Synthesis of (Z)-Enediynes via Stereoinvertive Nucleophilic Substitution of (E)-Sulfonylethenes with Arylethynide, and Their Aggregation-Induced Optical Properties.

(Z)-Enediynes were successfully synthesized from a trio of terminal ethynes through consecutive three-step reactions: iodosulfonylation of ethyne with I2/PhSO2Na, followed by ethynylations of iodo and sulfonyl moieties of the resulting iodosulfonylethene via Sonogashira-Hagihara coupling and nucleophilic addition-elimination, respectively. The molecular structure of the obtained (Z)-enediyne was fully characterized by X-ray crystal structure analysis, revealing that the nucleophilic substitution of (E)-sulfonylethene with arylethynide underwent a selective stereoinversion. The (Z)-enediynes exhibited photoluminescence in both the solution and solid states (crystals and powders). Ph2N-substituted derivatives showed remarkable solvatofluorochromism, and upon replacing the solvent from toluene to acetonitrile, the emission color changed from blue to yellow.

Chemodivergent Synthesis of Polycyclic Aromatic Diarylamines and Carbazoles by Thermal/Photochemical Process-Controlled Dephosphinylative Functionalizations of Amino(phosphinyl)arenes.

A chemodivergent synthesis of polycyclic aromatic diarylamines and carbazoles was established by employing thermally or photochemically controlled processes using KOtBu/1,10-phenanthroline. The synthetic processes involved the dephosphinylation of 9-amino-10-(phosphinyl)phenanthrenes, which were obtained through a regioselective palladium-catalyzed direct [4 + 2] benzannulation of phosphinyl ynamines with 2-iodobiphenyls. When the dephosphinylation was conducted under heating conditions (∼100 °C), it proceeded to yield 9-aminophenanthrene. However, when the reaction was performed under the illumination of purple light (LEDs, λmax = ca. 390 nm), KOtBu/1,10-phenanthroline promoted single-electron-transfer-triggered dephosphinylation followed by cyclization, producing the corresponding π-expanded carbazoles. We successfully synthesized a highly π-expanded dicarbazole through a dual dephosphinylative cyclization. Additionally, we present the optical properties of a series of amino compounds produced through the dephosphinylative processes.

Process-Divergent Syntheses of 4- and 5-Sulfur-Functionalized 1,2,3-Triazoles via Copper-Catalyzed Azide-Alkyne Cycloadditions of 1-Phosphinyl-2-sulfanylethynes.

4-Sulfanyl-substituted 1,2,3-triazoles were provided regioselectively with good yields and broad scope via consecutive t-BuOK-promoted dephosphinylation of 1-phosphinyl-2-sulfanylethynes and copper-catalyzed azide-alkyne cycloadditions (CuAAC) with alkyl azides. Unsymmetrically substituted ditriazoles were successfully obtained using a tandem dephosphinylative CuAAC protocol with diazides. Direct CuAAC of the 1-phosphinyl-2-sulfanylethynes with azides afforded regioisomeric mixtures of 4-phosphinyl-5-sulfanyl- and 5-phosphinyl-4-sulfanyl-1,2,3-triazoles that were easily separable from one another. When the phosphinyl- and sulfanyl-substituted triazoles were treated with t-BuOK, the dephosphination proceeded smoothly, yielding the corresponding 5- and 4-sulfanyltriazoles, respectively. 5-(1-Aryl-1-hydroxymethyl)-4-sulfanyltriazoles were synthesized by stepwise treatment of 5-phosphinyl-4-sulfanyltriazole with MeMgBr and arylaldehydes. Additionally, Ph2P(O) and RS groups in the triazoles were easily converted to Ph2P and RSO2 by PhSiH3-reduction and m-CPBA-oxidation, respectively. Following the dephosphinylative CuAAC of 1-phosphinyl-2-(4-t-butylphenylsulfanyl)ethyne with aryl azides and m-CPBA-oxidation, potent antagonists of pregnane X receptor LC-58 and LC-59 were successfully produced.

