Functionalization of Siloxanes with Arynes Generated from o-Triazenylarylboronic Acids.

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

The crucial role of SETDB1 in structural and functional transformation of epithelial cells during regeneration after intestinal ischemia reperfusion injury.

Su (var) 3-9, enhancer of seste, trithorax (SET)-domain bifurcated histone lysine methyltransferase (SETDB1) plays a crucial role in maintaining intestinal stem cell homeostasis; however, its physiological function in epithelial injury is largely unknown. In this study, we investigated the role of SETDB1 in epithelial regeneration using an intestinal ischemia/reperfusion injury (IRI) mouse model. Jejunum tissues were sampled after 75 min of ischemia followed by 3, 24, and 48 h of reperfusion. Morphological evaluations were performed using light microscopy and electron microscopy, and the involvement of SETDB1 in epithelial remodeling was investigated by immunohistochemistry. Expression of SETDB1 was increased following 24 h of reperfusion and localized in not only the crypt bottom but also in the transit amplifying zone and part of the villi. Changes in cell lineage, repression of cell adhesion molecule expression, and decreased histone H3 methylation status were detected in the crypts at the same time. Electron microscopy also revealed aberrant alignment of crypt nuclei and fusion of adjacent villi. Furthermore, increased SETDB1 expression and epithelial remodeling were confirmed with loss of stem cells, suggesting SETDB1 affects epithelial cell plasticity. In addition, crypt elongation and increased numbers of Ki-67 positive cells indicated active cell proliferation after IRI; however, the expression of PCNA was decreased compared to sham mouse jejunum. These morphological changes and the aberrant expression of proliferation markers were prevented by sinefungin, a histone methyltransferase inhibitor. In summary, SETDB1 plays a crucial role in changes in the epithelial structure after IRI-induced stem cell loss.

Development of 3-triazenylaryne and its application to iterative aryne reactions via o-triazenylarylboronic acids.

Herein, a novel aryne species, 3-triazenylaryne, was developed and its regioselectivity was revealed. Based on the regioselectivity, various alkyne moieties were introduced by iodoalkynylation, and further derivatization to o-triazenylarylboronic acids as 3-alkynylaryne precursors was enabled. Therefore, 3-triazenylaryne was developed as a divergent platform for the generation of various 3-alkynylarynes.

Preparation of Alkyl Di(p-tolyl)sulfonium Salts and Their Application in Metal-Free C(sp3)-C(sp3) and C(sp3)-C(sp2) Bond Formations.

Alkyldiarylsulfonium salts were synthesized by a combination of active sulfonium species, prepared through the activation of diarylsulfoxide, and alkyl nucleophiles. The isolated sulfonium salts were subjected to the allylation and cyclopropanation of the active methylene compounds and metal-free C(sp3)-C(sp2) couplings via oxyallyl cation intermediates under mild conditions. The series of reactions included an umpolung strategy for the coupling of alkyl nucleophiles and metal-free C-C bond formation using sulfonium salts.

Aryne Generation from o-Triazenylarylboronic Acids Induced by Brønsted Acid.

We report aryne generation from 2-triazenylarylboronic acids using an activator such as Brønsted acids, Lewis acids, and solid acids. With the use of (±)-Camphorsulfonic acid [(±)-CSA], the aryne precursors provided cycloadducts with a range of arynophiles in high yields. Aryne generated under the acidic conditions underwent chemoselective cycloaddition with a furan in the presence of a basic arynophile, namely an amine. Hammett plot analyses revealed that an aryne generation mechanism induced by (±)-CSA is distinct from the mechanism induced by silica gel.

Short-term experience with aspiration embolectomy using a ACE68 reperfusion catheter to treat embolic superior mesenteric artery occlusion.

We report the short-term results with aspiration embolectomy using an ACE68 reperfusion catheter to treat patients with acute embolic superior mesenteric artery (SMA) occlusion. Our study included 4 consecutive male patients ranging in age from 72 to 86 years (mean age 79 years). In all patients, the main trunk of the SMA was occluded. The technical success rate was 100% for all procedures. There were no major procedure-related complications. One patient underwent laparotomy with intestinal resection after successful recanalization. No patient reported clinical symptoms of abdominal ischemia at follow-up. Our short-term experience shows that percutaneous aspiration embolectomy using an ACE68 reperfusion catheter is an effective treatment for acute mesenteric ischemia.

