Enzymatic Synthesis and Polymerization of Cyclic Trimethylene Carbonate Monomer with/without Methyl Substituent

The direct enzymatic synthesis of a cyclic trimethylene carbonate (1,3‐dioxane‐2‐one) monomer with/without a methyl substituent was carried out using dimethyl or diethyl carbonate and 1,3‐diol with the objective of producing aliphatic poly(trimethylene carbonate), a typical biodegradable synthetic plastic. The lipase‐catalyzed condensation of dimethyl or diethyl carbonate with aliphatic 1,3‐diols using immobilized Candida antarctica lipase (lipase CA) in an organic solvent at 70 °C afforded the corresponding methyl‐substituted and unsubstituted cyclic trimethylene carbonates. The cyclic trimethylene carbonates obtained by the reaction of dimethyl or diethyl carbonates with 1,3‐propanediol and 2‐methyl‐1,3‐propanediol were polymerized by lipase to produce the corresponding polycarbonates.

Total TMC yield as a function of the reaction time.     

Fast and quantitative analysis of branched-chain amino acids in biological samples using a pillar array column

In this study, a fast and quantitative determination method for branched-chain amino acids (BCAAs), namely leucine, isoleucine, and valine, was developed using a pillar array column. A pillar array column with low-dispersion turns was fabricated on a 20?×?20-mm² microchip using multistep ultraviolet photolithography and deep reactive ion etching. The BCAAs were fluorescently labeled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), followed by reversed-phase separation on the pillar array column. The NBD derivatives of the three BCAAs and an internal standard (6-aminocaproic acid) were separated in 100 s. The calibration curves for the NBD-BCAAs had good linearity in the range of 0.4–20 μM, using an internal standard. The intra- and interday precisions were found to be in the ranges of 1.42–3.80 and 2.74–6.97 %, respectively. The accuracies for the NBD-BCAA were from 90.2 to 99.1 %. The method was used for the analysis of sports drink and human plasma samples. The concentrations of BCAAs determined by the developed method showed good agreements with those determined using a conventional high-performance liquid chromatography system. As BCAAs are important biomarkers of some diseases, these results showed that the developed method could be a potential diagnostic tool in clinical research.     

Reversible switching of high-speed air-liquid two-phase flows using electrowetting-assisted flow-pattern change

This work is the first demonstration of electrical modulation of surface energy to reversibly switch dynamic high-speed gas-liquid two-phase microfluidic flow patterns. Manipulation of dynamic two-phase systems with continuous high-speed flows is complex and interesting due to the multiple types of forces that need to be considered. Here, distinct stable flow patterns are formed through a multipronged approach: both surface tension forces generated by surface chemistry modulation as well as viscous and inertial forces produced by fluid flows are employed. The novel fluidic actuation mechanism provides insights into better understanding microscale two-phase flow dynamics and offers new opportunities for the development of two-phase biochemical microsystems that are mechanically simple and operational at high speeds.     

Synthesis and Magnetic Properties of (Pyrrolidin‐1‐oxyl)–(Nitronyl Nitroxide)/(Iminonitroxide)‐Dyads

Unlike extensively studied diradicals linked by π‐conjugated systems, only a few studies have investigated weakly coupled diradicals linked by an sp³ carbon atom. Herein, we prepared pyrrolidin‐1‐oxyl–(nitronyl nitroxide)‐dyad 5 and pyrrolidin‐1‐oxyl–iminonitroxide‐dyad 6 . From the observed temperature dependence of the magnetic susceptibility, 5 and 6 were determined to be in singlet ground states with 2J_intra/k_B=?35.2 K and ?13.6 K, respectively. From these results and theoretical calculations of related diradicals, the spin‐polarization model counting the small spin density of the sp³ carbon atom could be used as a spin‐prediction model.     

Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group

Rhodium(I)‐catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh?C(sp²) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ‐bond metathesis of a tethered O?H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.     

