Computational insight into the effect of C(19) substituents on [1,7]-hydrogen shift in previtamin D |
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| Authors: | Olga Dmitrenko Robert D. Bach Rafal R. Sicinski Wolfgang Reischl |
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| Affiliation: | (1) Department of Chemistry and Biochemistry, University of Delaware, Delaware, USA, US;(2) Department of Chemistry, University of Warsaw, Warsaw, Poland, PL;(3) Department of Chemistry, University of Vienna, Vienna, Austria, AT |
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| Abstract: | B3LYP calculations in conjunction with natural bond orbital population analysis have been performed for a previtamin D model and corresponding transition structures for the [1,7]-hydrogen migration. In addition the 19,19-difluoro, 19-methoxy and 19-fluoro substituted analogs were investigated. The calculated activation barriers decrease in the following order: CHF2>CH3>CH2OCH3 (24.8, 23.5 and 20.1 kcal/mol). This is in qualitative agreement with experiments. It has been suggested that a decrease of the barrier by a 19-methoxy substituent and its increase by a 19,19-difluoro substituent are phenomena of different origin. In the case of 19-methoxy substitution, the effect is due to the charge redistribution in the triene system and the decrease of the C(19)–H bond energy. The effect of two fluorine substituents at C-19 on the activation barrier is suggested to originate from the combination and balance of several factors: electrostatic repulsion between the negative fluorine atom and the π-electron cloud over the conjugated system, an increase of the HOMO–LUMO gap, and geminal difluoro substitution affecting C–F and C–C bond energies. Received: 17 May 2002 / Accepted: 11 September 2002 / Published online: 14 February 2003 |
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| Keywords: | : Vitamin D – Density functional calculations – Orbital– orbital interactions – Bond dissociation energies – G2 calculations |
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