Dehydrogenative Coupling of Alkylamines with Primary Alcohols Forming α-Amino Ketones.

Acceptorless dehydrogenative coupling reactions between C-H bonds offer straightforward and atom-economical methods connecting readily available materials while liberating gaseous hydrogen as the sole byproduct. Despite the growing interest in such transformations, their realization still poses a significant challenge. Here we report a photoinduced dehydrogenative coupling reaction of alkylamines with primary alcohols. C-H bonds adjacent to nitrogen and oxygen are site-selectively cleaved, and a C-C bond is created between the carbon atoms in a cross-selective manner to produce α-amino ketones. Diverse polar functionalities such as esters, amides, and carboxylic acids survived, demonstrating the broad applicability of the present method.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice.

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Photocatalytic 1,2-Phosphorus-Migrative [3 + 2] Cycloaddition of Tri(t-butyl)phosphine with Terminal Alkynes.

Tri(t-butyl)phosphine and terminal alkynes undergo 1,2-phosphorus-migrative [3 + 2] cycloaddition in the presence of a proton source under photocatalytic conditions. The reaction exhibits broad functional group tolerance and affords substituted cyclic phosphonium salts, which are amenable to further derivatization by Wittig olefination. Theoretical studies suggest that the phosphorus 1,2-migration of a ß-phosphonioalkyl radical proceeds through a phosphine radical cation-alkene complex as a pseudointermediate, and the two fragments in the intermediate are bound to each other through multiple noncovalent interactions.

Cleavage of Carbon-Carbon σ-Bonds of Four-Membered Rings.

This article reviews synthetic transformations involving cleavage of a carbon-carbon bond of a four-membered ring, with a particular focus on the examples reported during the period from 2011 to the end of 2019. Most significant is the progress of catalytic reactions involving oxidative addition of carbon-carbon bonds onto transition metals or ß-carbon elimination of transition metal alkoxides. When they are looked at from synthetic perspectives, they offer unique and efficient methods to build complex natural products and structures that are difficult to construct by conventional methods. On the other hand, ß-scission of radical intermediates has also attracted increasing attention as an alternative elementary step to cleave carbon-carbon bonds. Its site-selectivity is often complementary to that of transition metal-catalyzed reactions. In addition, Lewis acid-mediated and thermally induced ring-opening of cyclobutanone derivatives has garnered renewed attention. On the whole, these examples demonstrate unique synthetic potentials of structurally strained four-membered ring compounds for the construction of organic skeletons.

Computed tomographic measures of renomegaly vary among dogs with different types of congenital portosystemic shunts.

Renomegaly has been reported in dogs with congenital portosystemic shunts (PSS). However, no study has objectively evaluated the degree of renomegaly in dogs with different types of PSS. The purpose of this retrospective, analytical, cross-sectional study was to determine kidney size (renal length-to-L2 vertebral body ratio; RL/L2 ratio) using CT in dogs with different types of PSS and correlate with clinical information. A medical record search for dogs with a PSS diagnosed using CT between 2016 and 2020 was conducted. Breed, age, sex, body weight, and biochemistry results were recorded. Kidney and L2 vertebral body lengths were measured using multiplanar reformatted CT images, and the RL/L2 ratio was calculated. Dogs were categorized into four groups based on PSS morphology for comparisons: intrahepatic (IH; n = 19), extrahepatic portocaval (EHPC; n = 20), extrahepatic portoazygos (EHPA; n = 7), or extrahepatic portophrenic (EHPP, n = 7). The RL/L2 ratio (mean ± SD) was largest in IH (3.55 ± 0.38) and EHPC (3.55 ± 0.38), followed by EHPP (3.10 ± 0.23), and EHPA (2.78 ± 0.18). RL/L2 ratio was significantly larger in EHPC and IH (vs. EHPA and EHPP [P < .01]). Significant correlations between kidney size and creatinine, alkaline phosphatase, albumin, total protein, and ammonia were present. Renomegaly was observed in 86.8% of dogs with PSS overall, but it was uncommon in dogs with EHPA and less common in dogs with EHPP, as these two groups showed clinical signs later in life, made evident by older age at presentation. The authors suggest that the severity of hepatic dysfunction and the shunted blood volume may influence the development of renomegaly in dogs with PSS.

