Structural and conformation analysis of sesquiterpene lactones by proton nuclear magnetic resonance

Abstract

The stereochemistry as well as the conformation of two germacranolides and two 3,4‐epoxyguaianolides were determined by computational methods employing LAOCOON‐III and DAERM programs. The chair‐chair conformation was shown to be preferred by the germacranolide macrocycle in solution, while the A‐ring of 1,10‐dehydro‐3,4‐epoxyguaianolides was shown to be approximately planar. The ten‐membered ring stereochemistry of germacranolides was deduced from the calculated results.

Cytotoxic Activity of Germacrane-Type Sesquiterpene Lactones from Dimerostemma aspilioides

“…The 1D and 2D NMR data of compound 1 (Table , Figure ), together with the proposed molecular formula and spectroscopic data previously reported in the literature, revealed that it corresponded to a bicyclic sesquiterpenoid with a germacrane-type skeleton with a 6,7- trans -fused lactone ring, and it was identified as tomenphantin A. , The relative stereochemistry was assigned according to previous data − and from a NOESY experiment (Figure and Table S1, Supporting Information) and matched those previously described for similar germacranolides . The coupling constants J 8β–9α = 11.2 Hz and J 8β–9β = 1.7 Hz were consistent with the ester side chain at C-8 being in an α-orientation, , while the signal for H-6 as a doublet of doublets at δ H 4.30 and J 5α,6β = 9.2 Hz and J 6β,7α = 6.6 Hz indicated a trans -axial relationship between H-5α, H-6β, and H-7α, assuming that the latter is in an α-orientation, as in all the known germacranolides obtained from plants . NOESY correlations of H-1/H-5α, H-7α suggested that these protons are cofacial and were observed as well between H6β and Me-15 (Figure and Table S1, Supporting Information) .…”

“…This compound yielded very similar spectroscopic data to compound 1 , and, in light of the probable same biogenetic origin, the same relative configuration was assigned. The α-orientation of the C-8 side chain as in compound 1 was confirmed by the coupling constants observed for H-8 ( J 8β,9α = 9.2 Hz and J 8β,9β = 1.2 Hz). , The trans -axial orientation of Hα-5, Hβ-6 and Hα-7 was supported by the coupling constants observed for H-6 ( J 5α,6β = 9.9 Hz and J 6β,7α = 6.7 Hz) . NOESY correlations of CH 3 -15 with both H-14 (δ H 3.89, 4.05) and H-6β (δ H 4.97) and also from H7α (δ H 3.24) to H-1 (δ H 5.11) and H-5α (δ H 4.93) confirmed the orientation assigned to H-5, -6, -7, and -8 (Figure and Table S1, Supporting Information).…”

“…14,15 The relative stereochemistry was assigned according to previous data 14−16 and from a NOESY experiment (Figure 3 and Table S1, Supporting Information) and matched those previously described for similar germacranolides. 17 The coupling constants J 8β−9α = 11.2 Hz and J 8β−9β = 1.7 Hz were consistent with the ester side chain at C-8 being in an α-orientation, 14,18 while the signal for H-6 as a doublet of doublets at δ H 4.30 and J 5α,6β = 9.2 Hz and J 6β,7α = 6.6 Hz indicated a trans-axial relationship between H-5α, H-6β, and H-7α, 16 assuming that the latter is in an α-orientation, as in all the known germacranolides obtained from plants. 19 NOESY correlations of H-1/H-5α, H-7α suggested that these protons are cofacial and were observed as well between H6β and Me-15 (Figure 3 and Table S1, Supporting Information).…”

“…16 The same chemical shifts and splitting pattern with the hydroxy-methacrylate chain at C-8 as in compound confirm this ester side chain (Figure 2), while an α-orientation followed from the J 8β-9α = 10.3 Hz and J 8β-9β = 1.9 Hz coupling constants seen. 14,18 An epoxy group was established between C-1 and C-10 from the presence of two carbon signals at δ C 66.8 and 60.5 in the 13 C NMR spectrum and by the HMBC correlations from H-9 (δ H 2.48) to C-1 and C-10 (Table 1 and Figure 2). Its relative configuration was established according to Bohlmann et al 23 A doublet at δ H 9.24 with a 13 C NMR resonance at δ C 200.6 implies the presence of a formyl group at H-14 showing, as depicted in Figure 2, an HMBC correlation to C-10 and a COSY correlation with the resonance at δ H 1.49 (H-14/H-9), which confirmed that the CHO group is attached to C-10.…”

Dynamic NMR and Computational Studies Inform the Conformational Description of Dendrillane Terpenes from the Nudibranch Goniobranchus coi

“…In cyclic systems, conformational averaging may have its origins in inversion of the ring, for example, the interconversion between different chair forms, termed a ring flip, or between chair and boat forms. In cases such as cycloheptane or cyclohexane, the energy barrier has been calculated to be between 7 and 10 kcal mol –1 . − Conformational averaging is also commonly encountered in fused ring systems including perhydroazulenes , and guaianolide sesquiterpenes, , where activation barriers are typically >10 kcal mol –1 . A second form of conformational averaging is restricted rotation.…”