Biological Evaluation of Lysionotin: a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma.

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.

Efficacy of Baduanjin for obesity and overweight: a systematic review and meta-analysis.

Background: According to data from the World Health Organization (WHO), there is a significant public health issue regarding the increasing number of individuals affected by obesity and overweight on an annual basis. Therefore, it is imperative to urgently identify interventions that can effectively control and improve this condition. Baduanjin, as a medium-intensity exercise, appears a suitable approach for weight reduction among individuals with obesity. This paper aimed to provide a systematic review and meta-analysis of the efficacy of Baduanjin in addressing obesity and overweight, with the ultimate goal of assisting individuals with obesity in finding an effective, safe, and engaging method for weight reduction. Methods: We conducted a comprehensive search of multiple databases including PubMed, Cochrane Library, Web of Science, Embase, The China National Knowledge Infrastructure (CNKI), The Chinese Scientific Journal Database (VIP), The Chinese Biomedical Literature Database (CBM), and WanFang Database to identify relevant articles published from the inception of each database until September 2023. Specifically, we focused on randomized controlled trials (RCTs) investigating the effects of Baduanjin on weight reduction. Data from these studies were extracted and analyzed using appropriate statistical methods. In cases where there was no significant heterogeneity (I 2 < 50%, p > 0.1), we employed a fixed effects model for data synthesis; otherwise, a random effects model was selected. Funnel plots were used to assess publication bias, and the mean difference (MD) was reported as an indicator of treatment group differences. Results: A total of 420 participants were included in 10 studies. The MD results of the experimental group when compared with the control group were -3.69 (95%CI = -4.97 to -2.40, p < 0.001) for body weight (BW), -5.42 (95%CI = -6.56 to -4.28, p < 0.001) for body mass index (BMI), -1.36 (95%CI = -1.76 to -0.96, p < 0.001) for waist circumference (WC), -3.40 (95%CI = -4.43 to -2.37, p < 0.001) for hip circumference (HC), and -0.03 (95%CI = -0.04 to -0.02, p > 0.1) for the waist-to-hip ratio (WHR). All of the values in the experimental group showed significant difference. The results of the Egger's test (t = 1.43, p = 0.190) suggest that there was no substantial bias present within the data analysis process. The safety profile revealed no adverse events reported across all 10 studies. Conclusion: Baduanjin could be effective in reducing weight, and the practice of Baduanjin has the potential to regulate BW, BMI, WC, HC, and WHR. However, further well-designed RCTs are still necessary to provide more robust evidence in the future. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024513789.

Residue and dietary intake risk assessment of lufenuron and chlorfenapyr and its corresponding metabolite in cabbage under field conditions.

A simple, low-cost, and highly sensitive method using a modified QuECHERS procedure based on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) was established to simultaneously quantify lufenuron and chlorfenapyr and the corresponding metabolite tralopyril in cabbage for the first time. On the basis of this method, terminal residue and dietary risk of lufenuron and chlorfenapyr in cabbage were investigated. The recoveries of lufenuron, chlorfenapyr, and tralopyril ranged from 88 to 110%, with relative standard deviation of less than 12.4%. The field trial results showed that at the pre-harvest interval (PHI) of 21 days, the terminal residues of lufenuron, chlorfenapyr, and tralopyril in the supervised trials were not higher than 0.02 mg/kg, and the highest detected residue levels of lufenuron, chlorfenapyr, and tralopyril were 0.047, 0.055, and <0.02 mg·kg-1 at 14-day pre-harvest respectively, which were lower than the maximum residue limits (MRLs) for cabbage established in China. For the dietary risk assessment, the national estimated daily intakes (NEDIs) as proportion of acceptable daily intakes (ADIs) were 80.4% and 29.9% for chlorfenapyr and lufenuron respectively indicating an acceptable dietary risk to Chinese population.

Synthesis of Azo-Substituted Bicyclo[1.1.1]pentanes (BCPs) via Base-Promoted Halogen Atom Transfer.

Because of the three-dimensional bioisosteric feature, bicyclo[1.1.1]pentylamines (BCPAs) are valuable scaffolds in synthetic chemistry and medicinal chemistry. Here, we report a Halogen Atom Transfer (XAT) mediated radical C-N coupling between C3-iodo-BCPs and diazonium salts in the presence of base. Similarly, a multicomponent reaction (MCR) enables the simultaneous construction of the C-C bond and C-N bond simultaneously. Versatile roles of diazonium salts were also explored.

A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.

The effects of different types of Tai Chi exercises on preventing falls in older adults: a systematic review and network meta-analysis.

