Specific Discrimination Polymerization for Highly Isotactic Polyesters Synthesis.

Isotactic polymers have emerged with unique and excellent properties in material sciences. Specific discrimination polymerization provides an ideal pathway to achieve highly isotactic polymers from their racemic monomers, which is of great significance and a challenge in polymeric chemistry. Although an enantioselective catalyst-mediated asymmetric kinetic resolution polymerization (AKRP) process makes it possible, a general and well-defined strategy for catalyst design is still rarely reported. Here, based on a novel dual-ligand strategy, a new type of chiral (BisSalen)Al complex with high enantioselectivity has been described, in which perfect AKRP of racemic phenethylglycolide (Pegl) is achieved for the first time. The more confined asymmetric microenvironment formed by a dual ligand is the key to improve the enantioselectivity of the original catalyst. To illustrate the generality of this strategy, a series of (BisSalen)Al complexes with homo- or heterodual ligands were designed for the AKRP of Pegl.

Asymmetric Kinetic Resolution Polymerization of Racemic Lactide Mediated by Axial-Chiral Thiourea/Phosphazene Binary Organocatalyst.

Asymmetric kinetic resolution polymerization (AKRP) provides an ideal way to obtain highly isotactic polylactide (PLA) with superior thermal-mechanical properties from racemic lactide (rac-LA). However, the development of a new catalytic system with concurrent high activity and selectivity at ambient temperature remains a great challenge. Here, a series of simple and effective binary organocatalytic pairs containing axial-chiral thioureas and commercially available phosphazene bases were designed. These chiral binary organocatalytic pairs allow for both high polymerization activity and moderate enantioselectivity for AKRP of rac-LA at room temperature, yielding semi-crystalline and metal-free stereoblock PLA with a melting temperature as high as 186 °C. The highest kinetic resolution coefficient (krel) of 8.5 at 47% conversion was obtained, and D-LA was preferentially polymerized via kinetic resolution with a maximum selectivity factor (kD/kL) of 18.1, indicating that an enantiomorphic site control mechanism (ESC) was involved.

Degradation Product-Promoted Depolymerization Strategy for Chemical Recycling of Poly(bisphenol A carbonate).

The accumulation of waste plastics has a severe impact on the environment, and therefore, the development of efficient chemical recycling methods has become an extremely important task. In this regard, a new strategy of degradation product-promoted depolymerization process was proposed. Using N,N'-dimethyl-ethylenediamine (DMEDA) as a depolymerization reagent, an efficient chemical recycling of poly(bisphenol A carbonate) (BPA-PC or PC) material was achieved under mild conditions. The degradation product 1,3-dimethyl-2-imidazolidinone (DMI) was proven to be a critical factor in facilitating the depolymerization process. This strategy does not require catalysts or auxiliary solvents, making it a truly green process. This method improves the recycling efficiency of PC and promotes the development of plastic reutilization.

Associations of device-measured physical activity and sedentary time with quality of life and fatigue in newly diagnosed breast cancer patients: Baseline results from the AMBER cohort study.

BACKGROUND: This study examined associations of device-measured physical activity and sedentary time with quality of life (QOL) and fatigue in newly diagnosed breast cancer patients in the Alberta Moving Beyond Breast Cancer (AMBER) cohort study. METHODS: After diagnosis, 1409 participants completed the SF-36 version 2 and the Fatigue Scale, wore an ActiGraph device on their right hip to measure physical activity, and an activPAL device on their thigh to measure sedentary time (sitting/lying) and steps. ActiGraph data was analyzed using a hybrid machine learning method (R Sojourn package, Soj3x) and activPAL data were analyzed using activPAL algorithms (PAL Software version 8). Quantile regression was used to examine cross-sectional associations of QOL and fatigue with steps, physical activity, and sedentary hours at the 25th, 50th, and 75th percentiles of the QOL and fatigue distributions. RESULTS: Total daily moderate and vigorous physical activity (MVPA) hours was positively associated with better physical QOL at the 25th (ß = 2.14, p = <.001), 50th (ß = 1.98, p = <.001), and 75th percentiles (ß = 1.25, p = .003); better mental QOL at the 25th (ß = 1.73, p = .05) and 50th percentiles (ß = 1.07, p = .03); and less fatigue at the 25th (ß = 4.44, p < .001), 50th (ß = 3.08, p = <.001), and 75th percentiles (ß = 1.51, p = <.001). Similar patterns of associations were observed for daily steps. Total sedentary hours was associated with worse fatigue at the 25th (ß = -0.58, p = .05), 50th (ß = -0.39, p = .06), and 75th percentiles (ß = -0.24, p = .02). Sedentary hours were not associated with physical or mental QOL. CONCLUSIONS: MVPA and steps were associated with better physical and mental QOL and less fatigue in newly diagnosed breast cancer patients. Higher sedentary time was associated with greater fatigue symptoms.

