Residual Dipolar Coupling Enhanced NMR Spectroscopy and Chiroptics: A Powerful Combination for the Complete Elucidation of Symmetrical Small Molecules

Collective Synthesis and Biological Evaluation of Tryptophan‐Based Dimeric Diketopiperazine Alkaloids

“…15,15′‐bis‐ epi ‐Eurocristatine ( 3 ), which contains two l ‐tryptophan and l ‐valine units, was prepared by using an enzymatic feeding experiment for the preparation of an analogue of compound 1 and it is reported to have moderate activity as a cholecystokinin type‐B receptor antagonist . The enantiomer of compound 3 was synthesized by de Lera and co‐workers for an analytical study of the configuration and conformation of this type of diketopiperazine alkaloid by using NMR and ECD spectroscopy supported by DFT calculations . The naturally occurring compounds 1 , 2 , and 3 are C 2 ‐symmetrical compounds that contain a dimeric tryptophan unit possessing a C3( R )−C2( R ) configuration, and the same two amino acids, l ‐phenylalanine, d ‐, or l ‐valine.…”

“…[2e] The enantiomer of compound 3 was synthesized by de Lera and co-workers for an analytical study of the configuration and conformationo ft his type of diketopiperazine alkaloid by using NMR and ECD spectroscopy supported by DFT calculations. [23] The naturally occurring compounds 1, 2,a nd 3 are C 2 -symmetricalc ompounds that contain ad imeric tryptophan unit possessing aC 3(R)ÀC2(R)c onfiguration, and the same two amino acids, l-phenylalanine, d-, or l-valine.T hus, the synthesis of compounds 1, 2,and 3 couldbeaccomplished by ac ondensation reactiono ft he dimeric intermediate 21 and the corresponding two amino acids followed by diketopiperazine formation.T he group of de Lera hada lready established an excellent procedure of ac ondensation reaction with the dimericc ompound prepared by four steps and 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino acids by using O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (HATU) as the coupling reagent. [10b, 13d] On the other hand, the one-potr eactioni so ne of the key topics in chemistry,u nderlining the importance of the "Pot economy."…”

Perspectives in the application of residual dipolar couplings in the structure elucidation of weakly aligned small molecules

“…Residual dipolar couplings will keep contributing to a variety of structure determination problems and will become an important tool for all NMR spectroscopists. If developments continue with the rapid speed the field has seen in the last years, RDC analysis will become a more generally applicable method, both on its own, and by combination with other computational or spectroscopic methods like chiroptic methods . If not already the case, they will complement NMR‐based structure determination protocols, where routine analysis of chemical shifts, J ‐couplings, or NOEs alone only gives an unambiguous or incomplete picture of the chemical structure.…”

The Use of a Combination of RDC and Chiroptical Spectroscopy for Determination of the Absolute Configuration of Fusariumin A from the Fungus Fusarium sp.

“…S5) can be excluded to be the major conformation. Although many studies show that the NMR data are corroborated by DFT-based energy calculations [ 26 , 27 ], on our example the DFT computation with the B3LYP functional do not accurately predict the relative energies [ 28 ].…”