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Six rare sesquiterpenoid dimers were isolated from Artemisia mongolica. Compound 1 exhibited inhibitory activity against HSC-LX2 cells with an IC50 value of 165.0 μM, equivalent to that of the positive control silybin (IC50, 144.4 μM).

The antidepressant activity of (+) and (-)-paeoveitol was first evaluated using the forced swimming test (FST), and (+)-paeoveitol showed potential antidepressant activity by decreasing immobility time of mice (by approximately 26.4%) in the FST at a dose of 20 mg/kg. To explore the structure-activity relationships (SARs) and obtain more potent compounds, twenty derivatives of (+)-paeoveitol were synthesized and evaluated for their agonistic activities on melatonin type I (MT

Artemeriopolides A–D (1–4), four novel cadinane sesquiterpenoid dimers featuring the rare 2-oxaspiro[4.6]undecan-1,7-dione, 2-oxaspiro[4.5]decan-1-one, and 2-oxaspiro[5.5]undecan-1-one ring systems, were isolated from Artemisia eriopoda.

Paeoveitol D derivatives were synthesized as potent MT1 and MT2 receptors agonists with in vivo antidepressant activity.

Ten new germacrane-type sesquiterpenoids, artemyrianosins A–J (1–10), were isolated from the aerial parts of Artemisia myriantha. Their structures were elucidated by spectral analyses including UV, IR, HRESIMS, 1D and 2D NMR, ECD and the absolute configurations of compounds 1 and 7–9 were characterized using X-ray crystallography. All isolates were tested their cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1), and compounds 1–3, 7, and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3 μM. Among them, the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7 μM (HepG2), 47.9 μM (Huh7), and 44.9 μM (SK-Hep-1). Graphical Abstract

Two sesquiterpenoid trimers, artematrotrimers A (1) and B (2), and two sesquiterpenoid dimers, artematrodimers A (3) and B (4), possessing unprecedented scaffolds with a methylene-bridged connection were identified from Artemisia atrovirens. Their structures and absolute stereochemistry were determined by comprehensive spectroscopic data, single-crystal X-ray diffraction analyses, and ECD calculations. Compounds 1–4 represent a new type of sesquiterpenoid oligomers featuring the connections between hetero sesquiterpenoid units via one or two C–C bonds. A possible biosynthetic pathway for 1–4 was also proposed. Compound 3 showed obvious cytotoxicity against HepG2 and Huh7 cell lines with IC50 values of 21.9 and 22.6 μM, respectively.

Artatrovirenols A and B (1 and 2), two novel cagelike sesquiterpenoids, possess a unique 5/5/6/5/5-pentacyclic and a 5/5/6/5-tetracyclic system with an unprecedented tetracyclo[5.3.1.1.4,1101,5]dodecane scaffold from Artemisia atrovirens. The structures of compounds 1 and 2 including their absolute stereochemistry were elucidated through extensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Plausible biosynthetic pathways for the new isolates were proposed from the naturally occurring arglabin (3) via the key intramolecular Diels-Alder cycloaddition. Compound 1 showed cytotoxicity against three human hepatoma cell lines (HepG2, SMMC-7721, and Huh7) with half maximal inhibitory concentration values of 123.8, 44.0, and 142.6 μΜ, respectively.

Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 μg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 μM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 μM (HepG2), 4.3 and 7.8 μM (Huh7), and 3.1 and 9.8 μM (SMMC-7721), respectively.

Abstract Four new sesquiterpenoids, artemyrianins A–D (1–4), and three new norlignans, artemyrianins E–G (5–7), together with five known compounds (8–12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 μM. Graphic Abstract

Abstract Two new sesquiterpenoids, artemlavanins A (1) and B (3), together with fifteen known compounds (2 and 4−17) were isolated from the EtOH extract of Artemisia lavandulaefolia. The structures of new compounds were elucidated by extensive spectroscopic analyses (HRESIMS, 1D and 2D NMR) and ECD calculations. Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton; compounds 2–5, 6–8, 9 and 10–12 belonged to the eudesmane, guaiane, oppositane and farnesane sesquiterpenoids, respectively; compounds 13–17 were the phenyl derivatives with a 4-hydroxyacetophenone moiety. Twelve compounds (1–3, 5–7, 10–12, 14, 15 and 17) displayed cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values ranging from 35.1 to 370.3 μM. Compounds 2, 7, 10–12 and 17 exhibited the stronger cytotoxicity than silybin (IC50, 169.6 μM) with IC50 values of 82.1, 35.1, 95.0, 83.8, 81.6 and 90.1 μM. Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I (Col I), human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 10.7, 24.5 and 13.3 μM. Graphic Abstract

Spiroseoflosterol (1), a 7(8→9)-abeo-ergostane steroid with a unique spiro[4.5]decan-6-one system, was isolated from the fruiting bodies of Butyriboletus roseoflavus. Its structure was determined by interpretation of comprehensive spectroscopic, X-ray, and computational data. A plausible biogenetic pathway for spiroseoflosterol (1) was postulated based on a key semipinacol rearrangement. Compound 1 was cytotoxic to HepG2 and Huh7/S (sorafenib-resistant Huh7) with IC50 values of 9.1 and 6.2 μM, respectively.