Endoscopic approach in the diagnosis of high-grade pancreatic intraepithelial neoplasia.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high-grade pancreatic intraepithelial neoplasia (HG-PanIN), whose tumorous lesion is undetectable on cross-sectional images such as computed tomography or magnetic resonance image, long-term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG-PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG-PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG-PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post-ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4-Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early-stage PDAC.

Dephosphinylative [4 + 2] Benzannulation of Phosphinyl Ynamines: Application to the Modular Synthesis of Polycyclic Aromatic Amines.

A series of 9-amino-10-halophenanthrenes were synthesized through a one-pot process, including dephosphinylative Sonogashira-Hagihara coupling of 2-bromobiphenyls with air-stable phosphinyl ynamines, followed by halonium-promoted [4 + 2] benzannulation of the resulting 2-(aminoethynyl)biphenyls. Nonsubstituted and methyl-substituted 2-bromobiphenyls rapidly underwent the Sonogashira-Hagihara aminoethynylation and the halogenative Friedel-Crafts benzannulation to provide the corresponding amino(halo)phenanthrenes in high yields, while electron-sufficient and -deficient substrates did slowly undergo the former and the latter to result in low yields, respectively. This protocol worked well for the syntheses of highly π-extended aminophenanthrenes and aminobenzonaphthothiophenes with different optical properties. Further application of this approach between 2,2″- and 2',5'-dibromo-p-terphenyls with phosphinyl ynamines led to the regioselective formation of 6,13-diamino-5,12-dihalo- and 5,12-diamino-6,13-dihalo-dibenz[a,h]anthracenes via dual aminoethynylation and [4 + 2] benzannulation. The obtained analogues showed different ultraviolet-visible absorption and photoluminescence spectra with different emission quantum yields in CH2Cl2 solution and the powder state.

Head-to-Tail Oligomerization by Silylene-Tethered Sonogashira Coupling on Ag(111).

On-surface synthesis is a powerful method for the fabrication of π-conjugated nanomaterials. Herein, we demonstrate chemoselective Sonogashira coupling between (trimethylsilyl)ethynyl and chlorophenyl groups in silylethynyl- and chloro-substituted partially fluorinated phenylene ethynylenes (SiCPFPEs) on Ag(111). The desilylative Sonogashira coupling occurred with high chemoselectivity up to 75 %, while the competing Ullmann and desilylative Glaser homocoupling reactions were suppressed. A combination of bond-resolved scanning tunneling microscopy/atomic force microscopy (STM/AFM) and DFT calculations revealed that the oligomers were obtained by the formation of intermolecular silylene tethers (-Me2 Si-) through CH3 -Si bond activation at 130 °C and subsequent elimination of the tethers at an elevated temperature of 200 °C.

A meso-meso ß-ß ß-ß Triply Linked Subporphyrin Dimer.

A meso-meso ß-ß ß-ß triply linked subporphyrin dimer 6 was synthesized by stepwise reductive elimination of ß-to-ß doubly PtII -bridged subporphyrin dimer 9. Dimer 6 was characterized by spectroscopic and electrochemical measurements, theoretical calculations, and picosecond time-resolved transient absorption spectroscopy. X-ray diffraction analysis reveals that 6 has a bowl-shaped structure with a positive Gaussian curvature. Despite the curved structure, 6 exhibits a remarkably red-shifted absorption band at 942 nm and a small electrochemical HOMO-LUMO gap (1.35 eV), indicating an effectively conjugated π-electronic network.

A Directly Fused Subporphyrin Dimer with a Wavelike Structure.

[Ni(cod)2 ]-mediated intramolecular reductive coupling of ß-ß' linked meso,meso'-dibromosubporphyrin dimer gave the anti-isomer of meso-meso', ß-ß' doubly linked subporphyrin dimer as the first example of a fused subporphyrin dimer. The fused dimer 3anti displays an wavelike coplanar structure, a perturbed and red-shifted absorption spectrum, reversible redox behaviors with a decreased electrochemical HOMO-LUMO band gap, and a short S1 -state lifetime owing to the delocalized π-electronic network.

