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N,N-Disubstituted thioamides coupled with N-tosylhydrazones under Pd(TFA)2/tBuXPhos catalyst and NaOtBu, and the intermediates from palladium carbene migratory insertion containing β-hydrogen were ...

Mild cobalt-catalyzed switchable regioselective and chemoselective thioenolization/C–H thiolation and C(sp2)–H/C(sp3)–H dehydrogenative couplings of N-aryl-N-alkyl-thioamides are developed, providi...

Reactions of thiocarbonyl fluoride derived from cheap, readily available, and widely used CF3SiMe3, elemental sulfur, and KF with secondary amines and primary amines at room temperature in THF provided a wide variety of thiocarbamoyl fluorides and isothiocyanates in moderate to excellent yields, respectively. The two reactions show broad substrate scope and good functional group tolerance. Moreover, AgSCF3 reacts with secondary/primary amines under KBr at room temperature, affording quantitative thiocarbamoyl fluorides/isothiocyanates, which feature late-stage application.

An FeCl3-catalyzed allenic Claisen rearrangement/regio- and chemoselective aerobic dehydrogenative cyclization domino reaction is developed, providing a wide range of 2-aryl/alkyl, 3-(substituted-vinyl)naphtho[2,1-b]furans in high yields at 95–130 °C in an atom- and step-economic fashion. Mechanistic studies suggest that the FeCl3 catalyst is responsible for the high regio- and chemoselectivity in reaction. A blue-emitting product shows quantum yield of 0.95. The reaction proceeds readily on the gram scale, and synthetic applications of the products are also demonstrated.

An efficient cascade reaction of propargyl amines with AgSCF3 and KBr is developed, affording allenyl thiocyanates at room temperature in high yields. This transformation proceeds via the in situ formation of isothiocyanate intermediates, followed by a [3,3]-sigmatropic rearrangement. The resulting allenyl thiocyanates bearing 3-(electro-donating phenyl) substitutions without isolation can then be reacted with di-tert-butyl peroxide and AgSCF3 under reflux to generate novel allenyl trifluoromethylthioether compounds in moderate to good yields via a “one-pot” three-step process.

Highly diastereoselective intramolecular trapping of ammonium ylides with enones has been developed through a Rh(II)/Brønsted acid cocatalytic strategy. This process allows rapid and efficient construction of N-unprotected polyfunctional 2,2,3-trisubstituted indolines in moderate to good yields with excellent diastereoselectivity.

Enantioselective three-component reactions of tert-butyl diazoacetate with arylamines and imines afford α,β-bis(arylamino) acid derivatives in good yields (56–90%) with high diastereoselectivities (up to >95:5 dr) and excellent enantioselectivities (up to 96% ee).

A practical and scalable synthesis of ethyl (R)-piperidine-3-acetate was achieved from commercially available 3-pyridylacetic acid in 76% overall yield. The practical synthesis was demonstrated on 100-g scale. One-pot reductive N-ethylation of the pyridinium salt with acetonitrile gave an N-ethyl piperidine derivative.

The diastereoselectively switchable enantioselective trapping of protic carbamate ammonium ylides with imines is reported. The intriguing Rh(2)(OAc)(4) and chiral Brønsted acid cocatalyzed three-component Mannich-type reaction of a diazo compound, a carbamate, and an imine provides rapid and efficient access to both syn- and anti-α-substituted α,β-diamino acid derivatives with a high level control of chemo-, diastereo-, and enantioselectivity.

A new approach to synthesize optically active β-amino-α-hydroxyl acid derivatives via chiral Brønsted acid-Rh(2)(OAc)(4) cocatalyzed three-component reactions of diazo acetates with alcohols and imines is reported. A matched reaction system was identified to give the products in moderate diastereoselectivity and good enantioselectivity. Application of this methodology is demonstrated in the efficient synthesis of a taxol side chain and (-)-epi-cytoxazone.

CuI/4-hydroxy-l-proline-catalyzed coupling of aryl bromides and N-Boc hydrazine takes place in DMSO at 80 degrees C to give N-aryl hydrazides. When aryl iodides are employed, this reaction completes at 50 degrees C and no ligand is required. Under the catalysis of CuI/4-hydroxy-l-proline, the coupling reaction of aqueous ammonia with aryl bromides proceeds smoothly at 50 degrees C to afford primary arylamines. In this case K(2)CO(3) is found as a better base than Cs(2)CO(3). These processes allow assembly of N-aryl hydrazides and primary arylamines that bear a wide range of functional groups including hydroxyl, amine, trifluoromethyl, ester, nitro, and ketone.

The fatty acid composition, total phenol content and tocopherol content of olive oils from Shodo Island of Japan were analyzed for different varieties, maturation stages and extraction methods. Radical-scavenging activity of olive oils was also determined spectrophotometrically by measuring the disappearance of 1,1-diphenyl-2-picrylhydrazyl radical at 517nm. The differences in fatty acids composition, total phenol and tocopherol content in virgin olive oils were not great among the varieties. The content of oleic acid was in range of 66-78%. Though virgin olive oils contained more phenolic compounds than hexane-extracted olive oils, tocophenol content was not very different. In hexane-extracted olive oils, the total phenol content decreased during olive maturation. The tocopherol content of three types of olive oils also decreased during maturation. Still, large amounts of phenolic compounds remained in the olive residue after hexane extraction. The contribution of tocopherols to radical-scavenging activity was 39-61% in virgin olive oil, which suggests that both tocopherols and phenolic compounds contribute to radical-scavenging activity.

