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C37H34NO2P, monoclinic, P21/c (no. 14), a = 9.3479(3) Å, b = 23.0805(8) Å, c = 13.7819(5) Å, β = 102.462(10)°, V = 2903.44(17) Å3, Z = 4, Rgt (F) = 0.0458, wRref (F 2) = 0.1309, T = 300(2) K.

The first carbene-catalyzed asymmetric chemoselective cross silyl benzoin (Brook-Benzoin) reaction has been developed. Key steps of this reaction involve activation of the carbon-silicon bond of an acylsilane by a chiral N-heterocyclic carbene (NHC) catalyst to form a silyl acyl anion intermediate. These acyl anions then undergo an addition reaction with indole aldehydes in a highly chemo- and enantioselective manner to afford α-silyloxy ketones with excellent optical purities. The reaction mechanism of this cross Brook-Benzoin reaction was investigated through both experimental and computational methods. The chiral α-hydroxy ketone derivatives obtained by this approach show promising, agrochemically interesting activity against harmful plant bacteria. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) We acknowledge financial support from the Qiandongnan Science and Technology Plan Project (Qiandongnan kehejichu [2021]17), the Youth Science and Technology Talent Growth Program of Guizhou Province's Department of Education (Qian Jiaohe KY [2022]074), the National Natural Science Foundation of China (21961006, 22071036, 32172459), The 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Science and Technology Department of Guizhou Province ([2019]1020, Qiankehejichu-ZK[2021]Key033), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], the Basic and Applied Research Foundation of Guangdong Province (2019A1515110906), the Guizhou Province First-Class Disciplines Project [(Yiliu Xueke Jianshe Xiangmu)-GNYL(2017)008], Guizhou University of Traditional Chinese Medicine, and Guizhou University (China). Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06), the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 3 Award (MOE2018-T3-1-003), the Agency for Science, Technology and Research (A*STAR) under its A*STAR AME IRG Award (A1783c0008, A1783c0010), GSK-EDB Trust Fund, Nanyang Research Award Grant, Nanyang Technological University.

(±)-Caryopterisines A (1) and B (2) featuring an unprecedented 6/5/5/5/6 pentacyclic rings system were isolated from Caryopteris glutinosa. The structures were determined by spectroscopic and X-ray crystallographic data analyses as well as theoretical calculations. Chiral HPLC resolution of both racemic 1 and 2 afforded their corresponding enantiotropic enantiomers. A plausible biogenesis for 1 and 2 may be originated from Diels-Alder reaction between pyridine-containing oxerine derivatives. The enantiotropic conversion mechanism of the enantiomers was demonstrated by H-D exchange and 18O incorporation studies. Compounds 1 and 2 showed moderate inhibition of estrogen E2 biosynthesis in human ovarian granulosa-like KGN cells. These two alkaloids reduced kynurenine biosynthesis at moderate level via inhibition of indoleamine 2,3-dioxygenase. Alkaloid 2 exhibited moderate inhibition of the release of interleukin-1β.

A direct functionalization of the β-sp3 carbon atom of α-chloro aldehyde has been developed. The reaction starts with the addition of a carbene catalyst to α-chloroaldehyde to eventually form the homoenolate intermediate. This overall redox-neutral process successfully converts the otherwise inert β-sp3 -carbon atom of the aldehyde substrate to a nucleophilic carbon atom for asymmetric reactions. This study constitutes the first success in activating α-chloroaldehydes to generate homoenolate intermediates by carbene organic catalysis and shall encourage further explorations in using organic catalysis for transforming inert chemical bonds. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

