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We synthesized cinnamoyl amide type compounds 1 with axial chirality. We demonstrated the use of (–)-1 for chiral ligands in Pd-catalyzed asymmetric allylic substitution reactions of allylic esters with indoles (up to 97% ee).

Asymmetric synthesis was performed by combining the photochemical reaction of an achiral substrate followed by crystallization-induced deracemization. The results indicated that a fused indoline produced by photochemical intramolecular δ-hydrogen abstraction and cyclization of N-(5-chloro-2-methylphenyl)phthalimide crystallized as a racemic conglomerate. Since this substrate has an aminal skeleton, racemization involving a ring-opening and ring-closing equilibrium process occurred under suitable conditions. Efficient racemization was observed in acetone containing a catalytic base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Crystallization-induced dynamic deracemization by Viedma ripening from racemic indoline was performed with an excellent enantioselectivity of 99 % ee. Furthermore, one-pot asymmetric synthesis of the indoline was achieved by the photochemical reaction of achiral phthalimide followed by continuous attrition-enhanced deracemization converging to 99 % ee of enantiomeric crystals. This is the first example of asymmetric expression and amplification by photochemical hydrogen abstraction and crystallization-induced dynamic deracemization.

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment.

Thermodynamic data for radium for radioactive waste management have been predicted using an electrostatic model and correlation with the ionic radii of the alkaline earth metals. Estimation of the standard Gibbs free energy of formation and standard molar entropy of aqueous radium species and compounds has been based on such approaches as extrapolation of the thermodynamic properties of strontium and barium, and use of a model of ion pair formation. The predicted thermodynamic data for radium have been compared with previously reported values.

We synthesized cinnamoyl amide type chiral P,olefin ligand (S)-4. We successfully obtained separable diastereomers of 4d and demonstrated Pd-catalyzed asymmetric allylic substitution reactions of indoles using (S,aS)-4d as a chiral ligand with high enantioselectivities (up to 98% ee).

Umpolung reactions of imines, especially the asymmetric reactions, have been extensively studied as they provide access to important chiral amines in an efficient manner. The reactions studied range from simple Michael reactions to several kinds of other reactions such as the aza-benzoin reaction, aza-Stetter reaction, addition with MBH carbonate, and Ir-catalysed allylation. Herein, we report the first umpolung alkylation reaction of α-iminoesters with alkyl halides mediated by iminophosphorane as an organic superbase. The desired products were obtained in up to 82% yield with almost perfect regioselectivities. The key to the regioselectivity of this reaction was the use of 4-trifluoromethyl benzyl imines as a substrate. The products were successfully derivatised into the more functionalised molecules in good yields.

Seven racemic 5,7-dimethoxyflavanones afforded conglomerate crystals upon recrystallization from a solvent. Three methodologies were investigated to achieve asymmetric transformation based on dynamic crystallization of the chiral conglomerate system. The first was chiral symmetry breaking of racemic flavanones by attrition-enhanced deracemization. Continuous suspension of racemic flavanones in a small amount of propanol in the presence of a base (1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU)) and glass beads promoted chiral symmetry breaking and converted the flavanones to crystals of (+)- or (−)-enantiomers with 78 to 99% ee. The second method involved cyclization of the intermediate aldol product to give optically active flavanone with 90% ee involving a reversible oxa-Michael addition reaction with attrition-enhanced deracemization. The third was a reaction starting from prochiral 2-hydroxy-4,6-dimethoxyacetophenone and 2-naphthaldehyde under basic conditions, which gave the corresponding flavanone in 89% ee.

Chiral symmetry breaking of thiohydantoins by attrition-enhanced deracemization was performed. It was found that three thiohydantoins afforded conglomerate crystals, and their absolute structures w...

We developed a chiral symmetry breaking method for monoacylated meso diols. The X-ray crystal structure analysis of monoacylated 1,4-anhydroerythritols, meso cyclic diols with a cis configuration, revealed that the O-(p-anisoyl) derivative crystallized as a racemic conglomerate of the P2

Atroposelective resolution for axially chiral nicotinamides was achieved by dynamic chiral salt formation with L-DBTA using six types of nicotinamides that could not be optically resolved by the preferential crystallization method. Kinetic studies of their racemization indicated that the chiral conformation was retained for a significant period of time. Two methods of crystallization-induced asymmetric transformation were examined by dynamic diastereomeric salt formation: solvent evaporation from a supersaturated solution, and attrition-enhanced asymmetric transformation. The attrition method was more effective for asymmetric amplification of diastereomeric salts of axially chiral materials. Attrition of equimolar amount of the nicotinamide salts with L-DBTA converged to one diastereomer salts, and the corresponding enantiomers in 87-99 % ee were obtained after the chiral acid was removed. Changing the ratio of two of the nicotinamides with L-DBTA to 1 : 2 inverted the axial chirality.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.