Associations between health-related fitness and quality of life in newly diagnosed breast cancer patients.

PURPOSE: Newly diagnosed breast cancer patients face substantial stress and uncertainty that may undermine their quality of life (QoL). The purpose of the present study was to examine the associations between health-related fitness (HRF) and QoL in newly diagnosed breast cancer patients from the Alberta Moving Beyond Breast Cancer Study. METHODS: Newly diagnosed breast cancer patients with early-stage disease (n = 1458) were recruited between 2012 and 2019 in Edmonton and Calgary, Canada to complete baseline HRF and QoL assessments within 90 days of diagnosis. HRF assessments included cardiorespiratory fitness (VO2peak treadmill test), muscular fitness (upper and lower body strength and endurance tests), and body composition (dual x-ray absorptiometry). QoL was assessed by the Medical Outcomes Study Short Form 36 (SF-36) version 2. We used logistic regression analyses to examine the associations between quartiles of HRF and poor/fair QoL (bottom 20%) after adjusting for key covariates. RESULTS: In multivariable analysis, the least fit groups compared to the most fit groups for relative upper body strength (OR = 3.19; 95% CI = 1.98-5.14), lean mass percentage (OR = 2.31; 95% CI = 1.37-3.89), and relative VO2peak (OR = 2.08; 95% CI = 1.21-3.57) were independently at a significantly higher risk of poor/fair physical QoL. No meaningful associations were found for mental QoL. CONCLUSIONS: The three main components of HRF (muscular fitness, cardiorespiratory fitness, and body composition) were independently associated with physical QoL in newly diagnosed breast cancer patients. Exercise interventions designed to improve these components of HRF may optimize physical QoL and help newly diagnosed breast cancer patients better prepare for treatments and recovery.

Upper Limb Morbidity in Newly Diagnosed Individuals After Unilateral Surgery for Breast Cancer: Baseline Results from the AMBER Cohort Study.

PURPOSE: We aimed to examine potential associations between post-surgical upper limb morbidity and demographic, medical, surgical, and health-related fitness variables in newly diagnosed individuals with breast cancer. METHODS: Participants were recruited between 2012 and 2019. Objective measures of health-related fitness, body composition, shoulder range of motion, axillary web syndrome, and lymphedema were performed within 3 months of breast cancer surgery, and prior to or at the start of adjuvant cancer treatment. RESULTS: Upper limb morbidity was identified in 54% of participants and was associated with poorer upper limb function and higher pain. Multivariable logistic regression analysis identified mastectomy versus breast-conserving surgery (odds ratio [OR] 3.51, 95% confidence interval [CI] 2.65-4.65), axillary lymph node dissection versus sentinel lymph node dissection (OR 2.67, 95% CI 1.73-4.10), earlier versus later time from surgery (OR 1.58, 95% CI 1.15-2.18), and younger versus older age (OR 1.01, 95% CI 1.00-1.03) as significantly associated with a higher odds of upper limb morbidity, while mastectomy (OR 1.57, 95% CI 1.10-2.25), axillary lymph node dissection (OR 2.20, 95% CI 1.34-3.60), lower muscular endurance (OR 1.10, 95% CI 1.01-1.16) and higher percentage body fat (OR 1.04, 95% CI 1.00-1.07) were significantly associated with higher odds of moderate or greater morbidity severity. CONCLUSIONS: Upper limb morbidity is common in individuals after breast cancer surgery prior to adjuvant cancer treatment. Health-related fitness variables were associated with severity of upper limb morbidity. Findings may facilitate prospective surveillance of individuals at higher risk of developing upper limb morbidity.

Depression, happiness, and satisfaction with life in women newly diagnosed with breast cancer: Associations with device-measured physical activity and sedentary time.

