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Esterase from Horse Liver (HLAP) was able to hydrolyze a series of linear and cyclic β,β-dialkyl-γ-nitroesters, in spite of the well-known reluctance of hydrolytic enzymes to recognize and transform hindered substrates, such as those possessing a stereogenic quaternary carbon atom next to the reaction site. The resulting optically active γ-nitroesters gave access to optically active β,β-disubstituted γ-aminoacids as well as α,α-disubstituted succinic acids, both being biologically relevant compounds.

Both enantiomerically pure antipodes of GABA analogues were prepared as hydrochloride salts, by enzymatic kinetic resolution of their precursors ethyl 2-(nitromethyl)alkanoates. These latter compounds can be easily transformed into enantiomerically pure 2-alkylsuccinic acids by a Nef reaction followed by oxidation. Interestingly, this reaction was particularly easy for the neopentyl derivative ( S )-(+)- 7d , which underwent conversion into its corresponding succinic acid derivative ( S )-(−)- 8d in buffered solution. The absolute configurations of the main compounds of interest involved are given, together with their CD spectra.

Two simple and efficient synthetic methods for the preparation of semicarbazide amino acid derivatives are reported. The procedures involve reaction between the carbamoyl azides of α-N-protected amino acids and hydrazine monohydrate: 4-[(alkoxycarbonylamino)(alkyl)methyl]semicarbazides 1 are obtained when hydrazine is added to the separated tetrahydrofuran (THF) solution containing the carbamoyl azide at 0 °C, whereas 1-[(alkoxycarbonylamino)(alkyl)methyl-carbamoyl]-4-[(alkoxycarbonylamino)(alkyl)methyl]semicarbazides 4 are produced by adding hydrazine directly into the final THF/aqueous buffer (KH 2 PO 4 ) biphasic mixture containing the prepared carbamoyl azide at 50 °C, respectively. NMR experimental data obtained from samples dissolved in [D 6 ]dimethyl sulfoxide suggest a dimeric association for semicarbazides 4 with intermolecular hydrogen bonds. Moreover, the ESI-MS-MS spectra reveal some interesting common features.

A simple and mild one-pot synthesis of potentially bioactive α-N-protected dipeptidyl ureas is reported. The procedure involves the reaction between the carbamoyl azide of an α-N-protected amino acid and an α-amino acid methyl ester. The reaction is fast (3 h at 45 °C), regardless of the nature of both the reagents, and racemization free. The reported protocol represents a valid alternative to existing methods.

A simple and efficient two-step synthesis of unsymmetrically substituted ureas containing an amino acid derivative is reported. The procedure involves the reaction between the carbamoyl azides of α-N-protected amino acids and ammonium hydroxide or a primary or a secondary amine. The reaction proved to be very fast (0.5 h) with small, highly reactive ammonium hydroxide and slower (4 h) with sterically hindered tert-butylamine. The 1H NMR spectra of the synthesized, new, unsymmetrical ureas carried out in [D6]DMSO suggest that the protons in the –αCH–NHCONH–CH– moiety assume a trans conformation. Moreover, analysis of the mass spectra (EI and ESI) revealed some interesting common features. The reported synthesis represents the first example of the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A simple and efficient two-step synthesis of unsymmetrically substituted ureas containing an amino acid derivative is reported. The procedure involves the reaction between the carbamoyl azides of α-N-protected amino acids and ammonium hydroxide or a primary or a secondary amine. The reaction proved to be very fast (0.5 h) with small, highly reactive ammonium hydroxide and slower (4 h) with sterically hindered tert-butylamine. The 1H NMR spectra of the synthesized, new, unsymmetrical ureas carried out in [D6]DMSO suggest that the protons in the –αCH–NHCONH–CH– moiety assume a trans conformation. Moreover, analysis of the mass spectra (EI and ESI) revealed some interesting common features. The reported synthesis represents the first example of the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)