One-pot synthesis of S-alkyl dithiocarbamates via the reaction of N-tosylhydrazones, carbon disulfide and amines.

A new, convenient and efficient transition metal-free synthesis of S-alkyl dithiocarbamates through one-pot reaction of N-tosylhydrazones, carbon disulfide and amines is reported. Tosylhydrazones derived from various aromatic and aliphatic ketones or aldehydes were tested and gave dithiocarbamates in good to excellent yields. The tosylhydrazones can be generated in situ without isolation, which provides a simpler one-pot method to synthesize dithiocarbamates via the reaction of carbonyl compounds, carbon disulfide and amines in the presence of 4-methylbenzenesulfonohydrazide.

Design, synthesis, biological activities and 3D-QSAR of new N,N'-diacylhydrazines containing 2,4-dichlorophenoxy moieties.

A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N'-diacylhydrazines were evaluated. The herbicidal activity results showed that most of these N,N'-diacyl-hydrazines showed excellent in vivo activities against Echinochloa crus-galli, Digitaria sanguinalis, Brassica napus, Amaranthus retroflerus. Most of them exhibited higher herbicidal activities against dicotyledonous weeds than monocotyledonous weeds. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this work.

Palladium-catalyzed intramolecular hydroamination of allenes coupled to aerobic alcohol oxidation.

Taking the air! A Pd(II)-catalyzed intramolecular hydroamination of allenes coupled to alcohol oxidation has been developed. This reaction is performed by using a nitrogen-based ligand under aerobic conditions, under which the molecular oxygen is used as the terminal oxidant for the reoxidation of Pd(0) species to complete the catalytic cycle.

The effect of stealth liposomes on pharmacokinetics, tissue distribution and anti-tumor activity of oridonin.

High-purity oridonin was isolated and identified from Rabdosia rubescens hemsl by preparative high-performance liquid chromatography (HPLC). Stealth liposomes of oridonin were prepared by thin-film ultrasonic dispersion using polyethylene glycol-distearoylphosphatidyleth-anolamine(PEG2000-DSPE) as the surface-coating material. A reversed-phase HPLC method was developed and validated to determine the concentrations of oridonin in the serum and tissues of mice. The tissue distribution and pharmacokinetics of oridonin stealth liposomes and oridonin solution in mice were investigated. The results showed that the distribution and pharmacokinetics of oridonin stealth liposomes in mice were changed as compared to the distribution and pharmacokinetics of oridonin solution. The levels of stealth liposomal oridonin in the heart tissues were reduced, while the levels of stealth liposomal oridonin in the blood were increased. The stealth liposomes were very effective at inhibiting the rate of solid tumor growth. The PEG2000-DSPE of liposomes prolonged the circulation time of oridonin in mouse blood, reduced accumulation in the reticuloendothelial system and increased the anti-tumor activity of oridonin.

Synthesis and analgesic activities of endomorphin-2 and its analogues.

Endomorphin-2 (1; H-Tyr-Pro-Phe-Phe-NH2; EM2) and its novel cyclic asparagine (cycloAsn) analogues, H-Tyr-cAsn(CHPh)-Phe-Phe-NH2 (2) and H-Tyr-cAsn(CHMe2)-Phe-Phe-NH2 (3), were synthesized via liquid-phase synthesis. The structures of the products and intermediates were characterized by IR, 1H-NMR, MS, and HR-MS analyses. The antinociceptive activity of EM2 and its cyclic asparagine analogues were assessed in AcOH-induced abdominal constriction tests in mice with i.p. injection. The results show that the antinociceptive activities of EM2 and its cyclic asparagine analogue 2 were higher than those of aspirine and meperidine. Analogue 2 was observed to be a stronger analgesic with dose-dependence than EM2. The test mice did not show any tendency to be addicted while administrated of analogue 2 repeatedly and regularly.

Dipeptide Surrogates Containing Asparagine-Derived Tetrahydropyrimidinones: Structure and Amide Rotomer Stereochemistry of a Proline Mimic.

Novel dipeptide surrogates Fmoc-Xaa-(cyclo)Asn-OBut are prepared from asparagine, aromatic aldehydes, and Fmoc-protected amino acid chlorides. Previous studies have focused on basic approaches to key synthetic intermediates containing the (cyclo)Asn fragment for polypeptide preparation. The synthesis of these systems has now been extended to electron-rich aromatic aldehydes, exemplified by p-anisaldehyde. One-dimensional nuclear Overhauser effect experiments confirm the trans configuration around the central secondary amide bond and the boat conformation of the pyrimidinone ring. Variable-temperature NMR at 500 MHz was employed both to obtain thermodynamic data on the cis-trans amide bond interconversion barrier and to probe for the presence of hydrogen bonding. Single-crystal X-ray analysis of Ac-d-Ala-(cyclo)Asn-NHMe shows a high degree of structural similarity to a known proline-containing dipeptide.

Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.

In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity.

Hypervalent iodine(III)-mediated benzannulation of enamines with alkynes for the synthesis of polysubstituted naphthalene derivatives.

A series of functionalized 1-amino-2-naphthalenecarboxylic acid derivatives were synthesized from enamines and alkynes via a benzannulation strategy mediated by iodosylbenzene and BF3·Et2O. The advantages of this novel benzannulation process include broad substrate scope, good functional group tolerance, and mild reaction conditions without the use of heavy metals.

Design, preparation, X-ray crystal structure, and reactivity of o-alkoxyphenyliodonium bis(methoxycarbonyl)methanide, a highly soluble carbene precursor.

The preparation, X-ray structure, and reactivity of new, highly soluble, and reactive iodonium ylides derived from malonate methyl ester and bearing an ortho substituent on the phenyl ring are reported. These new reagents show higher reactivity than common phenyliodonium ylides in the Rh-catalyzed cyclopropanation, C-H insertion, and transylidation reactions under homogeneous conditions.

New highly soluble dimedone-derived iodonium ylides: preparation, X-ray structure, and reaction with carbodiimide leading to oxazole derivatives.

Highly soluble dimedone-derived o-alkoxyphenyliodonium ylides have been prepared and characterized by single crystal X-ray diffraction. These new iodonium ylides are useful reagents for the preparation of oxazole derivatives by reaction with carbodiimides.