Here is a story that must drive chemical database quality control personnel nuts. Song, et al. noticed that the reported 13C NMR of the natural products cephalosporolide C 1, cephalosporolide J 2 and bassianolone 3 are identical.1 Given that it is highly unlikely that two diastereomers would have identical NMR spectra, the likelihood that these three have identical spectra seemed remote at best.
Compounds 1 and 2 were synthesized and their structures confirmed by x-ray crystallography. Their 13C NMR spectra show clear distinctions, indicating that the isolated “2” is actually 1. Experimental support for the notion that 1 and 3 are actually the same was provided by preparing the diacetylide of 1 and comparing its NMR spectra to that of natural “3”.
Quantum computations confirmed that in fact the natural product thought to be 3 is actually 1. The structures of 1 and 3 were optimized at B3LYP/6-311+G(2d,p) and 13C chemical shifts were computed with these geometries at mPW1PW91/6-311+G(2d,p)/CPCM(chloroform). (The computed structures are shown in Figure 1.) The mean absolute deviation (MAD) between the computed and experimental spectra for 1 is 0.97 ppm, while the MAD for the computed spectrum of 3 compared with the experimental values is 2.44 ppm, with a maximum error of 5.13ppm, more than twice the maximum error with structure 1. The authors attribute the misassignments to a faulty initial spectra of authentic cephalosporolide C 1.
Figure 1. B3LYP/6-311+G(2d,p) optimized geometries of 1 and 3.
(1) Song, L.; Lee, K.-H.; Lin, Z.; Tong, R. "Structural Revision of Cephalosporolide J and Bassianolone," J. Org. Chem. 2014, 79, 1493-1497, DOI: 10.1021/jo402602h.