Ten new diarylheptanoid dimers, katsumadainols C

The biomimetic synthesis of guaianolide dimers lavandiolides H, I, and K and artematrolide F containing a spirolactone moiety has been accomplished for the first time from naturally abundant arglabin in four to six steps with an overall yield up to 60%, and a series of natural product-like guaianolide dimers, trimer, and tetramer were also successfully synthesized. Notably, the trimeric compound exhibited antihepatoma cytotoxicity more potent than that of sorafenib with IC50 values of 6.2 μM (HepG2), 6.8 μM (Huh7), and 7.2 μM (SK-HEP-1).

In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 μg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 - A21 (1-21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1, 13, and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 μg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A–P (1–16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 μM, as well as against Huh7 cell line with values of 18.2 and 32.2 μM.

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls ( 1 − 9 ), including six new ones ( 2 − 5 , 7 and 9 ), were isolated from the EtOAc extract of G. elata . Five compounds 1 , 3 , 4 , 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT 1 and MT 2 receptors with EC 50 values of 237 and 244 μM. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para -hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT 2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.

Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 μM. To explore the structure–activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25–27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 μM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 μM.

As a successful anti-tumor drug target, the family of histone deacetylases (HDACs) is also a critical player in immune response, making the research of anti-inflammatory HDAC inhibitors an attractive new focus. In this report, triterpenoids nigranoic acid (NA) and manwuweizic acid (MA) were identified as HDAC inhibitors through docking-based virtual screening and enzymatic activity assay. A series of derivatives of NA and MA were synthesized and assessed for their biological effects. As a result, hydroxamic acid derivatives of NA and MA showed moderately increased activity for HDAC1/2/4/6 inhibition (the lowest IC50 against HDAC1 is 1.14 μM), with no activity against HDAC8. In J774A.1 macrophage, compound 1–3, 13 and 17–19 demonstrated inhibitory activity against lactate dehydrogenase (LDH) and IL-1β production, without affecting cell viability. Compound 19 increased the histone acetylation level in J774A.1 cells, as well as inhibited IL-1β maturation and caspase-1 cleavage. These results indicated that compound 19 blocks the activation of NLRP3 inflammasome, probably related to HDAC inhibition. This work provided a natural scaffold for developing low-cytotoxic and anti-inflammatory HDAC inhibitors, as well as a class of tool molecules for studying the relationship between HDACs and NLRP3 activation.

In order to discover and develop the new RSK kinase inhibitor, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of 7d compound to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among them, after preliminary screening, compound 7d showed good activity in inhibiting cell proliferation. Therefore, we took 7d as an example and performed molecular docking analysis on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound 7d has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound 7d is in line with the RSK inhibitor we designed and could be developed to a promising anti-tumor drug in the future.

The ent-kaurane diterpenoid chepraecoxin A (CA) obtained in our previous study showed a potential inhibitory activity on α-glucosidase (IC50 274.5 ± 12.5 μM). In order to figure out the structure-activity relationships (SARs), twenty-two derivatives of chepraecoxin A were synthesized by modifying the ester, allyl, double bond and carboxyl groups, and assayed for their α-glucosidase inhibitory activity. Of them, eight compounds (14–17, 19–22) significantly increased activity with IC50 values ranging from 16.1 to 71.4 μM, even higher than the positive control, acarbose (IC50 130.3 μM). Especially, compounds 17, 19 and 21 could inhibit α-glucosidase with IC50 values of 16.9 ± 3.4, 16.1 ± 1.2, and 17.1 ± 0.6 μM, 17-fold higher than CA. The most active compound 19 was proven to be a non-competitive inhibitor with a Ki value of 19.4 μM based on enzyme kinetics study. The primary SARs of CA derivatives were summarized for exploring antidiabetic candidates.

Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC50 values of 396.5 and 383.0 μM agitating on MT1 and MT2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p. o. A total of 25 metabolites of 7c were identified, including 5 metabolites in phase I and 20 metabolites in phase II. Altogether, these results indicate that magnolol derivative 7c is a promising lead compound for the development of a new chemical class of antidepressant drugs.

Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 μg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A–N (1–14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 μM. The most active artemicapillasin B (2) gave an IC50 value of 24.5 μM, which was about 7 times more toxic than the positive drug silybin (IC50, 162.3 μM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC50 values of 11.0, 14.4 and 13.8 μM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study.

Twenty-four gramine derivatives were synthesized and evaluated on MT1 and 5-HT1A receptors in vitro. Among them, seven derivatives (7, 8, 16, 19, 20, 21, and 24) exhibited higher agonisting activities on MT1 or 5-HT1A receptors. Compared with gramine, derivatives 7, 8, 16, 19, 20, 21, and 24 displayed 1.6–3.5-fold increase in agonistic rates on 5-HT1A receptor. Particularly, derivatives 7, 19, and 21 exhibited significant agonistic activities on MT1 and 5-HT1A receptors with EC50 values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure–activity relationships of gramine derivatives were summarized for further investigation on MT1 and 5-HT1A receptors as new potential agonists.

