Double catalytic enantioselective Michael addition reactions of tertiary nucleophile precursors—tertiary/quaternary and quaternary/quaternary carbon–carbon bond formations

Enantioselective Michael addition reactions of tertiary nucleophile precursors, such as substituted malononitriles and cyclic 1,3-diketones, can be successfully activated by the metal complexes derived from R,R-DBFOX/Ph chiral ligand and cationic metal salts. With this method, the enantioselective tertiary/quaternary and quaternary/quaternary carbon–carbon bond formations can be achieved. Use of alcohol solvents is essential for the success, and ,β-unsaturated amides of 3,5-dimethylpyrazole are much better acceptors than those of 2-oxazolidinone.     

pH-regulated formation of amyloid-like beta-sheet assemblies from polyglutamate grafted polyallylamine

A novel artificial protein with simple primary structure, poly(gamma-methyl-L-glutamate)-grafted polyallylamine, has been prepared and the resultant peptide has shown a unique property of pH-regulated conformation and morphology.     

Synthetic approach toward antibiotic tunicamycins — VI total synthesis of tunicamycins

Tunicamycins and their eight analogs have been synthesized by condensation of a N-acetyl-D-glucosamine derivative and an anomeric chloride of tunicaminyl uracil, followed by deprotections and N-acylation.     

Determination of total dietary fiber in selected foods containing resistant maltodextrin by enzymatic-gravimetric method and liquid chromatography: collaborative study

A method was developed for determination of total dietary fiber (TDF) in foods containing resistant maltodextrin (RMD) which includes nondigestible carbohydrates that are not fully recovered as dietary fiber by conventional TDF methods such as AOAC 985.29 or 991.43. Because the average molecular weight (MW) of RMD is 2000 daltons, lower MW soluble dietary fiber components do not precipitate in 78% ethanol; therefore, RMD is not completely quantitated as dietary fiber by current AOAC methods. The accuracy and precision of the method was evaluated through an AOAC collaborative study. Ten laboratories participated and assayed 12 test portions (6 blind duplicates) containing RMD. The 6 test pairs ranged from 1.5 to 100% RMD. The method consisted of the following steps: (1) The insoluble dietary fiber (IDF) and high MW soluble dietary fiber (HMWSDF) were determined by AOAC 985.29. (2) Ion exchange resins were used to remove salts and proteins contained in the AOAC 985.29 filtrates (including ethanol and acetone). (3) The amount of low MWRMD (LMWRMD) in the filtrates were determined by liquid chromatography. (4) The TDF was calculated by summation of the IDF, HMWSDF, and LMWRMD fractions having nondigestible carbohydrates with a degree of polymerization of 3 and higher. Repeatability standard deviations (RSDr) were 1.33-7.46%, calculated by including outliers, and 1.33-6.10%, calculated by not including outliers. Reproducibility standard deviations (RSDR) were 2.48-9.39%, calculated by including outliers, and 1.79-9.39%, calculated by not including outliers. This method is recommended for adoption as Official First Action.     

Rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones: involvement of an unexpected reaction cascade

A rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones has been developed under mild conditions. Considering the ease of preparation of these propargyl alcohols (terminal alkynes + aromatic aldehydes), this method provides a new way of constructing indanones with high efficiency. By the mechanistic investigations using deuterium-labeled substrates, it has also been demonstrated that the reaction goes through an unexpected cascade, with a 1,4-hydrogen shift being the turnover-limiting step of the catalytic cycle.     

Further studies on the reaction of amines and proteins with 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole

The reaction of glycine with NBD-F (4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole) is investigated to establish conditions that provide a high formation rate of NBD-glycine and a low hydrolysis rate of the reagent. The reaction rate increases with higher temperature, larger contents of organic solvent and a sodium borate buffer. The use of borate buffer decreases ther ate of hydrolysis of the reagent. For low-molecular-weight amines, condition for a suitable liquid chromatographic postcolumn reactor include a high content of acetonitrile and 0.1 M sodium borate (pH 8.0–8.5). For proteins, separated by molecular-exclusion chromatography, water is needed for sensitive reactions. Suitable postcolumn reactor conditions include borate buffer (pH 7.9) containing 0.1 M potassium chloride, a 0.02% (w/v) NBD-F solution in acetonitrile with reaction at 50°C for about 45 s. The detection limits for human serum albumin, β-lactoglobulin and myoglobin are 6.6 pmol, 8.4 pmol and 11 pmol, respectively.     

Highly efficient, one-step macrocyclizations assisted by the folding and preorganization of precursor oligomers

Highly efficient, one-step macrocyclizations leading to the formation of macrocyclic hexa(aramides) in high yields (69-82%) are described. The one-step macrocyclizations were facilitated by the preorganization or folding of the backbones of uncyclized precursors in the course of macrocyclization. The preorganization of backbones was achieved by the presence of localized three-centered hydrogen bonds that were adopted in the design of a class of closely related, backbone-rigidified foldamers. The macrocyclization involved reactions between diacid chloride 1 and diamine 2. The crude reaction mixtures and products were conveniently examined by mass spectrometric method (MALDI-TOF). Compared to most traditional one-step macrocyclizations that usually require high dilution conditions and often lead to very low overall yields of the desired products, cyclic hexamers 3 were obtained as the overwhelmingly major product under a variety of reaction conditions, suggesting the generality of this approach.     

A lithiation approach to cordycepin analogues variously substituted at the C-8 position

Several 8-substituted cordycepins were prepared via LDA lithiation of 2′,5′-bis-O-(t-butyldimethylsilyl)-cordycepin and successive reactions of its C-8 lithiated species with various types of electrophiles. Wittig reaction of the 8-formyl derivative was also examined.     

Improved assay for catechol-O-methyltransferase activity utilizing norepinephrine as an enzymatic substrate and reversed-phase high-performance liquid chromatography with fluorescence detection

We have previously established a rapid catechol-O-methyltransferase (COMT) assay using norepinephrine (NE) as a natural substrate and flow-injection analysis. In this study, the method is improved for screening of COMT inhibitors or activators using reversed-phase high-performance liquid chromatographic separation with fluorescence detection. The excess substrate, NE, was removed by the addition of borate in the eluent for HPLC to make an ionic complex with NE, which was eluted faster than the enzymatic product, normetanephrine. The method had good precision and accuracy, and was able to assay one sample in 5 min, showing the usability for screening of COMT inhibitors or activators.