Hexadepsipeptide 2, the precursor of Hirsutellide A (1), was synthesized in an overall yield of 45% from N-Boc-Me-Gly via three coupling reactions using dicyclohexylcarbodiimide (DCC), O-(7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyl- uronium hexafluorophosphate (HATU) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl), respectively.

The described procedure gives access to a large variety of the title compound class in moderate to good yields with excellent diastereoselectivities.

Enantioselective three-component reactions of tert-butyl diazoacetate with arylamines and imines afford α,β-bis(arylamino) acid derivatives in good yields (56–90%) with high diastereoselectivities (up to >95:5 dr) and excellent enantioselectivities (up to 96% ee).

Liqin Jiang,1 Xuemin Li,1 Lingrong Liu,1 Qiqing Zhang1,21Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Research Center of Biomedical Engineering, Xiamen University, Xiamen, People's Republic of ChinaAbstract: The cellular uptake mechanism and intracellular fate of self-assembled nanoparticles (NPs) of cholesterol-modified pullulan (CHSP) by human hepatocellular carcinoma (HepG2) cells were investigated. Covalent conjugation with fluorescein isothiocyanate (FITC) yielded stably labeled CHSP (FITC-CHSP), which was successfully formulated into NPs (mean particle size 63.0 ± 1.9 nm) by dialysis. A cytotoxicity assay clearly indicated that the CHSP NPs did not show significant toxicity in HepG2 cells. The effects of NP concentration, incubation time, and temperature on the cellular uptake of the NPs were systematically evaluated by fluorometry, and the results suggested that cellular uptake of the NPs was concentration-, time-, and temperature-dependent. In vitro experiments with endocytic inhibitors revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the internalization of CHSP NPs. The intracellular trafficking study demonstrated that CHSP NPs were entrapped in the lysosomes at 1 hour after incubation; colocalization of NPs with either the Golgi apparatus or the endoplasmic reticula was not observed during the entire course of the study. These results suggested that the CHSP NPs may serve as a versatile carrier for intracellular delivery of therapeutic agents.Keywords: cholesterol-modified pullulan, self-assembled nanoparticles, FITC, endocytosis, intracellular trafficking

Reactions with the unstable and highly reactive zwitterionic intermediates generated in processes catalysed by transition metals are providing new opportunities for molecular constructions. Insertion reactions involve the collapse of zwitterionic intermediates, but trapping them would allow structural elaborations that are not currently available. To synthesize complex molecules in this manner, reactive electrophiles can be used to trap the zwitterionic intermediates. Here, we describe the use of imines, activated by chiral organocatalysts, and a highly efficient integrated rhodium and chiral Bronsted acid co-catalysed process to trap zwitterionic intermediates that have been proposed previously to undergo a formal C-H insertion reaction, allowing us to obtain polyfunctionalized indole and oxindole derivatives in a single step with excellent diastereoselectivity and enantioselectivity.

Three-component Mannich-type reaction of diazoacetates (I) and (VI) with carbamate (III) and imines (II) and (VII) in the presence of a chiral phosphoric acid—Rh catalyst provides access towards enantioenriched α-substituted α,β-diamino acid derivatives.

The total synthesis of hirsutellide A 1 was described. The linear hexadepsipeptide precursor 2 was synthesized in 45% yield from N-Boc-Me-Gly by three coupling reactions with DCC, HATU and BOP–Cl, respectively. Macrocyclization was successfully performed on the fully deprotected amino acid 14 with BOP–Cl in 15% yield and with FDDP in 22% yield.

Yuandong Ma1,2*, Yi Zheng1,2*, Xiaowei Zeng1-3*, Liqin Jiang4, Hongbo Chen1,2, Ranyi Liu5, Laiqiang Huang1,2, Lin Mei1,21School of Life Sciences, Tsinghua University, Beijing, 2Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, 3Materials and Environment Experimental Center, Department of Materials Science and Engineering, Qinhuangdao Branch, Northeastern University, Qinhuangdao, 4Insitute of Biomedical Engineering, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin, 5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this workBackground: The formulation of docetaxel available for clinical use (Taxotere®) contains a high concentration of polysorbate 80 (Tween 80). After incorporation of Tween 80 into poly-ε-caprolactone (PCL)-Tween 80 copolymer, the relative amount of Tween 80 should be decreased and the advantages of PCL and Tween 80 should be combined.Methods: A novel PCL-Tween 80 copolymer was synthesized from ε-caprolactone and Tween 80 in the presence of stannous octoate as a catalyst via ring opening polymerization. Two types of nanoparticle formulation were made from commercial PCL and a self-synthesized PCL-Tween 80 copolymer using a modified solvent extraction/evaporation method.Results: The nanoparticles were found by field emission scanning electron microscopy to have a spherical shape and be 200 nm in diameter. The copolymers could encapsulate 10% of the drug in the nanoparticles and release 34.9% of the encapsulated drug over 28 days. PCL-Tween 80 nanoparticles could be internalized into the cells and had higher cellular uptake than the PCL nanoparticles. The drug-loaded PCL-Tween 80 nanoparticles showed better in vitro cytotoxicity towards C6 cancer cells than commercial Taxotere at the same drug concentration.Conclusion: Nanoparticles using PCL-Tween 80 copolymer as drug delivery vehicles may have a promising outcome for cancer patients.Keywords: cancer chemotherapy, docetaxel, nanoparticles, PCL-Tween 80