Highlights • We presented a patient with gastric tube cancer who successfully underwent subtotal gastrectomy with intraoperative ICG fluorescence. • ICG fluorescence is useful for evaluating the flow of the gastric tube and helping to determine the operating method., Introduction Currently, the frequency of evaluating the flow of a reconstructed gastric tube using indocyanine green (ICG) fluorescence has been increasing. However, it has been difficult to decide on the operation method for patients with gastric tube cancer (GTC). We herein report a case in which ICG was effective in a patient with resection of GTC. Presentation of case An 83-year-old man underwent subtotal esophagectomy with gastric tube reconstruction via the retrosternal route for esophageal cancer and right hemicolectomy for ascending colon cancer 16 years earlier. Postoperatively, the proximal part of the gastric tube had poor blood flow. Therefore, the patient underwent proximal-side resection of the gastric tube. Thereafter, free jejunal graft reconstruction was performed. The patient had not developed recurrence at that point. Recently, the patient visited the hospital complaining of nausea and chest discomfort. Upper gastrointestinal endoscopy revealed a type 0-IIa + IIc lesion located around the pylorus. A biopsy showed adenocarcinoma. Based on these findings, the patient was diagnosed with gastric tube cancer (cT1bN0M0StageI). The invasion depth of the cancer was predicted to be widespread submucosal invasion. Therefore, the patient underwent surgery. Intraoperatively, we evaluated the flow of the gastric tube after clamping the right gastroepiploic artery using ICG fluorescence. As a result, the flow of the gastric tube was deemed insufficient. Consequently, subtotal gastrectomy was performed with preservation of the right gastroepiploic artery via Roux-en-Y reconstruction. Discussion ICG fluorescence is useful for evaluating the flow of the gastric tube helping to decide the operating method. Conclusion We herein report a case of subtotal gastrectomy for GTC using intraoperative ICG fluorescence.

The asymmetric synthesis of an aspartic acid derivative, N-succinopyridine, from prochiral starting materials involving dynamic enantioselective crystallization was accomplished without using any external chiral source. The aza-Michael addition reaction of prochiral maleic acid and pyridine afforded racemic conglomerate N-succinopyridine in water. Continuous stirring of the suspension of the reaction mixture with acetic acid promoted gradual deracemization to afford a crystal with an excellent optical purity of 99 % in 71 % yield.

A new class of flavonoids bearing cyclic polyethers involving a phenyl ring was conveniently provided by the intramolecular photochemical dimerization of 2-chromonecarboxylic esters. Irradiation of 2-chromonecarboxylate with a polyether tethered at both ends promoted intramolecular [2 + 2] cyclobutane formation leading to 14- to 27-membered cyclic polyethers. The efficiency depended on the substituted position of the phenyl ring, with ortho- and meta-substituted derivatives giving cycloadducts in good chemical yields and quantum efficiencies, whereas the para-derivatives were inert toward photolysis. X-ray crystallographic analysis revealed that the stereochemistry of the macrocyclic cycloadducts exhibited C2-symmetry.

Novel optically active hypervalent iodine(V) reagents with planar chiral crown ether backbones were synthesized using the intramolecular Huisgen reaction as a key step and l -methyl lactate as the source of chirality. The relative configurations of these reagents and stabilities of planar chiralities were determined by DFT calculations. These planar chiral reagents were applied to the hydroxylative dearomatization/[4 + 2]-dimerization reactions of phenols to afford bisthymol and biscarvacrol, a natural product, with moderate enantioselectivities.

The efficient chemo- and regioselective catalytic asymmetric syntheses of enamides, which are important core structures of bioactive natural products, have been achieved through the first umpolung organocascade reaction of α-imino amides. A variety of enamides have been synthesized enantioselectively in high yields with up to 99% ee. Notably, both enantiomers of the products can be selectively prepared by the simple pretreatment of the substrate. Mechanistic studies reveal that E/ Z-geometry information from the substrate is transferred to the product. The present method can be applied to a wide range of α-imino amides, irrespective of the electronic nature of the substituents.

Chiral amino thioesters are important scaffolds owing to their widespread use in organic synthesis and biosynthesis. Despite their usefulness, their asymmetric synthesis, especially the catalytic asymmetric synthesis of α-chiral tetrasubstituted α-aminothioesters, is limited, with only one example reported so far. Herein, we report the first phase-transfer catalysed asymmetric synthesis of α-chiral tetrasubstituted α-aminothioesters to afford the corresponding products in up to 81% ee.

Bromonium salts have been typically but infrequently used in various reactions as good leaving groups or as aryl or vinyl transfer reagents owing to their extremely high nucleofugality. Herein, we report the synthesis of novel, stable bromonium salts and their first catalytic application to the Michael reaction, with excellent product yield (up to 96%).

