Development of a high-performance liquid chromatographic glycated albumin assay using finger-prick blood samples.

BACKGROUND: Home blood glucose monitoring can be effective for the self-management of diabetic patients. Hemoglobin A1c (HbA1c) is a widely used marker that reflects the average blood glucose within 1-2 months but does not sensitively respond to behavioral changes. Self-monitoring of blood glucose, continuous glucose monitoring, and flush glucose monitoring are sensitive; however, the cost and invasiveness of these tests prevent their widespread use. We focused on glycated albumin (GA), which reflects the average blood glucose levels over 1-2 weeks, and established a GA measurement method for self-sampling, finger-prick blood, which may be submitted for testing through postal service to receive weekly results. METHODS: A high-performance liquid chromatography assay was established to measure GA levels in finger-prick blood samples from 103 diabetic patients and the results were compared with venous blood measurements using an enzymatic method. Furthermore, conditions for sending blood samples by mail were evaluated. Under these conditions, samples from 27 healthy and 32 patient volunteers sent through postal service were compared with samples stored in the laboratory. RESULTS: GA levels were measured in samples containing > 20 µg albumin, which resulted in a CV less than 0.3%. The correlation between the GA levels of finger-prick blood measured using HPLC and the GA levels of venous blood measured using the enzymatic method was R2 = 0.988 with the slope âˆ¼ 1.0, suggesting that the two were nearly equivalent. GA levels were stable for four days at 30 °C and two days at 37 °C. Mail-delivered samples exhibited a high correlation with samples that were not sent (R2 > 0.99). CONCLUSIONS: We established a method to measure GA levels in self-sampled, finger-prick blood sent through postal service in Japan. The method is applicable for weekly feedback of GA levels, which is potentially useful for motivating behavioral changes. In addition to markers such as HbA1c and blood glucose, GA can be used as a marker for assessing dietary and physical activities. This study highlighted the importance of GA monitoring by developing a suitable measurement method for weekly monitoring of GA levels.

5-Position-selective C-H trifluoromethylation of 8-aminoquinoline derivatives.

We developed a copper-catalyzed 5-position-selective C-H trifluoromethylation of 8-aminoquinoline derivatives. The reaction proceeded with high functional group tolerance under mild conditions. In the case of quinolines with an amide, carbamate, urea, or sulfonamide group at the 8-position of quinoline moieties, a radical scavenger experiment indicated that the reaction proceeded via a radical pathway. The protecting group of an 8-amidoquinoline derivative could be removed by hydrolysis. On the other hand, the trifluoromethylation of 8-aminoquinolines was also promoted by other Lewis acids as well as a copper catalyst and proceeded even in the presence of a radical scavenger. These results indicated that the trifluoromethylation of 8-aminoquinolines proceeded via a Friedel-Crafts-type reaction. Interestingly, the copper salt works as either a catalyst for the formation of a CF3 radical or a Lewis acid to promote a Friedel-Crafts-type reaction, depending on the substrate.

A meta-selective C-H borylation directed by a secondary interaction between ligand and substrate.

Regioselective C-H bond transformations are potentially the most efficient method for the synthesis of organic molecules. However, the presence of many C-H bonds in organic molecules and the high activation barrier for these reactions make these transformations difficult. Directing groups in the reaction substrate are often used to control regioselectivity, which has been especially successful for the ortho-selective functionalization of aromatic substrates. Here, we describe an iridium-catalysed meta-selective C-H borylation of aromatic compounds using a newly designed catalytic system. The bipyridine-derived ligand that binds iridium contains a pendant urea moiety. A secondary interaction between this urea and a hydrogen-bond acceptor in the substrate places the iridium in close proximity to the meta-C-H bond and thus controls the regioselectivity. (1)H NMR studies and control experiments support the participation of hydrogen bonds in inducing regioselectivity. Reversible direction of the catalyst through hydrogen bonds is a versatile concept for regioselective C-H transformations.

Rhenium-catalyzed regio- and stereoselective synthesis of γ-thio-α,ß-unsaturated ketones via insertion of terminal alkynes into the C-S bond.

The reaction of α-thioketones and alkynes in the presence of a rhenium catalyst, [HRe(CO)(4)](n), gave γ-thio-α,ß-unsaturated ketones in excellent yields. The alkynes were inserted into the carbon-sulfur bond of the α-thioketones, and isomerization of a double bond provided the products with high regio- and stereoselectivities. This reaction also proceeded in an intramolecular fashion.

