Enantiomeric Discorhabdin Alkaloids and Establishment of Their Absolute Configurations Using Theoretical Calculations of Electronic Circular Dichroism Spectra

Grkovic, Tanja; Ding, Yuanqing; Li, Xing-Cong; Webb, Victoria L.; Ferreira, Daneel; Copp, Brent R.

doi:10.1021/jo801622n

Cited by 50 publications

(86 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TDDFT calculations of their ECD spectra are particularly suitable for the determination of the AC of this class of compounds, including conformationally ridgid 11–13 and the conformationally flexible 14 . 68 …”

Section: Tddft Calculation Of Ecd Spectra Of Structually Diverse Nmentioning

confidence: 99%

Determination of Absolute Configuration of Natural Products: Theoretical Calculation of Electronic Circular Dichroism as a Tool

Ferreira

Ding

2010

COC

Self Cite

262

156

View full text Add to dashboard Cite

Determination of absolute configuration (AC) is one of the most challenging features in the structure elucidation of chiral natural products, especially those with complex structures. With revolutionary advancements in the area of quantum chemical calculations of chiroptical spectroscopy over the past decade, the time dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra has emerged as a very promising tool. The principle is simply based on the comparison of the calculated and experimental ECD spectra: the more closely they match, the more reliable conclusion for the AC assignment can be drawn. This review attempts to use several examples representing monomeric flavonoids, rotationally restricted biflavonoids, complex hexahydroxydiphenoyl-containing flavonoids, conformationally flexible and restrained sesquiterpenoids, cembrane-africanene terpenoids, dihydropyranocoumarins, alkaloids, and dihydroxanthones to illustrate the applicability of this approach in determining the AC of structurally diverse natural products. The findings clearly indicate that the TDDFT calculation of ECD spectra can quantify the contribution of individual conformers and the interaction of multiple chromophores, making it possible to determine the AC of complex chiral molecules. The calculated electronic transitions and molecular orbitals provide new insight into the interpretation of ECD spectra at the molecular level.

show abstract

Section: Tddft Calculation Of Ecd Spectra Of Structually Diverse Nmentioning

confidence: 99%

Determination of Absolute Configuration of Natural Products: Theoretical Calculation of Electronic Circular Dichroism as a Tool

Ferreira

Ding

2010

COC

Self Cite

262

156

View full text Add to dashboard Cite

show abstract

“…Both tsitsikammamines and discorhabdins have been reported to show potent anticancer activities in vitro [28,30,40]. On a molecular level, DNA intercalation, topoisomerase I and II, indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) enzymes have been identified as potential targets for tsitsikammamines or their synthetic derivatives, while the inhibition of HIF-1α/p300 interaction has been reported as potential target of discorhabdins [28,34,35,36].…”

Section: Resultsmentioning

confidence: 99%

Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity

Janussen

Peifer

et al. 2018

Marine Drugs

View full text Add to dashboard Cite

The Antarctic deep-sea sponge Latrunculia (Latrunculia) biformis Kirkpatrick, 1908 (Class Demospongiae Sollas, Order Poecilosclerida Topsent, Latrunculiidae Topsent) was selected for chemical analyses due to its potent anticancer activity. Metabolomic analysis of its crude extract by HRMS/MS-based molecular networking showed the presence of several clusters of pyrroloiminoquinone alkaloids, i.e., discorhabdin and epinardin-type brominated pyridopyrroloquinolines and tsitsikammamines, the non-brominated bis-pyrroloiminoquinones. Molecular networking approach combined with a bioactivity-guided isolation led to the targeted isolation of the known pyrroloiminoquinone tsitsikammamine A (1) and its new analog 16,17-dehydrotsitsikammamine A (2). The chemical structures of the compounds 1 and 2 were elucidated by spectroscopic analysis (one-dimensional (1D) and two-dimensional (2D) NMR, HR-ESIMS). Due to minute amounts, molecular modeling and docking was used to assess potential affinities to potential targets of the isolated compounds, including DNA intercalation, topoisomerase I-II, and indoleamine 2,3-dioxygenase enzymes. Tsitsikammamines represent a small class of pyrroloiminoquinone alkaloids that have only previously been reported from the South African sponge genus Tsitsikamma Samaai & Kelly and an Australian species of the sponge genus Zyzzya de Laubenfels. This is the first report of tsitsikammamines from the genus Latrunculia du Bocage and the successful application of molecular networking in the identification of comprehensive chemical inventory of L. biformis followed by targeted isolation of new molecules. This study highlights the high productivity of secondary metabolites of Latrunculia sponges and may shed new light on their biosynthetic origin and chemotaxonomy.

show abstract

“…The optimized geometries were used for TDDFT calculations at the B3LYP/6-31G(d,p) level applying the same solvation model. The generated excitation energies and rotational strengths were Boltzmann averaged and then fitted to Gaussian functions to generate computed ECD spectra normalized and overlaid with the experimental spectra for comparison [28,29]. The NMR calculations were performed by using the Gauge-invariant atomic orbital (GIAO) method at the B3LYP/6-31G(d,p) and MPW1PW91/6-31G(d,p) levels, and the calculated chemical shifts for TMS at the corresponding levels were used as references (computational details for Compounds 1 – 5 are provided in the Supplementary Information).…”

Section: Methodsmentioning

confidence: 99%

Relative and Absolute Stereochemistry of Diacarperoxides: Antimalarial Norditerpene Endoperoxides from Marine Sponge Diacarnus megaspinorhabdosa

et al. 2014

View full text Add to dashboard Cite

Five new norditerpene endoperoxides, named diacarperoxides H–L (1–5), and a new norditerpene diol, called diacardiol B (6), were isolated from the South China Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including conformations and absolute configurations, were determined by using spectroscopic analyses, computational approaches and chemical degradation. Diacarperoxides H–J (1–3) showed some interesting stereochemical issues, as well as antimalarial activity.

show abstract

Enantiomeric Discorhabdin Alkaloids and Establishment of Their Absolute Configurations Using Theoretical Calculations of Electronic Circular Dichroism Spectra

Cited by 50 publications

References 26 publications

Determination of Absolute Configuration of Natural Products: Theoretical Calculation of Electronic Circular Dichroism as a Tool

Determination of Absolute Configuration of Natural Products: Theoretical Calculation of Electronic Circular Dichroism as a Tool

Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity

Relative and Absolute Stereochemistry of Diacarperoxides: Antimalarial Norditerpene Endoperoxides from Marine Sponge Diacarnus megaspinorhabdosa

Contact Info

Product

Resources

About