Chiroptical study and absolute configuration of securinine oxidation products

Abstract

Time-dependant density functional theory-electronic circular dichroism spectra prediction was carried out to study the absolute configuration of phyllanthidine-type derivatives 5 and 6, derived from securinine (1) and its enantiomer virosecurinine (2), respectively. This method demonstrated to be very reliable in this alkaloid series. Thus, 5 and 6 shared the same stereochemistry as their parent precursors, confirming the retentive nature of the oxidation sequence. In addition, this study highlighted the key role of the methylene bridge (BC ring) in the chiroptical activity of these compounds. These results fully clarified the stereochemical relationships between the phyllanthidine and the securinine subgroups.

Flueggeacosines A–C, Dimeric Securinine-Type Alkaloid Analogues with Neuronal Differentiation Activity from Flueggea suffruticosa

“…The NOE correlation between H-2′ and H-8′a in the NOESY spectrum of 2, as well as the significant similarities between the NMR data assigned to unit 2b and those of phyllanthidine suggested that 2b possessed consistent relative stereochemistry with phyllanthidine. 9 Besides, as depicted in the optimized molecular model of 2 (Figure 3), the NOE interactions between H 2 -5 and H-7/H-15 as well as between 15-OCH 3 and H-8b indicated that 15-OCH 3 and the C-7−C-8−C-9 carbon bridge were of the same orientation. To determine the absolute configuration of 2, the theoretical ECD spectra of four possible stereoisomers of 2 were predicted by TDDFT calculation.…”

“…In addition, the HMBC correlations between H-2′ and C-6′/C-8′/C-13′, between H 2 -3′ and C-9′, between H-7′ and C-9′, between H 2 -8′ and C-13′/C-15′, between H-12′ and C-9′, as well as between H-14′ and C-7′/ C-9′/C-12′ established a phyllanthidine motif with a tetrahydro-1,2-oxazine ring (2b). 9 Furthermore, the HMBC correlations between H-7′/H-14′ and C-3 implied that two substructures 2a and 2b were also connected through the C-3−C-15′ bond. Hence, the gross structure of 2 was established and shown in Figure 3.…”

“…In the HMBC spectrum, key correlations between H 2 -5 and C-3, between H 2 -6 and C-2, between H-7 and C-2/C-6/C-9, between H 2 -8 and C-2/C-13, between H-12 and C-9/C-14, between H-15 and C-13, as well as between 15-OCH 3 and C-15 suggested the existence of an unprecedented ring A opened 15-methoxy-14,15-dihydrosecurinine unit ( 2a ). In addition, the HMBC correlations between H-2′ and C-6′/C-8′/C-13′, between H 2 -3′ and C-9′, between H-7′ and C-9′, between H 2 -8′ and C-13′/C-15′, between H-12′ and C-9′, as well as between H-14′ and C-7′/C-9′/C-12′ established a phyllanthidine motif with a tetrahydro-1,2-oxazine ring ( 2b ) . Furthermore, the HMBC correlations between H-7′/H-14′ and C-3 implied that two substructures 2a and 2b were also connected through the C-3–C-15′ bond.…”

“…The relative configuration of 2 could be determined by NOESY experiment as well as comparison of the NMR spectral data of 2 with those of the known compound. The NOE correlation between H-2′ and H-8′a in the NOESY spectrum of 2 , as well as the significant similarities between the NMR data assigned to unit 2b and those of phyllanthidine suggested that 2b possessed consistent relative stereochemistry with phyllanthidine . Besides, as depicted in the optimized molecular model of 2 (Figure ), the NOE interactions between H 2 -5 and H-7/H-15 as well as between 15-OCH 3 and H-8b indicated that 15-OCH 3 and the C-7–C-8–C-9 carbon bridge were of the same orientation.…”

L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

“…The resin petroleum extract was parboiled with agitation at 50˚C, then filtered until the crystals were separated out. Spectral techniques, including infra-red spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify the structure of the crystal, and X-ray crystallography, circular dichroism and Mosher chiral reagents were used to determine the absolute configuration of the product, as previously described (22,23). Finally, L-securinine was extracted and isolated, as described in the previous studies (Fig.…”