BACKGROUND: Few studies have examined depression after a cancer diagnosis and before initiating adjuvant or neoadjuvant systemic treatments. In this study, we present baseline data on device-measured physical activity, sedentary behaviour, depression, happiness, and satisfaction with life in newly diagnosed breast cancer survivors. PURPOSE: To examine associations of accelerometer-assessed physical activity and sedentary time with depression symptoms and prevalence, happiness, and satisfaction with life. METHODS: Shortly after diagnosis, 1425 participants completed depression, happiness, and satisfaction with life measures and wore an ActiGraph® device on their hip to measure physical activity and the activPALTM inclinometer on their thigh for 7 days to measure sedentary time (sitting/lying) and steps (1384 completed both device measures). ActiGraph® data were analysed using a hybrid machine learning method (R Sojourn package, Soj3x), and activPALTM data using activPALTM algorithms (PAL Software version 8). We used linear and logistic regression to examine associations of physical activity and sedentary time with depression symptom severity (0-27) and depression prevalence, happiness (0-100), and satisfaction with life (0-35). For the logistic regression analysis, we compared participants with none-minimal depression (n = 895) to participants with some depression (that is, mild, moderate, moderately-severe, or severe depression [n = 530]). RESULTS: Participants reported a mean depression symptom severity score of 4.3 (SD = 4.1), a satisfaction with life score of 25.7 (SD = 7.2), and a happiness score of 70 (SD = 21.8). Higher moderate-to-vigorous physical activity (MVPA) was associated with reduced depression symptom severity scores (ß = -0.51, 95% CI: -0.87 to -0.14, p = 0.007). A 1 hour increase in MVPA was associated with a reduced odds of at least mild or worse depression by 24% (Odds Ratio [OR] = 0.76, 95% CI: 0.62-0.94, p = 0.012). Higher daily step counts were associated with lower depression symptom severity scores (ß = -0.16, 95% CI: -0.24 to -0.10, p < 0.001). Perceptions of happiness was associated with higher MVPA (ß = 2.17, 95% CI: 0.17-4.17, p = 0.033). Sedentary time was not associated with depression severity, but higher sedentary time was associated with lower perceptions of happiness (ß = -0.80, 95% CI: -1.48 to -0.11, p = 0.023). CONCLUSIONS: Higher physical activity was associated with fewer depression symptom severity scores and reduced odds of mild or worse depression in women newly diagnosed with breast cancer. Higher physical activity and daily step counts were also associated with stronger perceptions of happiness and satisfaction with life, respectively. Sedentary time was not associated with depression symptom severity or odds of having depression, but was associated with stronger perceptions of happiness.

Relationships Between Soil Microbial Diversities Across an Aridity Gradient in Temperate Grasslands : Soil Microbial Diversity Relationships.

Soil microbes assemble in highly complex and diverse microbial communities, and microbial diversity patterns and their drivers have been studied extensively. However, diversity correlations and co-occurrence patterns between bacterial, fungal, and archaeal domains and between microbial functional groups in arid regions remain poorly understood. Here we assessed the relationships between the diversity and abundance of bacteria, fungi, and archaea and explored how environmental factors influence these relationships. We sampled soil along a 1500-km-long aridity gradient in temperate grasslands of Inner Mongolia (China) and sequenced the 16S rRNA gene of bacteria and archaea and the ITS2 gene of fungi. The diversity correlations and co-occurrence patterns between bacterial, fungal, and archaeal domains and between different microbial functional groups were evaluated using α-diversity and co-occurrence networks based on microbial abundance. Our results indicate insignificant correlations among the diversity patterns of bacterial, fungal, and archaeal domains using α-diversity but mostly positive correlations among diversity patterns of microbial functional groups based on α-diversity and co-occurrence networks along the aridity gradient. These results suggest that studying microbial diversity patterns from the perspective of functional groups and co-occurrence networks can provide additional insights on patterns that cannot be accessed using only overall microbial α-diversity. Increase in aridity weakens the diversity correlations between bacteria and fungi and between bacterial and archaeal functional groups, but strengthens the positive diversity correlations between bacterial functional groups and between fungal functional groups and the negative diversity correlations between bacterial and fungal functional groups. These variations of the diversity correlations are associated with the different responses of microbes to environmental factors, especially aridity. Our findings demonstrate the complex responses of microbial community structure to environmental conditions (especially aridity) and suggest that understanding diversity correlations and co-occurrence patterns between soil microbial groups is essential for predicting changes in microbial communities under future climate change in arid regions.

Social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in newly diagnosed women with breast cancer.