Rhenium-catalyzed regio- and stereoselective addition of two carbon units to terminal alkynes via carbon-carbon bond cleavage of ß-keto sulfones.

Treatment of ß-keto sulfones with terminal alkynes gave unsaturated δ-keto sulfones in good to excellent yields under rhenium catalysis. In this reaction, the insertion of the alkynes into the nonstrained carbon-carbon single bond between the α- and ß-positions of the ß-keto sulfones proceeded smoothly, and (Z)-isomers were produced with high regio- and stereoselectivities.

Iron-catalyzed synthesis of glycine derivatives via carbon-nitrogen bond cleavage using diazoacetate.

Treatment of tertiary amines with diazoacetate in the presence of a catalytic amount of an iron salt, FeCl(3), in ethanol gave glycine derivatives. In this reaction, a carbon-nitrogen single bond of the amine was cleaved.

Rhenium- and manganese-catalyzed synthesis of aromatic compounds from 1,3-dicarbonyl compounds and alkynes.

We have succeeded in the development of three approaches to the synthesis of aromatic compounds from 1,3-dicarbonyl compounds and alkynes. The first approach is a manganese-catalyzed [2+2+2] cycloaddition between 1,3-dicarbonyl compounds, which have no substituents at the active methylene moiety, and terminal alkynes. This reaction proceeds with high regioselectivity when aryl acetylenes are employed as the alkyne component. The second approach is a rhenium- or manganese-catalyzed formal [2+1+2+1] cycloaddition between beta-keto esters and two kinds of alkynes. In this reaction, the aromatic compounds are obtained by the following reaction sequence: (1) insertion of the first alkyne into a carbon-carbon single bond of a beta-keto ester, (2) formation of 2-pyranones via intramolecular cyclization with the elimination of ethanol, and (3) Diels-Alder reaction between the formed 2-pyranone and the second alkyne. This reaction provides multisubstituted aromatic compounds in a regioselective manner. The third approach is a rhenium-catalyzed formal [2+2+1+1] cycloaddition reaction from two 1,3-diketones and one alkyne. In this reaction, the aromatic skeleton is constructed from three carbons of the first 1,3-diketone, two carbons of the alkyne, and one carbon of the second 1,3-diketone.

Rhenium- and manganese-catalyzed insertion of alkynes into a carbon-carbon single bond of cyclic and acyclic 1,3-dicarbonyl compounds.

Treatment of alkynes with cyclic and acyclic 1,3-dicarbonyl compounds in the presence of a catalytic amount of a rhenium or manganese complex gives ring-expanded and carbon-chain extension products, respectively. In these reactions, alkynes insert into a non-strained carbon-carbon single bond of 1,3-dicarbonyl compounds. The ring-expansion reaction is also promoted by the addition of 4-A molecular sieves instead of a catalytic amount of an isocyanide.

Rhenium-catalyzed formation of bicyclo[3.3.1]nonene frameworks by a reaction of cyclic beta-keto esters with terminal alkynes.

Treatment of cyclic beta-keto esters with terminal alkynes in the presence of a catalytic amount of a rhenium complex, [ReBr(CO)(3)(thf)](2), gave bicyclo[3.3.1]nonene derivatives. The reaction conditions and yields of the bicyclo[3.3.1]nonenes were improved by the sequential use of tetrabutylammonium fluoride (TBAF) after the rhenium-catalyzed reactions.

Rhenium- and manganese-catalyzed insertion of acetylenes into beta-keto esters: synthesis of 2-pyranones.

Rhenium- and manganese-catalyzed reactions between beta-keto esters and acetylenes, followed by treatment with tetrabutylammonium fluoride, gave 2-pyranone derivatives regioselectively.

Manganese-catalyzed construction of tetrasubstituted benzenes from 1,3-dicarbonyl compounds and terminal acetylenes.

Treatment of beta-keto esters with terminal acetylenes in the presence of a catalytic amount of a manganese complex, MnBr(CO)5, and molecular sieves, gave multisubstituted aromatic compounds in good to excellent yields. This reaction employs [2 + 2 + 2] cycloaddition of beta-keto esters and 2 equiv of terminal acetylenes with dehydration. In the case of a 1,3-diketone, the corresponding acetophenone derivative and its deacylated compound can be synthesized selectively.