Divergent Total Syntheses of Napelline-Type C20-Diterpenoid Alkaloids: (-)-Napelline, (+)-Dehydronapelline, (-)-Songorine, (-)-Songoramine, (-)-Acoapetaldine D, and (-)-Liangshanone.

The napelline-type alkaloids possess an azabicyclo[3.2.1]octane moiety and an ent-kaurane-type tetracyclic skeleton (6/6/6/5) along with varied oxidation patterns embedded in the compact hexacyclic framework. Herein, we disclose a divergent entry to napelline-type alkaloids that hinges on convergent assembly of the ent-kaurane core using a diastereoselective intermolecular Cu-mediated conjugate addition and subsequent intramolecular Michael addition reaction as well as rapid construction of the azabicyclo[3.2.1]octane motif via an intramolecular Mannich cyclization. The power of this strategy has been demonstrated through efficient asymmetric total syntheses of eight napelline-type alkaloids, including (-)-napelline, (-)-12-epi-napelline, (+)-dehydronapelline, (+)-12-epi-dehydronapelline, (-)-songorine, (-)-songoramine, (-)-acoapetaldine D, and (-)-liangshanone.

Sequence-Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones.

The stereodivergent iridium-catalyzed allylic alkylation and fluorination of acyclic ketones is described. α-Pyridyl-α-fluoroketones with vicinal tertiary and quaternary stereocenters were obtained in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence-dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.

Iridium-Catalyzed Asymmetric Allylic Aromatization Reaction.

Described herein is an asymmetric allylic aromatization (AAAr) strategy that employs readily accessible equivalents of benzylic nucleophiles in iridium-catalyzed allylic substitution reactions with the concomitant formation of aromatic rings by aromatization. The optimized reaction conditions involving a catalyst derived from a commercially available iridium precursor and the Carreira ligand are compatible with equivalents of benzylic nucleophiles derived from 4- or 5-methyloxazoles, 5-methylthiazoles, 4- or 5-methylfurans, 2- or 3-methylbenzofurans, 3-methylbenzothiophene, 3-methylindole, 1-methylnaphthalene, and methylbenzene. This strategy provides straightforward accesses to valuable heterocyclic aromatic compounds, bearing a homobenzylic stereogenic center, in an enantiopure form and would be difficult to access otherwise. The versatility of the reaction was showcased by the further elaboration of the products into useful building blocks and a drug analogue.

Enzyme-Inspired Chiral Secondary-Phosphine-Oxide Ligand with Dual Noncovalent Interactions for Asymmetric Hydrogenation.

Inspired by the unique character of enzymes, we developed novel chiral SPO (secondary-phosphine-oxide) ligand (SPO-Wudaphos) which can enter into both ion pair and H-bond noncovalent interactions. The novel chiral SPO-Wudaphos exhibited excellent results in the asymmetric hydrogenation of α-methylene-γ-keto carboxylic acids, affording the chiral γ-keto acids with up to over 99 % ee. A series of control experiments and DFT calculations were conducted to illustrate the critical roles of both the ion pair and H-bond noncovalent interactions.

Rhodium/Yanphos-Catalyzed Asymmetric Interrupted Intramolecular Hydroaminomethylation of trans-1,2-Disubstituted Alkenes.

The first interrupted asymmetric hydroaminomethylation reaction was developed. The challenging trans-1,2-disubstituted olefins were employed as substrates, and a series of valuable chiral pyrrolidinones and pyrrolidines were obtained in high yields with high regioselectivities and excellent enantioselectivities. Several synthetic transformations were conducted, demonstrating the high synthetic utility of our method. A creative route for the synthesis of vernakalant and Enablex was also developed.

Superior acetone sensor based on hetero-interface of SnSe2/SnO2 quasi core shell nanoparticles for previewing diabetes.

To improve gas sensing performance of SnO2 sensor, a heterostructure constructed by SnO2 and SnSe2 is designed and synthesized via hydrothermal method and post thermal oxidation treatment. The obtained SnSe2/SnO2 composite nanoparticles demonstrate a special core-shell structure with SnO2 nanograins distributed in the shell and mixed SnSe2 and SnO2 nanograins in the core. Owning to the promoted charge transfer effect invited by SnSe2, the sensor based on SnSe2/SnO2 composite nanoparticles exhibit expressively enhanced acetone sensing performance compared to the pristine SnO2 sensor. At the working temperature of 300 °C, the SnSe2/SnO2 composite sensor with optimized composition exhibits superior sensing property towards acetone, including high response (10.77-100 ppm), low theoretical limit of detection (0.354 ppm), high selectivity and good reproducibility. Moreover, the sensor shows a satisfactory sensing performance in trace acetone gas detection under high humidity condition (relative humidity: 70-90%), making it a promising candidate to constructing exhaled breath sensors for acetone detection.

Retinal Displacement: Providing New Insights for Retinal Detachment Surgery.

