Chromane helicity rule – scope and challenges based on an ECD study of various trolox derivatives

Abstract

The validity of the chromane helicity rule correlating the sense of twist within the dihydropyran ring with the CD sign of the (1)Lb band observed at ca. 290 nm in their electronic circular dichroism (ECD) spectra is examined using a set of natural (S)-trolox derivatives. To investigate both the scope and the limitations of the rule a combination of ECD spectroscopy, especially the temperature dependence of the ECD spectra, single crystal X-ray diffraction analyses, and density functional theory (DFT) calculations was used. A thorough conformational analysis supported by the X-ray data led to the identification of predominant conformers. Then, a comparison of the experimental ECD spectra with the spectra simulated by TDDFT calculations allowed for a reasonable interpretation of the accumulated data. The results clearly indicated that to avoid the possibility of erroneous conclusions the chromane helicity rule should be used with great caution. This is likely related to the conformational flexibility of tested compounds by which conformers of different helicities can be produced. Therefore, based on the results presented here, it is strongly recommended that the conclusions derived from analysis of experimental data are supported with the appropriate theoretical computations.

Synthesis, structure, antioxidant activity, and water solubility of trolox ion conjugates

“…In UV spectra of the obtained compounds 2a – 2q , maximums of absorption were observed in the range of 288–299 nm, which is typical for trolox derivatives (λ max = 292 nm) (Gorecki et al, 2014) and verified the existence of a chromane core. In UV spectra of ICs with convolvine 2m and lappaconitine 2p , additional aromatic ring absorption bands were observed at 265 and 254 nm, respectively.…”

Complementarity of electronic and vibrational circular dichroism based on stereochemical studies of vic-diols

“…Very recently, such a combined approach was successful in determining the AC in trolox derivatives [66] and 4-hydroxy-5-methylcyclopent-2-en-1-one [67]. In the chromane chromophore, VCD spectroscopy supported by DFT calculations enabled revision of the AC assignment based on the chromane helicity rule of two compounds isolated from the leaves of Peperomia obtusifolia [68].…”

Vibrational Circular Dichroism: Recent Advances for the Assignment of the Absolute Configuration of Natural Products

“…Of relevance is also to note that most AC determinations made during the 20 th century were based on comparisons with model compounds, which in some cases led to the wrong AC assignment, which of course can be established correctly by VCD, as is the case of esquelane derivatives, which are constituents of a commercial fragrance [4]. A similar situation was observed for chromane derivatives, for which the relationship between the stereostructure and their ECD was determined almost exclusively by the empirical chromane helicity rule, although failures of the rule have been detected in some cases [5].…”