[A Case of Rectal Neuroendocrine Carcinoma with Iris Metastasis].

A 62-year-old man with anal pain was diagnosed with rectal neuroendocrine carcinoma. There were multiple metastases in the liver, lung, paraaortic lymph node, and bone of the patient. After performing a diverting colostomy, irinotecan and cisplatin were administered. Partial response was obtained after 2 courses, and anal pain improved. However, after 8 courses, multiple skin metastases were found on his back. At the same time, the patient also complained of redness, pain, and impaired vision in the right eye. Iris metastasis was diagnosed clinically by ophthalmologic examination and with contrast- enhanced MRI. Iris metastasis was treated with 5 doses of 4 Gy irradiation, ameliorating the eye symptoms. The patient died of the original disease 13 months after the initial diagnosis; however, multidisciplinary treatment appeared effective for palliating cancer symptoms.

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Vinylcyclopropane Rearrangement.

A ligand-controlled regiodivergence in Ni-catalyzed rearrangement of vinylcyclopropanes to 1,4- or 1,5-disubstituted cyclopentenes is reported. The 1,4- or 1,5-disubstituted cyclopentene is selectively obtained depending on the choice of ligands. Detailed kinetic studies and density functional theory calculations on the catalytic cycle revealed that the product selectivity is determined at the reductive elimination step from the six-membered η1 -allyl intermediate.

Synthesis, Structure, and Dynamics of Chiral Eight-Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected.

A rhodium(II)-catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3- and 3,4-positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight-membered rings in the center are non-planar and adopt a tub-shaped conformation. We also observe the phenomenon of racemization caused by a tub-to-tub ring-flipping, the activation energy of which is determined as 108 kJ mol-1 by electronic circular dichroism spectra measurement.

Sclerosing encapsulating peritonitis in a dog with pancreatic ductal adenocarcinoma.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a rare clinical syndrome characterised by fibrosis and thickening of the peritoneum with massive adhesions of the abdominal organs. In humans, abdominal tumours, such as pancreatic adenocarcinoma, can be underlying diseases of SEP. This report describes a case of SEP in a dog with pancreatic ductal adenocarcinoma. CASE PRESENTATION: An 11-year-old male neutered French Bulldog presented with chronic vomiting. Ultrasonography revealed a mass in the centre of the abdomen. A small amount of ascites, interpreted as modified transudate, was present in the abdominal cavity. Computed tomography (CT) revealed peritoneal effusion with a thickened peritonium. Laparoscopy revealed a large nodular lesion occupying the central portion of the abdomen, continuous with the falciform ligament. Histological examination of the biopsy specimens of the mass, abdominal wall, and gastric peritoneum revealed marked fibroplasia with mild lymphoplasmacytic infiltrates. Based on these results, a tentative diagnosis of early stage sclerosing encapsulating peritonitis (SEP) was made. Prednisolone and tamoxifen were administered with the expectation of ameliorating SEP, however, the dog died 61 days post diagnosis. At autopsy, the intestinal loop and mesentery were encased in the fibrous membrane, which is a typical finding in SEP. Histopathology and immunohistochemistry of the samples obtained at autopsy supported the diagnosis of pancreatic ductal adenocarcinoma with peritoneal dissemination and distant metastasis with desmoplasia. The unexpectedly hardened skin, where previously laparoscopic ports were inserted, histologically contained the same carcinoma cells with desmoplasia. CONCLUSIONS: To the best of our knowledge, this is the first report of canine SEP with pancreatic ductal adenocarcinoma that also caused metastasis to port insertion sites as well as distant organs.

CT features of confirmed and presumed gastric wall edema in dogs.