(±)-Uncarilins A and B (1a/1b and 2a/2b), two pairs of unusual dimeric isoechinulin-type enantiomers with a symmetric four-membered core, were isolated from Uncaria rhynchophylla driven by LCMS-IT-TOF analyses. Their structures were elucidated by extensive 1D and 2D NMR spectra, X-ray diffraction, and ECD spectroscopic data. (−)-Uncarilin B (2a) showed activities on MT1 and MT2 receptors with agonistic rates of 11.26% and 52.44% at a concentration of 0.25 mM.

The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A1−A16 (1–16), together with 13 known analogues (17–29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1–3, 5–7, 11–14, 21–25, and 27 showed PTP1B/TCPTP selective inhibition with IC50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC50, 215.7 μM). All compounds exhibited obvious inhibition against α-glucosidase with IC50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC50, 170.9 μM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with Ki values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively.

Seven new phenolic glycosides including two heterocyclic phenolic derivatives orcinosides I-J (1-2) and five chlorophenolic glycosides curculigines J-N (3-7), together with nineteen known compounds were isolated from the rhizome of Curculigo orchioides. Based on extensive spectroscopic analyses (UV, IR, HRESIMS, 1D and 2D NMR), the structures of the new compounds were identified. Orcinoside I (1) and J (2) displayed xanthine oxidase inhibitory activities with IC50 values 0.25 and 0.62mM respectively.

Sixteen tropinone derivatives were prepared, and their antitumor activities against five human cancer cells (HL-60, A-549, SMMC-7721, MCF-7 and SW480) were evaluated with MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium] assay. Most of the derivatives exhibited better activities compared with tropinone at the concentration of 40 μM. Particularly, derivative 6 showed significant activities with IC50 values of 3.39, 13.59, 6.65, 13.09 and 12.38 μM respectively against HL-60, A-549, SMMC-7721, MCF-7 and SW480 cells, which suggested more potent activities than that of cis-dichlorodiamineplatinum (DDP). Graphical Abstract

The method offers a highly enantioselective access to novel spirocyclic dihydropyranone derivatives.

The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho-alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide.

The enantioselective addition of alcohols to isatin-derived N -Boc ketimines was investigated for the first time. Isatin-derived N , O -aminals were obtained in excellent yields with moderate-to-good enantioselectivities (up to 78% ee) in the presence of a quinine-based bifunctional catalyst.

1,2-Diketones are employed, for the first time, as electrophiles in the vinylogous aldol reaction. With 5 mol% of chiral tertiary amine-thiourea C8, a direct vinylogous aldol-cyclization cascade reaction between β,γ-unsaturated amides and o-quinones has been achieved to produce spirocyclic dihydropyranones in 76–99% yield and 82–95% ee.

The first enantioselective aza-Morita—Baylis—Hillman reaction of acrylates with ketimines derived from isatins is developed.

The first enantioselective vinylogous aldol–cyclization cascade reaction of allyl pyrazoleamides with isatins is reported. With 1 mol% of Takemoto catalyst, optically active spirocyclic oxindole–dihydropyranones were obtained in excellent yields (93–99%) and good-to-excellent enantioselectivities (82–97% ee).

Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier K+ channel (hKv1.5), cloned from human heart and stably expressed in Ltk- cells, as well as the corresponding K+ current (the ultrarapid delayed rectifier, I(KUR)) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an IC50 value of 2.51+/-0.34 microM at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a use-dependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.

The first enantioselective aza-Morita–Baylis–Hillman reaction of acrylates with ketimines derived from isatins has been developed. With 2 mol% of chiral bifunctional phosphine-squaramide 4e, optically active 3-substituted-3-amino-2-oxindoles were obtained in excellent yields with up to 91% ee.

The first organocatalytic enantioselective Mannich reaction of pyrazoleamides with isatin-derived N-Boc ketimines has been developed to afford 2-oxindole-based chiral β-amino amides in good yields (84–97%) with excellent diastereo- and enantioselectivities (up to 99:1 dr and >99% ee).

The enantioselective addition of alcohols to isatin-derived N-Boc ketimines is investigated for the first time.

Large-scale tetracene-doped anthracene nanowire arrays were prepared, and the doping effects were studied. The high doping concentration up to 10% (molar ratio) has been achieved, attributed to both the unique long-nanowire geometry and the excellent structural compatibility of anthracene and tetracene. The incorporation of long tetracene molecules into the matrix of short anthracene molecules induced an enlarged interlayer thickness, a decreased nanowire thickness, and an expanded nanowire width. The tetracene molecules were homogeneously embedded into the anthracene matrix at low doping concentrations (

Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects on hKv1.5 stably expressed in Ltk cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5, 9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent in blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC50 value of 27.4 +/- 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open channel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studies were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

An enantioselective domino reaction of 4-bromo-3-oxobutanoates with isatin-derived ketimines was developed to construct 3-amino-2-oxindoles with a quaternary stereocentre. In the presence of 1 mol-% of a bifunctional squaramide organocatalyst, the desired products were achieved in high yields (90–97 %) and with excellent enantioselectivities (92–99 % ee).