Photocatalytic Cross-Pinacol Coupling Promoted by Carbon Dioxide.

Cross-pinacol coupling of two different carbonyl compounds was achieved through successive one-electron transfer processes under photocatalytic conditions. In the reaction, an umpoled anionic carbinol synthon was generated in situ to react nucleophilically with a second electrophilic carbonyl compound. It was revealed that a CO2 additive promoted the photocatalytic generation of the carbinol synthon to suppress undesired radical dimerization. A wide variety of aromatic and aliphatic carbonyl substrates underwent the cross-pinacol coupling to afford the corresponding unsymmetric vicinal 1,2-diols, in which even a combination of carbonyl reactants with similar structures such as two aldehydes and two ketones were also well tolerated with high cross-coupling selectivity.

Sensitive Method for the Identification of Potential Sensitizing Impurities in Reaction Mixtures by Fluorescent Nitrobenzoxadiazole-Labeled Glutathione.

Allergic contact dermatitis is a critical issue in the development of new chemicals. Minor impurities with strong skin-sensitizing properties can be generated as byproducts. However, it is very difficult to identify these skin sensitizers in product mixtures. In this study, fluorescent nitrobenzoxadiazole-labeled glutathione (NBD-GSH) was synthesized to identify small amounts of skin sensitizers in reaction mixtures. Twelve known skin sensitizers and three nonsensitizers were reacted with NBD-GSH. Adducts formed only with the skin sensitizers, which allowed for their detection by a fluorescence detector. Liquid chromatography-mass spectrometry (LC-MS) analyses showed that NBD-GSH reacted with the skin sensitizers via its thiol and amino groups. An adduct of NBD-GSH with the strong skin sensitizer 1-chloro-2,4-dinitrobenzene was detected with a limit of detection of 6 × 10-8 mol/L by high-performance liquid chromatography with fluorescence detection. When a reaction mixture from primary alcohol oxidation was incubated with NBD-GSH, a NBD-GSH adduct formed with skin-sensitizing aldehyde impurities and could be specifically detected by LC-MS with fluorescence detection. This method will be useful for detection and identification of small amounts of skin sensitizers in raw materials, intermediates, reaction mixtures, and end products in the chemical industry.

Development of chemically stable solid phases for the target isolation with reduced nonspecific binding proteins.

Poly(methacrylate) matrices for affinity resins were designed and synthesized based on our previous results that nonspecific protein absorption on affinity resins strongly depended on their hydrophobic property. The novel affinity resins bearing FK506 (6a, 6b) captured specific binding protein, FKBP12, with a small amount of nonspecific binding proteins. The amount of nonspecific binding proteins on 6a-6b was much reduced compared to that on commercially available poly(methacrylate) resins, Toyopearl (8), and was almost the same as that on one of the most popular resins, Affigel (9). Interestingly, 6a and 6b could isolate FKBP52 as a specific binding protein as well, although 8 and 9 could not.

Isolating the whole complex of target proteins of FK506 using affinity resins from novel solid phases.

The development of novel solid phases enabled us to create affinity resins that could be used to isolate the whole complex of target proteins responsible for the immunosuppressive effects of FK506 from rat brain lysate, whereas the affinity resins from commercially available matrices could not achieve this isolation. The results illustrate the enhanced effectiveness of the affinity resin made from this novel material at identifying the target protein of the bioactive compound compared to resins made from the well-known materials Affigel or Toyopearl. This effectiveness arises because the novel material is hydrophilic enough to reduce nonspecific binding proteins and because it has a higher density of ligands that capture the nonubiquitous target protein.

An easy preparation of 'monolithic type' hydrophilic solid phase: capability for affinity resin to isolate target proteins.

An easy preparation method of monolithic type hydrophilic solid phase was discussed. Newly invented functional monomer with a hydrophilic cross-linking agent was co-polymerized to realize well-controlled monolithic co-continuous structure by use of diethylene glycol as porogenic solvent. We were able to control the content of the functional monomer up to 40 vol% without loss of monolithic structure. Those prepared were utilized as affinity resins after immobilization of FK506, an immunosuppressive drug as a ligand. It was found that the affinity resins prepared were hydrophilic enough to eliminate non-specific adsorption of proteins, while two of the target proteins of FK506 tested were successfully captured.