Asymmetric synthesis of enantioenriched α-allyl esters through Pd(BINAPHANE)-catalysed allylation of disubstituted ketenes.

Pd2dba3·CHCl3 (2.5 mol%)-BINAPHANE (5 mol%) was used to promote the first catalytic enantioselective allylation of disubstituted ketenes to give α-allyl esters. The ester products were formed in good to excellent yields (61-93% yield for 13 examples, 16 examples in all), with moderate to good enantioselectivity (68-80% ee for 7 examples).

Characteristics of Electronic Health Services in Saudi Arabia During the COVID-19 Pandemic.

INTRODUCTION: Saudi Arabia's experience using digital technology during the COVID-19 pandemic helped the country in tackling the pandemic. We aim to explore a bundle of consumer-directed electronic health services released by the Ministry of Health (MOH) in Saudi Arabia in response to the COVID-19 pandemic. METHODS: We reviewed all electronic health services that have been released in response to the COVID-19 pandemic by the MOH in Saudi Arabia. A list of the services has been prepared and each service has been explored in detail. The service terms and procedures have also been reviewed for pertinent information. RESULTS: There were 13 services noted in total. Services were devoted to the general public and healthcare practitioners. Services ranged from simple appointment booking for the COVID-19 vaccine to interactive maps of all available healthcare centers and electronic prescriptions of medications. In addition, 10 applications were published for use on smartphones. CONCLUSION: The digitalization of healthcare services in Saudi Arabia has eased communication between the public and healthcare professionals. Furthermore, electronic health services served as an effective tool against the spread of COVID-19 infection during the pandemic.

Testing for anosmia and ageusia in patients presenting to the emergency department with suspected coronavirus disease 2019 in Saudi Arabia.

OBJECTIVE: This study investigated the role of objective olfactory dysfunction (OD) and gustatory dysfunction (GD) testing among patients with suspected coronavirus disease 2019 (COVID-19) who presented with respiratory symptoms. METHODS: A prospective, blinded, observational study was conducted in the emergency units of two tertiary hospitals. Participants were asked to identify scents in the pocket smell test (PST) and flavors in four different solutions in the gustatory dysfunction test (GDT). We assessed the level of agreement between objective findings and self-reported symptoms. We evaluated the diagnostic accuracy of chemosensory dysfunction for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Of 250 participants, 74 (29.6%) were SARS-CoV-2-positive. There was slight agreement between self-reported symptoms and objective findings (kappa = 0.13 and 0.10 for OD and GD, respectively). OD assessed by the PST was independently associated with COVID-19 (adjusted odds ratio = 1.89, 95% confidence interval, 1.04-3.46). This association was stronger when OD was combined with objective GD, cough, and fever (adjusted odds ratio = 7.33, 95% confidence interval, 1.17-45.84). CONCLUSIONS: Neither the PST nor GDT alone are useful screening tools for COVID-19. However, a diagnostic scale based on objective OD, GD, fever, and cough may help triage patients with suspected COVID-19.

Tin-Free Access to the ABC Core of the Calyciphylline A Alkaloids and Unexpected Formation of a D-Ring-Contracted Tetracyclic Core.

A tin-free strategy for the successful cyclization of a variety of internal alkyne-containing N-chloroamine precursors to the ABC core via cyclization of a neutral aminyl radical is established. Deuterium labeling experiments confirm that the solvent is the primary source of the final H atom in the cyclization cascade. These conditions enabled a streamlined route to a ß-ketoester intermediate poised for intramolecular Knoevenagel condensation to construct the seven-membered D-ring of calyciphylline A alkaloids. However, exposure to CsF in t-BuOH at elevated temperatures led to an unexpected decarboxylation to form a D-ring-contracted tetracyclic core.

Asymmetric Synthesis of Dipropionate Derivatives through Catalytic Hydrogenation of Enantioenriched E-Ketene Heterodimers.

A highly diastereoselective approach to dipropionate derivatives through Pd/C-catalyzed hydrogenation of enantioenriched E-ketene heterodimers is described. Catalytic hydrogenation of the E-isomer of ketene heterodimer ß-lactones (12 examples) provides access to syn,anti-ß-lactones (dipropionate derivatives) bearing up to three stereogenic centers (dr up to 49:1), and with excellent transfer of chirality (ee up to >99%).

Catalytic Asymmetric Synthesis of Ketene Heterodimer ß-Lactones: Scope and Limitations.

