Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity

Previously, we reported that vitamin K3 (VK3), but not VK1 or VK2 (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS). Moreover, MK-2 was found to inhibit the action of nuclear factor (NF)-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates

Visualization of Molecular Length of α, ω-Diamines and Temperature by a Receptor Based on Phenolphthalein and Crown Ether (SYNTHETIC ORGANIC CHEMISTRY-Fine Organic Synthesis)

The hybrid molecule 1 consisting of phenolphthalein and crown ether moieties can discriminate the chain length of the α,ω-diamines by color change, while 2 can not. Thus, it is suggested that two crown ether part are necessary to visualize the chain length by the color. The pink color faded at 50 °C and reappeared at 20 °C, which could repeated more than 10 times

Synthesis and Structural Characterization of Natural Benzofuranoids

The synthesis of ustusoranes A, B, and E, pergillin, dihydropergillin, (±)-penicisochroman A, and (−)-brassicadiol, starting from optically active (<i>R</i>)-benzolactone, is described. The synthesis of ustusoranes A and E established the absolute configurations of these natural products. The synthesis of pergillin and (±)-penicisochroman A led to the structural revision of aspergiones E and F. This study clearly indicates that (<i>R</i>)-benzolactone is a potential intermediate in the synthesis of natural benzofuranoids

Ester-Amide Exchange Reactions Using 2-Pyridone derivatives as Tautomeric Catalysts

The application of 2-pyridone as a tautomeric catalyst for ester-amide exchange reactions was investigated. This compound was found to be most effective at accelerating these reactions when 4-nitrophenyl acetate was used as an acylating agent in toluene. Primary amines without branching at the α-position were determined to be the most suitable substrates. Various 2-pyridone derivatives having an electron-donating group at the 5-position (including methoxy and pirrolidino groups) exhibited superior performance. Acylation reactions of mixtures of primary and secondary amines preferentially acylated the latter compounds in the absence of a catalyst or with N,N-dimethylaminopyridine (DMAP) as the catalyst, whereas primary amines were acylated in the case that a 2-pyridone derivative with a pirrolidino group was employed. The reaction mechanism associated with this preferential acylation process was evaluated and is discussed herein

Bioinspired Synthesis of Juglorubin from Juglomycin C

In this paper, the synthesis of juglorubin, a natural red dye, from juglomycin C, a plausible biogenetic precursor, is reported. Sequential intermolecular and intramolecular Michael additions of juglomycin C, oxidation, and skeletal transformation proceeded in phosphate buffer to afford an undehydrated derivative of juglorubin. Subsequent dehydration of the secondary alcohol afforded juglorubin. The one-pot synthesis of juglorubin from juglomycin C was also achieved. The photophysical properties of synthetic juglorubin and its derivatives were evaluated