- Solution phase synthesis of imidazo[1,2-b]pyrazol-2-one, an interesting 5,5-fused heterocyclic ring system
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The solution phase synthesis of a series of imidazo[1,2-b]pyrazol-2-ones, a fused 5,5-ring system, based on diverse set of hydrazino acids and malononitriles is described. The method involves formation of 5-aminopyrazoles followed by intra-molecular cyclodehydration.
- Blass, Benjamin E.,Srivastava, Anil,Coburn, Keith R.,Faulkner, Amy L.,Janusz, John J.,Ridgeway, James M.,Seibel, William L.
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- Syntheses of hydrazino peptides and conjugates
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(α-Benzyloxycarbonyl-aminoacyl)benzotriazolides (Cbz = benzyloxycarbonyl) underwent a coupling reaction with α-hydrazino acids under microwave irradiation to form hybrid hydrazino dipeptides (42-71 %). Chiral acylations of β-N-Cbz-α-hydrazino acylbenzotriazolides were successfully carried out with N-, S-, O-, and C-nucleophiles in yields of 49-88 %. Benzyloxycarbonyl-protected hybrid hydrazino dipeptides and benzyloxycarbonyl-protected hydrazino aminoacyl conjugates with N-, S-, O-, and C-nucleophiles were prepared by using benzotriazole methodology. Copyright
- Panda, Siva S.,El-Nachef, Claudia,Bajaj, Kiran,Katritzky, Alan R.
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p. 4156 - 4162
(2013/07/19)
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- New pyrazole containing bicarboxylic α-amino acids: Mimics of the cis amide bond
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A series of novel optically active α-amino acids, containing a pyrazole ring, which can be regarded as building blocks for peptidomimetics, have been prepared starting from readily available α-amino acids. The synthetic strategy employed allows the regio- and stereoselective preparation of 1,3- or 1,5-substituted pyrazolyl rings. The pyrazole containing peptidomimetics can be considered as analogues of peptides with a cis amide bond.
- De Luca, Lidia,Falorni, Massimo,Giacomelli, Giampaolo,Porcheddu, Andrea
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p. 8701 - 8704
(2007/10/03)
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- Ribosome-mediated incorporation of hydrazinophenylalanine into modified peptide and protein analogues
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(S)-α-Hydrazinophenylalanyl-tRNA(Phe), an aminoacyl-tRNA derivative containing the unnatural amino acid (S)-α-hydrazinophenylalanine, was prepared in an effort to examine the stereochemical requirements of the A- site of the ribosome during in vitro protein synthesis. The (S)-α- hydrazinophenylalanine moiety was of interest because it contains two nucleophilic centers, the secondary nitrogen attached to C(α), which is normally acylated during the course of peptide bond formation, and the sterically less hindered primary nitrogen. To determine the position of acylation, (S)-α-hydrazinophenylalanyl-tRNA(Phe) was tested in an Escherichia cull in vitro protein biosynthesizing system lacking elongation factor G, such that only dipeptide products were formed. The dipeptide product mixture was analyzed by HPLC in direct comparison with authentic synthetic standards. The dipeptide assay utilizing (S)-α- hydrazinophenylalanyl-tRNA(Phe) as the A-site tRNA established that the analogue functioned well as an acceptor tRNA; HPLC analysis of the products showed that both dipeptides were formed in approximately equal amounts. When attached to a suppressor tRNA transcript, (S)-α-hydrazinophenylalanine was also incorporated into position 27 of dihydrofolate reductase in an E. coli protein synthesizing system by readthrough of a nonsense codon. This finding expands the currently accepted model of peptide bond formation at the ribosome and adds to the repertoire of peptide-like products shown to form at the peptidyltransferase center of the ribosome.
- Killian, Jennifer A.,Van Cleve, Mark D.,Shayo, Yuda F.,Hecht, Sidney M.
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p. 3032 - 3042
(2007/10/03)
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- Synthesis of fused 1,2,5-triazepine-1,5-diones and some N2- and N3-substituted derivatives: Potential conformational mimetics for cis-peptidyl prolinamides
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The synthesis of a new fused 1,2,5-triazepine-1,5-dione heterocycle, which is expected to mimic structural features of cis-peptldyl prolinamides, is described. The required parent heterocycle, corresponding to cis-glycy-(2S)-prolinamide, has been prepared in good yield by the cyclisation of N-(2-bromoacetylprolyl)-hydrazine which is itself generated in situ from the bromoacetyl proline methyl ester. Analogues corresponding to cis-(2R)-alanyl- and cis-(2S)-alanyl-(2S)-prolinamide have been similarly prepared from the appropriate N-(2-bromopropionyl)proline methyl esters and hydrazine hydrate where the cyclisation step, involving the displacement of bromide, has been shown to occur with inversion of configuration at C-2 of the propionyl moiety. Acylation at the N-3 position of the triazepine is equivalent to N-terminal acylation of the residue preceding the proline residue in cis-aminoacyl prolinamides. This has been achieved without incident using standard peptide coupling procedures. Extension at the 'C-terminal' has been achieved by preparing elaborated hydrazine precursors which are reacted with suitably activated esters of N-α-halogenoacylprolines, prior to cyclisation, to give the required fused triazepine dione. Thus it is possible to prepare constrained cis-peptidyl prolyl peptide mimetics of defined stereochemistry based upon this new triazepine dione in which all of the non-proline residues can be varied.
- Lenman, Morag M.,Lewis, Arwel,Gani, David
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p. 2297 - 2311
(2007/10/03)
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- Amination with N-Benzyloxycarbonyl-3-Phenyloxaziridine as a Route to Sensitive Chiral α-Hydrazino Acids: Synthesis of L-Hydrazino Serine
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N-Cbz-3-phenyloxaziridine can be generated in a two step process.This is a new reagent for direct electrophilic N-amination of chiral α-amino acids and their derivatives which affords the corresponding hydrazino acids protected with a readily removable N-Cbz group.Application of this methodology to a facile synthesis of L-hydrazino serine, a potentially useful biological tool, is described.
- Niederer, Daniel A.,Kapron, James T.,Vederas, John C.
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p. 6859 - 6862
(2007/10/02)
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- PRACTICAL SYNTHESIS OF OPTICALLY ACTIVE α-HYDRAZINO ACIDS FROM α-AMINO ACIDS
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Simple amino acids (1) can be converted in fair to good yield into hydrazino acids (3) of like configuration by using KOCl instead of NaOCl to promote the Shestakov rearrangement of the intermediate hydantoic acids (2).
- Viret, Joelle,Gabard, Jacqueline,Collet, Andre
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p. 891 - 894
(2007/10/02)
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