Molecular structures and ab initio molecular orbital calculations of the optically active derivatives of 1-aminocyclopropane-1-carboxylic acid

Abstract

The novel optically active derivatives of 2,2′-disubstituted-1-aminocyclopropane-1-carboxylic acid (−)- 2 and (+)- 3 were synthesised from the spiro-azlactone (+)- 1. Oxidation of the diol moiety of (+)- 3 gave by ring enlargement the racemic mixture of 2,3-dihydrofuran derivative (±)- 6. This conversion is explained by stepwise rearrangement of the initially formed tetrasubstituted cyclopropanecarbaldehyde 4 through zwitterionic's reactive intermediate 5. The formation of (±)- 6 is preferred energetically as established by ab initio calculations of the ground states and possible intermediates for that rearrangement. The crystal structure and absolute configuration of the compounds (+)- 1, (−)- 2, (+)- 3 and (−)- 7 were determined by single-crystal X-ray diffraction method. All four compounds possess Z-configuration of the cyclopropane ring. The dioxolane ring in the structures (+)- 1 and (−)- 2 adopts half-chair conformation, while the cyclopropane ring and geminally substituted groups in the structures (−)- 2, (+)- 3 and (−)- 7 possess the anticlinal conformation. The molecules of the compound (+)- 1 are connected by very weak intermolecular hydrogen bond of C-H⋯O type. In the compounds (−)- 2, (+)- 3 and (−)- 7 inter- and intramolecular hydrogen bonds of N-H⋯O type were observed. The spiro-compound (+)- 1 exhibited a more pronounced inhibitory activity against the proliferation of murine leukemia and human T-lymphocytes cells than other type of tumor cell lines and normal human fibroblast cells.