The gut microbiota inhabits the animal intestinal tract, and dysbiosis of the gut microbiota may result in disease. Senecio scandens has pharmaceutical antibacterial activities and is regarded as a broad-spectrum antibiotic in traditional Chinese medicine. Extracts of S. scandens are reported to show strong antimicrobial activity, and quercetin significantly decreases some species in the caecal microflora. However, the bactericidal effects of the extracts on the gut microbiota remain obscure. Here, we supplied ethanol extract of S. scandens, which might possibly be used as an alternative for chemical antibiotics, to mice to investigate the state of the intestinal microbiota. Our studies included a control group, low-, moderate-, and high-dose ethanol extract groups, and cefixime capsule group. The ethanol extract groups did not present reduced diversity or differences in the gut microbiota balance. There were significant differences between the ethanol extract and cefixime capsule groups in terms of the gut microbiota. The control and ethanol extract groups contained similar bacteria, which suggested that the ethanol extract has no inhibitory effect on the gut microbiota in vivo. Bifidobacteriales and Lactobacillus acidophilus were significantly increased in the high-dose group. Both secretory immunoglobulin A and mucin 2 concentrations increased as the dose of ethanol extract increased. The functional prediction differences between the control and ethanol extract groups decreased with increasing extract doses, which indicated that the low-dose and high-dose extract treatments might regulate different pathways and functions of the gut microbiota. The results also highlighted the prevention of bacterial drug resistance in the ethanol extract groups.

The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Accepted version We acknowledge financial support from the National Natural Science Foundation of China (No.21772029, 21801051, 21961006), the National Key Technologies R&D Program (No. 2014BAD23B01), The 10 Talent Plan (Shicengci) of Guizhou Province [2016] 5649, the Guizhou Province Re-turned Oversea Student Science and Technology Activity Program, the Science and Technology Department of Guizhou Province [2018] 2802, Guizhou University, the Guizhou Province First-Class Disciplines Project (Yiliu Xueke Jianshe Xiangmu)-GNYL(2017)008, Guizhou Universityof Traditional Chinese Medicine (China), the Singapore National Research Foundation (NRF-NRFI2016-06), the Ministry of Education of Singapore (MOE2013-T2-2-003; MOE2016-T2-1-032; RG108/16), an A*STAR Individual Research Grant (A1783c0008), a Nanyang Research Award Grant, and Nanyang Technological University.

A direct functionalization of the β-sp

An N-heterocyclic carbene (NHC)-catalyzed reaction between α-bromoenals and 2-aminoaldehydes has been developed. Key steps include chemoselective reaction of the NHC catalyst with one of the aldehyde substrates (the bromoenal) to eventually generate an α,β-unsaturated acylazolium intermediate. Addition of the nitrogen atom of aminoaldehyde to the unsaturated azolium ester intermediate followed by intramolecular aldol reaction, β-lactone formation, and decarboxylation leads to chiral dihydroquinolines with high optical purity. The dihydroquinoline products, which are quickly prepared by using this method, can be readily transformed into a diverse set of functional molecules such as pyridines and chiral piperidines. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

Disclosed herein is a new catalytic approach for an efficient access to cyclic β-amino acids widely found in bioactive small molecules and peptidic foldamers. Our method involves addition of the remote γ-carbon atoms of α,β-unsaturated imines to enals by iminium organic catalysis. This highly chemo- and stereo-selective reaction affords cyclic β-amino aldehydes that can be converted to amino acids bearing quaternary stereocenters with exceptional optical purities. Our study demonstrates the unique power of organic catalytic remote carbon reactions in rapid synthesis of functional molecules. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) participates in diverse cancer-associated signaling pathways, playing an oncogenic role in multiple human cancers, including hepatocellular carcinoma (HCC). Our recent works clarify that Pin1 modulates miRNAs biogenesis by interacting with ERK-phosphorylated exportin-5 (XPO5) and changing XPO5 conformation, giving a potential target for HCC treatment. Herein, we discover 4,6-bis(benzyloxy)-3-phenylbenzofuran (TAB29) as a novel Pin1 inhibitor that targets Pin1 PPIase domain. TAB29 potently inhibits Pin1 activity with the IC50 value of 874 nM and displays an excellent selectivity toward Pin1 in vitro. Cell-based biological evaluation reveals that TAB29 significantly suppresses cell proliferation of HCC cells through restoring the nucleus-to-cytoplasm export of XPO5 and upregulating mature miRNAs expression. Collectively, this work provides a promising small molecule lead compound for Pin1 inhibition, highlighting the therapeutic potential of miRNA-based treatment for human cancers.

