| Autor: |
Shepherd ED; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom., Dyson BS; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom., Hak WE; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom., Nguyen QNN; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom., Lee M; The Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea., Kim MJ; The Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea., Sohn TI; The Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea., Kim D; The Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea., Burton JW; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom., Paton RS; Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom.; Department of Chemistry , Colorado State University , Fort Collins , Colorado 80523 , United States. |
| Abstrakt: |
Despite numerous advances in spectroscopic methods through the latter part of the 20th century, the unequivocal structure determination of natural products can remain challenging, and inevitably, incorrect structures appear in the literature. Computational methods that allow the accurate prediction of NMR chemical shifts have emerged as a powerful addition to the toolbox of methods available for the structure determination of small organic molecules. Herein, we report the structure determination of a small, stereochemically rich natural product from Laurencia majuscula using the powerful combination of computational methods and total synthesis, along with the structure confirmation of notoryne, using the same approach. Additionally, we synthesized three further diastereomers of the L. majuscula enyne and have demonstrated that computations are able to distinguish each of the four synthetic diastereomers from the 32 possible diastereomers of the natural product. Key to the success of this work is to analyze the computational data to provide the greatest distinction between each diastereomer, by identifying chemical shifts that are most sensitive to changes in relative stereochemistry. The success of the computational methods in the structure determination of stereochemically rich, flexible organic molecules will allow all involved in structure determination to use these methods with confidence. |