Postcontrast computed tomographic (CT) characteristics of gastrointestinal (GI) wall edema in humans have been described as GI wall thickening with a thickened submucosal layer and thin enhanced inner and outer layers. Published studies describing CT features of gastric wall edema in dogs are currently lacking. The aim of this retrospective, case series was to describe CT features of gastric wall edema in a group of dogs. Medical records were searched for dogs with postcontrast abdominal CT scans and a diagnosis of gastric wall edema based on histopathology (group I) or CT characteristics consistent with those reported in humans (group II). Clinical diagnosis, mean serum albumin concentration, and histopathological diagnosis were recorded. The following CT characteristics were recorded: numbers of wall layers, attenuation and contrast enhancement, presence of blood vessels, locations, distribution, and thickness. Twelve dogs (3 in group I and 9 in group II) were included. The most common clinical finding was hypoalbuminemia. In group I, a well-defined three-layer appearance with a non-enhancing fluid-attenuating middle layer was observed in three dogs and thin blood vessels in the middle layer in two dogs. In group II, nine dogs had a three-layer appearance with a non-enhancing fluid-attenuating middle layer. Locations of gastric wall thickening were diffuse in two, focal concentric in six, and focal asymmetric in four dogs. Findings supported including gastric wall edema as a differential diagnosis for dogs with hypoalbuminemia and CT characteristics of a three-layer appearance in the gastric wall, with a non-enhancing fluid-attenuating middle layer and thin blood vessels.

Radiographic characteristics of canine subungual keratoacanthoma.

Subungual keratoacanthoma (SKA) is a rare benign nail bed tumor in dogs, and its radiographic characteristics have not been reported based on the authors' review of the literature. The purpose of this multicenter, retrospective, observational, descriptive study was to describe the radiographic features of SKA in dogs. Twelve dogs for a total of 12 digits with histologically confirmed SKA met the inclusion criteria. The radiographs of the manus or pes were reviewed by two veterinary radiologists and one veterinarian. The radiology reports were interpreted based on a consensus. In six dogs, there was lysis of both the middle phalanx (P2) and the distal phalanx (P3), whereas in the other six dogs, there was only lysis of P3. In all dogs with osteolysis of P2, the lysis involved the distal articular surface. Osteolysis of P3 was more severe in the ungual process than in the ungual crest in all dogs. The margins of the lytic regions of P2 and P3 were well defined and smoothly marginated in most dogs. Expansile changes in the P3 crest were observed in 83.3% (10/12 dogs), and the nail of the affected digit was enlarged and deformed in 91.6% (11/12 dogs). In summary, the radiographic features of canine SKA include severe pressure resorption of the P3 ungual process, expansile change of the P3 ungual crest, and nail enlargement and deformation. With these radiographic features, SKA should be considered as a differential diagnosis.

[A Case of Jejunal Cancer Treated by Laparoscopic Partial Jejunectomy].

The patient was a 30s male visited our hospital with the complaints of abdominal pain and melena. The internal medicine physician could not detect the cause of the melena by upper and lower gastrointestinal endoscopy. Although the patient resolved with a fast as conservative management so he left our hospital once, he relapsed nausea and abdominal pain. He visited our department. We performed surgery under a preoperative diagnosis of intestinal obstruction. The histopathological diagnosis was moderate differentiated jejunal adenocarcinoma(Stage ⅡA). At present, 1 year 7 months since surgery, the patient survives although with lymphnode recurrence.

Sustainable System for Hydrogenation Exploiting Energy Derived from Solar Light.

Herein described is a sustainable system for hydrogenation that uses solar light as the ultimate source of energy. The system consists of two steps. Solar energy is captured and chemically stored in the first step; exposure of a solution of azaxanthone in ethanol to solar light causes an energy storing dimerization of the ketone to produce a sterically strained 1,2-diol. In the second step, the chemical energy stored in the vicinal diol is released and used for hydrogenation; the diol offers hydrogen onto alkenes and splits back to azaxanthone, which is easily recovered and reused repeatedly for capturing solar energy.

Stereo- and Enantioselective Synthesis of Propionate-Derived Trisubstituted Alkene Motifs.

We report a new method for constructing propionate-derived trisubstituted alkene motifs in a stereoselective manner. 1-Substituted 1,1-di(pinacolatoboryl)-(E)-alk-2-enes are generated in situ from 1-substituted 1,1-di(pinacolatoboryl)alk-3-enes through ruthenium(II)-catalyzed double-bond transposition. These species undergo a chiral phosphoric acid catalyzed allylation reaction of aldehydes to produce the E isomers of anti-homoallylic alcohols. On the other hand, the corresponding Z isomers of anti-homoallylic alcohols are obtained when a dimeric palladium(I) complex is employed as the catalyst for this double-bond transposition. Thus, both E and Z isomers can be synthesized from the same starting materials. A B-C(sp2 ) bond remaining with the allylation product undergoes the Suzuki-Miyaura cross-coupling reaction to furnish a propionate-derived trisubstituted alkene motif in a stereo-defined form. The present method to construct the motifs with (E)- and (Z)-alkenes are successfully applied to the syntheses of (+)-isotrichostatic acid, (-)-isotrichostatin RK, and (+)-trichostatic acid, respectively.