Intramolecular Aminolactonization for Synthesis of Furoindolin-2-One.

Propellanes are polycyclic compounds in which tricyclic systems share one carbon-carbon single bond. Propellane frameworks that consist of larger sized rings are found in a variety of natural products. As an approach to the stereoselective synthesis of the propellane framework, one of the efficient methods is forming several rings in a single operation. Lapidilectine B (1) is composed of a propellane framework and was synthesized through the oxidative cyclization of trisubstituted alkenes. When the alkene with an ester moiety was treated with N-iodosuccinimide (NIS), iodocyclization proceeded to give the cyclic carbamate. On the other hand, when PhI(OAc)2 was allowed to react in the carboxyl form, a furoindolin-2-one structure corresponding to the A-B-C ring of lapidilectine B (1) was produced. Furthermore, when Pd(OAc)2 catalyst was used for cyclization under oxidative conditions, the product yield was improved.

Congenital Abdominal Aortic Aneurysm in a Four Year Old Girl.

INTRODUCTION: Abdominal aortic aneurysm (AAA) in neonates, infants, and children is uncommon, usually occurring as a result of infections, connective tissue disorders, vasculitis, or iatrogenic trauma. A case of idiopathic congenital AAA, an extremely rare disease of unknown origin, is described. REPORT: In March 2018, a 40 mm hypoechoic mass adjacent to the left kidney was detected incidentally by abdominal ultrasound for investigation of hypercalciuria in a four year old girl. Contrast enhanced computed tomography (CT) revealed an infrarenal fusiform AAA measuring 39 mm in maximum diameter, a 15 mm left renal artery aneurysm, a 14 mm right hypogastric artery aneurysm, and a 12 mm left hypogastric artery aneurysm. Cerebral magnetic resonance imaging revealed multiple intracranial aneurysms between 8 and 15 mm in diameter. Considering the size of the AAA and risk of rupture, surgical repair was planned. In May 2018, the congenital AAA was successfully repaired with a 10 mm Dacron aorto-aortic tube graft. Increases in the size of the left renal artery aneurysm and a left middle meningeal artery aneurysm were detected 12 and 14 months post-operatively, respectively. Coil embolisations were performed. An intracranial dural arteriovenous fistula (AVF) was discovered incidentally by cerebral angiography for treatment of the left middle meningeal artery aneurysm. Transarterial embolisation for AVF was also performed. At the 21 month post-operative follow up, the patient is doing well, and the untreated aneurysms have not grown. CONCLUSION: Long term outcomes after surgical repair for congenital AAA are unclear. Moreover, growth of residual aneurysms was detected post-operatively, so follow up with frequent multimodality imaging for multiple aneurysms is necessary.

Nasogastric administration of lenvatinib solution in a mechanically ventilated patient with rapidly growing anaplastic thyroid cancer.

SUMMARY: A 54-year-old woman was referred to our hospital with a cervical tumor. CT revealed a cervical tumor extending to the upper mediastinum, tracheal deviation and tumor infiltration in the cervical vessels. She was followed-up because no diagnosis of malignancy was made by cytology. However, 2 months later, a CT scan showed enlargement of the tumor and tracheal stenosis, and a surgical biopsy was performed and she was diagnosed with anaplastic thyroid cancer (ATC). The tracheal tube with tracheal stenosis could not be removed due to the rapid growth of the tumor, necessitating management by mechanical ventilation. Due to the difficulty of surgical resection, she was treated with lenvatinib. A lenvatinib solution was made and administered via a nasogastric tube. After lenvatinib treatment, the tumor volume decreased and the tracheal stenosis improved. The tracheal tube was removed and oral intake became possible. She was discharged and received ambulatory lenvatinib therapy. The tumor was significantly reduced in size, but gradually grew and was exposed through the cervical wound 6 months later. Esophageal perforation occurred 10 months after the start of treatment. Lenvatinib was re-administered via a nasogastric tube. Eleven months later, the patient died of massive bleeding from the exposed cervical tumor. Patients with advanced ATC may require management with mechanical ventilation for airway stenosis or with a nasogastric tube for esophageal stenosis and perforation. We experienced a case in which lenvatinib was safely administered via a nasogastric tube while performing mechanical ventilation. LEARNING POINTS: An anaplastic thyroid cancer patient under mechanical ventilator management was treated with lenvatinib via a nasogastric tube. The lenvatinib solution can easily be prepared and administered via a nasogastric tube. The lenvatinib solution was effective for a patient with difficulty in oral intake. Lenvatinib could also improve the prognosis of an anaplastic thyroid cancer patient with severe airway and esophageal trouble.

