Yu-ng Li

Simple, efficient and reusable Pd–NHC catalysts for hydroamination

A series of chelating NHC–palladium complexes with different alkane-bridges of the type Pd[NHC–(CH2)n–NHC]X2 (X = Br or Cl, n = 2–4) were synthesized, where NHC is a triazolyl-N-heterocyclic carbene donor ligand. The bromide complexes with n = 2 and 3 were characterized by X-ray crystallography. The effects of the length of the bridge and halide ligand on the catalytic reactivity in the hydroamination reaction were investigated. The best catalytic performance was observed with the propylene-bridged Pd–NHC bromide complex 2. The hydroamination of phenylacetylene or 4-methylphenylacetylene with various substituted anilines catalyzed by 2 yielded only Markovnikov addition products in good yield. Interestingly, this homogenous catalyst can be reused three times without significant loss in activity.

Disulfide cross-linked cholic-acid modified PEG–poly(amino acid) block copolymer micelles for controlled drug delivery of doxorubicin

Reduction responsive biodegradable core-cross-linked micelles are developed form lipoic acid (LA) and cholic acid (CA) decorated poly(ethylene glycol)-b-poly(L-glutamic acid) (PEG-pGlu(EDA-LA)-CA) block copolymers and investigated for intracellular doxorubicin (DOX) release. The amphiphilic polymers can self-assemble into nano-sized core–shell micelles that are easily cross-linked in the presence of a catalytic amount of dithiothreitol (DTT). The cross-linked micelles (CLM) show excellent stability against extensive dilution and high salt concentration but rapid dissociation and drug release in reductive environments. Confocal laser scanning microscopy further demonstrates that DOX was delivered and released into the nuclei of HeLa cells following 8 h incubation with DOX-loaded CLM. MTT assays reveal that DOX-loaded CLM had similar anti-tumor activity to non-cross-linked micelles (NCLM) for HeLa cells following 48 h incubation, while blank micelles were practically nontoxic up to a tested concentration of 1.0 mg mL−1. These reduction responsive core-cross-linked micelles have great potential for drug delivery in cancer chemotherapy.

Reversibly cross-linked poly(ethylene glycol)–poly(amino acid)s copolymer micelles: a promising approach to overcome the extracellular stability versus intracellular drug release challenge

Reversibly shell cross-linked micelles based on a lipoic acid (LA) decorated triblock copolymer poly(ethylene glycol)-b-poly(γ-benzyl-L-glutamate)-b-poly(L-phenylalanine) (PEG–PGlu(EDA–LA)–PPhe) have been developed for active loading and efficient intracellular delivery of DOX. The triblock copolymer was synthesized through consecutive ring-opening polymerization of cyclic monomers γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and L-phenylalanine N-carboxyanhydride (Phe-NCA) using amino-terminated poly(ethylene glycol) (PEG–NH2) as macroinitiator, followed by conjugation with LA for reversible cross-linking. The amphiphilic polymer was self-assembled to core shell corona micelles, which could be further crosslinked in the presence of a catalytic amount of dithiothreitol (DTT) in phosphate buffer (pH 7.4) to form shell-cross-linking micelles (SCLM). The SCLM showed excellent stability under physiological conditions but rapid dissociation and drug release in reductive environments mimicking those of the cytoplasm and the cell nucleus. Confocal laser scanning microscopy further demonstrated that DOX was delivered and released into the nuclei of HeLa cells following 12 h incubation with DOX-loaded SCLM. MTT assays revealed that DOX-loaded SCLM had similar anti-tumor activity as non-cross-linked micelles (NCLM) for HeLa cells following 48 h incubation. PEG–PGlu(EDA–LA)–PPhe micelles displayed low cytotoxicity up to a concentration of 1.0 mg mL−1. These biodegradable reversibly shell-cross-linked micelles provide a promising platform for intelligent intracellular drug delivery in clinical chemotherapy.

Efficient one-pot three-component synthesis of 3,4-dihydro-12-phenyl-2H-benzo[b] xanthene-1,6,11(12H)-trione derivatives in ionic liquid

A series of 3,4-dihydro-12-phenyl-2H-benzo[b]xanthene-1,6,11(12H)-trione derivatives have been synthesized in high yields in the presence of ionic liquid [bmim+]Br−. The reaction work-up is simple and the ionic liquid can be easily separated from the product and reused.

CAN-catalyzed synthesis of 10-arylpyrano[3,2-b]chromene-4,9-diones under solvent-free conditions

A novel and efficient one-pot synthesis of 10-aryl-7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-diones by three-component reaction of aromatic aldehydes, 5-hydroxy-2-methylpyran-4-one, and cyclic 1,3-dicarbonyl compounds in the presence of a catalytic amount of ceric ammonium nitrate under solvent-free conditions is described. The advantages of this method include operational simplicity, short reaction time, recyclable catalyst, and high yields.

Mild and efficient one-pot three-component synthesis of benzopyrimidoquinoline-tetraone derivatives in ionic liquids

An efficient one-pot synthesis of 5-aryl-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-2,4,6,11(1H,3H)-tetraone derivatives via three-component reaction of aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone and 6-aminouracil in ionic liquid [bmim]BF4 is reported. This method had the advantages of easier work-up, environmentally benign procedure, high yields and ease of recovery and reuse of reaction media.

One-pot, three-component, green procedure for efficient synthesis of allomaltol derivatives

We report an efficient, mild, one-pot, three-component method, catalyzed by Et3N in the ionic liquid [bmim+][BF4−], for synthesis of 2-[(aryl)-(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)methyl]indan-1,3-diones from aromatic aldehydes, 1,3-indanedione, and 5-hydroxy-2-methyl-4H-pyran-4-one. The method has the advantages of high yields, mild reaction conditions, convenient operation, and environmental friendliness.

Green synthesis of naphthyridine derivatives in ionic liquid via three-component reaction

A mild, green, and facile method for the synthesis of naphthyridine derivatives is described in high yields using ionic liquids as a green media. The method involves a three-component reaction of aldehyde, enamine, and tert-butyl 2,4-dioxopiperidine-1-carboxylate.Graphical Abstract

An efficient three-component synthesis of amino-substituted pyrano[3,2- b ] pyranones

A green, efficient and mild one-pot synthesis of pyrano[3,2-b]pyran derivatives via a three component reaction in the ionic liquid [bmim]BF4 is reported. This method has the advantages of environmental friendliness, operational simplicity, high yields and reuse of the ionic liquid.

Convenient synthesis of naphtho[1,6] naphthyridine derivatives under catalyst-free conditions

A three-component reaction of aromatic aldehyde, naphthalene-2-amine or naphthalen-1-amine, and tert-butyl 2,4-dioxopiperidine-1-carboxylate in reflux EtOH, gave naphtho[1,6]naphthyridine derivatives in high yields under catalyst-free conditions.Graphical Abstract