Ruthenium(II)-Catalyzed Oxidative Annulation of Imidazo[1,5-a]quinolin-2-iums Salts and Internal Alkynes via C-H Bond Activation.

Ruthenium(II)-catalyzed synthesis of π-conjugated fused imidazo[1,5-a]quinolin-2-ium derivatives have been achieved via C-H activation of quinoline-functionalized NHC (NHC = N-heterocyclic carbene) and oxidative coupling with internal alkynes. The reaction occurred with high efficiency, broad substrate scope, tolerates a wide range of functional groups and utilized into a gram-scale. Synthetic applications of a coupled product have been exemplified in the late-stage derivatization of various highly functionalized scaffolds. Moreover, most of the annulated products exhibit intense fluorescence and have potential applications in optoelectronic devices. Mechanistic studies have provided insights into the spectroscopic characterization of key five-membered ruthenacycle intermediate and Ru(0) sandwich species. Based on several control experiments, deuterium-kinetic isotope effect, and thermodynamic activation parameters the mechanistic finding demonstrated that fused imidazo-[1,5-a]quinolin-2-ium C(2)-H bond cleavage is the rate-determining step and ruling out the possibility of reductive elimination for controlling the rate of reaction.

Triple Role of Proton Sponge (DMAN) in the Palladium-Catalyzed Direct Stereoselective Synthesis of C-Aryl Glycosides from Glycals.

The triple role of 1,8-bis(dimethylamino)naphthalene (proton sponge) as a reductant, ligand precursor, and organic base in the palladium-catalyzed Heck-type coupling reaction of glycals with aryl iodides affords the rapid and stereoselective synthesis of 2',3'-unsaturated α-C-aryl glycosides in excellent yields. The role of the proton sponge in reducing palladium(II) to (0) has been studied using cyclic voltammetry, UV-vis, HRMS, and other spectroscopic techniques. This is the first example of a palladium proton sponge complex utilized in coupling reactions. The method is observed to be tolerant of various functional groups, as demonstrated by the huge substrate scope. Moreover, the 2',3'-unsaturated α-C-aryl glycosides were also converted to 3-keto-ß-C-glycosides under sterically hindered pyridinium salt catalysis via a ring-opening and -closing mechanism.

Ru/O2-Catalyzed Oxidative C-H Activation/Alkyne Annulation Using Quinoline-Functionalized NHC as a Directing and Functionalizable Group.

The ruthenium/O2-catalyzed oxidative annulation reaction of imidazo[1,5-a]quinolin-2-ium salts with alkynes via N-heterocyclic carbene-directed C-H activation to obtain π-conjugated fused imidazo[1,5-a]quinolin-2-ium derivatives is reported. Molecular oxygen has been explored as an economic and clean oxidant and an alternative to metal oxidants. The current protocol exhibits a wide range of substrate scope including bioactive (±)-α-tocopherol derivatives. Moreover, most of the annulated products show strong fluorescence properties, indicating their potential for making new light-emitting materials.

Cyclometalated Ruthenium Catalyst Enables Selective Oxidation of N-Substituted Tetrahydroquinolines to Lactams.

Herein, we report an unusual α-methylene oxidation of N-substituted tetrahydroquinoline to lactams using the cyclometalated Ru(II)-complex as a catalyst. Cyclic-α-methylene C-H bonds are selectively oxidized under the reaction conditions even in the presence of α-methyl or reactive α-methylene C-H bonds. This methodology is also useful in the late-stage functionalization of pharmaceuticals. Mechanistic study demonstrates that the high-valent Ru(VI)-cis-dioxo species plays an important role in controlling selectivity.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Shrinking lung syndrome mimicking diaphragmatic palsy in systemic lupus erythematosus.

A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.

Chromium-Catalyzed Cross-Coupling of Methyl Ketones with Cyclic Ketones toward the Selective Synthesis of ß-Branched ß,γ-Unsaturated Ketones.

Chromium-catalyzed cross-coupling of methyl ketones with cyclic ketones to ß-branched ß,γ-unsaturated ketones are reported. Interestingly, single-crossed aldol condensation products are formed, even in reactions in which a mixture of products is possible. The reaction is highly chemoselective and regioselective. This catalytic route gives a unique opportunity to integrate the chemistry of the synthetic challenge cross-coupling reaction of ketones and the alkene migration reaction into a reaction pot.

Chemo- and Regioselective Catalytic Cross-Coupling Reaction of Ketones for the Synthesis of ß, γ-Disubstituted ß, γ-Unsaturated Ketones.

C-C bond forming reaction of ketone with aldehyde is well-studied for the synthesis of α, ß-unsaturated ketones, however, the reaction with two different ketones to unsaturated carbonyl compound has not yet been systematically studied. Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro-aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity (self- vs. crossed aldol products) and regioselectivity (thermodynamic vs. kinetic enolate). In this quest, we report here for the first time selective cross-coupling reaction of ketones to ß-branched ß, γ-unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H2 O as the only byproducts making the protocol environmentally benign. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three-carbon feedstock for the syntheses of simple ß, γ-unsaturated ketone compounds. The process can further be extended to the gram-scale reaction and late-stage functionalization of natural products. With the help of DFT calculations, several control experiments, and deuterium-labeling experiments, the mechanistic finding demonstrated that initial aldol-condensation of ketones to a ß, ß-disubstituted α, ß-unsaturated ketone, which further isomerizes to a ß, γ- unsaturated ketone via η3 -allyl ruthenium complex.