PURPOSE: Identifying correlates of physical activity and sedentary behaviour allows for the identification of factors that may be targeted in future behaviour change interventions. This study sought to determine the social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in individuals recently diagnosed with breast cancer. METHODS: Data were collected from 1381 participants within 90 days of diagnosis in the Alberta Moving Beyond Breast Cancer (AMBER) Cohort Study. Physical activity and sedentary behaviour were measured with ActiGraph GT3X+® and activPALTM devices, respectively, for seven consecutive days. Correlates were collected via a self-reported questionnaire, medical record extraction, or measured by staff. RESULTS: Multivariable models were fitted for sedentary behaviour, light physical activity, and moderate-to-vigorous physical activity. Greater sedentary behaviour was associated with higher body fat percentage (BF%) (ß=0.044; p<0.001) and being single (ß=0.542; p<0.002). Lower light physical activity was associated with higher BF% (ß=-0.044; p<0.001), higher body mass index (ß=-0.039; p<0.001), greater disease barrier influence (ß=-0.006; p<0.001), a HER2-positive diagnosis (ß=-0.278; p=0.001), and being single (ß=-0.385; p= 0.001). Lower moderate-to-vigorous physical activity was associated with higher BF% (ß =-0.011; p=0.001), greater disease barrier influence (ß=-0.002; p<0.001), and being of Asian (ß=-0.189; p=0.002) or Indian/South American (ß=-0.189; p=0.002) descent. Greater moderate-to-vigorous physical activity was associated with having greater intentions (ß=0.049; p=0.033) and planning (ß=0.026; p=0.015) towards physical activity. CONCLUSION: Tailoring interventions to increase physical activity for individuals recently diagnosed with breast cancer may improve long-term outcomes across the breast cancer continuum.

The Alberta moving beyond breast cancer (AMBER) cohort study: baseline description of the full cohort.

PURPOSE: The Alberta Moving Beyond Breast Cancer (AMBER) Study is an ongoing prospective cohort study investigating how direct measures of physical activity (PA), sedentary behavior (SB), and health-related fitness (HRF) are associated with survival after breast cancer. METHODS: Women in Alberta with newly diagnosed stage I (≥ T1c) to IIIc breast cancer were recruited between 2012 and 2019. Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak); upper and lower body muscular strength and endurance; dual-X-ray absorptiometry to measure body composition; and questionnaires to measure self-reported PA and SB. RESULTS: At baseline, the 1528 participants' mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%. CONCLUSION: We have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.

Health-Related and Behavioral Factors Associated With Lung Cancer Stage at Diagnosis: Observations From Alberta's Tomorrow Project.

BACKGROUND: Lung cancer is the leading cause of cancer death in Canada, with stage at diagnosis among the top predictors of lung cancer survival. Identifying factors associated with stage at diagnosis can help reduce lung cancer morbidity and mortality. This study used data from a prospective cohort study of adults living in Alberta, Canada to examine factors associated with lung cancer stage at diagnosis. METHODS: This cohort study used data from adults aged 35-69 years enrolled in Alberta's Tomorrow Project. Partial Proportional Odds models were used to examine associations between sociodemographic characteristics and health-related factors and subsequent lung cancer stage at diagnosis. RESULTS: A total of 221 participants (88 males and 133 females) developed lung cancer over the study period. Nearly half (48.0%) of lung cancers were diagnosed at a late stage (stage IV), whereas 30.8 % and 21.3% were diagnosed at stage I/II and III, respectively. History of sunburn in the past year was protective against late-stage lung cancer diagnosis (odds ratio (OR) .40, P=.005). In males, a higher number of lifetime prostate specific antigen tests was associated with reduced odds of late-stage lung cancer diagnosis (odds ratio .66, P=.02). Total recreational physical activity was associated with increased odds of late-stage lung cancer diagnosis (OR 1.08, P=.01). DISCUSSION: Lung cancer stage at diagnosis remains a crucial determinant of prognosis. This study identified important factors associated with lung cancer stage at diagnosis. Study findings can inform targeted cancer prevention initiatives towards improving early detection of lung cancer and lung cancer survival.

P(III) vs P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to an Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist.

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than 16-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

[Assessing in-situ conservation status of threatened medicinal vascular plants in central China].

