np049899e_si_001.pdf (26.02 kB)

Molecular Bilateral Symmetry of Natural Products:  Prediction of Selectivity of Dimeric Molecules by Density Functional Theory and Semiempirical Calculations

Download (26.02 kB)
journal contribution
posted on 23.07.2004, 00:00 by Tatyana Voloshchuk, Nicola S. Farina, Orrette R. Wauchope, Magdalena Kiprowska, Paul Haberfield, Alexander Greer
A literature survey and theoretical calculations have been applied to explore bilateral symmetry in natural product systems. Molecular bilateral symmetry is defined to include C2 (sigma plane or axis), Cs, and C2v point groups in molecules. Natural products that possess chirality in the form of C2-axes or sigma planes of symmetry are present in higher proportions (69%) compared to molecules bearing achiral Cs or C2v point groups (14% and 16%, respectively). Density functional theoretical and semiempirical calculations indicate that the dimers 3,3‘-dibromo-5,5‘-[N-(2-(3-bromo-4-hydroxyphenyl)ethyl)-2-hydroxyiminoacetamide]biphenyl-2,2‘-diol (1), (S,S)-1,2-bis(2-amino-3H-imidazol-4-yl)-(R,R)-3,4-bis(1H-pyrrole-2-amido)cyclobutane (2), 2-oxo-dimethyl-1,3-bis(3,4-dibromobenzene-1,2-diol) (11), 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione (12), and bis(5-isopropyl-8-methylazulene)methane (13) evolve more energy per connecting bond than the corresponding trimers or tetramers would. This we propose is a guiding parameter that may adjust molecule growth. The corresponding trimers, tetramers, or higher oligomers of 1, 2, and 1113 appear to represent “missing” compounds in nature. Natural products 1, 2, and 1113, having 3-fold and higher levels of symmetry, would founder on the lack of a facile method of synthesis and on the prohibitively high-energy costs caused by steric crowding at their core.