Congenital Myasthenic Syndrome Caused by DOK7 Mutation in a Quinquagenarian Male with Calf Hypertrophy.

ABSTRACT: Congenital myasthenic syndromes (CMS) are relatively rare neurologic syndromes of defective neuromuscular transmission that stem from mutations in various proteins at the myoneural junction. Classically, the patients present within the first 2 years of life; however, the disease can also have onset in the second or third decade of life. The disease characteristically involves the skeletal muscles and spares smooth and cardiac muscles. The patients present with weakness involving ocular, limb, axial, or bulbar muscles. The specific diagnosis in most cases is clinched by genetic testing. We report a 59-year-old man presenting with neuromuscular weakness for 3 years and calf hypertrophy. He had myopathic features on electrophysiologic studies with a decremental response on repetitive nerve stimulation. Genetic testing confirmed a diagnosis of DOK7 CMS. He was managed with salbutamol and showed significant improvement.

Direct C(3)5-H Polyfluoroarylation of 2-Amino/alkoxy Pyridines Enabled by a Transient and Electron-deficient Palladium Intermediate.

Herein, we present an unprecedented azine-limited C5-H polyfluoroarylation of 2-aminopyridines enabled by a transient and electron-deficient perfluoroaryl-Pd species via C-H/C-H coupling. The protocol further allows C3(5)-H polyfluoroarylation of 2-alkoxypyridines guided by sterics and electronics for the first time. The late-stage C-H functionalization of drugs, drug derivatives, and natural product derivatives and synthesis of C5-aryl drug derivatives further demonstrated the method's utility. The preliminary mechanistic studies reveal that the synergistic combination of the bulky yet electrophilic perfluoroaryl-Pd species and the partial nucleophilicity of the C5-position of 2-amino/alkoxy-pyridines is the origin of reactivity and selectivity. Importantly, the first experimental evidence for the role of diisopropyl sulfide is provided.

Prevalence and determinants of post-stroke sleep disorders: a cross-sectional hospital-based study.

INTRODUCTION: Post-stroke sleep disorders (PSSD) are an important part of post-stroke disability. PSSD is neglected as a part of stroke rehabilitation. We aimed to study the prevalence and determinants of PSSD in a hospital based, single center setting. METHODS: In a cross-sectional study, adult patients (≥ 18 years) with stroke (one month to one year after the onset), were enrolled in the study. Demographic, clinical, radiological, and motor and functional disabilities were assessed. Sleep quality was assessed with Pittsburg Sleep Quality Index (PSQI) and STOP BANG questionnaire (for obstructive sleep apnea [OSA]). Patients with poor sleep quality (PSQI > 5) were analyzed for risk factors. RESULTS: A total of 103 patients were recruited in the study period (January 2021 to June 2022). The self-reported prevalence of PSSD was 16% which increased to 72% when the PSQI was administered. High risk of OSA was present in 33%. In bivariate analysis, factors associated with PSQI > 5 were involvement of ≥ 2 lobes, lower body mass index (BMI), worse modified Rankin Scale (mRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Stroke Specific Quality of Life (SSQoL). In multivariate analysis, only depression was associated with PSQI > 5 (OR: 1.3 (1.0; 1.7); p-value = 0.03). CONCLUSION: PSSD had a prevalence of 72%. In multivariate analysis, the factor associated with PSQI > 5 was worse HAM-D score.

Complex motor tics and neurobehavioral syndrome in diencephalic-mesencephalic junction dysplasia: Association or causation?

Too little is known about DMJD in adults. Various phenotypic presentations in adults with DMJD and long-term follow-up is needed to further characterise this disease.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

Electrophysiology and Magnetic Resonance Neurography Findings of Nontraumatic Ulnar Mononeuropathy From a Tertiary Care Center.

BACKGROUND: Ulnar nerve is frequently involved in mononeuropathies of the upper limb. Ulnar neuropathies have been diagnosed conventionally using clinical and electrophysiological findings. Physicians opt for nerve imaging in patients with ambiguous electrophysiological tests to gain additional information, identify etiology and plan management. OBJECTIVES: The aim of this study was to describe the electrophysiological and the magnetic resonance neurography (MRN) findings in patients with nontraumatic ulnar neuropathy. METHODS: All consecutive patients with suspected nontraumatic ulnar mononeuropathy were recruited; clinical assessment and electrophysiological studies (EPSs) were done in all. After EPS, patients with localization of lesion along the ulnar nerve underwent MRN. RESULTS: All 39 patients recruited had clinical findings suggestive of ulnar neuropathy; Electrophysiological confirmation was possible in 36/39 (92.30%) patients. Localization of ulnar nerve lesion to elbow and wrist was possible in 27 (75%) and 9 (25%) patients, respectively. MRN was done in 22 patients; a lesion was identified in 19 of 22 (86.36%) ulnar nerves studied. Thickening and hyperintensity in T2 W/short TI inversion recovery images of ulnar nerve at the level of olecranon, suggesting ulnar neuropathy at elbow, was the commonest (8/22) imaging finding. CONCLUSIONS: MRN acts as a complimentary tool to EPS for evaluating nontraumatic ulnar neuropathy. By identifying the etiology, MRN is likely to modify the management decision.