Synthesis and Evaluation of DHMEQ Derivatives with Tertiary Hydroxyl Group Instead of Secondary Hydroxyl Group.

Newly synthesized dehydroxymethyl epoxyquinomycin (DHMEQ) derivatives 6-9, which contain a tertiary hydroxyl group instead of the original secondary hydroxyl group, showed improved solubility in alcohol while maintaining their inhibitory activity against nitric oxide (NO) production, which is used as an indicator of nuclear factor-kappa B (NF-κB) inhibitory activity. We also synthesized a derivative 5 having a cyclopropane ring and a tertiary hydroxyl group and examined its inhibitory activity against NO production. Although it reacted with a nucleophile in a flask, it did not inhibit NO production. The change from a secondary hydroxyl group to a tertiary hydroxyl group contributed to improve the solubility of the compounds while retaining NO inhibitory activity, but had no effect on improving the activity of the cyclopropane form. Compounds in which the secondary hydroxyl group of DHMEQ was converted to a tertiary hydroxyl group would be excellent NF-κB inhibitor candidates because their solubility is improved without decreasing NO inhibitory activity.

Visible-light-induced superhydrophilicity of crystallized WO3 thin films fabricated by using a newly isolated W6+ complex salt of citric acid.

Transparent tungsten trioxide thin films, which demonstrated visible-light (Vis-light)-induced superhydrophilicity, with thicknesses of 100-120 nm, adhesion strengths greater than 49 MPa, bandgap energies of 2.8-2.9 eV, and haze values of 0.4-0.5%, were fabricated using a solution-based process on quartz glass substrates. The precursor solution was prepared by dissolving a W6+ complex salt isolated from a reacted solution of tungstic acid, citric acid, and dibutylamine in H2O, in ethanol. By heating the spin-coated films in air for 30 min at temperatures higher than 500 °C, crystallized WO3 thin films were obtained. The O/W atomic ratio was evaluated to be 2.90, based on the peak area analysis of X-ray photoelectron spectroscopy spectra of the thin-film surfaces, indicating the co-presence of W5+ ions. The water contact angle on film surfaces, which was approximately 25° prior to light irradiation, decreased to less than 10° upon irradiation with 0.06 mW cm-2 Vis-light for only 20 min at 20-25 °C and a relative humidity (RH) of 40-50%. By comparing the contact angle changes at RH values of 20-25%, it was revealed that the interaction between ambient water molecules and the partially O-deficient WO3 thin films plays an important role in achieving photoinduced superhydrophilicity.

Reductive SN 2' Reaction of Epoxydienoate with Borane and its Application to the Synthesis and Structural Revision of an Antitumor Active Torrubiellutin Analogue.

A reductive SN 2' reaction of epoxydienoates and epoxyenoates with borane was developed to afford skipped dienoates and unconjugated enoates with trisubstituted Z-alkene linked to asymmetric centers on one side or both sides. This reaction was successfully applied to the alternative synthesis of an antitumor active artificial analogue of torrubiellutin C. A geometric isomer for α,ß-unsaturated amide of the artificial analogue was also synthesized. These syntheses clarified the true structure of the antitumor active artificial analogue of torrubiellutin C.

Total Synthesis of Sekothrixide Strategically Utilizing Regioselective Coupling of TMS-Protected Epoxy sec-Alcohol with Gilman Reagent.

A new efficient synthesis of sekothrixide was established on the basis of our developed regioselective coupling of epoxy sec-alcohol with Gilman reagent guided by a TMS group. The new synthetic route allowed an overall yield of 6.3% (26 steps) from optically active 3-silyloxy-2-methylaldehyde.

Syntheses of Polycyclic Tetrahydrofurans by Cascade Reactions Consisting of Five-Membered Ring Selective Prins Cyclization and Friedel-Crafts Cyclization.

A novel cascade reaction consisting of a five-membered ring selective Prins cyclization and a subsequent Friedel-Crafts cyclization is reported. Treatment of homocinnamyl alcohols and aromatic aldehydes with BF3·OEt2 in CH2Cl2 afforded hydrocyclopentafurans. Also hydrocyclopentafurans underwent the same cascade reaction after its furan ring cleavage upon treatment with BF3·OEt2 at room temperature. Various combinations of hydropentafurans and aromatic aldehydes or indole aldehydes permitted divergent synthesis of diquinane-furans stuck in aromatic rings.

Selective Mono-reduction of Pyrrole-2,5 and 2,4-Dicarboxylates.

