CD Exciton Chirality Method Research Articles

Alstomaphylines A–K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A−K (1−11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1−3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C−C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1−3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 μM, respectively. Enzyme kinetic study revealed compounds 1−3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12−14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Albifimbrins A and B, a pair of epimeric tetrahydrofuran-containing linear polyketide derivatives from the marine-derived fungus Albifimbria verrucaria CD1-4

A pair of new epimeric polyketides, named albifimbrins A and B (1 and 2), were isolated from the cultures of the shellfish-derived fungus Albifimbria verrucaria CD1–4. Their structures were determined by extensive spectroscopic analysis including HR-MS, 1D and 2D NMR data, together with the CD exciton chirality method. Compounds 1 and 2 possess unusual tetrahydrofuran moiety in their linear molecule structures. The antimicroalgal assay indicated that compounds 1 and 2 shown moderate inhibitory activities against marine harmful microalgae, Prorocentrum donghaiense, Amphidinium carterae and Heterocapsa circulariaquama.

Rare noreudesmane sesquiterpenoids from the fruits of Dysoxylum densiflorum

Seven rare noreudesmane sesquiterpenoids (dysoxydenones M-S, 1–7), including three 11,12,13-trinoreudesmanes, three 13-noreudesmanes and one spirovetivane-type sesquiterpenoid, along with two known analogues were isolated from the fruits of Dysoxylum densiflorum. The planar structures were elucidated by a combination of 1D, 2D NMR and HRESIMS analyses. Their absolute configurations were determined by combination of single-crystal X-ray diffraction, CD exciton chirality method and ECD calculation. All compounds were screened for anti-inflammatory activity on LPS-induced RAW 264.7 cells and IL-1β inhibitory activity.

Kojicone C, new anti-inflammatory polyketide from insect-associated fungus Aspergillus versicolor

The chemical study of EtOAc extracts of the insect-associated fungus Aspergillus versicolor led to the isolation of a new polyketide kojicone C ( 1 ) and its precursor (2 R ,4 R )−4-hydroxy-5-methoxy-2,4-dimethyl-2-[(2 R )−2-methylbutyryloxy]−5-cyclohexen-1,3-dione ( 2 ). Kojicone C belongs to the rare tricycle cyclohexen-1,3-dione adduct class. The structures of 1 and 2 were determined by HRESIMS (high resolution electrospray ionization mass spectroscopy) data, 1D and 2 D NMR (nuclear magnetic resonance) spectroscopic analysis, ECD (electronic circular dichroism) calculations, and CD exciton chirality method. Compound 1 exhibited moderate anti-inflammatory activities that reduced LPS-induced NO production of RAW 264.7 cells (IC 50 = 35.8 μ Μ). It could also significantly inhibit LPS-induced mRNA expression of TNF- α , IL-1 β , and IL-6 of this cell line at a concentration of 20 μ Μ. • One new polyketide was isolated from Aspergillus versicolor . • The new compound is a rare tricycle cyclohexen-1,3-dione adduct. • The new compound exhibited potent anti-inflammatory activities.

Cucurbitane-type triterpenoids from the fruits of Citrullus colocynthis

A phytochemical investigation of the fruits of Citrullus colocynthis resulted in the isolation of 21 structurally diverse cucurbitane triterpenoids, including 9 previously undescribed ones, colocynins A-I (1–9). Their absolute configurations were elucidated by means of quantum chemical electronic circular dichroism (ECD) calculations, CD exciton chirality method, and single-crystal X-ray crystallography. Colocynins A-C (1–3) represent the first examples of nonanorcucurbitane-type triterpenoids. An anti-acetylcholinesterase activity assay showed that 6, 10, 13, 18, and 20 exhibited inhibitory activities, with IC50 values ranging from 5.0 to 21.7 μM. In addition, 18 and 21 showed significant cytotoxicity against PACA, A431, and HepG2 cells, with IC50 values ranging from 0.042 to 0.60 and 3.6–14.4 μM, respectively.

