A new efficient method was developed to provide modified tryptophan peptides through NIS (N-iodosuccinimide) mediated N2-selective coupling of a Trp unit with 1,2,3-triazoles, of which, the preliminary spectral properties were also studied.

A new method was developed to synthesize N2-alkyl-substituted 1,2,3-triazole through N-iodosuccinimide (NIS) mediated iodofuctionalization reaction of the alkene group with bi-, mono-, and unsubstituted NH-1,2,3-triazoles. The favored N-1 type hydrogen bond between the iodonium ion intermediate and 1,2,3-triazole was supposed to be generated, which gave the desired N2-alkyl triazole with a high N2-selectivity.

A new method was developed to enantioselectively synthesize pyrroloindolines from the reaction of allenoamides with tryptamines by using BINOL derived phosphoramidate ligated gold catalyst. Electrophilic addition of the gold–allene complex led to tryptamine’s C-3-dearomatization, which, followed by C-2 cyclization, provided the desired annulation product. In addition, furoindoline product could also be prepared from the reaction of tryptol.A new method was developed to enantioselectively synthesize pyrroloindolines from the reaction of allenoamides with tryptamines by using phosphoramidate ligated gold catalyst.

A new method was developed to synthesize polyfunctionalized dihydrofuran and tetrahydrofuran derivatives from the three-component [2 + 2 + 1] cycloaddition of the diazoesters with aryl/alkenyl aldehydes and alkyne/olefin dipolarophiles by using a Ag(I) N-heterocyclic carbene complex as the catalyst. A carbonyl ylide intermediate was generated, which undertook an endo-type 1,3-dipolar cycloaddition to provide the desired dihydro-/tetrahydrofurans in high regio- and diastereoselectivities by using α-aryl or α-alkenyl diazoesters.

A new type of ratiometric fluorescent probe capable of detecting Hg2+ ions at nanomolar-concentration level with high selectivity was developed based on an indole-trizole-rhodamine triad and its practicability for intracellular Hg2+ sensing was verified. The as-prepared fluorescent probe is capable of detecting Hg2+ over other competing metal ions including Ag+ with high selectivity. The synergistic effect of Hg2+-assisted conversion of the nonfluorescent ring-closed rhodamine moiety to the highly fluorescent ring-open form as well as the fluorescence signal amplification originating from the Förster resonance energy transfer (FRET) from indole-trizole conjugate to rhodamine moiety contributed to a detection limit of 11 nM of the probe for Hg2+ sensing.

•New type of fluorescent probe for Ag+ and Hg2+ sensing with high selectivity and sensitivity.•First demonstration of single-fluorophore-based Ag+-selective TURN-ON and Hg2+-selective TURN-OFF type dual-channel fluorescence signaling system.•Single-fluorophore-based probes for simultaneous determination of Ag+ and Hg2+ without crosstalk.A new type of fluorescent probe capable of detecting Ag+ and Hg2+ in two independent channels was developed in the present work. Specifically, in CH3CN–MOPS mixed solvents with CH3CN/MOPS ratio (v/v) of 15/85, this type of probe fluoresced weakly, and the addition of Ag+ remarkably induced fluorescence enhancement of the probe. In CH3CN–MOPS mixed solvents with the percentage of CH3CN increased up to 65%, the probe was highly fluorescent and addition of Hg2+ dramatically induced the fluorescence quenching. Thus, using such single-fluorophore-based probe and tuning the polarity of the mixed solvent, Ag+, and Hg2+ can be detected in independent channels with high selectivity and sensitivity. As a result, the mutual interference usually encountered in most cases of Ag+ and Hg2+ sensing owing to the similar fluorescence response that these two ions induced, can be effectively circumvented by using the probes developed herein.A new type of single-fluorophore-based fluorescent probes that displayed Ag+-selective TURN-ON and Hg2+-selective TURN-OFF type dual-channel antiphase-like fluorescence signaling features was developed, and their unique ability of enabling simultaneous determination of Ag+ and Hg2+ over other reference metal ions was confirmed.

A new method was developed to synthesize oxirane products from the reaction of diazocarbonyl substrates with aryl aldehydes by using Ag(I) N-heterocyclic carbene complex as the catalyst. A combination of N-heterocyclic carbene silver complex (IPrAgCl) with another silver salt (AgOTf) generated the catalytic active IPr-Ag+ intermediate, which then catalyzed the epoxidation reaction.N-Heterocyclic carbene ligated silver catalyst was utilized to mediate [2+1] cycloaddition of diazo esters with aryl aldehydes to give oxirane derivatives.

A gold catalyzed enantioselective [3+2] dipolar cycloaddition of N-allenyl amides with nitrones was developed to give chiral 4-alkylidenyl isoxazolidine derivatives in high yields and excellent enantioselectivities by using BINOL derived chiral phosphoramidate Au(I) catalysts.

