Shunying Liu

Calix[4]arenes containing thiourea and amide moieties: neutral receptors towards α,ω-dicarboxylate anions

Two-armed neutral anion receptors (4, 5), were prepared and examined for their anion-binding ability using UV-vis, fluorescence and 1H NMR spectra in DMSO. The results of non-linear curve fitting indicate that 4 or 5 form 1 : 1 stoichiometric complexes with dicarboxylate anions by multiple hydrogen bonding interactions and the sensitivity for recognition of dicarboxylate depends on the chain length of these dicarboxylate anions. Receptors 4 and 5 have no binding ability with acetate, dihydrogen phosphate and the halogen (Cl−, Br−, I−) anions. This demonstrates that receptors 4 or 5 could be used as chemical sensors for some special dicarboxylate anions.

An Ylide Transformation of Rhodium(I) Carbene: Enantioselective Three‐Component Reaction through Trapping of Rhodium(I)‐Associated Ammonium Ylides by β‐Nitroacrylates

The chiral Rh(I)-diene-catalyzed asymmetric three-component reaction of aryldiazoacetates, aromatic amines, and β-nitroacrylates was achieved to obtain γ-nitro-α-amino-succinates in good yields and with high diastereo- and enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of Rh(I)-associated ammonium ylides by nitroacrylates. This new transformation represents the first example of Rh(I)-carbene-induced ylide transformation.

FSH Aggravates Periodontitis-related Bone Loss in Ovariectomized Rats

Alveolar bone loss is one of the prominent pathologic and clinical features of periodontitis. Recently, the direct effect of follicle-stimulating hormone (FSH) on bone resorption has been demonstrated. However, the effect of FSH on alveolar bone loss remains unknown. This study tested the hypothesis that FSH would exacerbate periodontitis-related alveolar bone loss. Experimental periodontitis was induced in ovariectomized rats, and the rats were treated with extrinsic FSH or its inhibitor, leuprorelin. After mandibles were collected, we performed morphological examinations to evaluate bone loss, enzyme histochemical tests for osteoclasts, and immunohistochemical examinations for FSH receptor (FSHR). The results showed that FSH significantly increased alveolar bone resorption compared with non-FSH-treated ovariectomized rats (P < 0.05), and the number of FSHR-positive cells was positively correlated with alveolar bone loss area (r = 0.682, P < 0.01). Our results suggested that FSH can aggravate alveolar bone loss by FSHR, independent of estrogen.

Asymmetric C-H functionalization of indoles via enantioselective protonation

Asymmetric C—H functionalization of indoles from Rh2(OAc)4 and chiral phosphoric acid co-catalyzed reactions of aryl diazoacetates with indoles has been investigated. Through mechanistic study regarding to the proton transfer pathway of the C—H functionalization of indoles, a new strategy to achieve the asymmetric C—H functionalization of indoles from metal carbenoids via enantioselective protonation has been proposed. We initially carried out a deuterium isotope experiments in order to obtain more insight into the proton transfer process of the C—H functionalization of indoles, and the experiments indicated an “indirect proton transfer” in the reaction. A proton-transfer shuttle such as H2O was needed to complete the reaction. The observation provides us an opportunity to design a chiral proton-transfer shuttle to achieve the asymmetric C—H functionalization. In this paper, Rh2(OAc)4 catalyzed diazo decomposition of a aryl diazoacetate generates a metal carbenoid. Reaction of the metal carbenoid with an indole at C-3 position generates a zwitterionic intermediate. A bifunctional chiral phosphoric acid serves as a chiral proton shuttle and helps the proton transfer process via an enantioselective protonation to finish the reaction in high yield and enantioselectivity. A number of indoles including N-alkyl, aryl , silyl and a number of α-aryl-α-diazoesters are well tolerated under the established catalytic conditions, providing good to high enantioselectivity (up to 94% ee) in excellent yield (up to 99% yield). A representative procedure for the enantioselective C—H functionalization of indoles is as following: A mixture of 6-chloro-N-methyl indole (1e) (41 mg, 0.25 mmol), transition metal catalyst Rh2(OAc)4 (1 mg, 0.0025 mmol, 1 mol%), chiral phosphoric acid co-catalyst (R)-4j (3.8 mg, 0.005 mmol, 2 mol%) and 4A MS (100 mg) in 1 mL of toluene was stirred at the 0 °C. Methyl phenyldiazo acetate (2a) (53 mg, 0.3 mmol) in 1 mL of toluene was added over 1 h period of time via a syringe pump. After completion of the addition, the reaction was stirred for additional 5 min at the same temperature. Solvent was evaporated under reduced pressure to give corresponding crude product. The crude product was purified by flask chromatography on silica gel (eluent: EtOAc/light petroleum ether, V∶V=1∶ 40~1∶10) to give the pure product 3q in 92% yield with 94% ee.

