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Background The NU-FLASH trial demonstrated that febuxostat was more effective for hyperuricemia than allopurinol. This time, we compared these medications in patients with chronic kidney disease (CKD) from the NU-FLASH trial. Methods and results In the NU-FLASH trial, 141 cardiac surgery patients with hyperuricemia were randomized to a febuxostat group or an allopurinol group. This study analyzed 109 patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2, and also analyzed 87 patients with stage 3 CKD. The primary endpoint was the serum uric acid level. Secondary endpoints included serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and high-sensitivity C-reactive protein. Among patients with an eGFR ≤ 60 mL/min/1.73 m2, uric acid levels were significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward. The serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, and high-sensitivity C-reactive protein were also significantly lower in the febuxostat group. Similar results were obtained in the patients with stage 3 CKD. Conclusion In cardiac surgery patients with renal dysfunction, febuxostat reduced uric acid earlier than allopurinol, had a stronger renoprotective effect than allopurinol, and also had superior antioxidant and anti-inflammatory effects.

The 7-endo Friedel–Crafts cyclization of vinyloxiranes, which have a nitrogen atom at the linker between the aromatic ring and the epoxide, was found to proceed regio- and stereoselectively to afford polyfunctional tetrahydro-1-benzazepine and tetrahydro-2-benzazepine.

Formal synthesis of tautomycin, which inhibits type 1 and type 2A protein phosphatases, was achieved. Spiroketal diol 21 was synthesized from alcohol 2 or 11 . The regioselective enzymatic acetylation of 21 with the lipase ‘Amano PS’ gave monoacetate 23 in 90% yield, which was converted into Ichihara's intermediate 31 based on Julia coupling and Wittig homologation.

A new type of bis(free base porphyrin) 1 , in which two porphyrin units are attached to the 5,5′-positions of the 2,2′-biphenyldiol group, has been synthesized. It exhibits exciton-coupled bisignate circular dichroism (CD) spectra upon interaction with chiral amino alcohols. The chiral information from the stereogenic center of amino alcohols is introduced as a twist of the porphyrin units in 1 via hydrogen bonding interactions, detectable by the signal in the CD spectrum. Based on these findings, it is proposed that 1 should serve as a reporter unit of chiral sensor systems.

A new synthetic route of (−)-TAN1251A possessing an antimuscarinic activity was developed on the basis of alkylation of a trans-4-hydroxy- l -proline derivative and the subsequent construction of an azaspiro ring as key steps.

Upon treatment with CF3COOH at 70°C, trisubstituted-tetrahydropyrans, which were stereoselectively prepared from δ-lactones, were found to be converted into the corresponding 2,5-disubstituted-tetrahydrofurans stereospecifically via a phenonium ion. Furthermore, the stereocontrolled formal synthesis of pamamycin 607 was achieved based on the ether-ring transformation.

A novel construction of hydroazulenones using skeletal rearrangement of epoxy-hydroindan derivatives via alkoxy radical was developed. The reaction was also found to proceed without damage of acetal or olefin group.

To develop a potent and effective anti-HIV compound with a definite polyanionic structure, synthesis of oligotyrosine sulfates by oligomerization with simultaneous sulfation of tyrosine was tried. One component was successfully isolated from the mixture containing many products as its sodium salt (Y-ART-4) and was identified as the salt of nonatyrosine N- and O1-9-decasulfate, NaO3S-[Tyr(SO3Na)]9-ONa. Anti-HIV activity of Y-ART-4, determined from the protection it provided against HIV-induced cytopathic effects, was almost the same with that of dextran sulfate and curdlan sulfate.

Synthesis and evaluation of three Fmoc–phosphotyrosine derivatives with a phosphate group protected as N,N′-dialkyldiamide (alkyl = Prn, Pri, and Bui) were studied. All the derivatives were obtained as crystals, among which the Buiderivative (4c) was the best in ease of preparation and excellence in cleavage property. Solid phase synthesis of a methionine-containing peptide, H–Tyr(PO3H2)–Val–Pro–Met–Leu–OH, could be done without any problems.

Z-Tyr[P(O)(NHR) 2 ]-OBzl (R= n -Pr and i -Pr) were obtained by reactions of Z-Tyr-OBzl, lithiated with LDA, with N , N ′-dipropyl- or diisopropyl-phosphorodiamidic chloride. Fmoc derivatives, Fmoc-Tyr[P(O)(NHR) 2 ]-OH, were obtained from them as stable crystals. The PN bonds are stable toward 20% piperidine in DMF and were cleaved completely with 95% trifluoroacetic acid.