In this article we describe extensive studies of the catalytic asymmetric heterodimerization of ketenes to give ketene heterodimer ß-lactones. The optimal catalytic system was determined to be a cinchona alkaloid derivative (TMS-quinine or Me-quinidine). The desired ketene heterodimer ß-lactones were obtained in good to excellent yields (up to 90%), with excellent levels of enantioselectivity (≥90% ee for 33 Z and E isomer examples), good to excellent (Z)-olefin isomer selectivity (≥90:10 for 20 examples), and excellent regioselectivity (only one regioisomer formed). Full details of catalyst development studies, catalyst loading investigations, substrate scope exploration, protocol innovations (including double in situ ketene generation for 7 examples), and an application to a cinnabaramide A intermediate are described. The addition of lithium perchlorate (1-2 equiv) as an additive to the alkaloid catalyst system was found to favor formation of the E isomer of the ketene heterodimer. Ten examples were formed with moderate to excellent (E)-olefin isomer selectivity (74:25 to 97:3) and with excellent enantioselectivity (84-98% ee).

Real-Time, Selective Detection of Copper(II) Using Ionophore-Grafted Carbon-Fiber Microelectrodes.

Rapid, selective detection of metals in complex samples remains an elusive goal that could provide critical analytical information for biological and environmental sciences and industrial waste management. Fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFMs) is an emerging technique for metal analysis with broad potential applicability because of its rapid response to changes in analyte concentration and minimal disturbance to the analysis medium. In this communication, we report the first effective application of covalently modified CFMs to achieve highly selective, subsecond Cu(II) measurements using FSCV. A two-part strategy is employed for maximum selectivity: Cu(II) binding is augmented by a covalently grafted ionophore, while binding of other metals is prevented by chemical blocking of nonselective surface adsorption sites. The resulting electrodes selectively detect Cu(II) in a complex medium comprising several interfering metals. Overall, this strategy represents a transformative innovation in real-time electrochemical detection of metal analytes.

Asymmetric Synthesis of Deoxypropionate Derivatives via Catalytic Hydrogenolysis of Enantioenriched Z-Ketene Heterodimers.

A diastereoselective approach to deoxypropionate derivatives through Pd/C-catalyzed hydrogenolysis of enantioenriched ketene heterodimers is described. Catalytic hydrogenolysis of the Z-isomer of ketene heterodimers facilitates access to anti-deoxypropionate derivatives (10 examples with dr 7:1 to >20:1). Transfer of chirality from the Z-ketene heterodimer to an acid product was good to excellent in most cases (78-99% ee for 12 examples).

Toward the ABCD Core of the Calyciphylline A-Type Daphniphyllum Alkaloids: Solvent non-Innocence in Neutral Aminyl Radical Cyclizations.

The Daphniphyllum alkaloids remain an attractive target in the synthetic community because of their unique framework and promising biological activities. We have shown that the ABC core of the calyciphylline A-type alkaloids can be rapidly accessed via the tandem cyclization of a neutral aminyl radical with a polarized cyclic olefin. Deuterium labeling experiments and reactions omitting a tin hydride reagent suggest that the solvent is the major source of the terminating hydrogen atom in the cyclization cascade. Incorporation of an internal alkyne in the radical pathway was tolerated in the reaction, and it provided the necessary atoms to enable completion of the D ring of the calyciphylline A-type alkaloids.

Phosphine-catalyzed asymmetric synthesis of ß-lactones from disubstituted ketenes and aldehydes.

In this article we describe a general catalytic procedure for the formation of ß-lactones bearing two stereogenic centers, from disubstituted ketenes and achiral aldehydes. BINAPHANE was found to display excellent enantioselectivity (≥90% ee for eight examples) and good diastereoselectivity (≥90:10 for 13 examples) in catalyzing the formation of ß-lactones bearing two stereogenic centers from achiral aldehydes (both aromatic and aliphatic) and alkylarylketenes or dialkylketenes. A preference for formation of the trans diastereomer was observed in these reactions. For those reactions where BINAPHANE failed as a catalyst, tri-n-butylphosphine was found to be an effective achiral nucleophilic catalyst, effecting good yield and diastereoselectivity in racemic ß-lactone formation. Evidence for the involvement of phosphonium enolate intermediates in the reaction mechanism was obtained through reaction monitoring by (31)P NMR spectroscopy and by comparison with previously characterized intermediates observed in the phosphine-catalyzed ketene homodimerization reaction.

Rapid access to the heterocyclic core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids via tandem cyclization of a neutral aminyl radical.

A streamlined approach to the tertiary amine-containing core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids is presented. A known carvone derivative is converted into the core structure in only four synthetic operations, and it is well poised for further elaboration. The key enabling methodology is a radical cyclization cascade beginning with addition of a secondary, neutral aminyl radical to the ß-position of an enone, followed by trapping with a pendant alkyne.