Diverse dihydroagarofuran sesquiterpene derivatives from the stem and branch of Tripterygium wilfordii

Ten new dihydroagarofuran sesquiterpene polyol esters, tripterdines A-J (1−10) were isolated from the stem and branch of Tripterygium wilfordii. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including UV, IR, HRESIMS, NMR, and CD exciton chirality method. The structures of compounds 1, 3, and 6 were confirmed by X-ray crystallographic analyses. The anti-inflammatory and cytotoxic activities were assessed for all the compounds (1–10). Compounds 3, 5 and 10 exhibited potent anti-inflammatory activities with the secretion level of TNF-α ranging from 43.86% to 51.27%, and the IL-6 ranging from 32.44% to 50.64%. In addition, compounds 1, 3, 7 and 9 showed weak cytotoxicities against three human tumor cell lines (Huh7, MCF-7 and HCT-116).

Sarglafuran A, a lindenane-type sesquiterpene dimers with unique furan ring from the leaves of Sarcandra glabra

Sarglafuran A (1), a new [4 + 2] type lindenane sesquiterpene dimer with an unique furan ring moiety, and a pair of new [2 + 2] type dimeric lindenane epimers, sarglalactones N and O (2 and 3), were isolated from the leaves of Sarcandra glabra. Their structures were elucidated by comprehensive spectroscopic analyses, and the absolute configurations of these compounds were determined by single crystal X-ray diffraction or CD exciton chirality method. In addition, a possible biosynthetic pathway of the unique furan ring moiety in 1 had been proposed. Their cytotoxicity against MCF-7 and MDA-MB-231, together with the inhibitory activity against nitric oxide (NO) production of LPS-induced RAW264.7 macrophages were evaluated.

A/D-rings-seco limonoids from the fruits of Aglaia edulis and their bioactivities

Agledulines A-K, eleven previously undescribed limonoids, including eight biogenic A/D-rings-seco limonoid analogs (agledulines A-H), one D-ring-seco limonoid (agleduline I) and two A-ring-seco limonoids with a rare Δ4,28 moiety (agledulines J-K), together with twelve reported limonoids, were isolated from the fruits of Aglaia edulis. Their structures were determined by NMR data, HRESIMS, X-ray diffraction, ECD spectra and the CD exciton chirality method. Observably, the absolute configurations of agleduline A, agleduline C and nymania 2 were unambiguously elucidated by single-crystal X-ray diffraction analyses. The biological evaluation showed that agleduline C exhibited significant cytotoxic activities with IC50 values of 10.05 μM, and 11α-acetoxygedunin showed notable anti-inflammatory activity (IC50: 4.70 μM). In addition, agleduline I and 11α-acetoxygedunin reversed the multidrug resistance with IC50 values of 5.05 and 1.49 μM (RI: 4.64 and 15.77) in the MCF-7/Dox cells.

Humulane-type and germacrane-type sesquiterpenoids from the fruits of Xanthium spinosum Linn.

Eight undescribed humulane-type sesquiterpenoids (xanthspinol A-E, I, J and N), three undescribed germacrane-type sesquiterpenoids (xanthspinol F, G and O) and twelve known compounds were isolated from the fruits of Xanthium spinosum. The structures of the undescribed compounds were elucidated by analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) spectra, a CD exciton chirality method and the modified Mosher's method. Xanthspinol A and B featured a humulane skeleton containing a 2,5-dihydrofuran fragment. Putative biosynthetic pathways for the undescribed compounds are proposed. Xanthspinol N, 8-epi-isoxanthanol and deacetyl-4-epixanthanol showed moderate activity against Coxsackie virus B3 (CVB3) with IC50 values of 8.70, 3.70 and 3.70 μM, respectively.

Antimicrobial and cytotoxic activities of indole alkaloids and other constituents from the stem barks of Rauvolfia caffra Sond (Apocynaceae)

Twenty indole alkaloids, among which two undescribed ones named rauvolfianoids A (1) and B (2), were isolated from the stem barks of Rauvolfia caffra Sond along with eight other compounds from other biosynthetic pathways. The structures were elucidated by analysis of spectroscopic data, including 1 D and 2 D NMR; absolute configurations of 1 and 2 were determined by CD exciton chirality method. Compounds 1 and 2 were evaluated for antimicrobial and anticancer activities against three bacterial strains (Escherichia coli, Shigella sp and Salmonella sp) and CRC-related opportunistic pathogens. 1 showed moderate antibacterial activity against Salmonella sp with the MIC value of 25 μg/ml, while 2 exhibited weak selective activity against all tested pathogens. In addition, these alkaloids were characterized as weak apoptosis inducers in HCT116 human colon carcinoma cell line.

