Titanocene(II)-promoted, one-pot, three-component coupling of thioacetals, alkynyl sulfones, and carbonyl compounds: highly stereoselective formation of tert-homopropargyl alcohols

Titanocene alkylidene complexes, generated by desulfurizative titanation of thioacetals with Cp2Ti[P(OEt)3]2, reacted with alkynyl methyl sulfones to produce organotitanium species, which gave tert-homopropargyl alcohols with high diastereoselectivity on treatment with aromatic and alpha,beta-unsaturated ketones.     

Functional Analysis of the GPI Transamidase Complex by Screening for Amino Acid Mutations in Each Subunit

Glycosylphosphatidylinositol (GPI) anchor modification is a posttranslational modification of proteins that has been conserved in eukaryotes. The biosynthesis and transfer of GPI to proteins are carried out in the endoplasmic reticulum. Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA) complex, which recognizes and cleaves the C-terminal GPI attachment signal of precursor proteins. Then, GPI is transferred to the newly exposed C-terminus of the proteins. GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU, and the absence of any subunit leads to the loss of activity. Here, we analyzed functionally important residues of the five subunits of GPI-TA by comparing conserved sequences among homologous proteins. In addition, we optimized the purification method for analyzing the structure of GPI-TA. Using purified GPI-TA, preliminary single particle images were obtained. Our results provide guidance for the structural and functional analysis of GPI-TA.     

Intramolecular Catalyst Transfer on a Variety of Functional Groups between Benzene Rings in a Suzuki–Miyaura Coupling Reaction

Suzuki–Miyaura coupling reaction of BrC₆H₄-X-C₆H₄Br 1 (X=CH₂, CO, N-Bu, O, S, SO, and SO₂) with arylboronic acid 2 was investigated in the presence of tBu₃PPd precatalyst and CsF/[18]crown-6 as a base to establish whether or not the Pd catalyst can undergo catalyst transfer on these functional groups. In the reaction of 1 (X=CH₂, CO, N-Bu, O, and SO₂) with 2 , aryl-disubstituted product 3 (Ar-C₆H₄-X-C₆H₄-Ar) was exclusively obtained, indicating that the Pd catalyst undergoes catalyst transfer on these functional groups. On the other hand, the reaction of 1 e (X=S) and 1 f (X=SO) with 2 afforded only aryl-monosubstituted product 4 (Ar-C₆H₄-X-C₆H₄-Br) and a mixture of 3 and 4 , respectively, indicating that S and SO interfere with intramolecular catalyst transfer. Furthermore, we found that Suzuki–Miyaura polycondensation of 1 (X=CH₂, CO, N-Bu, O, and SO₂) and phenylenediboronic acid 5 in the presence of tBu₃PPd precatalyst afforded high-molecular-weight polymer even when excess 1 was used. The polymers obtained from 1 (X=CH₂, N-Bu, and O) and 5 turned out to be cyclic.     

Partially saturated fluorinated heterocycles: diastereo- and enantioselective synthesis of β-trifluoromethyl-pyrroline carboxylates

The first asymmetric synthesis of β-trifluoromethylated pyrroline carboxylates has been achieved by organocatalytic conjugated addition of adamantyl glycine imine to β-trifluoromethylated enones, followed by a deprotection/cyclization/dehydration sequence.     

Platinum-catalyst-assisted metalorganic vapor phase epitaxy of InN

This paper reports the first attempt of the Pt-catalyst-assisted MOVPE growth of InN. In order to enhance NH₃ decomposition at a relatively low growth temperature (～550 °C), Pt is used as a catalyst. The catalyst is installed in the NH₃ introduction tube in the MOVPE reactor and the tube is located just above the susceptor to be heated. Compared with InN films grown without the catalyst, the samples grown with Pt catalyst show improved electrical properties; a carrier concentration in the order of 10¹⁸ cm^?3 and a Hall mobility as high as 1350 cm²/Vs are obtained. The crystalline quality is also improved by employing the catalyst and a tilt fluctuation as low as 8.6 arcmin is obtained for a sample grown on a GaN/sapphire template. It is confirmed that for InN films grown at 550 °C with Pt catalyst, the electrical and crystallographic properties are also improved with increase in thickness. These results indicate that the growth at around 550 °C with the Pt catalyst is performed under the circumstances where NH₃ is effectively decomposed, whereas the deterioration of InN during growth is significantly suppressed.     

Inhibition of restriction enzymes EcoRI, BamHI and HindIII by phenethylphenylphthalimides derived from thalidomide

We discovered inhibitors of the restriction enzymes EcoRI, BamHI and HindIII by screening our library of compounds with a phenethylphenylphthalimide skeleton, based on α-glucosidase inhibitors and liver X receptor antagonists derived from thalidomide. Structural development afforded the potent restriction enzyme inhibitors 25 and 26.     

A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging

Significant advances have been made in the past decade in the field of mass spectrometry imaging (MS imaging). It is a relatively unestablished technique aimed at direct, high-sensitive and spatially exclusive detection of biological molecules from the surface of tissue sections, so that semi-quantitative distribution map of the analyte can be reconstituted from the mass spectra obtained. There is tremendous potential in its application especially in clinical field, such as biomarker discovery or pharmacokinetic study. However, vast majority of the work has been performed on frozen tissue sections, while it remains generally unpractical to produce frozen sections with clinically resected tumor samples. Here we report our novel sample preparation technique that enabled MS imaging from formalin-fixed paraffin embedded (FFPE) tissue section, including retrospective archive as old as 11 years. FFPE sections were first dewaxed with pre-warmed xylene, and exposed tissue surface was enzymatically digested in nanoliter scale droplets to retain analyte localization. As a result, we succeeded in obtaining MS images of peptide peaks derived from several proteins, identified by MS/MS analysis, using ovarian cancer FFPE sections. The qualities of mass spectra obtained by this method were not significantly different from those obtained from frozen sections. By this, we opened the door to retrospective study of past clinical cases in aim to discover molecular biomarker.     

Carbon-14 labelled sucrose transportation in an Arabidopsis thaliana using an imaging plate and real time imaging system

As an approach to increased production of rape seed oil from Brassica napus L., Arabidopsis thaliana, a species from the same Brassicaceae family, was used to investigate transport behavior and distribution of matter in the plant body. In this study, sucrose, an initial metabolic product of photosynthesis, labeled with carbon-14 was used. The sucrose was applied to A. thaliana via the surface of a rosette leaf. Using the real time radioisotope imaging system we developed and an imaging plate (IP), images of whole or part of the sample were obtained. The sucrose assimilation products were accumulated in maturing tissue such as flowers and fruits, and in a joint part. From the comparison among branches and stems, it was indicated that there were different patterns of demand and distribution of sucrose assimilation products depending on the tissue and its growing stage. This might be caused by either morphological reason such as diameter and location of the sieve tube, or genetic factors such as an activity of a membrane transport protein. Because of self-absorption of carpels, it was difficult to observe the accumulation of carbon-14 in the seeds inside the fruits; however, an IP image of a frozen section of a fruit revealed that carbon-14 transport to seeds was higher than that of carpels. These methods will help us gain insight into matter transport and strategies to improve the production of rape seed oil.