ß,ß-Diborylated Subporphyrinato Boron(III) Complexes as Useful Synthetic Precursors.

Iridium-catalyzed borylation of B-aryl meso-free subporphyrinato boron(III) complexes (hereinafter referred to simply as subporphyrins) with bis(pinacolato)diboron gave 2,13-diborylated subporphyrins regioselectively, which served as promising synthetic precursors for 2,13-diarylated subporphyrins and doubly ß-to-ß 1,3-butadiyne-bridged subporphyrin dimers. 2,13-Diarylated subporphyrins display perturbed absorption spectra, depending upon the ß-aryl substituents. Doubly 1,3-butadiyne-bridged syn and anti subporphyrin dimers thus prepared exhibit differently altered absorption spectra with split Soret-like bands, which have been accounted for in terms of exciton coupling.

Effectiveness and safety of a new clip for delivery using a duodenoscope for bleeding after endoscopic sphincterotomy.

Background and study aims Hemostasis for post-endoscopic sphincterotomy (post-EST) bleeding involves no standard strategy. New clips designed for delivery using the duodenoscope (SureClip, Micro-Tech, Nanjing, China) have been utilized for gastrointestinal bleeding hemostasis and bleeding prevention after polypectomy and papillectomy. We retrospectively analyzed the effectiveness and safety of SureClip for post-EST bleeding. Patients and methods Of 608 patients with endoscopic sphincterotomy (EST), 41 cases (6.7%) experienced post-EST bleeding from 2019 to 2023. Of these patients, 24 underwent hemostasis by SureClip, and the success rate of complete hemostasis and complication by hemostasis by SureClip was analyzed. Results In 12 and 12 patients with urgent and delayed bleeding, 11 (91.7%) and 11 (91.7%) had successful hemostasis, respectively. In addition, missed patients achieved complete hemostasis with additional transcatheter arterial embolization and balloon compression, respectively. No complications were observed, including perforation, pancreatitis, and clipping bile duct and pancreatic duct by mistake. Conclusions Hemostasis with SureClip is safe, effective, and not expensive for post-EST bleeding. It could be the first choice for hemostasis in patients with post-EST bleeding refractory to balloon compression.

Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma.

BACKGROUND/PURPOSE: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). METHODS: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. RESULTS: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. CONCLUSIONS: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.

Curative surgery for primary squamous cell carcinoma of the liver: a rare case study.

Primary squamous cell carcinoma (SCC) of the liver is an extremely rare disease with a very poor prognosis. An 83-year-old woman was referred to our hospital with left abdominal pain. Laboratory data showed mildly elevated C-reactive protein and biliary enzymes. The tumor markers carcinoembryonic antigen, alpha-fetoprotein, and carbohydrate antigen 19-9 were within normal ranges. Contrast-enhanced computed tomography revealed a 60 mm-sized low-density mass with poor contrast enhancement located in the lateral segment of the liver. The tumor showed low signal on T1-weighted magnetic resonance imaging (MRI) and high signal on T2-weighted MRI. The cytology of bile juice showed no malignant findings. Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed, which was suggestive of primary hepatic SCC. Tumor markers cytokeratin 19 fragment (CYFRA) and SCC-related antigen were elevated, at 25.2 ng/mL and 14.7 ng/mL, respectively. Left lobectomy and hilar lymph node dissection were performed. One month after surgery, the tumor marker values showed a marked decrease of 1.8 ng/mL for CYFRA and 0.3 ng/dL for SCC-related antigen. The patient has been without recurrence for more than one and half year postoperatively. SCC-related antigen and CYFRA were markedly decreased after tumor resection in this case, which may suggest their utility as tumor markers for SCC of liver origin.

