Three-Component Ring-Expansion Reaction of Indoles Leading to Synthesis of Pyrrolo[2,3-c]quinolines.

Herein, we have developed an atom- and step-economic three-component cascade reaction that enables a modular platform for the synthesis of pyrrolo[2,3-c]quinoline compounds through ring-expansion/cyclization by way of novel N1-C2 cleavage of indoles. The metal-free catalytic system exhibits a broad functional group tolerance.

Three-Component Synthesis of Dibenzoxazepinamines and Dibenzothiazepinamines under Transition-Metal-Free Conditions.

A convenient and efficient strategy for the synthesis of dibenzoxazepinamines and dibenzothiazepinamines has been developed. This three-component approach started from 2-nitrobenzaldehydes, 2-aminophenols, and methoxyammonium chlorides under metal-free conditions. The protocol has the advantages of readily available starting materials, simple and facile conditions, gram-scale synthesis, and broad substrate scope, providing an efficient and practical strategy for the preparation of potential drug-active dibenzoxazepinamines and dibenzothiazepinamines in one pot.

Acid-catalyzed three-component addition of carbonyl compounds with 1,2,3-triazoles and indoles.

A facile and efficient acid-catalyzed three-component reaction of indoles, 1-tosyl-1,2,3-triazoles and carbonyl compounds has been developed. The use of TsOH with a small amount of water significantly promoted the reaction yield. This method provided a general and one-pot approach for the synthesis of structurally diverse C3-alkylated indole derivatives. The alkylation exclusively occurred at the N2 position of triazoles. Various functional groups were tolerated under the optimized simple reaction conditions.

The activation effects of fucoidan from sea cucumber Stichopus chloronotus on RAW264.7 cells via TLR2/4-NF-κB pathway and its structure-activity relationship.

Sea cucumber Stichopus chloronotus is a traditional tonic food with high nutritive value in Southern China. Fucoidan from sea cucumber Stichopus chloronotus (Fuc-Sc) is its main bio-active polysaccharide, the immune-activation effects of which have been fully investigated on RAW264.7 cells in the present study. The results indicated that Fuc-Sc could stimulate the RAW264.7 cells by promoting the production of NO, TNF-α, IL-6 and IL-10. Western blot and RT-PCR analysis revealed that TLR4 and TLR2 were involved in the recognition of Fuc-Sc and activation of downstream NF-κB signal pathway. Moreover, the chemical structure parameter molecular weight showed obvious impact on the stimulation effects of Fuc-Sc on NO production. Degraded product of Fuc-Sc with weight average molecular weight of 113.1 × 104 Da exhibited higher activities than that of intact Fuc-Sc, suggesting the existent of optimum chain length to exert its highest activities. Taken together, Fuc-Sc exerted its immunostimulating activity via TLR2/4 activation of NF-κB pathway and showed potentials to be a good immunoadjuvant.

Immunomodulatory effects of fucosylated chondroitin sulfate from Stichopus chloronotus on RAW 264.7 cells.

Sea cucumbers were nutritional food and traditional Chinese medicine. In this study, fucosylated chondroitin sulfate from sea cucumber Stichopus chloronotus (fCS-Sc), a potential anticoagulant agent and immunological adjuvant, was investigated for its immune activation effects on RAW 264.7 macrophage for the first time. The results indicated that fCS-Sc could significantly promote the proliferation, the pinocytic activity of RAW 264.7 cells, and the production of NO, TNF-α, IL-1ß, and IL-6. The fluorescence labeling assay indicated that fCS-Sc could bind to the macrophage. Moreover, the specific pattern recognition receptor inhibition assays showed that toll-like receptor 4 (TLR4) and TLR2 were involved in the recognition of fCS-Sc. Western blot assays indicated that fCS-Sc could induce degradation of cytoplasm IκB-α, and promotion of NF-κB p65 subunit translocation to nucleus, leading to a functional improvement of macrophage through NF-κB pathway. The results suggested that fCS-Sc might served as a promising candidate of immunomodulator.

Structure characterization, antioxidant and immunoregulatory properties of a novel fucoidan from the sea cucumber Stichopus chloronotus.

The detailed chemical structure and chain conformation of a novel fucoidan from the sea cucumber Stichopus chloronotus (Fuc-Sc) were investigated by HPLC, IR, NMR spectroscopy and multi-angle light scattering. It mainly consisted of l-fucose and sulfate esters at mole ratio of 1.0:1.3 and contained a →3)-α-l-fucose-2S-(1→ linear backbone. Besides, the chain conformation parameters αη (0.658 ± 0.001) and αh (0.612 ± 0.002) indicated that Fuc-Sc exhibited a random coil conformation in PBS. The worm-like cylinder model parameters ML (526 g/mol•nm) and q (6.9 nm) confirmed that Fuc-Sc adopted a flexible chain. Fuc-Sc possessed negative charges and good thermal stability. Moreover, Fuc-Sc showed significant inhibition of lipid peroxidation and obvious activation effects on RAW 264.7 cells by promoting their proliferation and the production of NO and TNF-α. The present study facilitated further understanding of the structure-activity relationship of Fuc-Sc and its application in food and pharmacy industries.