It is of great significance to carry out scientific investigation of threatened species and assess their in-situ conservation status in order to guide the conservation and management of these species within a region. In this study, we explored and assessed the biodiversity and in-situ conservation status of the threatened medicinal vascular plants(TMVPs) in central China. The results showed that there were 276 TMVPs in central China, including 18 critically endangered(CR), 77 endangered(EN), and 181 vulnerable(VU) species. Of which, 222 TMVPs were distributed in 49 national nature reserves, with an in-situ conservation rate of 80.43%. And the in-situ conservation rate of CR, EN and NR species were 83.33%, 77.92% and 81.22%, respectively. The complementary algorithm was used to select the nine national nature reserves with the highest protection and complementary contribution to the TMVPs. The cumulative protection contribution rate of these nine nature reserves was 81.98%. Fifty-four TMVPs were distributed outside of national nature reserves, while mainly distributed within 10 hotspot counties including Badong county, Hubei province, Sangzhi county, Hunan province, Jianghua Yao Autonomous county, Hunan province and so on. In general, TMVPs are well protected by the national nature reserves in central China. However, there are still some conservation gaps. It is necessary to carry out further field investigation on the species with conservation gaps and identify the gap areas, so as to provide scientific guidance for the optimization of the conservation of TMVPs in this region.

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation.

BACKGROUND/AIMS: Human enterocytic differentiation is altered during development, fasting, adaptation, and bariatric surgery, but its intracellular control remains unclear. We hypothesized that Schlafen 12 (SLFN12) regulates enterocyte differentiation. METHODS: We used laser capture dissection of epithelium, qRT-PCR, and immunohistochemistry to evaluate SLFN12 expression in biopsies of control and fasting human duodenal mucosa, and viral overexpression and siRNA to trace the SLFN12 pathway in human Caco-2 and HIEC6 intestinal epithelial cells. RESULTS: Fasting human duodenal mucosa expressed less SLFN12 mRNA and protein, accompanied by decreases in enterocytic markers like sucrase-isomaltase. SLFN12 overexpression increased Caco-2 sucrase-isomaltase promoter activity, mRNA, and protein independently of proliferation, and activated the SLFN12 putative promoter. SLFN12 coprecipitated Serpin B12 (SERPB12). An inactivating SLFN12 point mutation prevented both SERPB12 binding and sucrase-isomaltase induction. SERPB12 overexpression also induced sucrase-isomaltase, while reducing SERPB12 prevented the SLFN12 effect on sucrase-isomaltase. Sucrase-isomaltase induction by both SLFN12 and SERPB12 was attenuated by reducing UCHL5 or USP14, and blocked by reducing both. SERPB12 stimulated USP14 but not UCHL5 activity. SERPB12 coprecipitated USP14 but not UCHL5. Moreover, SLFN12 increased protein levels of the sucrase-isomaltase-promoter-binding transcription factor cdx2 without altering Cdx2 mRNA. This was prevented by reducing UCHL5 and USP14. We further validated this pathway in vitro and in vivo. SLFN12 or SERPB12 overexpression induced sucrase-isomaltase in human non-malignant HIEC-6 enterocytes. CONCLUSIONS: SLFN12 regulates human enterocytic differentiation by a pathway involving SERPB12, the deubiquitylases, and Cdx2. This pathway may be targeted to manipulate human enterocytic differentiation in mucosal atrophy, short gut or obesity.

Niche conservatism and elevated diversification shape species diversity in drylands: evidence from Zygophyllaceae.

The integrated contributions of climate and macroevolutionary processes to global patterns of species diversity are still controversial in spite of a long history of studies. The niche conservatism hypothesis and the net diversification rate hypothesis have gained wide attention in recent literature. Many studies have tested these two hypotheses for woody species in humid forests; however, the determinants of species diversity patterns for arid-adapted plants remain largely ignored. Here, using a molecular phylogeny and the global distributions of Zygophyllaceae, a typical arid-adapted plant family, we assessed the effects of contemporary climate and net diversification rates on species diversity patterns in drylands. We found the variables representing water availability to be the best predictors for Zygophyllaceae diversity. Specifically, Zygophyllaceae species diversity significantly decreased with the increase in water availability, probably owing to phylogenetic conservatism of water-related niches. The net diversification rates of Zygophyllaceae accelerated sharply in the recent 10 Myr, coinciding roughly with the period of global aridification. The species diversity of Zygophyllaceae significantly increased with the increase in mean net diversification rates per geographical unit, especially in the Old World, supporting the net diversification rate hypothesis. Our study provides a case exploring climatic and evolutionary mechanisms of dryland species diversity patterns, and suggests that the conservatism in water-related niches and elevated net diversification rates in drylands may have jointly determined the global patterns of dryland species diversity.

