Direct Monitoring of γ‐Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized 13C‐Labeled Molecular Probe

The γ‐glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ‐Glu‐[1‐¹³C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) ¹³C magnetic resonance (MR). The properties of γ‐Glu‐[1‐¹³C]Gly are suitable for in vivo HP ¹³C metabolic analysis since the chemical shift between γ‐Glu‐[1‐¹³C]Gly and its metabolic product, [1‐¹³C]Gly, is large (4.3 ppm) and the T₁ of both compounds is relatively long (30 s and 45 s, respectively, in H₂O at 9.4 T). We also demonstrate that γ‐Glu‐[1‐¹³C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.     

N-cyclopropylation of indoles and cyclic amides with copper(II) reagent

Copper-mediated coupling reactions of cyclopropylboronic acid with indoles and cyclic amides are described. The process utilizes catalytic or stoichiometric amounts of copper(II) acetate, DMAP, and NaHMDS at 95 degrees C under an atmosphere containing oxygen. A variety of functional groups remain intact throughout the reaction.     

Studies on electron spin resonance spectroscopy of biradical molecules containing N-O and N-O moieties

The biradicals with ¹⁴N-Oxide and ¹⁵N-Oxide at the both ends of a molecule are synthesized for the molecular ruler of protein structure, and a potential device for quantum computing. We also establish a general synthetic method for reliable biradical formation. ESR spectra are recorded for the biradicals containing ¹⁵N-Oxide and ¹⁴N-Oxide with various interdistance separations. We find that two types of biradicals yielded different ESR spectra depending upon the distance between the ¹⁵N-O and ¹⁴N-O moieties in a molecule. This is due to electron spin dipole–dipole interaction occurring between the radicals. We also find that there is an indication of isotopic nuclear effects in the dipole–dipole interactions. The present study implies feasibility of the distance measurement between two different N-Oxides containing ¹⁴N and ¹⁵N isotopes. We conclude that quantum entanglement effects are observed through the dipolar interactions, which enable application of quantum computing devices operating in the liquid state.     

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.     

Glycopolymers Mimicking GM1 Gangliosides: Cooperativity of Galactose and Neuraminic Acid for Cholera Toxin Recognition

Glycopolymers mimicking GM1 gangliosides were synthesized by incorporating multiple types of carbohydrates into the polymer backbone. The glycopolymers were immobilized onto gold surfaces, and the interactions with the cholera toxin B subunit (CTB) were analyzed using surface plasmon resonance imaging. The glycopolymer containing both galactose and neuraminic acid showed enhanced recognition of CTB. The interaction was enhanced mainly because of an improvement in the dissociation process by the binding of the neuraminic acid group in the GM1 binding pocket. This cooperativity of galactose and neuraminic acid was achieved by incorporation into the same flexible polymer backbone, and the importance of the close placement of galactose and neuraminic acid groups was revealed. These results will be valuable in medical fields and also for the development of biofunctional materials.     

Minimum standards of clinical practice for physical therapists working in intensive care units in Japan

Objective: Early mobilization and rehabilitation has become common and expectations for physical therapists working in intensive care units have increased in Japan. The objective of this study was to establish consensus-based minimum clinical practice standards for physical therapists working in intensive care units in Japan. It also aimed to make an international comparison of minimum clinical practice standards in this area. Methods: In total, 54 experienced physical therapists gave informed consent and participated in this study. A modified Delphi method with questionnaires was used over three rounds. Participants rated 272 items as “essential/unknown/non-essential”. Consensus was considered to be reached on items that over 70% of physical therapists rated as “essential” to clinical practice in the intensive care unit. Results: Of the 272 items in the first round, 188 were deemed essential. In round 2, 11 of the 62 items that failed to reach consensus in round 1 were additionally deemed essential. No item was added to the “essential” consensus in round 3. In total, 199 items were therefore deemed essential as a minimum standard of clinical practice. Participants agreed that 42 items were not essential and failed to reach agreement on 31 others. Identified 199 items were different from those in the UK and Australia due to national laws, cultural and historical backgrounds. Conclusions: This is the first study to develop a consensus-based minimum clinical practice standard for physical therapists working in intensive care units in Japan.     

Application of α-chloroaldoxime O-methanesulfonates to one-pot synthesis of N,N′,N″-substituted guanidines via Tiemann rearrangement

A practical one-pot synthesis of N,N′,N″-trisubstituted guanidines via Tiemann rearrangement involving the reaction of α-chloroaldoxime O-methanesulfonates with alkyl amines is disclosed.     

Total Syntheses of (−)-Strictosidine and Related Indole Alkaloid Glycosides

A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α-cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)-strictosidine, which is an important intermediate in biosynthesis. This two-step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)-strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)-strictosamide, (−)-neonaucleoside A, (−)-cymoside, and (−)-3α-dihydrocadambine.     

Reaction of B2(o‐tol)4 with CO and Isocyanides: Cleavage of the C≡O Triple Bond and Direct C−H Borylations

The reaction of highly Lewis acidic tetra(o‐tolyl)diborane(4) with CO afforded a mixture of boraindane and boroxine by the cleavage of the C≡O triple bond. ¹³C labeling experiments confirmed that the carbon atom in the boraindane stems from CO. Simultaneously, formation of boroxine 3 could be considered as borylene transfer to capture the oxygen atom from CO. The reaction of diborane(4) with ^tBu?NC afforded an azaallene, while the reaction with Xyl?NC furnished cyclic compounds by direct C?H borylations.