The thermal decomposition of 3-azido-4-benzylideneamino-s-triazoles

The synthesis and thermal decomposition of a series of 3-azido-4-benzylideneamino-s-triazoles are described. The decompositions resulted in a loss of nitrogen and intra-molecular cyclization at the carbon atom of the azomethine linkage to produce 1H-2-aryl-s-triazolo-[3,2-c]-s-triazoles.     

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.     

Agents for the treatment of overactive detrusor. II. Synthesis and inhibitory activity on detrusor contraction of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicarboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.     

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.     

Novel alkenylative cyclization using a ruthenium catalyst

Novel alkenylative cyclization of enyne was developed using Cp*RuCl(cod) under ethylene gas at room temperature.     

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.