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Herein, we report an efficient kinetic resolution of alkyl allylic alcohols enabled by an iridium-catalyzed enantioselective alkynylation of alkyl allylic alcohols with potassium alkynyltrifluoroborates. A wide range of chiral 1,4-enynes bearing various functional groups and unreacted enantioenriched allylic alcohols were obtained with excellent enantioselectivities and high kinetic resolution performance (

A highly regio- and chemoselective synthesis of 1H-isoindoliums through a novel cascade cyclization reaction of propargylamine-based 1,6-diynes has been developed.

A highly regio- and chemoselective synthesis of 1

Chiral gold(iii) complex was found to be a “golden key” to unlock (±)-1,16-dihydroxytetraphenylene (DHTP), leading to enantiopure DHTP in a large quantity. This approach provided convenient access to 2,15-diaryl (S)-DHTPs and phosphoramidites.

Unprecedented stable BINOL/gold(III) complexes, adopting a novel C,O-chelation mode, were synthesized by a modular approach through combination of 1,1'-binaphthalene-2,2'-diols (BINOLs) and cyclometalated gold(III) dichloride complexes [(C^N)AuCl2 ]. X-ray crystallographic analysis revealed that the bidentate BINOL ligands tautomerized and bonded to the AuIII atom through C,O-chelation to form a five-membered ring instead of the conventional O,O'-chelation giving a seven-membered ring. These gold(III) complexes catalyzed acetalization/cycloisomerization and carboalkoxylation of ortho-alkynylbenzaldehydes with trialkyl orthoformates.

An efficient modular approach for the synthesis of propargylamine modified β-cyclodextrins has been developed. Using mono-(6-benzylamino-6-deoxy)-β-cyclodextrins, formaldehyde, and alkynes, mono-(6-(benzylpropargyl)amino-6-deoxy)-β-cyclodextrins have been synthesized through a three-component coupling reaction catalyzed by gold(III) salt in water at 40 °C.

A new approach for selective hydroxylation of non-activated cyclohexanes using dioxirane generated in situ in water through supramolecular control has been developed. Using β-CD and γ-CD as the supramolecular hosts, selective hydroxylation of cyclohexane substrates, including trans/cis-1,4-, 1,3- and 1,2-dimethylcyclohexanes and trans/cis-decahydronaphthalene, was achieved in up to 54% yield in water. Furthermore, site-selective C–H bond hydroxylation of (+)-menthol was achieved by obstructing the approach of dioxirane to the C–H bond with higher steric hindrance through inclusion complexation with β-CD and γ-CD in water.

Alkyne is a useful functionality incorporated in proteins for site-selective bioconjugation reactions. Although effective bioconjugation reactions such as copper(I)-catalyzed and/or copper-free 1,3-dipolar cycloadditions of alkynes and azides are the most common approaches, the development of new alkyne-based bioconjugation reactions is still an ongoing interest in chemical biology. In this work, a new approach has been developed for selective modification of alkyne-linked peptides and proteins through the formation of arylacetylenes by a cross-coupling reaction of 6-membered ring cyclometalated gold(III) (C^N) complexes (HC^N = 2-arylpyridines) with terminal alkynes. Screening of the reaction conditions with a series of cyclometalated gold(III) complexes with phenylacetylene gave an excellent yield (up to 82%) by conducting the reaction in slightly alkaline aqueous conditions. The reaction scope was expanded to various alkynes, including alkyne-linked peptides to achieve up to >99% conversion. Using fluorescent dansyl (1l) and BODIPY (1m)-linked gold(III) complexes, alkyne-linked lysozyme has been selectively modified.

It is of ongoing interest to develop new approaches for efficient and selective modification of cysteine residues on biomolecules. Here we present a comprehensive study on a newly developed isoxazolinium-mediated cysteine modification of peptides and proteins. Using a stoichiometric amount of isoxazolinium reagents generated in situ from a catalytic amount of silver salts, cysteine-containing peptides can be efficiently modified to afford products in nearly complete conversions. With the optimized conditions, free cysteine containing proteins HSA and BSA, as well as a site-directed mutated therapeutic protein (BCArg) can be efficiently and selectively labelled using small amounts of the isoxazolinium reagents. We find that the phenylacyl thioether linkage bearing an alkyne moiety can be rapidly cleaved under irradiation of UV-A light, giving the formation of a thioaldehyde moiety, which can be converted back to cysteine by reduction. Selective labeling of biomolecules is a powerful technology for chemical biology. Here a silver-catalysed chemoselective modification of cysteine residues by isoxazolinium reagents is described.