Household cost of antenatal care and delivery services in a rural community of Kaduna state, northwestern Nigeria.

BACKGROUND: Maternal mortality remains a leading cause of death among women of reproductive age. While Nigeria has only two percent of the global population, it contributes 10% to the global maternal mortality burden. Antenatal care (ANC) reduces the incidence of maternal mortality. However, financial capability affects access to antenatal care. Thus, the rural poor are at a higher risk of maternal mortality. MATERIALS AND METHODS: A cross-sectional descriptive study involving 135 women (pregnant women and those who are 6 weeks postpartum). Structured interviewer-administered questionnaires were used for data collection. Data analysis was carried out using statistical package for social sciences software (version 17). RESULTS: The average amount spent on booking and initial laboratory investigations were N77 (half a dollar) and N316 ($2), respectively. Per ANC visit, average amount spent on drugs and transportation were N229 ($1.5) and N139 ($0.9) respectively. For delivery, the average amount spent was N1500 ($9.6). On an average, ANC plus delivery cost about N3,365.00 ($22). There was a statistically significant association between husband's income and ANC attendance (X(2) = 2.451, df = 2, P = 0.048). CONCLUSION: Cost of Antenatal care and delivery services were not catastrophic but were a barrier to accessing antenatal care and facility-based delivery services in the study area. ANC attendance was associated with the income of household heads. Pro-poor policies and actions are needed to address this problem, as it will go a long way in reducing maternal mortality in this part of the country.

Household Cost of Antenatal Care and Delivery Services in a Rural Community of Kaduna State; Northwestern Nigeria

Maternal mortality remains a leading cause of death among women of reproductive age. While Nigeria has only two percent of the global population; it contributes 10 to the global maternal mortality burden. Antenatal care (ANC) reduces the incidence of maternal mortality. However; financial capability affects access to antenatal care. Thus; the rural poor are at a higher risk of maternal mortality. Materials and Methods: A cross-sectional descriptive study involving 135 women (pregnant women and those who are 6 weeks postpartum). Structured interviewer-administered questionnaires were used for data collection. Data analysis was carried out using statistical package for social sciences software (version 17). Results: The average amount spent on booking and initial laboratory investigations were N77 (half a dollar) and N316 ($2); respectively. Per ANC visit; average amount spent on drugs and transportation were N229 ($1.5) and N139 ($0.9) respectively. For delivery; the average amount spent was N1500 ($9.6). On an average; ANC plus delivery cost about N3;365.00 ($22). There was a statistically significant association between husband's income and ANC attendance (X 2 = 2.451; df = 2; P = 0.048). Conclusion: Cost of Antenatal care and delivery services were not catastrophic but were a barrier to accessing antenatal care and facility-based delivery services in the study area. ANC attendance was associated with the income of household heads. Pro-poor policies and actions are needed to address this problem; as it will go a long way in reducing maternal mortality in this part of the country

Endoscopic endonasal multilayer repair of traumatic ethmoidal roof cerebrospinal fluid rhinorrhea in children.

OBJECTIVE: Pediatric traumatic cerebrospinal fluid (CSF) leak is a challenging problem in diagnosis and management. Posttraumatic leaks frequently present by intermittent rhinorrhea or by recurrent attacks of meningitis, which can be the only presenting symptom. The objective of this study is to present our experience in management of pediatric traumatic ethmoidal roof CSF leaks using a multilayer repair technique via an endoscopic approach. METHODS: Ten pediatric patients (aged 4-14 years, six males and four females) presenting with posttraumatic ethmoidal roof CSF rhinorrhea were operated upon between January 2007 and December 2010, using an endoscopic endonasal multilayer repair technique. Preoperative radiological evaluation included both multidetector computed tomography (MDCT) with ultra-thin 1mm cuts, and magnetic resonance imaging (MRI) high resolution coronal T2-weighted sequence. Intraoperatively, the GE InstaTrak™ 3500 electromagnetic navigation system was used in all cases. Postoperative follow-up was done clinically by regular endoscopic examinations and radiologically by MRI assessment using the same preoperative protocol. RESULTS: Clinically all patients presented with unilateral intermittent watery rhinorrhea with periods ranging from 5 to 24 months before operation. Seven cases had a history of recurrent meningitis. Defects were confined to ethmoidal roof in all 10 cases (right side in seven and left side in three), and ranged in size from 2 to 7 mm(2) (mean 3.9 ± 1.5 mm(2)). Two cases had more than one defect on the same side. All defects were identified preoperatively using our radiological protocol. One case was associated with a meningocele with no brain herniation and another case was associated with a small meningoencephalocele. Mean postoperative hospitalization was 6 days (range 4-8 days). None of our patients developed any intra or postoperative complications or required revision surgery with a 100% success rate after a mean follow-up duration of 29.4 ± 14.4 months (range 12-52 months). CONCLUSIONS: Pediatric posttraumatic CSF leaks involving the ethmoidal roof can be successfully managed via the endonasal endoscopic route using a multilayer repair technique, thus limiting complications associated with external approaches. Preoperative imaging including MDCT and high resolution MRI is of paramount importance for detecting the defect site and for planning surgery.