The enduring legacy of Koji Nakanishi's research on natural products and bioorganic chemistry. Part 2. Inception and establishment of the ECD exciton chirality method in 1960s to 1970s: A marvel of Nakanishi's Japanese team.

The electronic circular dichroism (ECD) exciton chirality method is very useful for determining the absolute configuration (AC) of chiral compounds. In the ECD spectroscopy, the chromophore-chromophore interaction, ie, exciton coupling, is very important. For example, Harada and Nakanishi first discovered in 1969 that chiral dibenzoates exhibit exciton split bisignate Cotton effects, from the sign of which the screw sense between two long axes of benzoate chromophores, ie, the AC of dibenzoate, can be determined. This method was named the dibenzoate chirality rule and has been successfully applied to various natural products to determine their ACs. During these studies, it was also found that this CD method was expanded to encompass other aromatic and olefin chromophores like naphthalene, diene, enone, etc. Therefore, the name of the dibenzaote chirality rule was changed to the CD exciton chirality method. In 1970s, there were heated controversies about the inconsistency between X-ray Bijvoet and CD exciton chirality methods, which was a shocking and serious problem in the community of molecular chirality research. Harada and coworkers synthesized the most ideal cage compound with two anthracene chromophores to connect X-ray Bijvoet and CD exciton chitality methods and proved that these two methods are consistent with each other.

Highly oxygenated and rearranged limonoids from the stem barks of Entandrophragma utile

Seventeen highly oxygenated and rearranged limonoids, including nine previously undescribed phragmalin-type limonoids with 1,8,9- and 8,9,30-orthesters (entanutilins C–K, 1–9), three undescribed limonoids with rare rearranged-6/6/7/5 skeleton (entanutilins L-N, 10–12), and 5 known limonoids, were isolated from the stem barks of Entandrophragma utile from Ghana (Africa). Their structures including absolute configurations were elucidated based on comprehensive spectroscopic analyses, such as HRESIMS, 1D/2D-NMR, CD exciton chirality method, time-dependent density functional theory (TDDFT)/ECD calculations, and single-crystal X-ray diffraction. Bioactivity screenings suggested that some of these compounds effectively reversed resistance in MCF-7/DOX cells at a nontoxic concentration of 30 μM with 6- to 19-fold enhancing effects.

Ingenane and jatrophane diterpenoids from Euphorbia kansui and their antiproliferative effects

In this study, fourteen ingenane-type and nine jatrophane-type diterpenoids were isolated from Euphorbia kansui, including seven undescribed compounds. Kansuingenol A-C have the 6,7-vicinal diol moiety, and Kansuijatrophanol A and B possess the 11,12-vicinal diol moiety, both of which are rarely reported. 3,4-(Methylenedioxy) cinnamyl moiety was found for the first time in jatrophane-type diterpenoids, as shown in Kansuijatrophanol C and D. The absolute configurations of seven undescribed compounds have been analyzed and assigned by the modified Mosher's method, Mo2(OAc)4-induced circular dichroism (ICD) method, and CD exciton chirality method. All compounds were screened for their antiproliferative effects against HepG2, MCF-7 and DU145 cell lines. Regarding the HepG2 cells, Kansuijatrophanol C exhibited the most promising inhibition with the IC50 value of 9.47 ± 0.31 μM. Regarding the MCF-7 and DU145 cells, Kansuijatrophanol D exhibited the most promising inhibition with the IC50 values of 6.29 ± 0.18 and 4.19 ± 0.32 μM, respectively.

Two Carotane Sesquiterpenoids from Gymnopus sp. 0612-9 Against Penicillium italicum and P. digitatum, Which Decay Postharvest Citrus

A new carotane sesquiterpenoid, 5-epi-fulvoferruginin (1), and its isomer fulvoferruginin (2), were isolated from the fermentation broth of the wild macrofungus Gymnopus sp. 0612-9. The structures and absolute configurations of compounds 1 and 2 were elucidated by comprehensive spectroscopic analysis and CD exciton chirality method. TLC-bioautography showed that compounds 1 and 2 exhibited moderate activity against pathogens Penicillium italicum and P. digitatum, which are responsible for the decay of postharvest citrus. The 5-epi-fulvoferruginin at C-5 with 5S configuration was weaker than fulvoferruginin at C-5 with 5R configuration.

