Synthesis of chiral polyazamacrocycles of variable ring size

Org Biomol Chem. 2010 Jun 7;8(11):2529-36. doi: 10.1039/c001228a. Epub 2010 Apr 1.

Abstract

Synthesis and structure elucidation of optically active tri-, tetra-, and penta-azamacrocycles having 4-methoxyphenyl pendants are described. Regioselective ring opening of a nosylaziridine with secondary benzyl amines was repeatedly performed to afford the cyclization precursors. Intramolecular N-alkylation of N-(omega-haloalkyl) nosylamide provided tri-, tetra-, and penta-azamacrocycles. On the basis of our study of the tetra-azamacrocycle previously elucidated by X-ray single-crystal analysis and in solution by NMR analysis, we conclude that the tri-azamacrocycle does not mainly have a vase-type conformation because of the steric hindrance of the 4-methoxyphenyl groups but the penta-azamacrocycle has a vase-type conformation in CDCl(3) and in CD(2)Cl(2). The vase-type conformation of the penta-azamacrocycle is, however, not as much stable as that observed in the tetra-azamacrocycle because conformational flexibility of the penta-azamacrocycle was observed in deuterated benzene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism

Substances

  • Aza Compounds
  • Macrocyclic Compounds