Structure and absolute configuration of ginkgolide B characterized by IR‐ and VCD spectroscopy

Abstract

Experimental and calculated (B3LYP/6-31G(d)) vibrational circular dichroism (VCD) and IR spectra are compared, illustrating that the structure and absolute configuration of ginkgolide B (GB) may be characterized directly in solution. A conformational search for GB using MacroModel and subsequent DFT optimizations (B3LYP/6-31G(d)) provides a structure for the lowest energy conformer which agrees well with the structure determined by X-ray diffraction. In addition, a conformer at an energy of 7 kJ mol(-1) (B3LYP/6-311+G(2d,2p)) with respect to the lowest energy conformer is predicted, displaying different intramolecular hydrogen bonding. Differences between measured and calculated IR and VCD spectra for GB at certain wavenumbers are rationalized in terms of interactions with solvent, intermolecular GB-GB interactions, and the potential presence of more than one conformer. This is the first detailed investigation of the spectroscopic fingerprint region (850-1300 cm(-1)) of the natural product GB employing infrared absorption and VCD spectroscopy.

Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products

“…93 Conformational exibility of (S)-(À)-perillaldehyde (38), a secondary metabolite and atmospheric pollutant, was also investigated using experimental and theoretical VCD. 104 Differences between measured and calculated IR and VCD spectra for 46 were rationalized in terms of interactions with solvent as well as intermolecular interactions. 95 Even though chiroptical methods are ideally used to tell apart enantiomers, the absolute conguration of the pacifenol derivative (À)-(40) was determined using VCD measurements and calculations for both diastereomers possible at C-8.…”

“…Compound 102, which is among the most exible small organic molecules studied by VCD spectroscopy, was assigned as S aer comparison of observed VCD, both in solution and KBr pellets, with calculated (B3LYP/aug-cc-pVDZ) data. Initially, the absolute conguration of (À)-podophyllotoxin (104) and (À)-deoxypodophyllotoxin (105) was assigned as 7R,7 0 R,8R,8 0 R and 7 0 R,8R,8 0 R, respectively, by comparison of experimental VCD and B3LYP/DGDZVP predicted spectra. Initially, the absolute conguration of (À)-podophyllotoxin (104) and (À)-deoxypodophyllotoxin (105) was assigned as 7R,7 0 R,8R,8 0 R and 7 0 R,8R,8 0 R, respectively, by comparison of experimental VCD and B3LYP/DGDZVP predicted spectra.…”

Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic

“…With 40 m in height, this tree is characterised by the fan-shaped leaves composed of more than two distinct lobes (a). Ginkgolide A, R 1 =H; R 2 =H; R 3 =OH, Ginkgolide B, R 1 =OH; R 2 =H; R 3 =OH, Ginkgolide C, R 1 =OH; R 2 =OH; R 3 =OH, Ginkgolide J, R 1 =H; R 2 =OH; R 3 =OH, Ginkgolide M, R 1 =OH; R 2 =OH; R 3 =H (b) [ 129 ].…”

Conformational Equilibria of Bridled Chiroporphyrins in Solution Investigated by Vibrational Circular Dichroism

“…Quantum mechanical predictions of VCD spectra are quite successful in replicating the corresponding experimental spectra in the mid‐IR region . Ab initio calculations at the Density Functional Theory (DFT) level combined with VCD experiments have been used during the two last decades to determine the absolute configuration and/or conformation of small and medium‐sized molecules, and more recently to investigate large molecules such as natural products, helical molecules, cryptophanes, and supramolecular assemblies …”

“…Quantum mechanical predictions of VCD spectra are quite successful in replicating the corresponding experimental spectra in the mid-IR region. 9 Ab initio calculations at the Density Functional Theory (DFT) level combined with VCD experiments have been used during the two last decades to determine the absolute configuration and/or conformation of small and medium-sized molecules, [8][9][10] and more recently to investigate large molecules such as natural products, [11][12][13][14][15][16] helical molecules, [17][18][19][20][21] cryptophanes, [22][23][24][25][26] and supramolecular assemblies. [27][28][29][30][31][32] We show in this article that IR and VCD associated with DFT calculations can be successfully used to determine the conformational equilibria of bridled chiroporphyrins and their metal complexes in solution.…”