86910-04-5Relevant academic research and scientific papers
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
