Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide

The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodi imide; 1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized bq; the: presence of a beta Vl-like turn around the N-termin al Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds s haring the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer fou nd in the crystal. the other bring unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axia l 2-amide N-x nitrogen atom. (C) 2001 Elsevier Science Ltd. All rights rese rved.