Melaleucadines A and B: Two rare benzylic phloroglucinol-terpene hybrids from Melaleuca leucadendron

Melaleucadines A and B (1 and 2), two rare benzylic phloroglucinol-terpene hybrids (meroterpenoids), have been isolated and identified from the branches and leaves of the Australian “tea tree” Melaleuca leucadendron L. Their structures including absolute configurations were determined by 1D/2D NMR, HR-MS, and the CD exciton chirality method. Compound 1 was a hybrid of a benzylic phloroglucinol and rearranged β-pinene via a rare 2,3,4,5-tetrahydrooxepine ring, and 2 was the adduct of a benzylic phloroglucinol and a humulene-type sesquiterpene via an oxa-heterocycle. Bioactivity screening revealed that compounds 1 and 2 exhibited neuroprotective effects at a concentration of 50.0 μM.

Cipaferoids A–C, Three Limonoids Represent Two Different Scaffolds from Cipadessa baccifera

Three limonoids cipaferoids A–C (1–3) representing two different scaffolds were isolated from Cipadessa baccifera. Their structures were completely assigned by spectroscopic data, CD exciton chirality method, and X‐ray crystallography. Compounds 2 and 3 exhibited moderate antimalarial activity with IC50 values of 9.3±0.1 and 14.7±4.8 μmol•L–1, respectively.

15 CD励起子法の新しい展開 : 単一官能基をもつ系への応用戦略(口頭発表の部)

15 CD励起子法の新しい展開 : 単一官能基をもつ系への応用戦略(口頭発表の部)

Aromatic compounds from an aqueous extract of “ban lan gen” and their antiviral activities

A pair of new diphenyl glycerol ether enantiomers (−)-1 and (+)-1 and two new methyl benzamidobenzoates 2 and 3, named (−)-(R)- and (+)-(S)-isatindigotrioic acid [(−)-1 and (+)-1] and isatindigoticamides A (2) and B (3), respectively, were isolated from an aqueous decoction of the roots of Isatis indigotica (ban lan gen). Their structures were elucidated by spectroscopic data analysis including 2D NMR experiments. The absolute configurations of (−)-1 and (+)-1 were assigned based on the CD exciton chirality method. Compounds 2 and 3 exhibited antiviral activities against HSV-1 with IC50 values of 4.87 and 25.87μmol/L, respectively. Compound 2 was also found active against Coxsackie virus B3 and LPS-induced NO production.

Sesquiterpenes from the whole plants of Parasenecio roborowskii

Six eremophilane-type (parasenolide A–F) and an eudesmane-type (parasenin) sesquiterpenoids, along with eight known sesquiterpenes, were isolated from the whole plants of Parasenecio roborowskii. The structures and absolute configurations of new compounds were elucidated using extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR experiments, the CD exciton chirality methods, and single-crystal X-ray crystallography. All isolated compounds were evaluated for cytotoxicity against five human cancer (HeLa, HepG2, K562, MDA231, and NCI-H460) cell lines and a murine melanoma B16 F10 cell line by MTT assay. Compounds 1–15 showed cytotoxic activities, especially compounds 3, 4, 8, 10, and 12. These five compounds showed broad spectrum activities against all the tested cancer cell lines with IC50 ranging from 9.2 to 35.5μM. The study supports that eremophilenolides and eudesmane-type sesquiterpenes occur mainly in the genus Parasenecio and can be used as a chemosystematic marker of the genus.

Two rare limonoids from the stem barks of Entandrophragma utile

Two rare limonoids (entanutilin A and B, 1–2) were identified from the stem barks of Entandrophragma utile collected in Ghana (Africa). Entanutilin A was isolated as the second limonoid possessing a cyclobutanyl ring incorporating C-19 and a cycloheptanyl ring C including C-30, and entanutilin B with a nicotinoyl group was also uncommon in natural products. Their structures were determined by extensive spectroscopic analyses (HR-ESI-MS, 1D/2D NMR), and the absolute configurations of 1 and 2 were determined by CD exciton chirality method.