Lipase-catalyzed transformation of poly(lactic acid) into cyclic oligomers

Enzymatic transformations into cyclic oligomers were carried out with the objective of developing chemical recycling of poly(lactic acid)s, such as poly(D,L-lactic acid) (PDLLA), poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA), which are typical biodegradable polymers. They were degraded by lipase in an organic solvent to produce the corresponding cyclic oligomer with a molecular weight of several hundreds. PDLLA (with a Mw of 84,000) was quantitatively transformed into cyclic oligomers by lipase RM (Lipozyme RM IM) in chloroform/hexane at 60 degrees C. PLLA (with a Mw of 120,000) was transformed into cyclic oligomer by lipase CA (Novozym 435) at a higher temperature of 100 degrees C in o-xylene. The oligomer structure was identified by 1H and 13C NMR spectroscopy and MALDI-TOF (matrix assisted laser desorption/ionization-time-of-flight) mass spectrometry.     

Chiral bifunctional organocatalysts bearing a 1,3-propanediamine unit for the aza-MBH reaction

The introduction of a 1,3-propanediamine unit at the 3-position of (S)-BINOL using a methylene spacer led to the formation of a chiral bifunctional organocatalyst for the aza-Morita–Baylis–Hillman (aza-MBH) reaction. The organocatalyst 1k mediated aza-MBH transformations with high chemical yields and with up to 82% ee.     

Essential Structure of Opioid κ Receptor Agonist Nalfurafine for Binding to κ Receptor 1: Synthesis of Decahydroisoquinoline Derivatives and Their Pharmacologies

On the basis of the three-dimensional pharmacophore model of opioid κ agonists, we simplified the structure of nalfurafine (selective κ agonist) to find the essential structural moieties for binding the opioid receptors, especially κ receptor type. As a result, we found that the trans-fused decahydroisoquinoline derivatives without a phenol ring bound the opioid receptor in micromolar order and that both the amide side chain and the nitrogen substituted by the cyclopropylmethyl group were indispensable moieties for eliciting the κ selectivity. The simple decahydroisoquinoline without amide side chain also bound the opioid receptor without receptor type selectivity, suggesting that the message-address concept would be applicable to even these simple derivatives. These findings that the simple decahydroisoquinoline derivatives showed the affinities for the opioid receptors, especially some of the compounds showed κ selectivity, are the first example in the opioid field.     

Structural confirmation of oligosaccharides newly isolated from sugar beet molasses

ABSTRACT: BACKGROUND: Sugar beet molasses is a viscous by-product of the processing of sugar beets into sugar. The molasses is known to contain sucrose and raffinose, a typical trisaccharide, with a well-established structure. Although sugar beet molasses contains various other oligosaccharides as well, the structures of those oligosaccharides have not been examined in detail. The purpose of this study was isolation and structural confirmation of these other oligosaccharides found in sugar beet molasses. RESULTS: Four oligosaccharides were newly isolated from sugar beet molasses using high-performance liquid chromatography (HPLC) and carbon-Celite column chromatography. Structural confirmation of the saccharides was provided by methylation analysis, matrix-assisted laser desorption/ionaization time of flight mass spectrometry (MALDI-TOF-MS), and nuclear magnetic resonance (NMR) measurements. CONCLUSION: The following oligosaccharides were identified in sugar beet molasses: beta-D-galactopyranosyl-(1- > 6)-beta-D-fructofuranosyl-(2 <-> 1)-alpha-D-glucopyranoside (named beta-planteose), alpha-D-galactopyranosyl-(1- > 1)-beta-D-fructofuranosyl-(2 <-> 1)-alpha-D-glucopyranoside (named1-planteose), alpha-D-glucopyranosyl-(1- > 6)-alpha-D-glucopyranosyl-(1 <-> 2)-beta-D-fructofuranoside (theanderose), and beta-D-glucopyranosyl-(1- > 3)-alpha-D-glucopyranosyl-(1 <-> 2)-beta-D-fructofuranoside (laminaribiofructose). 1-planteose and laminaribiofructose were isolated from natural sources for the first time.