An enantioselective functionalization of the indole NH group is developed. The reaction stereoselectivity is controlled by an N-heterocyclic carbene catalyst that adds to an aldehyde moiety at the C7-carbon of indole. The NH group participating in the carbene-catalyzed reaction is part of the heteroaromatic rings of the indole substrate. Our reactions afford multicyclic products bearing pyrroloquinazoline or oxazinoindole scaffolds widely present in bioactive molecules. Our study will encourage further exploration of carbene-catalyzed reactions of aromatic molecules and asymmetric transformation of heteroatoms in various functional molecules. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

A radio-frequency (RF) dissemination system using an optical comb over a 50-km fiber link has been demonstrated in this paper. An optical filter is utilized to suppress the dispersion influence of the optical comb in the transfer fiber link. The compensation scheme, based on an electrical compensation structure with an optical-microwave phase detector, cancels the phase fluctuation introduced by the temperature variation and the mechanical vibration in the transfer fiber link. It has been demonstrated that the relative frequency instability of a 100-MHz transfer signal is 1.9 × 10-14 at 1 s and 4.7 × 10-18 at 16400 s. It indicates that our frequency dissemination system can be used to transfer the most precise RF signal in the world to meet the demand of multiply applications.

The antioxidant compounds in the stems and leaves of Gynura bicolor were studied. 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays were employed to evaluate antioxidant capacity. By solvent extraction and Sephadex LH-20 column chromatography in sequence, ethanol extracts of Gynura bicolor stems and leaves were fractionated to obtain their active fractions, which were further separated to obtain 12 compounds: 1–8 from stems, and four, 8–12, from leaves. Their structures were elucidated on the basis of spectroscopic data (nuclear magnetic resonance and mass spectrometry). Among these substances, compounds 1, 2, 3, 4, and 8 with significant antioxidant activity were determined to be responsible active components for stems, and compounds 4, 8, and 12 for leaves.

Two new 3-formyl-2-arylbenzofurans, iteafuranals A and B, were isolated from the 95% EtOH extract of the aerial parts of Itea ilicifolia. Their structures were elucidated as (E)-2-(3,4-dihydroxyphenyl)-3-formyl-4-hydroxy-5-(prop-1-en-1-yl) benzofuran (1, iteafuranal A) and (E)-2-(3-hydroxy-4-methoxyphenyl)-3-formyl-4-hydroxy-5-(prop-1-en-1-yl) benzofuran (2, iteafuranal B) by comprehensive analyses of spectroscopic data including 1- and 2-D NMR, UV, IR, and HRMS data. The structure of 1 was confirmed by X-ray crystallography analysis. Compound 1 showed DPPH free radical scavenging capacity with an IC50 value of 0.34 mg/mL. Compounds 1 and 2 showed ABTS cation radical scavenging capacity with IC50 values of 0.23 and 0.30 mg/mL, respectively. (C) 2014 Phytochemical Society of Europe. Published by Elsevier B. V. All rights reserved.

Activity-guided fractionation of Neosinocalamus affinis leaves led to obtain two new flavonoids, 4'-O-((7″R,8″S)-8″-guaiacylglyceryl)-pleioside B (9) and apigenin 6-C-β-d-fucopyranosyl-7-O-β-d-glucopyranoside (10) along with eight known compounds. Their structures were elucidated on the basis of spectroscopic data (UV, IR, NMR, and MS). Among these 10 compounds, farobin A (4) and isoorientin (7) showed significant antioxidant activity evaluated by 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), superoxide anion and nitric oxide (NO) radical-scavenging assays.

C18H16O2, orthorhombic, Pnma (no. 62), a = 14.474(6) Å, b = 6.815(3) Å, c = 13.738(6) Å, V = 1355.1(10) Å3, Z = 4, R gt(F) = 0.0583, wR ref(F 2) = 0.1759, T = 173 K.

C19H22O2, triclinic, P1̄ (no. 2), a = 8.4768(13) Å, b = 8.7667(14) Å, c = 11.1282(17) Å, α = 73.284(3)°, β = 73.041(3)°, γ = 83.391(3)°, V = 757.1(2) Å3, Z = 2, R gt(F) = 0.0509, wR ref(F 2) = 0.1613, T = 173 K.