Synthesis, optical properties and crystal structure of (E,E)-1,3-(3,4:9,10-dibenzododeca-1,11-diene-5,7-diyne-1,12-di-yl)benzene.

The de-hydro-benzannulene (E,E)-1,3-(3,4:9,10-dibenzododeca-1,11-diene-5,7-diyne-1,12-di-yl)benzene, C26H16, was successfully synthesized via photocatalyst-assisted stereoselective reductive de-sulfonyl-ation of 1,3-bis-{1-phenyl-sulfonyl-2-[2-(tri-methyl-silylethyn-yl)phen-yl]ethen-yl}benzene, C44H42O4S2Si2, and subsequent desilylative cyclization of the resulting (E,E)-bis-silyl-protected dienyne, C32H34Si2. The structure of the de-hydro-benzannulene thus obtained was confirmed by single-crystal X-ray analysis; three benzene rings are connected to one another by a 1,3-butadiynylene and a pair of ethenylene arrays. Although the π-system expanded efficiently in the de-hydro-benzannulene, it was observed that the butadiynylene and ethenylene arrays were strained, showing smaller [171.3 (2)-172.6 (2) °] and larger bond angles [122.5 (2)-131.9 (2)°] than the conventional bond angles, respectively. In CHCl3, the de-hydro-benzannulene showed the longest absorption band at 377 nm. When irradiated by UV light, it emitted fluorescence at 468 nm (ΦF = 0.26) and 504 nm (ΦF = 0.24) in CHCl3 and in the powdered state, respectively.

Acute necrotic disorder of the small intestine post-coronavirus disease-2019 vaccination.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is extensively used worldwide, and its safety has been proven. Herein, we report a case of an acute necrotic disorder in the small intestine post-COVID-19 vaccination. The patient developed severe abdominal pain the day after the first vaccination. Contrast-enhanced computed tomography showed extensive ileum wall thickening and ascites. Colonoscopy revealed a ring-shaped ulcer and stricture in the terminal ileum. Ileocecal resection was performed, and the patient did not have further episodes of a necrotic disorder in the small intestine. Although it is unknown if this event is associated with vaccination, and this occurrence also does not outweigh the efficacy and safety of the Pfizer-BioNTech COVID-19 vaccine, gastroenterologists need to be aware of this rare case, given its noteworthy timing.

Pathological Features and Imaging Findings in Pancreatic Carcinoma In Situ.

OBJECTIVES: This study aimed to evaluate the pathological features and imaging findings of pancreatic carcinoma in situ (PCIS). METHODS: Twenty patients with PCIS were categorized as flat (F) (n = 6) and low papillary (LP) (n = 14) types. RESULTS: None of F type and 8 (57%) of 14 with LP type lesions showed intraductal infiltrations of the main pancreatic duct (MPD) greater than 10 mm. None of F type and 3 (21%) of 14 with LP type lesions showed skip lesions in the MPD. Magnetic resonance cholangiopancreatography showed irregular MPD stenoses in 5 (83%) of 6 with F and 13 (100%) of 13 with LP type lesions. Magnetic resonance cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 3.6 mm for F, and 11.6 mm for LP type lesions. Endoscopic retrograde cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 2.8 mm for F, and 14.3 mm for LP type lesions. Pancreatic cancer recurrences limited to the remnant pancreas occurred in 2 patients with LP type lesions. CONCLUSIONS: In LP type PCIS, intraductal infiltration of the MPD occurs frequently. There may be multiple lesions, and lesions may recur in the remnant pancreas. Long-term strict follow-up assessments should be implemented for LP type PCIS.

Process-Controlled Regiodivergent Copper-Catalyzed Azide-Alkyne Cycloadditions: Tailor-made Syntheses of 4- and 5-Bromotriazoles from Bromo(phosphoryl)ethyne.