Catalytic asymmetric heterodimerization of ketenes.

In this Communication we describe an unprecedented catalytic asymmetric heterodimerization of ketenes of wide substrate scope. The alkaloid-catalyzed method provides access to ketene heterodimer ß-lactones and allows even two different monosubstituted ketenes to be cross-dimerized, with excellent enantioselectivity (17 examples with ≥90% ee) and excellent heterodimer regioselectivity observed in all cases.

Josiphos-catalyzed asymmetric homodimerization of ketoketenes.

In this paper the development of a chiral phosphine-catalyzed homodimerization of ketoketenes that provides access to a variety of highly substituted ketoketene dimer ß-lactones (11 examples) is reported. The Josiphos catalytic system displays good to excellent enantioselectivity (up to 96% ee). Ring-opening reactions of the enantioenriched ketoketene dimers were also carried out to access 1,3-diketones, enol esters, and ß-hydroxyketones with good diastereoselectivity.

Phosphine-catalyzed asymmetric synthesis of beta-lactones from arylketoketenes and aromatic aldehydes.

In this paper, the development of a chiral phosphine-catalyzed formal [2 + 2] cycloaddition of aldehydes and ketoketenes that provides access to a variety of highly substituted beta-lactones (14 examples) is reported. The BINAPHANE catalytic system displays excellent enantioselectivity (seven examples with ee >or=90%) and high diastereoselectivity favoring formation of the trans-diastereomer (nine examples with dr >or=90:10).

Endoscopic choanoplasty without stenting for congenital choanal atresia repair.

OBJECTIVE: To present our experience with an endoscopic technique for congenital choanal atresia transnasal repair without the use of intranasal stents. METHODS: Twenty-one patients with congenital choanal atresia (11 bilateral aged 2-27 days and 10 unilateral aged 2-16 years) were operated upon between December 2005 and January 2009, using an endoscopic choanoplasty technique in which a laterally based mucoperiosteal flap was elevated off the posterior nasal septum and atretic plate. Endoscopic resection of bony atresia including abnormally thickened vomer and pterygoid processes was done until a widely patent 'neo-uni-choana' was created. Two surgeons worked simultaneously using the "four-hand" technique. No stents were used. All patients received prophylactic systemic antibiotics and local steroid-antibiotic intranasal drops for 1 week postoperatively. Parents were taught to irrigate and clean both nasal cavities using frequent saline nasal drops and a portable home suction device. RESULTS: Preoperative computed tomography showed that among bilateral choanal atresia (BCA) patients, 9 (81.8%) were bony-membranous and 2 (18.2%) were pure bony atresia. All unilateral choanal atresia (UCA) cases had pure bony atresia. Two neonates with BCA had associated congenital cardiac anomalies. None had the CHARGE association. Operative time ranged from 30 to 75 min (mean 51.4+/-13.4 min.) for BCA and 35 to 90 min (mean 57.5+/-18 min.) for UCA repairs. Mean estimated intraoperative blood loss was 35.5+/-15.1 cc. in BCA and 204+/-105.6 cc. in UCA surgery. No intraoperative complications such as skull base damage or CSF leak were encountered. Patients were followed-up for periods ranging from 6 to 18 months in BCA and 12 to 24 months in UCA cases. Three BCA cases showed postoperative restenosis by granulation tissue that was successfully managed by endoscopic excision with good nasal breathing thereafter. Complications included mid-nasal synechiae, not interfering with nasal breathing, in three BCA cases and a small hard palate perforation in one UCA patient that healed conservatively, without further surgery needed. CONCLUSIONS: Transnasal endoscopic choanoplasty repair for both unilateral and bilateral choanal atresia without intranasal stenting was found to be an expedient and safe procedure that affords minimal blood loss, minimal complications with a high rate of success.

Organocatalytic dimerization of ketoketenes.

A general method for the catalytic dimerization of ketoketenes is described. Tri-n-butylphosphine was found to be the optimal organocatalyst for the racemic reaction. When lithium iodide was used as an additive, the reaction was rendered selective for dimer formation (dimer/trimer > or = 16:1). Ring-opening reactions of the ketoketene dimers as well as preliminary studies toward the development of an asymmetric variant are also reported.