Achievements of the Late Professor Teruaki Mukaiyama.

This essay illuminates the quintessence of the life of the late Professor Teruaki Mukaiyama, the founding editor of The Chemical Record. It shares first-hand knowledge of his heartfelt and enlightening mentorship as well as his major scientific contributions to the chemical community. It will serve as an ever-lasting message of the didactic guidance and encouragement he provided for the future generations.

Ultrasonographic diagnosis of a hair foreign body in the urinary bladder of a dog.

A 13-year-old male neutered mixed-breed dog with a history of gallbladder mucocele and urolithiasis was evaluated by ultrasound. Two hyperechoic, linear foreign bodies with no distal acoustic shadowing were detected in the urinary bladder and urethra. Following the ultrasound examination, the patient underwent cystoscopy, and two single hairs were found and successfully retrieved. Considering that urinary bladder foreign bodies may be a source for urinary tract infection and can act as a nidus for urocystolith formation, removal is recommended. This is the first published report describing ultrasonographic diagnosis of a hair foreign body in the canine urinary bladder and urethra.

Tracheal stenosis following endotracheal intubation in a dog.

A 2-month-old intact female Rottweiler was presented for investigation of coughing and respiratory distress 9 d after an exploratory laparotomy for intestinal foreign body removal. Tracheal stenosis was suspected by radiography and confirmed with computed tomography (CT) and tracheoscopy. After 1 wk of medical management, clinical signs had resolved and the severity of the tracheal narrowing was markedly improved, as confirmed by radiography and tracheoscopy. Tracheal stenosis is a considerable complication of endotracheal intubation in veterinary medicine and may be medically managed, depending on the severity of the tracheal injury. Key clinical message: To our knowledge, this is the first clinical case report of tracheal stenosis resulting from endotracheal intubation in a dog and its resolution after medical management.

Sténose trachéale après intubation endotrachéale chez un chien. Une femelle Rottweiler intacte âgée de deux mois a été présentée pour examen de la toux et de la détresse respiratoire neuf jours après une laparotomie exploratrice pour le retrait d'un corps étranger intestinal. Une sténose trachéale a été suspectée par radiographie et confirmée par tomodensitométrie et trachéoscopie. Après une semaine de prise en charge médicale, les signes cliniques avaient disparu et la sévérité du rétrécissement trachéal s'était nettement améliorée, tel que confirmés par la radiographie et la trachéoscopie. La sténose trachéale est une complication majeure de l'intubation endotrachéale en médecine vétérinaire et peut être prise en charge médicalement, selon la gravité de la lésion trachéale.Message clinique clé:À notre connaissance, il s'agit du premier cas clinique de sténose trachéale résultant d'une intubation endotrachéale chez un chien et de sa résolution après prise en charge médicale.(Traduit par Dr Serge Messier).

Photoinduced Dearomatizing Three-Component Coupling of Arylphosphines, Alkenes, and Water.

A unique photoinduced reaction that couples a triarylphosphine, an alkene, and water to produce 2-(cyclohexa-2,5-dienyl)ethylphosphine oxide is reported herein. The alkene inserts into a C(aryl)-P bond of the arylphosphine, the aryl ring is dearomatized into the cyclohexadienyl ring, and the phosphorus is oxidized. The three components are all readily available, and their intermolecular coupling significantly increases molecular complexity. The products formed are applicable to the Wittig olefination.

Dehydrogenative Coupling of Benzylic and Aldehydic C-H Bonds.

A photoinduced dehydrogenative coupling reaction between benzylic and aldehydic C-H bonds is reported. When a solution of an alkylbenzene and an aldehyde in ethyl acetate is irradiated with visible light in the presence of iridium and nickel catalysts, a coupled α-aryl ketone is formed with evolution of dihydrogen. An analogous C-C bond forming reaction occurs between a C-H bond next to the nitrogen of an N-methylamide and an aldehydic C-H bond to produce an α-amino ketone. These reactions provide a straightforward pathway from readily available materials leading to valued structural motifs of pharmacological relevance.