An Intramolecular CAr–H•••O=C Hydrogen Bond and the Configuration of Rotenoids

Abstract

Over the past half a century, the structure and configuration of the rotenoids, a group of natural products showing multiple promising bioactivities, have been established by interpretation of their NMR and electronic circular dichroism spectra and confirmed by analysis of single-crystal X-ray diffraction data. The chemical shift of the H-6' 1H NMR resonance has been found to be an indicator of either a cis or trans C/D ring system. In the present study, four structures representing the central rings of a cis-, a trans-, a dehydro-, and an oxadehydro-rotenoid have been plotted using the Mercury program based on X-ray crystal structures reported previously, with the conformations of the C/D ring system, the local bond lengths or interatomic distances, hydrogen bond angles, and the H-6' chemical shift of these compounds presented. It is shown for the first time that a trans-fused C/D ring system of rotenoids is preferred for the formation of a potential intramolecular C6'–H6'•••O=C4 H-bond, and that such H-bonding results in the 1H NMR resonance for H-6' being shifted downfield.

The effects of flavonoids in experimental sepsis: A systematic review and meta‐analysis

“…Sulfated flavonoids can present themselves as single‐ or multi‐sulfate esters, while rotonoid isoflavonoids are chemically biosynthesized from isoflavones and are characterized by a four‐ring chromanochromanone structure (Dixon, 1999) (Figure 2). Studies have described their anti‐inflammatory, antioxidant, antitumor, antimicrobial properties (Habbu et al, 2009; Ren et al, 2017; Teles et al, 2018), antidiabetic, and cytotoxic properties (Suthiphasilp et al, 2022). Treatment with the sulfated flavonoid persicarin (Per) (25), improved the survival rate and life expectancy of animals with sepsis (Kim et al, 2013).…”

Rotenoids and Other Specialized Metabolites from the Roots of Mirabilis multiflora: Opioid and Cannabinoid Receptor Radioligand Binding Affinities

“…Similarly, for 6-methoxyboeravinone C ( 6 ), isolated from a manipulated plant cell culture of M. jalapa , was reported with (6a,12a)- trans configuration based on the combination of ROESY data, molecular modeling, and comparison of the 3 J 6,6a values . The ECD data of mirabijalone A ( 2 ), boeravinone C ( 5 ), and 6-methoxyboeravinone C ( 6 ) gave evidence for an unusual trans -B/C ring. − The chemical shift value for H-1 [(δ H 7.76 ( 2 ), 7.81 ( 5 ), and 7.84 ( 6 ) in methanol- d 4 )] was strongly deshielded, and this could imply either a (6a R ,12a S ) or a (6a S ,12a R ) absolute configuration. The ECD spectra of 2 , 5 , and 6 showed sequential positive and negative CEs at 300–330 and 348–360 nm that were consistent with a (6a S ,12a R )- trans absolute configuration …”

“…322 nm and a negative CE at ca. 357 nm, consistent with a (6a S ,12a R ) absolute configuration. − Table shows a collation of the typical H-1 chemical shift values, the specific rotation data, and the ECD Cotton effects as they relate to the absolute configurations of C-6a and C-12a of 12a-hydroxyrotenoids. − Thus, the structure of multiferone A ( 3 ) was assigned unambiguously as (6 R ,6a S ,12a R )-4,11,12a-trihydroxy-6,9-dimethoxy-8,10-dimethylrotenone.…”

“…Primary screening of rotenoids from M. multiflora was conducted at a final concentration of 10 μM for competitive binding to the corresponding receptor using the reported methodology. − For the cannabinoid subtype receptor assays, rotenoids were added into a 96-well plate loaded with CHO-K1 cells, followed by 0.6 nM [ 3 H]-CP-55,940 and 10 μg of a cannabinoid membrane resuspended in 50 mM Tris (pH 7.4), 154 mM NaCl, and 20 mM Di-Na-EDTA supplemented with 0.02% BSA. Saturation experiments were performed to determine the optimal radioligand ([ 3 H]-enkephlin and [ 3 H]-DAMGO) and membrane concentrations for the opioid receptor subtype assays.…”

“…313 nm and a negative CE at ca. 348 nm, reminiscent of a (6a S ,12a R ) absolute configuration. − Based on the above spectroscopic data, the structure of multiferone B ( 7 ) was assigned unequivocally as (6 R ,6a S ,12a R )-11,12a-dihydroxy-4,6,9-trimethoxy-10-methylrotenone (Figure ). This compound was described by us in 2013, but without defining its absolute configuration and reporting its physical data.…”