Left Subclavian Artery Revascularization for Delayed Paralysis after Thoracic Endovascular Aortic Repair.

Spinal cord ischemia (SCI) is a devastating complication following thoracic endovascular aortic repair (TEVAR). A man with a ruptured thoracic aortic aneurysm (TAA) was transferred to our hospital. Emergency TEVAR, with left subclavian artery (LSA) coverage, was performed for the ruptured TAA. On postoperative day two, the patient had incomplete paralysis in his legs, presumably caused by SCI. We performed LSA revascularization (LSAR) to provide blood supply to the spinal cord; his paralysis improved and almost resolved after surgery. To our knowledge, this is the first report on LSAR's efficacy for delayed paraplegia due to SCI.

Resected Intrahepatic Cholangiocarcinoma with Anaphylactic Shock from a Preoperative Liver Function Test before Hepatectomy.

The indocyanine green test is a reliable liver function examination before major hepatectomy, and anaphylaxis is rarely a concern. A 65-year-old male patient without epigastralgia was diagnosed with a 2.2-cm intrahepatic cholangiocarcinoma. He had no history of allergic reactions. Some liver dysfunction was indicated by the laboratory data; however, there was no marked obstructive jaundice and the liver functional reserve was maintained by technetium-99m galactosyl serum albumin. The indocyanine green test was routinely performed, but the patient immediately demonstrated severe anaphylaxis due to indocyanine green administration. He had cardiorespiratory arrest, but recovered after immediate resuscitation. Although acute renal and respiratory failure was significant, the patient recovered at day 10 after the event, and his liver function and other organ functions were improved. Then, the scheduled left hepatectomy with caudate and extrahepatic duct resection was successfully performed without issues. The patient exhibited no allergic response against the administration of antibiotics or other drugs and the postoperative course was uneventful. The patient was discharged on day 17. The tumor was diagnosed as stage III intrahepatic cholangiocarcinoma and R0 resection was accomplished. Preoperative management, including the liver functional loading test, should be carefully carried out before major hepatectomy.

A rare case of simultaneous rectal and gastric carcinomas accompanied with inferior mesenteric arterioportal fistula: case report.

BACKGROUND: Inferior mesenteric arterioportal fistula (APF) is rare as only 35 case reports in the literature. We herein presented a case of simultaneously double cancer in the rectum and stomach with inferior mesenteric APF, which is the first case report by searching using PubMed. Combination of interventional embolization and surgical operation seemed to be optimal treatment for avoiding postoperative complications and the curability. CASE PRESENTATION: A 66-year-old male with epigastric pain was admitted to a practitioner. He underwent a gastroscopy with biopsy, and cancer located in the lesser curvature of the gastric cardia was found. Enhanced CT did not reveal wall thickening of the stomach and distant metastases, but several swollen lymph nodes were observed in the right cardia. In the arterial phase, dilation of inferior mesenteric vein (IMV) and superior rectal artery (SRA) were noted, which raised suspicions of an arterioportal communication. Colonoscopy revealed a type 2 rectal tumor located 12 cm from the anal verge. The histological diagnosis of well-differentiated tubular adenocarcinoma was confirmed by biopsy. At a first step, we planned to perform a radiological embolization of inflow vessels to APFs except for SRA. Additionally, we determined the interval time of 1 month between the first low anterior rectal resection and the sequential gastrectomy for the purpose of decreasing portal pressure. The postoperative course was uneventful without hemorrhagic complications, and S-1 was taken internally 1 year as adjuvant chemotherapy for gastric cancer. The patient still lives without recurrence of this cancer with APF and portal vein thrombosis 2.5 years after the aforementioned surgeries. CONCLUSION: Inferior mesenteric APF and/or arteriovenous fistula (AVF) would be consisted of the several inflow arteries as superior rectal, internal iliac, and median sacral arteries, and outflow veins as inferior mesenteric, internal iliac, and median sacral veins. To determine the therapeutic strategy for left-sided colorectal cancers with abnormal vessel communications of the pelvis, it is significant to comprehend distribution and component vessels of APF and/or AVF.