We developed a regiodivergent syntheses of 4- and 5-bromo-substituted 1,2,3-triazoles in copper-catalyzed azide-alkyne cycloadditions (CuAACs) by taking advantage of bromo(phosphoryl)ethyne 1 as a bromoethyne equivalent. A one-shot dephosphorylative CuAAC of 1 afforded 4-bromotriazoles, which was transformed into a histone deacetylase 8 (HDAC8)-selective inhibitor, NCC-149. However, the direct CuAAC catalyzed by CuI/Cu(OAc)2 provided 5-bromo-4-phosphoryltriazoles. The consecutive nucleophilic substitution of the bromo group with thiols followed by MeOK-promoted dephosphorylation gave 5-thio-substituted triazoles.

Disproportionation-induced solid-state fluorescence in 6,13-dihydropentacenes.

The thermally and photolytically induced disproportionation of 6,13-dihydropentacene derivatives into tetrahydropentacenes and pentacenes results in unique solid-state fluorescence. The fluorescence thereby depends on the molecular structure and the molecular arrangement in the solid state.

Cobalt-Catalyzed Hydroacylative Dimerization of Allenes Leading to Skipped Dienes.

A cobalt-diphosphine catalyst has been found to promote a selective 1:2 coupling reaction between aldehydes and allenes to form ß,δ-dialkylidene ketones, featuring skipped diene moieties, with high regioselectivities and stereoselectivities. The reaction is distinct from previously reported, rhodium-catalyzed aldehyde-allene 1:2 coupling to afford ß,γ-dialkylidene ketones bearing 1,3-diene moieties. The present hydroacylative dimerization involves a unique allene/allene oxidative cyclization mode to form a C1-C2 linkage between the allene molecules.

Nickel-Catalyzed Decarbonylative Alkylation of Aroyl Fluorides Assisted by Lewis-Acidic Organoboranes.

Herein, nickel-catalyzed decarbonylative C-F bond alkylation of aroyl fluorides with organoboron reagents is reported. Aroyl fluorides are more chemically stable than the corresponding aroyl chlorides and can be readily synthesized from the corresponding carboxylic acids. The fluoronickel intermediate formed via oxidative addition interacts with Lewis-acidic trialkylboranes, and the subsequent decarbonylative alkylation proceeds. This new synthetic methodology allows 1,2-bifunctionalization of aromatic carboxylic acids via palladium-catalyzed ortho-C-H arylation. In addition, an unprecedented 1,4-nickel migration on ortho-arylated aroyl fluorides was observed. As a demonstration of the synthetic utility of the present reaction, the sequential 1-alkyl-2-arylation of 3-hydroxy-2-naphthoic acid was accomplished via chemoselective alkylation at a fluorocarbonyl moiety and the subsequent C-O bond arylation at an acetoxy group.

Experimental study on stability of a high-porosity expanded polytetrafluoroethylene graft in dogs.

PURPOSE: The purpose of the present study was to evaluate the stability of a high-porosity expanded polytetrafluoroethylene (ePTFE) graft, which has been shown to possess excellent biocompatibility and tissue integration. METHODS: The graft used in the present study was a high-porosity ePTFE graft , which had an average internodal distance of approximately 60 microm and a random node architecture with tortuous path channels extending from the outer to the inner surface. Eleven beagle dogs (each group n = 3 or 4) weighing 10-12 kg were used. The graft, with a 6 mm inside diameter and a 30-40 mm length, was implanted into the canine abdominal aorta and retrieved after 2-80 weeks. The deformation of the graft was evaluated by conventional computed tomography (CT). The radial tensile strength, longitudinal tensile strength, and suture retention strength of the graft were measured after 2-80 weeks. RESULTS: CT studies showed no anastomotic aneurysm or deformation of the graft. Physical tests demonstrated no significant deterioration in suture retention strength, radial tensile strength or longitudinal tensile strength for periods ranging from 2-80 weeks compared to pre-implantation grafts. CONCLUSION: The graft possesses adequate stability that ensures safe and effective clinical use.