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Direct catalytic asymmetric Michael addition reactions of ketones to nitroolefins using newly developed chiral pyrrolidine-pyridine conjugate bases as catalysts are described. The desired 1,4-adducts are obtained in excellent yields with high enantio- and diastereoselectivities.

A dehydration of fructose in the water/methyl isobuthyl ketone (MIBK) biphasic system can yield 5hydroxymethylfurfural (HMF) to be successfully extracted into the organic MIBK phase. The HMF production and yield in MIBK phase was discussed by using a simplified model taking into consideration of the slug flow. The extraction resistance of HMF across the interface between water and MIBK depended on the line velocity and the flow rate ratio. It was likely that the velocity field generated in the slug flow contributed to an increase in the mass transfer of HMF.

Starting from a previously reported RORγ inhibitor (1), successive efforts to improve in vivo potency were continued. Introduction of metabolically beneficial motifs in conjunction with scaffold hopping was examined, resulting in discovery of the second generation RORγ inhibitor composed of a 4-(isoxazol-3-yl)­butanoic acid scaffold (24). Compound 24 achieved a 10-fold improvement in in vivo potency in a mouse CD3 challenge model along with significant anti-inflammatory effects in a mouse dermatitis model.

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Most anti-cancer drug screening assays are currently performed in two dimensions, on flat, rigid surfaces. However, there are increasing indications that threedimensional (3D) platforms provide a more realistic setting to investigate accurate morphology, growth, and sensitivity of tumor cells to chemical factors. Moreover, interstitial flow plays a pivotal role in tumor growth. Here, we present a microfluidic 3D platform to investigate behaviors of tumor cells in flow conditions with anti-migratory compounds. Our results show that interstitial flow and its direction have significant impact on migration and growth of hepatocellular carcinoma cell lines such as HepG2 and HLE. In particular, HepG2/HLE cells tend to migrate against interstitial flow, and their growth increases in interstitial flow conditions regardless of the flow direction. Furthermore, this migratory activity of HepG2 cells is enhanced when they are co-cultured with human umbilical vein endothelial cells. We also found that migration activity of HepG2 cells attenuates under hypoxic conditions. In addition, the effect of Artemisinin, an antimigratory compound, on HepG2 cells was quantitatively analyzed. The microfluidic 3D platform described here is useful to investigate more accurately the effect of antimigratory drugs on tumor cells and the critical influence of interstitial flow than 2D culture models.

The clarification of the partition property of substrates in a water / organic biphasic system is useful in the development of a reaction / separation process for value-added materials, especially under high temperature and pressure conditions. In this study, the water / methyl isobuthyl ketone (MIBK) biphasic system was investigated under various temperatures (25 -190 o C) at 10 MPa. The partitioning behavior of substrates such as furfural derivatives, amino acids, and saccharides, depended on the temperature and the flow rate ratio of MIBK to the water phase. The scale of hydrophobicity (HF) of the water / MIBK biphasic system to determine the partitioning behavior of substrates was estimated based on the partitioning behavior of amino acids. The HF value for the water / MIBK phase flow system of was greater than that for the batch system and comparable to that for conventional aqueous two-phase systems such as polyethylene glycol / dextran and liposome membrane systems. It was probably because an increase of the surface-to-volume ratio and the vortex field in the slug flow contributed to the mass transfer of substrates and their distribution.