PURPOSE: To review the current literature on retinal displacement and provide a discussion of potential risk factors, postoperative outcomes, and future directions. METHODS: Two databases, MEDLINE and EMBASE, were mined using a directed search strategy to identify all articles on retinal displacement. RESULTS: We identified 1522 articles. A total of n = 14 articles were retained. We provide an overview on the potential influence of surgical type (n = 4), tamponade agents (n = 5), postoperative posture (n = 6), and preoperative retinal status (n = 5) on incidence of retinal displacement and visual outcomes (n = 8). Discussion. Pars plana vitrectomy (PPV) with gas tamponade is associated with displacement rates of up to 72%, typically in a downward direction. Meanwhile, pneumatic retinopexy and PPV with silicone oil may offer similar surgical success with a significantly lower risk of displacement. The impact of heavy liquids such as perfluorocarbon liquid, postoperative positioning and preoperative extent of detachment on displacement remains inconclusive. Patients with displacement had a significantly lower visual acuity and higher rates of distortion than those without displacement. However, not all patients with displacement experienced visual symptoms. CONCLUSION: Retinal displacement is a new concept in our understanding of retinal detachment. Additional studies are needed to better define its impact on postsurgical outcomes.

Pneumatic Retinopexy in Patients with Primary Rhegmatogenous Retinal Detachment Meeting PIVOT Trial Criteria.

PURPOSE: To identify the proportion of patients with primary rhegmatogenous retinal detachment (RRD) presenting to a retina practice that meet 'Pneumatic Retinopexy versus Vitrectomy for the Management of Primary RRD' (PIVOT) trial criteria and to assess anatomic and functional outcomes of pneumatic retinopexy (PnR) in this population. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Patients with primary RRD treated between October 2009 and November 2017 at an academic vitreoretinal practice in Canada. METHODS: Medical records of all cases >18 years old with primary RRD were reviewed and the proportion of patients meeting PIVOT criteria was determined. Patients that met PIVOT criteria who underwent PnR with a follow-up >3 months were included for further analysis. MAIN OUTCOME MEASURES: The primary outcome was the primary retinal reattachment rate at 12 months among patients meeting PIVOT criteria undergoing PnR. RESULTS: A total of 1,091 patients were identified, of which 577 (52.9%) met PIVOT criteria. Of these, 482/577 (83.5%) underwent PnR, but 54/482 (11.2%) were excluded as these had been enrolled in the PIVOT trial, and another 40/482 (8.3%) were excluded due to short follow-up (<3 months). Therefore, data pertaining to 388 patients is included in our analysis. 79.4% (308/388), 78.2% (280/358), 76.5% (241/315) and 73.9% (178/241) of patients who followed up at 3, 6, 12, and 24 months, respectively, had primary anatomic reattachment. A total of 20.6% (80/388) of patients did not reattach with the initial PnR or re-detached in the early post-procedure period (3 months), 2.1% (8/388) of patients re-detached between 3-12 months, and 1.3% (5/388) re-detached after 1 year. Phakic lens status was the only significant predictor of PnR success at 12 months in a multivariate logistic regression analysis (P = 0.006). Mean logMAR VA improved from 0.90 ± 0.90 (Snellen 20/159) at baseline t 0.34 ± 0.40 (Snellen 20/44) at 12 months (P < 0.001). CONCLUSIONS: Over 50% of patients presenting to an academic tertiary retina practice with primary RRD met PIVOT criteria and were eligible for PnR. Evidence from this study demonstrates a durable primary anatomic retinal reattachment rate with PnR in patients fulfilling PIVOT criteria, with similar results to those encountered in the PIVOT trial.

Distribution gaps in cataract surgery care and impact on seniors across Ontario.

OBJECTIVE: To assess recent cataract service delivery across communities of all sizes in Ontario. DESIGN: Retrospective analysis of health records. PARTICIPANTS: All Ontario Health Insurance Plan users. METHODS: Raw physician Ontario Health Insurance Plan claims data for cataract surgery (E140A, E214A) from April 1, 2009, to March 31, 2014, were extracted from the Ontario Ministry of Health and Long-Term Care (MOHLTC) IntelliHealth database. Cataract surgery claims data were sorted by sex, by age, and by Ontario's 444 municipalities based on patient residence. Cataract surgery distribution was examined by population centre: Large Urban (≥100 000 persons), Medium (30 000-99 999 persons), Small (1000-29 999 persons), and Rural (<1000 persons) as defined by Statistics Canada. Wait times were extracted from the MOHLTC wait times database. Cataract surgery rate (CSR), defined as the number of cataract surgeries performed per million, was calculated. RESULTS: Cataract surgery volumes remained unchanged from 2010 to 2014. Mean patient age was 71.6 ± 10 years. Patients lived in large urban (63%), medium (15%), small (21%), and rural (0.6%) communities. Mean wait times increased by 28% to 68.5 days, and 90th percentile wait times increased by 44% to 154.3 days. A reduction in CSR was observed among seniors aged 65-74 years (-10%) and 75+ years (-16%). Rural communities showed the largest decline (-19%). Among seniors aged ≥75 years, CSR declined the most for those living in rural communities (-25%). CONCLUSIONS: Adjusting the current government policy of zero-growth in cataract surgery volumes will support growing demands for cataract care in our aging population.

Reduced social participation among seniors with self-reported visual impairment and glaucoma.