Pyrrole-2,5-dicarboxylates were rapidly and selectively reduced to the corresponding mono-alcohol using 3 eq of diisobutylaluminum hydride at 0°C. Pyrrole-2,4-dicarboxylate showed the same reactivity; however, the selectivity decreased with pyrrole-3,4-dicarboxylate. When the nitrogen atom of the pyrrole-2,5-dicarboxylate is protected with a benzyl group, selective mono-reduction does not occur. Considering that furan-2,5-dicarboxylates did not give the corresponding mono-alcohol under the same conditions, the unprotected nitrogen atom of pyrrole apparently plays an important role in this selective mono-reduction.

Total synthesis and structural revision of sekothrixide.

The first total synthesis of 14-membered macrolide sekothrixide and the originally proposed structure are reported. Seven contiguous asymmetric centers in the side chain were constructed using ring-openings of several kinds of epoxide. Assembly of the left segment and right segment was performed on the basis of the RCM reaction to generate 14-membered lactones having an E-trisubstituted olefin. These synthetic results led to a revision of C4, C6, and C8 stereochemistry in the structure of natural sekothrixide.

Synthesis of 1-(4-aminobutyl)-2-iminoimidazolidin-4-one aimed at preparation of a creatinine-specific antibody.

For the purpose of obtaining a creatinine-specific antibody, a creatinine derivative with 4-aminobutyl, which was served as a linker for preparing the creatinine-bovine serum albumin (BSA) conjugate, was synthesized from 4-benzylaminobutan-1-ol in 8 steps. Production of anti-creatinine antibodies was observed in two rabbits using the creatinine-BSA conjugate, although their titer was rather low.

Synthesis and evaluation of a cyclopropane derivative of DHMEQ.

Dehydroxymethylepoxyquinomycin (DHMEQ, 1) is well known to inhibit nuclear factor-kappa B (NF-κB), which is closely associated with immune, inflammatory, and apoptotic processes as an inducible transcription factor. The inhibitory effect seems to be the result of the ring opening of an epoxide of 1 with Cys(38) of p65. We have synthesized an analog 4 containing a cyclopropanated quinol skeleton and examined its ability to inhibit NF-κB. Surprisingly, 4 showed no remarkable NF-κB inhibitory activity as determined through expression of cyclooxygenase-2 (COX-2) in an RAW264.7 macrophage cell line.

Synthetic studies of the lichen macrolide lepranthin. Stereoselective synthesis of the diolide framework based on regioselective epoxide-opening reactions.

Stereoselective synthesis of the 16-membered diolide 27, a fully functionalized congener of lepranthin (1), is described. The requisite five asymmetric carbon centers in monomer 23 were constructed in a highly stereoselective manner by using different epoxide-opening reactions of α,ß-unsaturated γ,δ-epoxy esters and epoxy alcohol derivatives as the key steps. The monomer 23 was successfully transformed into the MOM protected diolide 27 by Yamaguchi macrolactonization.

New entry for synthesis of N-acylhydrazones, pyridazinones, and 1,3,4-oxadiazin-6-ones from alpha-amino acid esters.

Versatile electrophiles N-acylhydrazones are synthesized via diazotization, reduction, and acylation of alpha-amino acid esters. Reduction of diazo esters with L-selectride or tributylphosphine affords the corresponding hydrazones in good yields. Both reducing agents give anti-hydrazones as the major product although the reactivity of each reductant is slightly different. The resulting hydrazones are acylated to give N-acylhydrazones, which are subjected to further reactions to give 1,3,4-oxadiazin-6-ones that serve as useful synthetic intermediates for the Diels-Alder reaction.

Synthesis and evaluation of fluorogenic reagents for simultaneous detection of peptides and proteins by HPLC in two different samples.

To find the pairs of fluorogenic reagents having similar retention times in HPLC but with different fluorescent characteristics, six fluorogenic reagents bearing benzoxadiazole or benzoselenadiazole skeletons were synthesized. The resultant derivatives obtained from the reaction of peptides and proteins with reagents which have a benzoselenadiazole skeleton showed different fluorescence characteristics from those with a benzoxadiazole skeleton. Since each corresponding derivatives of trypsin inhibitor and BSA with DAABD-Cl and 7-fluoro-N-[2-(diethylamino)ethyl]-2,1,3-benzoselenadiazole-4-sulfonamide (DEAEABSeD-F) have similar retention times, the pair of reagents was adopted for the sensitive simultaneous detection of proteins in two different samples. When the soluble fraction of mouse hippocampus was divided into the two samples (A and B), each was reacted with DEAEABSeD-F for A and DAABD-Cl for B, respectively. The two reaction solutions were combined and subjected to HPLC analysis with two fluorescent detectors in series (excitation and emission at different wavelengths for A and B, respectively). The resultant two chromatograms had quite similar patterns for each other. The new pair of fluorogenic reagents (DAABD-Cl and DEAEABSeD-F) would be applicable to proteomics studies using the previously reported FD-LC-MS/MS method.