Computer-aided determination of relative stereochemistry and 3D models of complex organic molecules from 2D NMR spectra

• Published in: Tetrahedron Vol. 61; no. 42; pp. 9980 - 9989
• Main Authors: Smurnyy, Yegor D., Elyashberg, Michail E., Blinov, Kirill A., Lefebvre, Brent A., Martin, Gary E., Williams, Antony J.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 17-10-2005
• Subjects: 2D NMR; Genetic algorithms; Natural products; NOESY; Nuclear Overhauser effect; Relative stereochemistry; ROESY; Structure elucidation; Relative stereochemistry; Nuclear Overhauser effect; Natural products; 2D NMR; ROESY; NOESY; Structure elucidation; Genetic algorithms
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.08.022

A method for elucidation of the relative stereoconfiguration of natural product molecular structures and their 3D models based on NOE data and the application of a genetic algorithm is described. The method is applicable mainly for rigid polycyclic structures commonly encountered in natural products. It is demonstrated that the technique of simulated annealing cannot be easily used when dealing with low-weight fused ring molecules but the application of a genetic algorithm is proven successful. Examples of a typical genetic algorithm workflow and the optimization of the algorithmic parameters are discussed. The efficiency of the approach developed here is demonstrated on the complex natural products of both Taxol
® (C
47H
51NO
14) and brevetoxin B (C
50H
70O
14).
The X-ray crystal structure of brevetoxin B (yellow) and the 3D model of the best stereoisomer (blue) from a stereochemistry determination system are superimposed. Small differences in the bond angles of some of the more flexible rings are present, but all stereocenters have been properly oriented.