We report dynamic self-assembly utilizing boronic ester formation with special emphasis on the following six points:  (1) two kinds of host molecule are constructed spontaneously with benzene or toluene as the guest molecule under neutral conditions simply by mixing a di(boronic acid) and a bis(1,2-diol) in methanol; (2) the precipitation process is essential for this selective preparation of host molecules; (3) recognition of the enantiomers of bis(1,2-diol) is achieved during host formation in this system; (4) it is possible to freeze or free the conversion between the two host molecules, thus enabling formation of complexes that cannot be prepared under thermodynamic conditions typical for such self-assembly; (5) naphthalene and triphenylene are even more efficient guest molecules in this system; and (6) almost complete separation of naphthalene and 1-methylnaphthalene is achieved utilizing this guest-induced precipitation process.

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Acyl CoA:monoacylglycerol acyltransferase-2 (MGAT2) has attracted interest as a novel target for the treatment of obesity and metabolic diseases. Starting from N-phenylbenzenesulfonamide derivative 1 with moderate potency for MGAT2 inhibition, we explored an effective location of the hydrophobic group at the 1-position to enhance MGAT2 inhibitory activity. Shifting the hydrophobic group to the adjacent position followed by introduction of a bicyclic central core to restrict the substituent orientation produced N-phenylindoline-5-sulfonamide derivative 10b, which displayed much improved potency, with an IC50 value of 1.0 nM. This compound also exhibited excellent selectivity (greater than 30,000-fold) against related acyltransferases (MGAT3, DGAT1, DGAT2, and ACAT1). Subsequent optimization efforts were directed toward improving pharmacokinetic profiles, which resulted in the identification of 5-[(2,4-difluorophenyl)sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-indole-1-carboxamide (24d) endowed with potent MGAT2 inhibitory activity (IC50 = 3.4 nM) and high oral bioavailability (F = 52%, mouse). In a mouse oral fat tolerance test, oral administration of this compound effectively suppressed the elevation of plasma triacylglycerol levels.

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Guest-induced self-assembly of a macrocyclic boronic ester containing photochromic diarylethene units is realized and this macrocycle showed high quantum yield of photoisomerization due to favourable conformational constraint.