OBJECTIVE: Social participation benefits health. We assessed the relationship between self-reported visual impairment (VI) and glaucoma versus seniors' social participation. METHODS: Data from individuals aged ≥65 years responding to the Canadian Community Health Survey Healthy Aging 2008/2009 (n = 16,369) was analyzed. Participation in eight social activities by seniors with and without self-reported VI or glaucoma was compared. RESULTS: Seniors with VI had significantly reduced participation (p<0.05) in sports/physical activities (18.0% vs. 33.6%), family/friendship activities outside the household (39.7% vs. 53.0%), service club/fraternal organization activities (11.4% vs. 18.4%), volunteer/charity work (13.4% vs. 24.9%), educational/cultural activities (16.2% vs. 24.5%), and other social recreational activities (21.6% vs. 31.0%) compared to those without VI. Differences in participation in church/religious activities (40.6% vs. 44.5%) and community/professional association activities (15.3% vs. 18.0%) were non-significant between seniors with and without VI. Seniors with glaucoma versus those without had significantly reduced participation (p<0.05) in family/friendship activities (46.6% vs. 52.9%), sports/physical activities (26.0% vs. 33.6%) and volunteer/charity work (20.4% vs. 24.9%). No participation in any social activity was significantly higher among seniors with VI versus those without (10.1% vs. 2.9%, p<0.05), but was similar among seniors with and without glaucoma (3.9% vs. 3.1%, p>0.05). After adjusting for the effects of age, sex, education, household income, ethnicity, job status and chronic diseases (adjusted odds ratio, aOR = 3.4 (95% confidence interval (CI) 2.0-5.8), seniors with VI but no glaucoma were more likely not to engage in any social activities compared to seniors without VI and no glaucoma. Seniors with glaucoma but without VI had a similar level of non-participation (aOR = 0.9, 95%% CI 0.5-1.7). CONCLUSIONS: Significantly reduced social participation was found across six community activities among seniors with self-reported VI and in three activities among those with self-reported glaucoma. Policies and programs that help seniors with VI or glaucoma engage in social activities are needed.

Canadians with visual impairment utilize home care services more frequently.

OBJECTIVE: To assess the impact of presenting visual impairment (PVI) on the utilization of formal home care services in Canada. Formal home care services were defined as services provided by professionals. Presenting visual impairment was self-reported impaired vision. DESIGN: Cross-sectional survey. PARTICIPANTS: Respondents to the Canadian Community Health Survey - Healthy Aging 2008/2009 (n = 30 865). METHODS: Self-reported utilization of formal home care services were compared by PVI status and sociodemographic groups. RESULTS: Overall, 23.9% of Canadians aged 45+ years with PVI utilized home care services versus 4.8% of those without (p < 0.0001). Canadians aged 65+ years (11.5%) used home care services more frequently than those aged 45-64 years (2.3%; p < 0.001). Among Canadians aged 65+ years, Caucasians (11.8%) were more frequent users than non-Caucasians (2.9%; p = 0.0002). Among Caucasians aged 65+ years, higher levels of utilization were documented in seniors with PVI (32.3%) versus those without (11.0%; p < 0.0001), females (14.5%) versus males (8.5%; p < 0.0001), seniors without a partner (18.6%) versus those with a partner (7.9%; p < 0.001), and seniors with incomes under the 20th percentile (14.7%) versus their peers with incomes ≥20th percentile (9.8%; p < 0.0001). Seniors with PVI were 30% more likely than those without to utilize home care services after adjusting for confounding effects (prevalence ratio = 1.3, 95% CI 1.1-2.5). Among nonusers of home care services, unmet needs for home care services were reported by 10.0% of Caucasian seniors with PVI versus 3.1% of those without PVI (p < 0.0001). CONCLUSIONS: Canadians with visual impairment are more likely to utilize formal home care services compared to those without.

A new ferrocenyl bisphosphorus ligand for the asymmetric hydrogenation of α-methylene-γ-keto-carboxylic acids.

Upon incorporation of a noncovalent ion pair interaction, a new chiral ferrocenyl bisphosphorus ligand t-Bu-Wudaphos was developed. t-Bu-Wudaphos can be easily synthesized with very high diastereoselectivity as a highly air stable solid. The new ligand exhibited excellent reactivities and enantioselectivities in the asymmetric hydrogenation of α-methylene-γ-keto-carboxylic acids via an ion pair noncovalent interaction (up to >99% conversion, >99% ee).

Ferrocenyl chiral bisphosphorus ligands for highly enantioselective asymmetric hydrogenation via noncovalent ion pair interaction.

A new class of ferrocenyl chiral bisphosphorus ligand, Wudaphos, was developed, and exhibits excellent ee and activity (ee up to 99%, TON up to 20 000) for the asymmetric hydrogenation of both 2-aryl and 2-alkyl acrylic acids through ion pair noncovalent interaction under base free and mild reaction conditions. Well-known anti-inflammatory drugs such as naproxen and ibuprofen together with the intermediate for the preparation of Roche ester and some bioactive compounds were also efficiently obtained with excellent ee. Control experiments were conducted and revealed that the ion pair noncovalent interaction and chain length played important roles.