Gold(I) catalyzed [3+2] cycloaddition of azomethine imines with N-allenyl amides was developed to provide two types of pyrazolyl based bicyclic heterocycles. Both pyrazolidin-3-one derived and dihydroisoquinoline derived azomethine imines reacted smoothly with N-allenyl amides to give 6-methylene bipyrazolidin-1-ones and 1-methylene hexahydropyrazolo[5,1-a] isoquinolines in moderate to good yields.

An efficient method was developed to construct the densely functionalized cyclobuane adducts through formal intermolecular cycloaddition of alleneamides with electron-rich olefins via gold catalysis, in which vinyl ethers/amides and electron-rich styrenes worked very well. In addition, a series of alleneamide dimerization products were prepared from the same alleneamide substrates.

An efficient new method was developed to synthesize multisubstituted 4, 5-dihydro-1H-azepine derivatives through the gold-catalyzed reaction of two molecules of propargylic esters with one molecule of alkyl azide. It was proposed that vinyl gold carbenoid, in situ generated from propargylic ester through gold-catalyzed 1, 2-rearrangement, was trapped by alkyl azide to give vinyl imine intermediate. These, in turn, could undergo a formal [4 + 3] cycloaddition with another molecule of vinyl gold carbenoid to afford the desired azepine product.

An efficient and environmentally benign method was developed to synthesize the benzocycles from phenyl substituted allylic acetates through gold catalyzed Friedel–Crafts type carbocyclization reaction. Different substitution patterns were investigated, which gave a series of benzocyclohexane derivatives in moderate to excellent yields.

A new efficient method was developed to transform cyclic alkanols into one-carbon higher homologated ketones using various esters as the leaving groups through gold-catalyzed allylic cation-promoted pinacol-type rearrangement. This reaction, coupled with oxy-Cope rearrangement, provided a new strategy to synthesize five-carbon homologated ring ketones. In addition, using ZnBr2, 2,5-dihydrofuran products were obtained in moderate to good yields via an intramolecular cyclization process.

A new tandem allylation/enyne cycloisomerization reaction was developed to construct densely functionalized oxygen hetereocycles with high diastereoselectivities from the intermolecular reaction of allylic acetates with propargylic alcohols via gold catalysis. Terminal and nonterminal propargylic alcohols take different reaction routes either to provide 3-oxa-bicyclo[4.1.0]hept-4-ene derivatives 5 or to give endocyclic rearrangement products 7 and alkoxycyclization adducts 8. Cyclopropane’s stereochemistry was mainly determined by allylic substituents.

An efficient method for the preparation of polysubstituted γ-vinyl butyrolactones was developed through gold catalyzed highly diastereoselective cyclization of the malonate substituted allylic acetates.

Glioblastoma (GBM) is the most aggressive tumor type in the central nervous system. Both tumor-targeting drug delivery and combination therapy of multiple therapeutic agents with distinct mechanisms are important for GBM treatment. We combined these two strategies and developed a new platform of peptide-drug conjugate (RGD-PEG-Suc-PD0325901, W22) for tumor-targeting delivery using a combination of PD0325901 (a MEK1/2 inhibitor) and RGD peptide. In the present study, the combination of PD0325901 and RGD peptide strongly inhibited U87MG model in vitro and in vivo. This inhibition contributed to synergistic suppression of cell proliferation by blocking ERK pathway activity and cell migration. Modified by conjugation strategy, their conjugate W22 enhanced PD0325901 delivery to GBM cells by receptor mediated cellular internalization. W22 showed great superiority in targeting to U87MG xenografted tumors and strong anti-tumor efficacy based on ERK pathway inhibition and tumor-targeted delivery in vitro and in vivo. Moreover, W22 was stable in serum and able to release PD0325901 in the enzymatic environment. These data indicated that the RGD-PEG-Suc-PD0325901 conjugate provided a strategy for effective delivery of PD0325901 and RGD peptide into the GBM cells and inhibition of tumor growth in a synergistic manner.Download high-res image (209KB)Download full-size image

A new efficient method was developed to provide modified tryptophan peptides through NIS (N-iodosuccinimide) mediated N2-selective coupling of a Trp unit with 1,2,3-triazoles, of which, the preliminary spectral properties were also studied.

A gold catalyzed enantioselective [3+2] dipolar cycloaddition of N-allenyl amides with nitrones was developed to give chiral 4-alkylidenyl isoxazolidine derivatives in high yields and excellent enantioselectivities by using BINOL derived chiral phosphoramidate Au(I) catalysts.

An efficient method for the preparation of polysubstituted γ-vinyl butyrolactones was developed through gold catalyzed highly diastereoselective cyclization of the malonate substituted allylic acetates.

Gold(I) catalyzed [3+2] cycloaddition of azomethine imines with N-allenyl amides was developed to provide two types of pyrazolyl based bicyclic heterocycles. Both pyrazolidin-3-one derived and dihydroisoquinoline derived azomethine imines reacted smoothly with N-allenyl amides to give 6-methylene bipyrazolidin-1-ones and 1-methylene hexahydropyrazolo[5,1-a] isoquinolines in moderate to good yields.