We synthesized N-trans-cinnamyl-N-cyclohexylaniline type aminophosphine 2 and a series of N-2-adamantyl-N-trans-cinnamylaniline type aminophosphines 3. Although aminophosphine 2 failed to find the existence of axial chirality, aminophosphines 3, which exist in the axial chirality in a C(aryl)-N(amine) bond by chiral HPLC analysis as 1-adamantyl type chiral ligands 1. Enantiomeric isomers of 3b, 3c, and 3d were obtained in an enantiomerically pure form. We also identified the palladium-catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-propenyl acetate with indoles using aminophosphines 3b-d as effective chiral ligands in high enantioselectivities (up to 96% ee).

Two boron complexes of 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine, which were named as BOHPIP, have been synthesized. These complexes exhibited blue emission in solution with high quantum yields (ΦFL = up to 0.71). In addition, 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine-BPh2 complex showed the strong blue emission even in the solid state (ΦFL = 0.58).

Asymmetric Diels-Alder reaction was achieved under achiral conditions. Reaction of prochiral 2-methylfuran and N-phenylmaleimide in heptane or hexane solution at 80 °C efficiently gave a conglomerate crystal of exo-type Diels-Alder adduct selectively, and continuous suspension of the reaction mixture with glass beads promoted attrition-enhanced deracemization, leading to an optically active exo-adduct in 90% ee.

The catalytic asymmetric umpolung reaction of ketimines is of great importance, because it can easily provide chiral amines bearing a tetrasubstituted carbon atom on its asymmetric center. Because amino acids with a tetrasubstituted carbon center are useful due to their wide applicability as pharmaceuticals and chiral building blocks, their enantioselective synthesis has great significance in organic synthesis. Herein, we demonstrate a metal-free novel phase-transfer-catalyzed highly regio- and enantioselective umpolung Michael reaction of α-imino esters, which provides amino acid derivatives in high yields with up to 98 % ee. The products are successfully converted into chiral amino acid derivative and δ-lactone with high enantiopurity.

We found that a Suzuki-Miyaura-type reaction of dibromoalkenes with arylboronic acids using a hydrazone-Cu catalyst system proceeded smoothly under mild conditions to afford the corresponding internal alkyne derivatives in good yields. Furthermore, we succeeded in synthesis of o-allyloxyethynylbenzene derivatives, which are known as effective precursors of various heterocyclic compounds, via this reaction.

We have found that Suzuki–Miyaura-type reactions of o-allyloxy(bromoethynyl)benzenes with arylboronic acids using a hydrazone/Cu catalyst system proceeded smoothly in iPrOH under mild conditions to afford the corresponding o-allyloxy(arylethynyl)benzene derivatives in good yields without decomposition of the allyloxy group. We have further demonstrated that annulation and enyne metathesis of the o-allyloxy(arylethynyl)benzene derivatives using transition-metal catalysts led to various heterocyclic compounds.

It is not uncommon for patients with lung cancer to receive supportive care alone. However, the clinical characteristics of these patients have not been fully studied. We conducted a retrospective study to identify the clinical characteristics of definitive lung cancer patients treated with supportive care alone. We retrospectively analyzed the percentage of and reasons for definitive lung cancer patients treated with supportive care alone at a regional cancer center. We also investigated the histological diagnostic approaches, palliative therapy types, primary treatment locations after hospital consultation, and places of death. A total of 1,223 patients were histologically diagnosed as having lung cancer between 2011 and 2014. Of these, 160 (13%) patients were treated with supportive care alone. The primary reason for treatment with supportive care alone was a poor performance status (PS) in almost half of the patients. Overall, 40% of the patients received supportive care at home, and 17% were admitted to a palliative care unit (PCU). Death occurred at home for 17% of the patients and in the PCU for 42% of the patients. This study revealed that 13% of histologically proven lung cancer patients were treated with supportive care alone, mostly because of a poor PS. Only 40% of these patients received home care, suggesting the need for a more accessible home care system for patients and their families.

Irradiation of prochiral (E)-aroylacrylamide with sunlight gave single-handed pyrrolinone quantitatively and with an enantiomeric excess (ee) of over 99 % under absolutely achiral conditions. The phenomenon was explained by photoisomerization and reversible cyclization followed by dynamic crystallization involving deracemization.

Amino acid-derived novel chiral hypervalent iodine(V) reagents were synthesized from the corresponding chiral iodoarenes through DMDO oxidations. Their oxidation states were determined by the 13 C NMR chemical shifts of the ipso -carbon of the iodine atom, HRMS analysis, and elemental analyses. They were applied to the enantioselective hydroxylative dearomatization/[4+2]-dimerization cascade reactions of phenol derivatives to afford the desired products with up to 58% ee.

Single-handed alpha-amino acid derivatives were generated from achiral precursors without an external chiral source. Conjugate addition of phenethylamine to an achiral aroylacrylamide under homogeneous conditions gave the alpha-amino amides in quantitative yields, which crystallized as a conglomerate of a P21 crystal system. Dynamic preferential crystallization or attrition-enhanced deracemization resulted in the formation of enantiomorphic crystals of 99% ee.

Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed.In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap.The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges.The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.