41518-17-6Relevant articles and documents
Ecological base-conditioned preparation of dipeptides using unprotected α-amino acids containing hydrophilic side chains
Ezawa, Tetsuya,Jung, Seunghee,Kawashima, Yuya,Noguchi, Takuya,Imai, Nobuyuki
, p. 689 - 696 (2017/07/22)
The coupling reactions of 3-phenylpropanoic acid and Ncarboxybenzyl á-amino acids with unprotected á-amino acids containing hydrophilic side chains such as aliphatic alcohol, aromatic alcohol, thiol, carboxylic acid, and amide afforded the corresponding amides in 6696% yield without racemization via the corresponding mixed carbonic carboxylic anhydrides under basic conditions through an ecological green synthetic method.
Sodium borohydride reduction of carbamoyl azide function: A synthesis of N-protected N'-formyl-gem-diaminoalkyl derivatives
Verardo, Giancarlo,Gorassini, Andrea
, p. 5387 - 5397 (2013/09/02)
A simple, efficient two-step synthesis of N-protected N′-formyl-gem- diaminoalkyl derivatives is reported. The procedure involves the unprecedented reduction of the carbamoyl azide of α-N-Boc/Fmoc/Z-protected amino acids and dipeptides (Boc = tert-butoxycarbonyl, Fmoc = 9-fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC-ESI-MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1H and 13C NMR analyses of the synthesized N-protected N′-formamides were carried out in [D 6]DMSO. The spectra exhibited the presence of two rotameric forms in solution as a result of the restricted rotation around the N-CO formyl bond. The integration of the N-CH-N protons of the two isomers showed that the cis isomer (rotamer B) was the more abundant conformer by 60 to 78 %. The reported synthesis represents the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes. A simple two-step synthesis of N-protected N′-formyl-gem-diaminoalkyl derivatives is reported that employs the reduction of the carbamoyl azide of N-protected amino acids and N-protected dipeptide acids with NaBH4. This racemization-free protocol is compatible with the most commonly used N-protecting groups. Copyright
Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
, p. 4815 - 4830 (2011/10/01)
Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