Fabrication of nanomicelle with enhanced solubility and stability of camptothecin based on α,β-poly[(N-carboxybutyl)-L-aspartamide]―camptothecin conjugate

This research is aimed to develop a nanomicelle delivery system in order to enhance the solubility and stability of camptothecin (CPT) in aqueous media. In this case, alpha,beta-poly[(N-carboxybutyl)-L-aspartamide] (PBAsp)-CPT was conjugated by the esterification between PBAsp and 20-OH of CPT, and hence used to fabricate nanomicelles with a particle size between the pore size of blood capillary in normal tissue and that in tumor tissue. It was worthy of note that the drug-loaded system of PBAsp-CPT nanomicelle improved the solubility and stability of CPT in aqueous media. However, with an increase of the CPT loading in PBAsp-CPT, the solubility sharply decreased. Meanwhile, the sizes of PBAsp-CPT nanomicelles showed a tendency of increase. Moreover, the drug release of PBAsp-CPT nanomicelles displayed a linear sustaining profile, and hence resulted in the essential decrease of cytotoxicity to L929 cell line. The assembled nanomicelles based on the PBAsp-CPT conjugates showed a great potential as polymer prodrug of tumor therapy, and the controlled nano-scale might achieve the passive tumor targeting.

Iron porphyrin-catalyzed three-component reaction of ethyl diazoacetate with aliphatic amines and β,γ-unsaturated α-keto esters.

An iron porphyrin-catalyzed three-component reaction of ethyl diazoacetate with aliphatic amines and β,γ-unsaturated α-keto esters is reported. The use of iron porphyrin catalyst allows aliphatic amines to be used as the substrate without encountering catalyst poisoning issue and a series of β-hydroxy-α-amino esters are produced in high yields with excellent regioselectivities.

Ruthenium(II)/Chiral Brønsted Acid Co‐Catalyzed Enantioselective Four‐Component Reaction/Cascade Aza‐Michael Addition for Efficient Construction of 1,3,4‐Tetrasubstituted Tetrahydroisoquinolines

An elegant synergistic catalytic system comprising a ruthenium complex with a chiral Brønsted acid was developed for a four-component Mannich/cascade aza-Michael reaction. The ruthenium-associated ammonium ylides successfully trapped with in situ generated imines indicates a stepwise process of proton transfer in the ruthenium-catalyzed carbenoid N-H insertion reaction. The different decomposition abilities of various ruthenium complexes towards diazo compounds were well explained by the calculated thermodynamic data. The transformation features a mild, rapid, and efficient method for the synthesis of enantiomerically pure 1,3,4-tetrasubstituted tetrahydroquinolines bearing a quaternary stereogenic carbon center from simple starting precursors in moderate yields with high diastereo- and enantioselectivity.

A highly enantioselective four-component reaction for the efficient construction of chiral β-hydroxy-α-amino acid derivatives

An enantioselective four-component reaction of a diazoketone, water, an aniline and ethyl glyoxylate in the presence of catalytic Rh2(OAc)4 and a chiral Brønsted acid was developed to efficiently produce β-hydroxy-α-amino acid derivatives in good yields with high diastereoselectivity and enantioselectivity.

Preparation and characterization of amino-functionalized magnetic nanogels via photopolymerization for MRI applications

To design peptide-targeted iron oxide as magnetic resonance imaging (MRI) contrast agents, amino-functionalized magnetic nanogels were prepared by using N-(2-aminoethyl) methacrylamide hydrochloride (AEM x HCl) as monomer via new photochemical approach. Their chemical structure and composition were characterized by Fourier transform infrared spectra (FTIR) and thermogravimetric analyses (TGA). The core-shell structure of magnetic nanogels was confirmed by high-resolution transmission electron microscopy (HRTEM). The good storage stability, high magnetic content (88.7%), high saturation magnetizations and superparamagnetic behavior suggested their great potentials as MRI contrast agents, which were confirmed by their measurements of r(2) and coronal image of the crossing of mouse kidney.

Anionic Fluororeceptors based on Thiourea and Hydrazide: Synthesis and Recognition Properties

Two new neutral receptors (1 and 2) containing thiourea and hydrazide groups were synthesized by simple steps in high yields. The binding properties of 1 and 2 for various anions were characterized by UV–Vis and fluorescence spectra. Receptor 1 had a good selectivity for AcO- in comparison with other anions. The association constants of 1·AcO- and 2·p-NO2PhO- were greater than those of other anions ( Cl-, Br- and I-). In particular, an obvious color change from light yellow to orange–red was observed upon addition of AcO- to the solution of 1 in DMSO. The results of nonlinear curve fitting by fluorescence spectral data indicate that a complex of 1:1 stoichiometry is formed between compound 1 or 2 and the anions through hydrogen-bonding interaction.