Absolute Configuration of Verticillane Diterpenoids by Vibrational Circular Dichroism

Abstract

Good agreement between theoretical and experimental vibrational circular dichroism curves of (1S,11S,12S)-(+)-verticilla-3E,7E-dien-12-ol (1) established the absolute configuration of this natural diterpene isolated from Bursera suntui. Molecular modeling of 1 was carried out using the Monte Carlo protocol followed by geometry optimization at the B3LYP 6-31G(d,p) level of theory. The 12-membered ring of 1 was found in a single preferred chair−chair−chair−chair conformation. In the six-membered ring a chair prevails over a distorted boat, and the C−OH bond rotation generates three predominant rotamers. Validation of the minimum energy conformation for 1 was achieved by comparison of theoretical and experimental infrared frequencies, vicinal 1H NMR coupling constants, and X-ray diffraction data. This study confirms that (+)-verticillol 1 isolated from Bursera species has the 1S,11S,12S absolute configuration that corresponds to the same enantiomeric series as verticillanes from Sciadopitys and Taxus, while verticillanes from Jackiella and Jungermannia have antipodal structures.

Absolute configuration determination and conformational analysis of (−)‐(3S,6S)‐3α,6β‐diacetoxytropane using vibrational circular dichroism and DFT techniques

“…Only the eight relevant conformations, accounting 99.97% in the first 10 kcal/mol range, were then submitted to geometry reoptimizations, followed by vibrational calculations using the DFT B3LYP hybrid functional and the DGDZVP basis set. The use of this combination of basis set and functional has shown to require less computing time than the 6-31G(d) basis set while producing very similar results, as is evident in figures of recently published work [11][12][13] as well as in Figure 1 of the Supporting Information. This situation, as recently highlighted, 12 seems to be associated to the fact that DGauss basis sets, such as DGDZVP, are optimized for DFT methods.…”

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

“…The reinvestigation of the absolute conguration of the iridoids plumericin (25) and isoplumericin (26) using the same combination of chiroptical methods and calculations presented above also conrmed the previous assignments of (+)-25 and (+)-26 as 1R,5S,8S,9S,10S. 87 The eremophilanoids 6-hydroxyeuryopsin (30), isolated from Senecio toluccanus, and compound 31 isolated from Psacalium paucicapitatum had their absolute conguration determined as 4S,5R,6S and 1S,4S,5R,8S,10S, respectively, by VCD and DFT calculations. 84,85 Interestingly, the signs of the OR of 25 and 27 are opposite despite their identical absolute conguration, that points out the risks of relying on the comparison of OR values for assigning absolute congurations.…”

Oxygenated verticillene derivatives from Bursera suntui

“…Therefore, this task was not undertaken. The absolute configuration of verticillol 1, also isolated from B. suntui, was securely assigned as 1S,3E,7E,11S,12S on the basis of a vibrational circular dichroism study (Cerda-García-Rojas et al, 2007). Therefore, the absolute configuration of the new verticillane derivatives 7-11 can be established on biogenetic grounds, taking into account that for the natural product 1.…”

“…Previously, several epoxyverticillanes were obtained by oxidation of verticillenes with peroxyacids, such as m-chloroperoxybenzoic acid (Nagashima et al, 2005) and monoperphthalic acid (Karlsson et al, 1978), or by treatment with H 2 O 2 and SeO 2 in t-BuOH (Cerda- García-Rojas et al, 2007). Finally, allylic alcohols 9-11 are relevant because they closely resemble some structural features of the cytotoxic verticillenes cespitularins C and E isolated from the soft coral Cespitularia hypotentaculata (Duh et al, 2002).…”