Efficient Protocol for Accurately Calculating 13C Chemical Shifts of Conformationally Flexible Natural Products: Scope, Assessment, and Limitations
- Warren Hehre*Warren Hehre*E-mail (W. Hehre): [email protected]Wavefunction, Inc., 18401 Von Karman Avenue, Suite 370, Irvine, California 92612-1542, United StatesMore by Warren Hehre,
- Phillip KlunzingerPhillip KlunzingerWavefunction, Inc., 18401 Von Karman Avenue, Suite 370, Irvine, California 92612-1542, United StatesMore by Phillip Klunzinger,
- Bernard DeppmeierBernard DeppmeierWavefunction, Inc., 18401 Von Karman Avenue, Suite 370, Irvine, California 92612-1542, United StatesMore by Bernard Deppmeier,
- Andy DriessenAndy DriessenWavefunction, Inc., 18401 Von Karman Avenue, Suite 370, Irvine, California 92612-1542, United StatesMore by Andy Driessen,
- Noritaka UchidaNoritaka UchidaWavefunction Japan, 3-5-2, Koji-Machi, Chiyoda-Ku, Tokyo 102-0083, JapanMore by Noritaka Uchida,
- Masaru Hashimoto*Masaru Hashimoto*E-mail (M. Hashimoto): [email protected]Faculty of Agriculture and Life Science, Hirosaki University, 3-Bunkyo-cho, Hirosaki 036-8561, JapanMore by Masaru Hashimoto,
- Eri FukushiEri FukushiGraduate School of Agriculture, Hokkaido University, Sapporo 060-8589, JapanMore by Eri Fukushi, and
- Yusuke TakataYusuke TakataGraduate School of Agriculture, Hokkaido University, Sapporo 060-8589, JapanMore by Yusuke Takata
Abstract
An efficient protocol for calculating 13C NMR chemical shifts for natural products with multiple degrees of conformational freedom is described. This involves a multistep procedure starting from molecular mechanics and ending with a large basis set density functional model to obtain accurate Boltzmann conformer weights, followed by empirically corrected density functional NMR calculations for the individual conformers. The accuracy of the protocol (average rms <4 ppm) was determined by application to ∼925 diverse natural products, the structures of which have been confirmed either by X-ray crystallography or independent synthesis. The protocol was then applied to ∼ 2275 natural products, the structures of which were elucidated mainly by NMR and MS data. Five to ten percent of the latter compounds exhibited rms errors significantly in excess of 4 ppm, suggesting possible structural or signal assignment errors. Both data sets are available from an online browser (NMR.wavefun.com). The procedure can be and has been fully automated and is practical using present-generation personal computers, requiring a few hours or days depending on the size of the molecule and number of accessible conformers.
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