Development of a Water Soluble Self-assembling Analogue of Vizantin.

Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, has been developed as a safe immunostimulator on the basis of a structure-activity relationship study with trehalose 6,6'-dicorynomycolate. Our recent study indicated that vizantin acts as an effective Toll-like receptor-4 (TLR4) partial agonist to reduce the lethality of an immune shock caused by lipopolysaccharide (LPS). However, because vizantin has low solubility in water, the aqueous solution used in in vivo assay systems settles out in tens of minutes.

Chemical Hybridization of Vizantin and Lipid A to Generate a Novel LPS Antagonist.

Lipopolysaccharide (LPS) antagonists have attracted considerable interest as promising candidates for the treatment of severe sepsis triggered by Gram-negative bacteria. In this article, we describe the development of a novel LPS antagonist based on chemical hybridization of vizantin and the hydrophobic molecular unit of LPS (lipid A). Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, was designed as an immunostimulator from a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM).

Vizantin inhibits endotoxin-mediated immune responses via the TLR 4/MD-2 complex.

Vizantin has immunostimulating properties and anticancer activity. In this study, we investigated the molecular mechanism of immune activation by vizantin. THP-1 cells treated with small interfering RNA for TLR-4 abolished vizantin-induced macrophage activation processes such as chemokine release.

Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.

Trehalose 6,6'-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties.

Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6,6'-dicorynomycolate.

Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.

Catalytic activation of the leaving group in the S(N)2 reaction.

A novel catalytic activation of the leaving group in the S(N)2 reaction is achieved as an extension of our mercuric triflate-catalyzed reactions. Derivatives of anilinoethyl 4-pentynoate reacted smoothly with catalytic amounts of Hg(OTf)(2) to give indoline derivatives in excellent yield with efficient catalytic turnovers under very mild conditions. The reaction of optically pure secondary alcohol derivatives resulted in inversion of stereochemistry, which is a definitive feature of the S(N)2 reaction.