Identification and prediction of health-related quality of life trajectories after a prostate cancer diagnosis.

The aim of our study was to identify physical and mental health-related quality of life (HRQoL) trajectories after a prostate cancer diagnosis and systematically characterize trajectories by behaviours and prognostic factors. Prostate cancer survivors (n = 817) diagnosed between 1997 and 2000 were recruited between 2000 and 2002 into a prospective repeated measurements study. Behavioural/prognostic data were collected through in-person interviews and questionnaires. HRQoL was collected at three post-diagnosis time-points, approximately 2 years apart using the Short Form (SF)-36 validated questionnaire. To identify physical and mental HRQoL trajectories, group-based trajectory modelling was undertaken. Differences between groups were evaluated by assessing influential dropouts (mortality/poor health), behavioural/prognostic factors at diagnosis or during the follow-up. Three trajectories of physical HRQoL were identified including: average-maintaining HRQoL (32.2%), low-declining HRQoL (40.5%) and very low-maintaining HRQoL (27.3%). In addition, three trajectories for mental HRQoL were identified: average-increasing HRQoL (66.5%), above average-declining HRQoL (19.7%) and low-increasing HRQoL (13.8%). In both physical and mental HRQoL, dropout from mortality/poor health differed between trajectories, thus confirming HRQoL and mortality were related. Furthermore, increased Charlson comorbidity index score was consistently associated with physical and mental HRQoL group membership relative to average maintaining groups, while behaviours such as time-varying physical activity was associated with physical HRQoL trajectories but not mental HRQoL trajectories. It was possible to define three trajectories of physical and mental HRQoL after prostate cancer. These data provide insights regarding means for identifying subgroups of prostate cancer survivors with lower or declining HRQoL after diagnosis whom could be targeted for interventions aimed at improving HRQoL.

The catalytic asymmetric Abramov reaction.

The first catalytic enantioselective Abramov reaction is described. The process is based on the utilization of a chiral disulfonimide catalyst, which efficiently avoids the difficulties encountered with metal-based catalysts. Several functionalized α-hydroxy phosphonates were synthesized in good yields and with excellent enantiomeric ratios of up to >99:1. The process was shown to be scalable and up to 1 g of starting material could be employed under mild reaction conditions.

Asymmetric disulfonimide-catalyzed synthesis of δ-amino-ß-ketoester derivatives by vinylogous Mukaiyama-Mannich reactions.

An organocatalytic asymmetric synthesis of δ-amino-ß-ketoester derivatives has been developed. A chiral disulfonimide (DSI) serves as a highly efficient precatalyst for a vinylogous Mukaiyama-Mannich reaction of readily available dioxinone-derived silyloxydienes with N-Boc-protected imines, delivering products in excellent yields and enantioselectivities. The synthetic utility of this reaction is illustrated in various transformations, including a new CC bond-forming reaction, which provide useful enantioenriched building blocks. The methodology is applied in a formal synthesis of (-)-lasubin.

Catalytic asymmetric Torgov cyclization: a concise total synthesis of (+)-estrone.

An asymmetric Torgov cyclization, catalyzed by a novel, highly Brønsted acidic dinitro-substituted disulfonimide, is described. The reaction delivers the Torgov diene and various analogues with excellent yields and enantioselectivity. This method was applied in a very short synthesis of (+)-estrone.

Mechanistic studies to understand peak tailing due to sulfinic acid- and carboxylic acid-silanophilic interactions in reversed-phase liquid chromatography.

Silanophilic interactions are a primary contributor to peak tailing of acidic pharmaceutical compounds, thus a thorough understanding is especially important for reversed-phase liquid chromatography (RPLC) method development. Herein, a sulfinic acid compound that exhibited severe peak tailing in RPLC with acidic mobile phases was carefully studied. Results indicated that the neutral protonated form of the sulfinic acid is involved in the strong interaction that leads to peak tailing, but that tailing can be mitigated with a blocking effect achieved through use of acetic acid modifier in the mobile phase. Peak tailing was also observed with other structurally-similar sulfinic acids and carboxylic acids but was, in general, less severe with the latter. The Hydrophobic Subtraction Model (HSM) was applied to six commercial C18 columns that exhibited different tailing behaviors for the sulfinic acid compound in attempts to identify key sites of interaction within the stationary phase. A combination of heated acid column wash experiments and density functional theory (DFT) calculations indicate that the differential interactions of the acids with vicinal silanol pairs in the stationary phase play a major role in peak tailing.