Configurational Study Based on the Analysis of Homonuclear and Heteronuclear Coupling Constants
Keywords:
Organic compounds, Stereochemistry, Flexibility, Heteronuclear coupling constantsAbstract
A crucial step in the discovery of any new molecule is to determine its complete structure, which includes determining the planar structure of the molecule and its stereochemistry. It has been seen that the latter is strongly linked to its chemical and biological properties. However, this is particularly difficult when the chiral center(s) are in portions with high flexibility that are easily exchanged between different conformations, as is the case with acyclic fragments or rings with high flexibility. Improvements in NMR spectroscopy methods have made it a powerful tool for determining the structure of organic molecules. One of the most popular strategies developed in recent decades to address many structural problems is J-constant-based analysis (JBA), which consists of the use of long-distance heteronuclear (C—H) coupling constants (two or three bonds) to determine the stereochemistry, even in systems with flexibility.
Downloads
References
(1) Beckett, A. H. Stereochemical factors in biological activity. En “Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques”; Jucker, E.; Birkhäuser Basel: Schweizer Wissenschafts, 1959, 1, 455-530. https://doi.org/10.1007/978-3-0348-7035-1_6
(2) Ariëns, E. J. Chirality in bioactive agents and its pitfalls. Trends Pharmacol. Sci., 1986, 7, 200-205. https://doi.org/10.1016/0165-6147(86)90313-5
(3) Simonyi, M.; Fitos, I.; Visy, J. Chirality of bioactive agents in protein binding storage and transport processes. Trends Pharmacol. Sci., 1986, 7, 112-116. https://doi.org/10.1016/0165-6147(86)90276-2
(4) James, H. K.; Anthony, R. S. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol. Sci., 2011, 122(1), 1–6. https://doi.org/10.1093/toxsci/kfr088
(5) Eriksson, T.; Björkman, S.; Höglund P. Clinical pharmacology of thalidomide. Eur. J. Clin. Pharmacol., 2001, 57(5), 365-76. https://doi.org/10.1007/s002280100320
(6) Flack, H. D.; Bernardinelli, G. The use of X-ray crystallography to determine absolute configuration. Chirality, 2008, 20, 681-690. https://doi.org/10.1002/chir.20473
(7) Sands, D. E. Introducción a la cristalografía, Reverté, S.A., New York , 1969, pp 86-90.
(8) Fukui, H.; Fukushi, Y. NMR determinations of the absolute configuration of α-chiral primary amines. Org. Lett., 2010, 12, 2856-2859. https://doi.org/10.1021/ol100951s
(9) Cen-Pacheco, F.; Mollinedo, F.; Villa-Pulgarin, J.; Martín, M. N.; Fernández, J. J.; Daranas, A. H. Saiyacenols A and B: the key to solve the controversy about the configuration of aplysiols. Tetrahedron, 2012, 68, 7275-7279. https://doi.org/10.1016/j.tet.2012.07.005
(10) Cen‐Pacheco, F.; Rodríguez, J.; Norte, M.; Fernández, J. J.; Hernández Daranas, A. Connecting discrete stereoclusters by using DFT and NMR spectroscopy: the case of nivariol. Chem. Eur. J., 2013, 19(26), 8525-8532. https://doi.org/10.1002/chem.201204272
(11) Matsumori, N.; Kaneno, D.; Murata, M.; Nakamura, H.; Tachibana, K. Stereochemical Determination of Acyclic Structures Based on Carbon-Proton Spin-Coupling Constants. A Method of Configuration Analysis for Natural Products. J Org Chem., 1999, 64(3), 866-876. https://doi.org/10.1021/jo981810k
(12) Cen-Pacheco, F.; Santiago-Benítez, A. J.; Tsui, K. Y.; Tantillo, D. J.; Fernández, J. J.; Hernández Daranas, A. Structure and computational basis for backbone rearrangement in marine oxasqualenoids. J. Org. Chem. 2021, 86(3), 2437-2446. https://doi.org/10.1021/acs.joc.0c02600
(13) Cen-Pacheco, F.; Santiago-Benítez, A. J.; García, C.; Álvarez-Méndez, S. J.; Martín-Rodríguez, A. J.; Norte, M.; Martín, V. S.; Gavín, J. A.; Fernández, J. J.; Hernández Daranas, A. Oxasqualenoids from Laurencia viridis: combined spectroscopic-computational analysis and antifouling potential. J. Nat. Prod., 2015, 78(4), https://doi.org/712-21.10.1021/np5008922
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Francisco Cen-Pacheco, Fernando C. López-Fentanes
This work is licensed under a Creative Commons Attribution 4.0 International License.
