Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non‐Lepidopteran Ecdysteroid Receptor Selectivity

Sun, Han; Dinan, Laurence; Lafont, René; Suksamrarn, Apichart; Griesinger, Christian; Reinscheid, Uwe M.; Lapenna, Silvia

doi:10.1002/ejoc.201000366

Cited by 6 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the Karplus equation (Equation 2.45) this pattern clearly indicates that C20' and C24' are antiperiplanar with respect to each other. This is the same side chain conformation found in a previous study of a structurally related steroid [Sun et al, 2010]. Due to the extreme 3 J H22 −H23 values, we can exclude from further analysis all conformations that don't have an anti conformation for the C20'-C22'-C23'-C24' moiety.…”

Section: Elucidation Of the Relative Configuration And Conformation B...supporting

confidence: 53%

“…Before this thesis all reported successful applications of the methodology using anisotropic NMR parameters have been performed with conventional 5 mm NMR tubes, which require a relatively large amount (>5 µmol) of sample to compensate for the low sensitivity and substantial background signal from the alignment medium used to achieve anisotropic conditions. This limitation hampers measurements for many natural products of poor availability (<3 µmol) and precludes the determination of their configuration by NMR [Sun et al, 2010]. The sensitivity problem of NMR spectroscopy has been significantly reduced since the commercial 1.7 mm microprobe became available in 2007.…”

Section: Motivation and Outline Of This Thesismentioning

confidence: 99%

See 1 more Smart Citation

Stereochemistry of Challenging Natural Products Studied by NMR-based Methods

Sun¹

View full text Add to dashboard Cite

Stereochemistry is a very important subject in chemistry and life sciences, as most of the biologically active molecules, including proteins, oligonucleotides, sugars, lipids and small molecules exist in one chiral form. In addition, small molecule compounds with biological activity -drugs -with the same constitution yet different configuration can exhibit divergent biological activities. The determination of the relative configuration of stereocenters was first established by Fischer in 1891 via organic synthesis. The question of absolute configuration was not solved until the work of Bijvoet in 1951 with anomalous X-ray diffraction of single crystals. For the compounds which can neither be crystallized nor easily be converted into crystallizable derivatives, it can still be difficult to establish their stereochemistry. Within this thesis, the development and application of Residual Dipolar Coupling (RDC)-enhanced NMR techniques for the stereochemical elucidation of organic molecules -the RDC-based approach -will be presented. Residual dipolar couplings provide valuable information about the orientation of internuclear vectors with respect to the molecular frame, which complements nuclear Overhauser effects (NOEs), scalar J-couplings and chemical shifts that are short-range in nature. RDCs have been used for structure determination and dynamic studies of biomolecules for decades, however the use of this anisotropic parameter for configurational and conformational studies of small molecules has yet to be fully tapped. Herein, the new developments and improvements of this RDC-based approach for the study of small molecules can be categorized as:Conformationally flexible molecules: Both single and multiple alignment tensor approaches were employed and compared. Molecular mechanics (MM) and molecular dynamics (MD) simulations were applied to statistically sample the extensive conformational space.Natural products with limited availability: The preparation of a slim PH-gel for 1.7 mm NMR tubes has been developed for reproducibility and efficiency. RDC measurements in this low volume gel system have been made using a V VI number of molecules.Large numbers of unknown stereocenters: NOE and J-coupling restrained MD simulations with the floating chirality method were investigated. Combined with an RDC analysis in the final step, this enables the determination of the relative stereochemistry of a large number of stereocenters in a complex natural product.Absolute configuration: An integrated approach is herein developed. This includes diastereomer differentiation using both isotropic and anisotropic NMR data. The chiroptical properties calculated using DFT of the NMR derived ensemble from this first step are used for enantiomer differentiation by comparison to experiments.Using these improved methods, the stereochemistry of six challenging natural products -LLG1, naphth 1, naphth 2, comp.540a, vatiparol, and fibrosterol sulfate A -and one synthetic molecule -a Michael addition product -has been successfully established. Z...

show abstract

Section: Elucidation Of the Relative Configuration And Conformation B...supporting

confidence: 53%

Section: Motivation and Outline Of This Thesismentioning

confidence: 99%

Stereochemistry of Challenging Natural Products Studied by NMR-based Methods

Sun¹

View full text Add to dashboard Cite

show abstract

“…But all reported successful applications of this methodology by using anisotropic NMR parameters have been performed with conventional 5 mm NMR tubes, which require a relatively large amount (>5 μmol) of sample to compensate the low sensitivity and substantial background signals from the alignment medium used to achieve anisotropic conditions. This limitation hampers such measurements23 for many natural products of poor availability (<3 μmol) and precludes the determination of their configuration by NMR spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

Relative and Absolute Configuration of Vatiparol (1 mg): A Novel Anti‐inflammatory Polyphenol

Sun

Jiang

et al. 2012

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Bioactive natural products offer multiple opportunities for the discovery of novel chemical entities with potential pharmaceutical, nutraceutical and agrochemical applications. Many new organic compounds with novel scaffolds are isolated in small quantities and established methods often fail to determine the structure and bioactivity of such novel natural products. To meet this challenge, we present here a new methodology combining RDC (residual dipolar coupling)-based NMR spectroscopy in microtubes, with a motif-inspired biological assessment strategy. Using only one milligram (ca. 1.5 μmol) of sample, the new protocol established the bioactivity as well as the relative and absolute configuration of vatiparol obtained from Vatica parvifolia. Vatiparol is unique in its unprecedented carbon skeleton and selective inhibitory effect on the expression of monocyte chemo-attractant protein-1 (MCP-1, also known as CCL2). The plausible biosynthetic pathway of vatiparol is briefly discussed. The approach introduced here promises to be widely applicable to the determination of the structure and bioactivity of structurally unknown organic samples available in very limited amounts.

show abstract