Asymmetric catalysis by using novel chiral O,O'-chelated 4,4'-biphenol cyclometalated oxazoline gold(III) complexes has been developed. A high yield (≤89%) and a high enantioselectivity (≤90% ee) were achieved in asymmetric carboalkoxylation of alkynes. Enantioselectivity could be significantly improved from 19% to 90% ee by increasing the steric size of the substituent on the chiral oxazoline ligand. Catalytically active Au

8-prenylgenistein (8PG) was previously reported to exert stronger osteogenic activity than genistein, a well-known soy phytoestrogen. However, the molecular mechanism underlying the actions of 8PG on osteoblasts was far from clear. In the present study, the osteogenic effects and mechanisms of 8PG and genistein were studied using human BMSC and murine pre-osteoblast MC3T3-E1 cells. Our results indicated that the stimulatory effects of 8PG and genistein on osteoblast differentiation were abolished by co-incubation with MPP (10−6 M, an ERα antagonist), but not PHTPP (10−6 M, an ERβ antagonist). Molecular docking indicated that the binding mode of 8PG toward ERα was similar to that of genistein and therefore could not account for their differential osteogenic actions. In silico target profiling identified the involvement of glycogen synthase kinase-3β (GSK-3β), a key mediator of Wnt/β-catenin pathway, in the actions of 8PG. However, instead of directly inhibiting GSK-3β enzymatic activities, 8PG and genistein were found to induce GSK-3β phosphorylation at Serine-9 in osteoblastic MC3T3-E1 cells. 8PG exerted more potent effects than genistein in stimulating expressions of LRP5, β-catenin, Runx2, osteocalcin, alp, opg, major protein and gene markers involved in Wnt signaling pathway in MC3T3-E1 cells. Moreover, the inhibition of Wnt signaling by DKK1 could be restored by treatment with 8PG and genistein. However, 8PG, but not genistein, stimulated ERα-dependent β-catenin protein expression in MC3T3-E1 cells. Furthermore, the increase in ALP activity, LRP5 and phospho-Akt/Akt expression by 8PG and genistein were abolished by co-treatment with LY294002 (10−5 M, a PI3K pathway inhibitor). Collectively, our results suggested that the osteogenic activities of 8PG was mediated by GSK-3β phosphorylation through the induction of Wnt/β-catenin and ERα-associated PI3K/Akt signaling.

An efficient method for photooxidative amidation of aldehydes with secondary amines has been developed. With the use of a readily available photocatalyst rose bengal, tertiary amides (with examples of oligosaccharides and endoperoxide artemisinin) were obtained in good yields with high chemoselectivity and functional-group compatibility under mild reaction conditions.

The propargylic amine N-oxides are formed in situ by oxygenation of the corresponding propargyl amines.

A new class of hydrogen bond donor–acceptor–donor (HB-DAD) organocatalysts has been developed for conjugate addition of benzylidene barbiturates. HB-DAD organocatalyst 1a (featuring para-chloro-pyrimidine as the hydrogen bond acceptor (HBA), N–H as the hydrogen bond donor (HBD) and a trifluoroacetyl group as the electron withdrawing group (EWG)) is able to activate benzylidene barbiturates through complementary DAD–ADA hydrogen bonding. Using 1a in benzylidene barbiturate conjugate addition, good yields were achieved. The relative rate constant (krel = 2.9) of 1a in catalyzing the conjugate addition of benzylidene barbiturates and the binding constant (KA = 8936 (±723) M−1) of 1a with benzylidene barbiturates were determined by NMR and UV/Vis. spectroscopy studies. The excellent correlation (R2 = 0.97) between the relative rate constant and binding affinity of 1a with benzylidene barbiturates provides support for the importance of DAD–ADA hydrogen bonding in organocatalysis.

A rationally designed 2,3,10,11-tetrahydroxytetraphenylene (1) has been synthesized. Employing 1 as a building block, a structurally novel tweezer-like host 2 containing dibenzo-24-crown-8 moieties has been prepared. Host 2 showed excellent molecular-recognition ability toward paraquat (=1,1′-dimethyl-4,4′-bipyridinium dichloride) derivative 3a to form a 1 : 1 stable complex in solution.

