -1, a linear relationship exists with a slope of 0.49. The reduced slope for the more hydrophilic molecules of the series offers some advantage for this type of hydroxypyridinone as the distribution coefficients for such complexes do not change so rapidly with increasing ligand hydrophilicity. The ability of selected 3-hydroxypyridinones to facilitate the excretion of iron in bile was investigated in non-iron-overloaded, bile duct-cannulated rats and in a [59Fe]ferritin-loaded rat model. Both systems compare the ability of chelators to remove iron from the liver, the prime target organ in thalassemia. The N-(hydroxyalkyl)-3-hydroxypyridin-4-ones are demonstrated to be orally active under the in vivo conditions adopted. Thus both 1-(hydroxyalkyl)- and 1-(carboxyalkyl)pyridinones are able to remove iron from the liver. Although 1-(carboxyalkyl)hydroxypyridinones are active, they do not demonstrate any clear advantage over Deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one). Indeed 1-(hydroxyalkyl)hydroxypyridinones which are known to be rapidly converted to 1-(carboxyalkyl)hydroxypyridinones are also marginally superior to Deferiprone. In contrast, 2-ethyl-1-(2'-hydroxyethyl)-3-hydroxypyridin-4-one, which is not metabolized to the corresponding (carboxyalkyl)hydroxypyridinone, was found to be superior to Deferiprone and therefore deserves further consideration as an orally active iron chelator with potential for the treatment of iron overload associated with transfusion-dependent thalassemia.

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Section: Chemistrymentioning

confidence: 99%

Synthesis, Physicochemical Properties, and Evaluation ofN-Substituted-2-alkyl-3-hydroxy-4(1H)-pyridinones

et al. 1998

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“…Therefore, some target peptides were also prepared from Bn-protected amino acids by use of a stronger coupling reagent, N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) and 1-hydroxybenzotriazole (HOBT). 26 Bn-protected compounds were synthesized as shown for the noncanonical amino acid (Scheme 3), which was first transformed to Boc derivative 23, and then the Bn group was introduced. The Boc group was cleaved off from 24 to afford Bn-proteced amino acid 25.…”

Section: ■ Resultsmentioning

confidence: 99%

“…6 General Procedure for the Peptide Coupling via HBTU-HOBT Activation. 26 A flask under N 2 atmosphere was charged with N-Boc-protected amino acid (1 mmol) triethylamine (TEA, 2.1 mmol), HBTU (1.1 mmol), HOBt (1.1 mmol), and dry DMF or CH 2 Cl 2 (5 mL). The reaction mixture was stirred at rt 10 min.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Photocyclization of Tetra- and Pentapeptides Containing Adamantylphthalimide and Phenylalanines: Reaction Efficiency and Diastereoselectivity

et al. 2018

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A series of tetrapeptides and pentapeptides was synthesized bearing a phthalimide chromophore at the N-terminus. The C-terminus of the peptides was strategically substituted with an amino acid, Phe, Phe(OMe), or Phe(OMe)2 characterized by different oxidation potentials. The photochemical reactivity of the peptides was investigated by preparative irradiation and isolation of photoproducts, as well as with laser flash photolysis. Upon photoexcitation, the peptides undergo photoinduced electron transfer (PET) and decarboxylation, followed by diastereoselective cyclization with the retention of configuration for tetrapeptides or inversion of configuration for pentapeptides. Molecular dynamics (MD) simulations and NOE experiments enabled assignment of the stereochemistry of the cyclic peptides. MD simulations of the linear peptides disclosed conformational reasons for the observed diastereoselectivity, being due to the peptide backbone spatial orientation imposed by the Phe amino acids. The photochemical efficiency for the decarboxylation and cyclization is not dependent on the peptide length, but it depends on the oxidation potential of the amino acid at the C-terminus. The results described herein are particularly important for the rational design of efficient photochemical reactions for the preparation of cyclic peptides with the desired selectivity.

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“…The title compound was synthesized using general procedure C using dry DMF as solvent. Acid 17 (400.0 mg, 0.96 mmol) and 192.0 (0.96 mmol) of 4-[(tert-butyloxycarbonyl) amino] piperidine afforded after chromatographic purification (ethyl acetate/n-heptane (1:1)) 353.0 mg (61.3 %) of an oil: TLC Rf -0.38 (ethyl acetate/n-heptane (2:1)); NMR (CDCla) = 8.26 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.75 (dd, J = 1.6, 7.6 Hz, 1H), 7.58-7.22 (m, 9H), 4.82 (m, 1H), 4.40 (m, 2H), 3.98 (dd, J = 2.0,8.8 Hz, 1H), 3.77-3.47 (br m, 4H), 3.33 (dd, J = 3.6,12.8 Hz, 1H), 3.20 (m, 1H), 3.02 (br m, 2H), 2.67 (br m, 2H), 2.36 (m, 1H), 1.86 (br m, 2H), 1.43 (s, 9H), 1.17 19). To a solution of 143.0 mg (0.24 mmol) of amide 18 in 4 mL of aqueous THF (20 % water) was added 20.1 mg (0.48n mmol) ofLiOHxHaO at 0 °C.…”

Section: (2jz)-3-[l-[[4-[(tert-butyloxycarbonyl)amino]piperidinyl]car...mentioning

confidence: 99%

Renin inhibitors containing a pyridyl amino diol derived C-terminus

Heitsch¹,

Henning²,

Kleemann³

et al. 1993

J. Med. Chem.

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Based on the concept of transition-state analogs, a series of nonpeptide renin inhibitors with the new (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-(2-pyridyl)hexane moiety at the C-terminal functionality were synthesized and evaluated for inhibition of renin both in vitro and in vivo. All compounds exhibited potencies in the nanomolar or even subnanomolar range when tested versus human renin in vitro. Selected inhibitors were evaluated in anesthetized, sodium-depleted rhesus monkeys and produced a marked reduction in mean arterial blood pressure (MAP) upon intraduodenal administration of a dose of 2 mg/kg. Compound 38 (S 2864) containing an amino piperidyl succinic acid derived N-terminal is the most promising member in this series. 38 inhibited human renin with an IC50 of 0.38 nM, did not affect other human aspartic proteinases, and decreased mean arterial blood pressure significantly by 27% with a duration of action of 90 min after administration of 2 mg/kg id in anesthetized, sodium-depleted rhesus monkeys.

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ChemInform Abstract: O‐BENZOTRIAZOLYL‐N,N,N′,N′‐TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE AS COUPLING REAGENT FOR THE SYNTHESIS OF PEPTIDES OF BIOLOGICAL INTEREST

Abstract: Tetramethylharnstoff (I) wird über das Iminiumsalz (III) mit Hydroxybenzotriazol (IV) zum O‐Benzotri‐ azolyl‐tetramethyluronium‐hexafluorophosphat (V) umgesetzt.

Cited by 12 publications

References 1 publication

Synthesis, Physicochemical Properties, and Evaluation ofN-Substituted-2-alkyl-3-hydroxy-4(1H)-pyridinones

Synthesis, Physicochemical Properties, and Evaluation ofN-Substituted-2-alkyl-3-hydroxy-4(1H)-pyridinones

Photocyclization of Tetra- and Pentapeptides Containing Adamantylphthalimide and Phenylalanines: Reaction Efficiency and Diastereoselectivity

Renin inhibitors containing a pyridyl amino diol derived C-terminus

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