Dirhodium(ii)-catalyzed ortho C-H amination of sterically congested N,N-dialkylanilines.

Dirhodium(ii)-catalyzed ortho C-H amination of N,N-dialkylanilines has been developed. Sterically congested 1,2-diaminobenzenes were obtained in high yields with excellent chemo- and regioselectivities from para-substituted anilines and even from para-unsubstituted anilines. The ortho selectivity observed was rationalized in terms of the interaction between the dialkylamino group and a Rh(ii)-nitrene intermediate.

Total Synthesis of (+)-Gliocladin C Based on One-Pot Construction of a 3a-(3-Indolyl)pyrroloindoline Skeleton by Sulfonium-Mediated Cross-Coupling of Tryptophan and Indole.

Total synthesis of (+)-gliocladin C has been achieved on the basis of one-pot construction of the 3a-(3-indolyl)pyrroloindoline core structure by the cross-coupling of a tryptophan derivative and an indole promoted by a sulfonium species generated from dialkylsulfoxide and triflic anhydride.

Direct C2-Functionalization of Indoles Triggered by the Generation of Iminium Species from Indole and Sulfonium Salt.

An indole core bearing a functional group on the C2 position is often found as a key structure in biologically active natural products and pharmaceuticals. Here, we report direct C2-functionalization of indoles triggered by the formation of an iminium species generated from indole and a sulfonium reagent. The reaction proceeded under very mild conditions to give the corresponding C2-substituted indole derivatives in good to high yields.

Design and Synthesis of Non-peptide RGD Mimics for Evaluation of Their Utility as Anti-platelet Agents.

Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and Wieland-Miescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC50 values of 3e were 0.91 mM (ADP initiation) and 0.54 mM (collagen initiation).

Port-site implantation of Type A Masaoka Stage I thymoma after video-assisted thoracic surgery: a case report.

A 60-year-old woman was referred to our hospital with an anterior mediastinal tumor measuring 3.5 cm in diameter on computed tomography (CT). We performed tumor resection by video-assisted thoracic surgery (VATS) with three ports. The final diagnosis was Type A Masaoka Stage I thymoma. On follow-up CT performed 36 months after the operation, two pleural tumors were detected at the port sites through which the forceps and ultrasonic scalpel had passed repeatedly during the operation. We therefore performed a second operation and enucleated the tumors while preserving the ribs. However, other tumor tissue was detected along the surgical marginal line during the pathological diagnosis after the operation. Surgeons should thus be aware that port-site recurrence can occur after VATS resection of Type A thymoma, despite its mild biological behavior. Wide resection of the chest wall is therefore recommended for operations of port-site recurrence after VATS thymectomy.

Synthesis and ABCG2 inhibitory evaluation of 5-N-acetylardeemin derivatives.

An efficient and versatile synthesis of 5-N-acetylardeemin (1a) and sixteen 2-, 3- and 13-substituted derivatives 1b-q was achieved through Ugi three-component reaction of 3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole and cyclization/epimerization. Their inhibitory activity on the drug efflux of breast cancer resistance protein (ABCG2) was evaluated by flow cytometric analysis of accumulation of Hoechst 33342 stain in Flp-In-293/ABCG2 cells. Most of the derivatives exhibited a stronger ABCG2 inhibitory effect compared with natural product 1a. The derivative 1m with a 4-tolyl substituent at the C-13 position exhibited the most potent ABCG2 inhibition. This preliminary structure-activity relationship study indicates that an electron-rich aryl moiety as the 13-substituent is key to increasing the inhibitory activity.

DMSO/Tf2O-mediated cross-coupling of tryptamine with substituted aniline to access C3a-N1'-linked pyrroloindoline alkaloids.

The cross-coupling of tryptamine with substituted aniline to access C3a-nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a-N1'-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.

Asymmetric total synthesis of (-)-leuconoxine via chiral phosphoric acid catalyzed desymmetrization of a prochiral diester.

The asymmetric total synthesis of (-)-leuconoxine has been achieved. The desymmetrization of a prochiral diester using a chiral phosphoric acid catalyst produced a highly enantioenriched lactam with excellent yield. The ring construction featuring an intramolecular N-acyliminium cyclization and the one-step pyrrolidone formation using Bestmann's ylide was successfully accomplished.