Evaluating the accuracy of theoretical one‐bond 13C─13C scalar couplings and their ability to predict structure in a natural product

This study explores the feasibility of using a combination of experimental and theoretical 1‐bond ¹³C─¹³C scalar couplings (¹J_CC) to establish structure in organic compounds, including unknowns. Historically, ⁿJ_CC and ⁿJ_CH studies have emphasized 2 and 3‐bond couplings, yet ¹J_CC couplings exhibit significantly larger variations. Moreover, recent improvements in experimental measurement and data processing methods have made ¹J_CC data more available. Herein, an approach is evaluated in which a collection of theoretical structures is created from a partial nuclear magnetic resonance structural characterization. Computed ¹J_CC values are compared to experimental data to identify candidates giving the best agreement. This process requires knowledge of the error in theoretical methods, thus the B3LYP, B3PW91, and PBE0 functionals are evaluated by comparing to 27 experimental values from INADEQUATE. Respective errors of ±1.2, ±3.8, and ±2.3 Hz are observed. An initial test of this methodology involves the natural product 5‐methylmellein. In this case, only a single candidate matches experimental data with high statistical confidence. This analysis establishes the intramolecular hydrogen‐bonding arrangement, ring heteroatom identity, and conformation at one position. This approach is then extended to hydroheptelidic acid, a natural product not fully characterized in prior studies. The experimental/theoretical approach proposed herein identifies a single best‐fit structure from among 26 candidates and establishes, for the first time, 1 configuration and 3 conformations to complete the characterization. These results suggest that accurate and complete structural characterizations of many moderately sized organic structures (<800 Da) may be possible using only ¹J_CC data.     

Synthetic Studies on Selectin Ligands/Inhibitors: One-Pot Synthesis of the Mono- and Oligo-Sulfated 2-(Tetradecyl)Hexadecyl β-D-Galacto- and Lactopyranosides as the Sulfatide Mimetics 1

Abstract

The ¹³C NMR spectra of inulin oligomers in D₂O with degree of polymerization (DP) of 3 through 9, along with two other inulin oligomer mixtures of average DP = 17 and DP = 31 were recorded. Significant variations in the chemical shift of some fructofuranose carbon signals indicates that unlike glucans, simple helical structures are not the predominant conformation for inulin oligomers—at least up to DP = 9. Models of the DP = 5 oligomer show that it should prefer a single helical conformation which however, would not be accessible to longer DP oligomers due to severe steric interactions.     

A general route to 5-substituted-2-furylacetic acids: a brief synthesis of plakorsin B

3,4-Dihydroxy-5-alkynylcarboxylic acids, readily obtained by the addition of lithium acetylides to α-acetoxysuccinic anhydride followed by reduction and hydrolysis, undergo smooth silver(I)-catalysed 5-endo-dig cyclisations and in situ dehydration to give excellent overall yields of 5-substituted-2-furylacetic acids, including the natural metabolite plakorsin B.     

Indirect detection of the 183W and 57Fe nuclei using 119Sn‐relayed 1H,X correlation spectroscopy

Recently reported triple‐resonance Y‐relayed ¹H,X correlation experiments have been utilized to characterize ¹⁸³W and ⁵⁷Fe chemical shifts using ¹¹⁹Sn as the Y‐relaying nucleus instead of the previously used ³¹P. Application of an adaptation of Gudat's original INEPT/HMQC sequence results in a significant enhancement of the signal‐to‐noise (S/N) ratio for two‐dimensional ¹¹⁹Sn‐relayed ¹H,¹⁸³W and ¹H, ⁵⁷Fe correlation spectra with efficient detection of the transition metal nucleus in tungsten and iron complexes lacking an observable direct scalar coupling between the transition metal and any hydrogen nuclei. Strengths and shortcomings of the novel sequence and the original sequences reported by Gudat are discussed in the context of ¹¹⁹Sn‐relayed proton detection of very low frequency transition metal nuclei. Copyright © 2010 John Wiley & Sons, Ltd.