Five new iridoid glucoside derivatives (1–5), three new diterpenoids (7, 12, and 15), and 11 known compounds were isolated from the aqueous EtOH extract of Caryopteris glutinosa. Cell-based estrogen biosynthesis assays indicated that caryopteriside C (3) and caryopterisoid B (12) promote the biosynthesis of estrogen E2, with EC50 values of 11.1 and 8.0 μM, respectively, in human ovarian granulosa-like KGN cells via upregulating the expression of aromatase.

Three new acylphloroglucinol glycosides, hypericumols A - C, together with fifteen known phenolic derivatives, were isolated from the total phenolic extract of Hypericum japonicum. Hypericumols A, B, and C were characterized as 4,6-dimethyl-2-methylpropanoylphloroglucinol-1- O-β-D-glucopyranoside (1), 4-methyl-2-methylpropanoylphloroglucinol-1- O-β-D-glucopyranoside (2), and (2′ S)-4,6-dimethyl-2-methylbutyrylphloroglucinol-1- O-β-D-glucopyranoside (3), respectively, on the basis of spectroscopic data interpretation and chemical degradation reaction.

The antioxidant compounds in the stems and leaves of Gynura bicolor were studied. DPPH and ABTS radical scavenging assays were employed to evaluate antioxidant capacity. By solvent extraction and Sephadex LH-20 column chromatography in sequence, ethanol extracts of Gynura bicolor stems and leaves were fractionated to obtain their active fractions, which were further separated to obtain twelve compounds: 1-8 from stems, and 4, 8-12 from leaves. Their structures were elucidated on the basis of spectroscopic data (NMR and MS). Among these substances, compounds 1, 2, 3, 4, and 8 with significant antioxidant activity were determined to be responsible active components for stems, and compounds 4, 8, and 12 for leaves.

Two novel 2-arylbenzofuran dimers, shandougenines A (1) and B (2), and two new polyisoprenylated flavanones 3 (shandougenine C) and 4 (shandougenine D) were isolated from the 95% EtOH extract of Sophora tonkinensis, together with 18 known compounds. Their structures were determined on the basis of spectral data interpretation and by comparing the spectral data with that reported previously for known compounds. Shandougenine A (1) is a unique dimeric 2-arylbenzofuran with a C-3C-5‴ bond linkage. Shandougenine B (2) is the first naturally occurring dimeric 2-arylbenzofuran with a novel C-3C-3″ bond linkage. Compound 1 showed moderate DPPH free radical scavenging capacity, whereas 2 has stronger DPPH free radical and ABTS cation radical scavenging capacity than Vc. Compounds 12, 19, and 20 showed parallel DPPH free radical scavenging capacity with Vc. Compounds 1, 3, 4, 19, 20, and 22 have parallel ABTS cation radical scavenging capacity to Vc. Compounds 1, 3, 4, and 18 showed slightly stronger superoxide anion radical scavenging capacity than the known flavanone luteolin. The antioxidant activities of shandougenines A (1) and B (2) indicated that compounds 1 and 2 may represent novel scaffolds for the development of new antioxidants.

Thunder god vine, the dried roots of Tripterygium wilfordii, is a widely used traditional Chinese medicine. More than 200 bioactive complex natural products have been isolated from this herb. Inspired by the diversity of chemical structures and bioactivities of the components of this herb, the investigation to mine new chemical entities as potential drug leads led to the identification of 36 nitrogen-containing compounds. Among them, 18 new dihydro-β-agarofuran alkaloids (tripterygiumines A-L (1-12), M-Q (22-26), and R (33)) were identified from the spectroscopic data and chemical degradation studies. Tripterygiumine Q (26) exhibited immunosuppressive activity against human peripheral mononuclear cells with an IC50 value of 8.67 μM and showed no cytotoxicity, even at 100 μM, indicating that 26 may represent a novel scaffold for the development of new immunosuppressants.