Synthesis and evaluation of three Fmoc–phosphotyrosine derivatives with a phosphate group protected as N,N′-dialkyldiamide (alkyl = Prn, Pri, and Bui) were studied. All the derivatives were obtained as crystals, among which the Buiderivative (4c) was the best in ease of preparation and excellence in cleavage property. Solid phase synthesis of a methionine-containing peptide, H–Tyr(PO3H2)–Val–Pro–Met–Leu–OH, could be done without any problems.

A novel construction of hydroazulenones using skeletal rearrangement of epoxy-hydroindan derivatives via alkoxy radical was developed. The reaction was also found to proceed without damage of acetal or olefin group.

15-Crown-5-appended metalloporphyrin causes a K(+)-driven self-organization to bind a bifunctional guest ditopically, thereby allowing the circular dichroism (CD) detection of chirality induced in the ensemble when chiral amines are employed as the guest; the chiroptical properties are discussed.

Synthesis of many potentially useful molecular units by chemists promotes the development of methods for constructing supramolecular architectures. Indeed, programmed supramolecular interactions play crucial roles in the preparation of well-defined nanoscale assemblies. This review highlights successful approaches in designing for specific functions systematically. The incorporation and synergistic communication of conformation-switchable segments into molecules bears great promise. Allostery, which is often observed in naturally occurring proteins, provides a hint for molecular manipulation. In supramolecular chemistry crown ethers can serve not only as substrate-binding sites but also as function-tuning sites. With the combination of synthetic versatility and well-tailored design, diverse capabilities (molecular recognition, catalytic properties, chirality, actuation, and so on) become possible at the molecular or mesoscopic level. The synthetic preparation of advanced molecular units allows the systems to become smarter, and promise nanosystems with programmable functions. This review considers mainly the use of crown ethers which act as anchoring as well as allosteric sites, from the standpoint of design for molecular manipulation. It also gives a brief discussion of recent progress in molecular manipulation, based on related systems. The "synthetic systems" described in the present review should contribute to not only to more elaborate "chemical systems", but also to the evolving field of "molecular machinery", that can utilize these systems.

In our program for developing chirality manipulation systems, we synthesized bis(zinc porphyrin) 1, with a dibenzodiaza-30-crown-10 as a linker unit. Two structural features were examined. The aza-crown segment exhibited an intermolecular interaction with the zinc(ii) of the porphyrin, capable of causing aggregation to form spherical nanostructures, as inferred by concentration-dependency of (1)H NMR as well as scanning electron microscopy (SEM) observation. We also consider the crown-based conformation flexibility, in which accommodated K(+) tunes the porphyrin orientation into the tweezers conformation, assisting chirality induction upon complexation with chiral diamine 2. The circular dichroism (CD) intensity change essentially reached a plateau at a [(1R,2R)-2] : [1] ratio of 2 : 1 for which a 45% enhancement in the amplitude of CD spectra was observed compared to the K(+)-free conditions. Use of the crown linker of is not limited to promoting chirality induction with diamines in the presence of K(+); chiroptical probing of unprotected amino acids (Lys, His, Trp, and Phe) using 1 was attained through liquid (1 in CH(2)Cl(2))-liquid (the amino acids in 1 N KOH) two-phase extraction. The amphiphilic properties of the crown segment, as well as the K(+)-assisted tweezers conformation, make it possible to explore a potent way to develop chirality sensors for amino acids in water.

Hydrophobic micropores created in the crystal lattice of a calix[4]arene–polyoxometalate hybrid (C2-PW) selectively accommodated heptane rather than the branched homologues. The sorption properties were tunable by slight modification of the calixarene unit, whereby the recognition of E–Z stereochemistry of 2-heptene was achieved.

The first rationalized crown ether–bis(porphyrin) conjugate with a large ring-based conformation flexiblity 1 has been synthesized; the achiral-to-chiral transformation upon complexation with chiral diamines is assisted by K+ accommodated in the crowned moiety, and it is possible to determine the chirality of carboxylates as potassium salts.

Stereoselective syntheses of optically active 2,5-dialkyltetrahydrofurans (8), (11) and (12), which correspond to a central moiety of pamamycin 607, have been achieved on the basis of lactone-ring transformation via a phenonium ion, intramolecular Friedel-Crafts reaction, oxidative decomposition of an aromatic ring and differentiation of two ester groups by a chemical or chemo-enzymatic method.