Primary liver cancer is one of the highly malignant tumours. The traditional surgery, chemotherapy and radiation therapy only established 6% of 5-year survival rate in HCC (hepatocellular carcinoma). Therefore there is an urgent need to develop new therapeutic strategies. HSP90 (heat shock protein 90) is one of the important molecular chaperones and was identified with high expression in the primary liver cancer. In this study, we evaluated the therapeutic effect of specific HSP90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxy geldanamycin) in HCC cells. The time and concentration effects of 17-DMAG were investigated in HCC cells. Cell proliferation was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and cell counting. Apoptosis was detected by flow cytometry with staining of Annexin V-FITC/PI (propidium iodide). The protein levels of survivin, cyclin D1, p53 and NF-κB (nuclear factor κB) were measured by Western blotting. 17-DMAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. Treatment with 400 nmol/l 17-DMAG for 48 h significantly induced early-stage apoptosis (22.4%). Conversely, it induced less late-stage apoptosis (3.03%). The 5 mg/l of cisplatin induced significantly less early-stage apoptosis (6.5%), but similar proportion of late-stage apoptosis (4.89%) compared with 17-DMAG. Inhibition of HSP90 activity by 400 nmol/l 17-DMAG decreased protein levels of survivin, cyclin D1 and NF-κB protein levels, whereas increased p53 protein level. HSP90 plays a key role in HCC cell growth and survival through regulation of survivin, cyclin D1, p53 and nucleus NF-κB protein levels and the specific HSP90 inhibitor 17-DMAG can play a therapeutic role in HCC treatment.

The strategies for tumor-specific expression of suicide genes and target tumor angiogenesis have been tested in tumors. However, the anti-tumor efficacy of the combination of these two strategies, particularly, delivering suicide gene and anti-angiogenesis agent by nanoparticles, has not yet been evaluated in colon carcinoma. We constructed a cassette to silence VEGF-A expression and express a fused yCDglyTK gene driven by tumor-specific promoter (shVEGF-CDTK). The DNA carrying shVEGF-CDTK was delivered into colon carcinoma cells by calcium phosphate nanoparticles (CPNPs). Cell proliferation was measured by MTT assay, and apoptosis was detected by flow cytometry. The anti-tumor effect of the combined cassette was tested in xenograft animal model. With 5-fluorocytosine (5-FC), CPNP-delivered shVEGF-CDTK DNA (CPNP-shVEGF-CDTK) showed high expression of fused yCDglyTK gene and effectively silenced VEGF-A expression in vitro and in vivo, which significantly inhibited colon carcinoma cell proliferation and induced apoptosis in vitro. With 5-FC, the systemic delivery of CPNP-shVEGF-CDTK significantly inhibited tumor growth in the colon carcinoma xenograft animal model. The combined cassette is obviously effective in inhibiting tumor cell proliferation and inducing apoptosis in vitro and tumor growth in vivo than the CPNP-shVEGF or CPNP-CDTK alone. The combination of VEGF-A-silencing and tumor-specific expression of suicide gene is an effective strategy for colon carcinoma treatment.

This communication is concerned with our efforts in improving the syntheses of five hydroxytetraphenylens, which we obtained before. A short consecutive direct ortho-metalation and oxidative coupling sequence from N-pivaloyl-protected substituted aniline provided the corresponding 2,2'-diiodobiphenyls. Subsequently, copper(II)-mediated oxidative coupling of 2,2'-diiodobiphenyls successfully led to the formation of the corresponding hydroxytetraphenylenes. This is the first time that hydroxytetraphenylenes 2, 4 and 5 were all realized via oxidative cross-coupling reactions from the corresponding 2,2'-diiodobiphenyls.

Xanthones and their derivatives have been reported to exhibit strong inhibitory activities toward α-glucosidase. To provide deep insight into the correlation between inhibitory activities and structures of xanthones, multiple linear regression (MLR) method was employed to establish QSAR models for 43 xanthone derivatives that have diverse structures. Among the 38 typical descriptors investigated, Hs (number of H-bond forming substituents), N π (number of aromatic rings), and S (softness value) can be utilized to model the inhibitory activity. Thus, inhibitory activities of xanthone derivatives can be regulated by H-bond forming substituents, π-stacking-forming aromatic rings and softness values on the xanthone skeleton. The accuracy and predictive power of the proposed QSAR model were verified by LOO validation, Y-randomization, and test group validation with newly synthesized xanthone derivatives.

The propargylic amine N-oxides are formed in situ by oxygenation of the corresponding propargyl amines.

Modular assembly of cyclometalated gold(III) complexes by choosing appropriate bidentate C,N-donor ligands and ancillary ligands for chemoselective cysteine modification of peptides and proteins via C–S bond-forming reductive elimination has been achieved.

