Wavefunction, Inc. , 18401 Von Karman Avenue, Suite 370 , Irvine , California 92612-1542 , United States.
Wavefunction Japan , 3-5-2, Koji-Machi , Chiyoda-Ku , Tokyo 102-0083 , Japan.
J Nat Prod. 2019 Aug 23;82(8):2299-2306. doi: 10.1021/acs.jnatprod.9b00603. Epub 2019 Jul 19.
An efficient protocol for calculating C 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.
描述了一种用于计算具有多个构象自由度的天然产物的 ¹³C NMR 化学位移的有效方案。该方案涉及从分子力学开始并以大基组密度泛函模型结束的多步过程，以获得准确的玻尔兹曼构象权重，然后对各个构象进行经验修正的密度泛函 NMR 计算。该方案的准确性（平均 rms <4 ppm）通过应用于约 925 种不同的天然产物来确定，这些天然产物的结构已经通过 X 射线晶体学或独立合成得到证实。然后，该方案应用于约 2275 种天然产物，这些天然产物的结构主要通过 NMR 和 MS 数据阐明。其中 5%至 10%的化合物的 rms 误差明显超过 4 ppm，这表明可能存在结构或信号分配错误。这两个数据集都可以从在线浏览器（NMR.wavefun.com）获得。该过程可以并且已经完全自动化，并且使用当前一代的个人计算机是实用的，具体取决于分子的大小和可访问的构象数量，需要几个小时或几天的时间。
