Absolute Configuration of (13R)- and (13S)-Labdane Diterpenes Coexisting in Ageratina jocotepecana

Abstract

Chemical investigation of the hexanes extracts of Ageratina jocotepecana afforded (-)-(5S,9S,10S,13S)-labd-7-en-15-oic acid (1), methyl (-)-(5S,9S,10S,13S)-labd-7-en-15-oate (2), (+)-(5S,8R,9R,10S,13R)-8-hydroxylabdan-15-oic acid (3), and (-)-(5S,9S,10S,13Z)-labda-7,13-dien-15-oic acid (5). The coexistence of (13R)- and (13S)-labdanes in this member of the Asteraceae family was demonstrated by vibration circular dichroism measurements of ester 2 and methyl (+)-(5S,8R,9R,10S,13R)-8-hydroxylabdan-15-oate (4) in comparison to the DFT B3LYP/DGDZVP-calculated spectra. In addition, transformation of 1 and 3 with HClO4 in MeOH yielded epimeric methyl (+)-(5S,10S,13S)-labd-8-en-15-oate (6) and methyl (+)-(5S,10S,13R)-labd-8-en-15-oate (7), respectively, confirming the presence of C-13 epimers in this plant. Diterpene 1 showed remarkable antibacterial activity against Bacillus subtilis (MIC 0.15 mg/mL) and Staphylococcus aureus (MIC 0.78 mg/mL), while diterpene 3 exhibited moderate activities against the same organisms.

DFT1H-1H coupling constants in the conformational analysis and stereoisomeric differentiation of 6-heptenyl-2H-pyran-2-ones: configurational reassignment of synargentolide A

“…The 13 C NMR data for the synthetic isomer 12 are close enough to those reported for the natural product, showing small but significant differences (up to 0.3 ppm deviation in the chemical shift values) that constituted the argument used by the synthetic groups to support the proposed 6 R ,4′ R ,5′ R ,6′ R ‐stereoisomer for natural synargentolide A. However, the inability of 13 C NMR spectroscopy under conventional measurements to distinguish between a pair of stereoisomers has been demonstrated when two chiral moieties are separated by a flexible connective chain, thus producing essentially identical 13 C NMR spectra but distinguishable 1 H NMR spectra, as observed for natural synargentolide A ( 8 ) and its synthetic isomer ( 12 ) (Fig. and Table ).…”

Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods

“…The absorption intensity of the experimental spectra was slightly weaker than the calculated data. These results were consistent with literature that focused on the VCD of labdane-type diterpene compound for AC determination [23,25]. The chemical environment, such as the solvent employed, is one reason why infrared energy was not absorbed for the vibrational transition within the molecule.…”

“…Table 2 gives comprehensive data of characteristic peaks identified by their type of bonding vibration energy and their contribution to chirality, indicating direct attachment or involvement of functional structure in chiral rotation and configuration. VCD analysis of 1 was recorded at 48000 scan number, which is equivalent to 8 h. As reported by García-Sánchez et al, 2014 [23], other labdane diterpenes may take 6 to 11 h of VCD analysis period depending on the flexibility of the compound tested. This phenomenon due to the fact that the vibrational transition of chemical bonding is a weak quantized energy produced by electron wavefunction [24].…”

“…In contrast, calculated IR and VCD frequencies are derived from a non-harmonic force field from the bending or stretching. Thus, the uncertainty of VCD experimental analysis can be justified by the calculated spectra and thereby establishing absolute configuration [23].…”

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

“…To gain chemical evidence for the configuration at C-13 in 18 and 20, these natural products were transformed into their respective 8en methyl ester derivatives. Interestingly, the 13 C NMR chemical shifts of 19 and 21 were very similar, revealing the inability of 13 C NMR spectroscopy to distinguish these C-13 epimers [43]. Hyptisolide A (22), isolated from Hyptis crenata Pohl ex Benth, was the first diterpenoid that had the 7,8;11,12-bis-secoabietane skeleton.…”