Molecular structures and ab initio molecular orbital calculations of the optically active derivatives of 1-aminocyclopropane-1-carboxylic acid |
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Authors: | Zoran D?oli? Damir Kova?ek Draginja Mrvoš-Sermek Neda Slade Jan Balzarini Oliver Zerbe Leonardo Scapozza |
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Institution: | a Faculty of Chemical Engineering and Technology, Department of Organic Chemistry, University of Zagreb, Marulicev trg 19, 10000 Zagreb, Croatia b Faculty of Textile Technology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia c Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia d Laboratory of General and Inorganic Chemistry, Faculty of Science, University of Zagreb, Zvonimirova 8, 10000 Zagreb, Croatia e Division of Molecular Medicine, Rud?er Boškovi? Institute, Bijeni?ka cesta 54, P. O. Box 1016, 10001 Zagreb, Croatia f Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium g Department of Applied Biosciences, ETH Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland |
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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 (−)-7inter- 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. |
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Keywords: | 1-Aminocyclopropane-1-carboxylic acid derivatives Synthesis Rearrangement Ab initio MO calculations Density functional theory Single crystal X-ray analysis Cytostatic activities Antiviral activities |
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