Stable bis-cyclometallated gold(III) complexes were developed as efficient catalysts for organic transformation reactions by using two strategies: (1) construction of distorted square planar gold(III) complexes and (2) dual catalysis by gold(III) complexes and silver salts.

Five dammarane-type aglycones, released from gypenosides following an alkaline cleavage procedure previously developed for ginsenosides, were separated and characterized by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation. A satisfactory identification among isomers of 20(S)-protopanaxadiol or 20(S)-protopanaxatriol was obtained.

Recently developed accurate GC and GC-MS methods were used to characterize various commercial ginseng preparations purchased from pharmacies or well reputed health stores in seven European countries, Argentina, Canada, China and the USA. The methods used are based on quantification of the aglycones (20s-protopanaxadiol, 20s-protopanaxatriol and oleanolic acid) of the ginsenosides after oxidative cleavage in alkali. The most pure ginseng preparations ( n = 14) contained from 1.9% to 8.1% (w/w) ginsenosides (using ginsenoside Rg 1 , Rb 1 and Ro as calibrators and panaxatriol as internal standard). The content of ginsenosides in different ginseng extracts (in 20 ginseng extract preparations) varied from 4.9% to 13.3% (w/w). Some liquid formulations as well as some preparations of red ginseng were shown to contain artifacts (epimerization and hydration products of 20s-protopanaxadiol and 20s-protopanaxatriol). The latter compounds are not likely to be detected by the common HPLC analysis of intact ginsenosides. American ginseng and San-chi ginseng were also analyzed. The present method is suitable for evaluation of different types of ginseng preparations.

Recent results in improving the syntheses of five symmetrical and unsymmetrical hydroxytetraphenylenes are reported.

The six Ephedra alkaloids (ephedrine, norephedrine, pseudoephedrine, norpseudoephedrine, methylephedrine and methylpseudoephedrine) in 12 species of Chinese Ephedra collected in 16 districts of China were separated and identified by gas chromatography combined with mass spectrometry following trimethylsilylation of the extract. The alkaloidal concentrations were determined using a gas chromatograph equipped with a nitrogen phosphorus detector. The methods described are sensitive, accurate and simple to perform.

Four main dammarane-type aglycones of gypenosides, extracted from the aerial parts of Gynostemma pentaphyllum were identified by gas chromatography-mass spectrometry. By detecting these aglycones as well as the aglycones of ginsenosides, a difference in sapogenin composition between Gynostemma pentaphyllum and Panax species was observed, which can be used in the differentiation of these plant drugs.

An improved gas chromatographic-mass spectrometric method (GC-MS) with a fast solid-phase extraction on a newly introduced C18 microcolumn, was applied to study the urinary excretion 20(S)-protopanaxadiol and 20(S)-protopanaxatriol glycosides in man after oral administration of ginseng preparations. Using panaxatriol as internal standard, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol (the aglycones of ginsenosides) could be determined at a detection level of a few ng per ml urine by GC-MS with selected-ion monitoring after their release from glycosides which occur in urine. The extraction recovery of ginsenosides from urine was more than 80% and the intra-assay coefficient of variation was less than 5.0%. The results after intake of single doses of ginseng preparations demonstrated a linear relation between the amounts of ginsenosides consumed and the 20(S)-protopanaxatriol glycosides excreted in urine. About 1.2% of the dose was recovered in five days.

Stable bis-cyclometallated gold(III) complexes were developed as efficient catalysts for organic transformation reactions by using two strategies: (1) construction of distorted square planar gold(III) complexes and (2) dual catalysis by gold(III) complexes and silver salts.

To facilitate studies on the possible presence of ginseng products in serum, tissues, and excretions, a procedure to optimize the analysis of the ginseng specific products, i.e., ginsenosides, had to be worked out. With the present method the two sapogenins, 20S-protopanaxadiol and 20S-protopanaxatriol, can be produced from ginsenosides Rb1, Rc, Rd, Re, and Rg1 in 80% yield by using an improved alkaline cleavage procedure. In contrast to previously described acid hydrolysis procedures for ginsenosides, our alkaline conditions caused no epimerization, no hydroxylation, and no cyclization of the side chain. Furthermore, no unchanged ginsenosides were recovered. The products of alkaline and acidic cleavage were separated, identified, and characterized by GC, GC-MS, and HPLC. In contrast to alkaline cleavage, treatment with acid afforded a number of side products. The C-20S-epimers of the ginseng sapogenins could be distinguished from C-20R epimers by difference in mass spectra and retention time after trimethylsilylation.