OBJECTIVES: Few studies comparing the effects of different types of Tai Chi exercises on preventing falls in older adults. We compared the effects for finding an optimal intervention. METHODS: We searched 12 databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and so on, from their inception to January 13, 2023. Randomized controlled trials incorporating different types of Tai Chi for preventing falls in older adults were included. The outcome measures were the incidence of falls and Berg Balance Scale (BBS). Network meta-analysis (NMA) was conducted using Stata 15.1 based on a frequentist framework. RESULTS: Seventeen trials were eligible, including 3470 participants and four types of Tai Chi. They were 24-form simplified Tai Chi (24-form), Yang style Tai Chi (Yang style), Sun style Tai Chi (Sun style) and Tai Chi exercise program (TCEP). In paired meta-analysis, for incidence of falls, 24-form (Relative Risk (RR) = 0.59, 95% confidence interval (CI) [0.40, 0.86]) was more efficient than the control group. For BBS outcome, 24-form (MD (mean difference) = 2.32, 95% CI [1.42, 3.22]) was better than the control group. In the NMA, the results of incidence of falls were as follows: 24-form > Yang style > Sun style > control > TCEP. The rank probability of BBS was as follows: 24-form > TCEP > Yang style > control. CONCLUSION: Among the four types of Tai Chi studied, the 24-form simplified Tai Chi has shown better efficacy than other types.

Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer.

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.

Benzyl Deuteriodifluoromethyl Sulfoxide: An Easily Accessible and Stable Reagent for Direct Deuterodifluoromethylthiolation.

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The reagent displays excellent reactivities toward Tf2O promoted C-H deuteriodifluoromethylthiolation of electron-rich arenes, indoles, alkenes, and intramolecular lactonization of 2-alkynylbenzoates. Moreover, high deuteration rates and good to excellent yields were achieved under metal-free reaction conditions. As a result, a wide range of deuteriodifluoromethylthilolated compounds were prepared, enabling further applications in drug discovery.

Impact of Removal of Lymph Nodes on Survival in Stage I-III Gastric Signet-Ring Cell Cancer: The More, the Better?

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.

Complexation of histone deacetylase inhibitor belinostat to Cu(II) prevents premature metabolic inactivation in vitro and demonstrates potent anti-cancer activity in vitro and ex vivo in colon cancer.

PURPOSE: The histone deacetylase inhibitor (HDACi), belinostat, has had limited therapeutic impact in solid tumors, such as colon cancer, due to its poor metabolic stability. Here we evaluated a novel belinostat prodrug, copper-bis-belinostat (Cubisbel), in vitro and ex vivo, designed to overcome the pharmacokinetic challenges of belinostat. METHODS: The in vitro metabolism of each HDACi was evaluated in human liver microsomes (HLMs) using mass spectrometry. Next, the effect of belinostat and Cubisbel on cell growth, HDAC activity, apoptosis and cell cycle was assessed in three colon cancer cell lines. Gene expression alterations induced by both HDACis were determined using RNA-Seq, followed by in silico analysis to identify master regulators (MRs) of differentially expressed genes (DEGs). The effect of both HDACis on the viability of colon cancer patient-derived tumor organoids (PDTOs) was also examined. RESULTS: Belinostat and Cubisbel significantly reduced colon cancer cell growth mediated through HDAC inhibition and apoptosis induction. Interestingly, the in vitro half-life of Cubisbel was significantly longer than belinostat. Belinostat and its Cu derivative commonly dysregulated numerous signalling and metabolic pathways while genes downregulated by Cubisbel were potentially controlled by VEGFA, ERBB2 and DUSP2 MRs. Treatment of colon cancer PDTOs with the HDACis resulted in a significant reduction in cell viability and downregulation of stem cell and proliferation markers. CONCLUSIONS: Complexation of belinostat to Cu(II) does not alter the HDAC activity of belinostat, but instead significantly enhances its metabolic stability in vitro and targets anti-cancer pathways by perturbing key MRs in colon cancer. Complexation of HDACis to a metal ion might improve the efficacy of clinically used HDACis in patients with colon cancer.

Modified stomach-partitioning gastrojejunostomy for initially unresectable advanced gastric cancer with outlet obstruction: A case report.

BACKGROUND: Chemotherapy followed by gastrojejunostomy remains the main treatment for unresectable gastric cancer (GC) in the middle- or lower-third regions with gastric outlet obstruction (GOO). Radical surgery is performed as part of a multimodal treatment strategy for selected patients who respond well to chemotherapy. This study describes a case of successful radical resection with completely laparoscopic subtotal gastrectomy after a modified stomach-partitioning gastrojejunostomy (SPGJ) for obstruction relief, in a patient with GOO. CASE SUMMARY: During the initial esophagogastroduodenoscopy, an advanced growth was detected in the lower part of the stomach, which caused an obstruction in the pyloric ring. Following this, a computed tomography (CT) scan revealed the presence of lymph node metastases and tumor invasion in the duodenum, but no evidence of distant metastasis was found. Consequently, we performed a modified SPGJ, a complete laparoscopic SPGJ combined with No. 4sb lymph node dissection, for obstruction relief. Seven courses of adjuvant capecitabine plus oxaliplatin combined with Toripalimab (programmed death ligand-1 inhibitor) were administered thereafter. A preoperative CT showed partial response; therefore, completely laparoscopic radical subtotal gastrectomy with D2 lymphadenectomy was performed after conversion therapy, and pathological complete remission was achieved. CONCLUSION: Laparoscopic SPGJ combined with No. 4sb lymph node dissection was an effective surgical technique for initially unresectable GC with GOO.

Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans.

Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS to extend longevity. However, the instability and impermeability of native enzyme limit its in vivo biomedical application. Currently, exosome as protein carriers attracts considerable attention in the disease treatment owing to low immunogenicity and high stability. Herein, SOD was encapsulated into exosomes via mechanical extrusion with saponin permeabilization to obtain SOD-loaded EXO (SOD@EXO). SOD@EXO with a hydrodynamic diameter of 101.7 ± 5.6 nm could scavenge excessive ROS and protect the cells from oxidative damage induced by 1-methyl-4-phenylpyridine. Compared with native SOD, SOD@EXO significantly extended the lifespan of N2 wild-type Caenorhabditis elegans under normal conditions. Moreover, SOD@EXO improved the resistance against heat and oxidative stress, leading to notable survival ratio under these hostile conditions. Overall, the exosome-mediated delivery of SOD could reduce ROS level and delay aging in C. elegans model, thereby providing potential strategies to treat ROS-related diseases in future.

Total Lymph Node Yield Is Associated with Prolonged Survival after Neoadjuvant Chemotherapy in ypN0 Gastric Cancer Patients.

INTRODUCTION: Lymph node status after neoadjuvant chemotherapy (NAC) plays the main role in predicting the survival of gastric cancer (GC) patients who underwent curative gastrectomy after NAC. NAC can reduce the number of involved lymph nodes. However, it is unknown whether other variables are associated with the survival outcomes for ypN0 GC patients. It is unknown whether lymph node yield (LNY) has prognostic value in ypN0 GC patients treated with NAC plus surgery. METHODS: In this retrospective study, we reviewed the data of patients treated with NAC plus gastrectomy and identified those with ypN0 disease. The LNY cut-off was calculated using the X-tile program to determine the greatest actuarial survival difference. Patients were categorized into the downstaged N0 (cN+/ypN0) and natural N0 (cN0/ypN0) groups based on nodal status. Multivariate analysis was used to identify the prognostic factors and the association between LNY and prognosis. RESULTS: A total of 211 GC patients with ypN0 status were included. The optimal LNY cut-off was 23. Kaplan-Meier analysis revealed no significant difference in overall survival between the natural and downstaged N0 groups, while ypN0 GC patients with an LNY of ≥24 had significantly longer overall survival than those with an LNY of ≤23. Univariate analysis identified that LNY, cT stage, tumor location, ypT stage, perineural invasion, lymphovascular invasion, tumor size, Mandard tumor regression grade, and extent of gastrectomy were significantly associated with overall survival. Multivariate analysis confirmed that perineural invasion (hazard ratio, 4.246; p < 0.001), lymphovascular invasion (hazard ratio, 2.694; p = 0.048), and an LNY of ≥24 (hazard ratio, 0.394; p = 0.011) were independent prognostic factors. CONCLUSIONS: Patients with natural and downstaged ypN0 GC had similar overall survival after NAC. LNY was an independent prognostic factor in these patients, and an LNY of ≥24 predicted prolonged overall survival.

Multiple toxicity evaluations of perfluorooctane sulfonate on intact planarian Dugesia japonica.

Perfluorooctane sulfonate (PFOS) is gaining widespread attention as a persistent organic pollutant with multiple mechanisms of toxicity. In this study, PFOS at different concentrations and different exposure times was used to evaluate the multiple toxicities on intact planarian Dugesia japonica. The proliferation of neoblasts, apoptosis, DNA damage and the expression levels of neuronal genes and the major genes of the Wnt pathway were effectively studied. The results demonstrated that the balance between proliferation and apoptosis of intact planarian cells was disrupted after PFOS exposure, which in turn affected tissue homeostasis and differentiation. PFOS exposure led to increased DNA damage and altered neuronal gene expression. In addition, PFOS exposure could down-regulate the expression of Wnt pathway genes, but the inhibition of the Wnt pathway by PFOS was time- and concentration-dependent. These findings suggest that PFOS has multiple toxic effects on planarians and may interfere with cell proliferation and neurodevelopment by affecting the key gene expression in the Wnt pathway, providing estimable information on the neurodevelopmental toxicity and ecotoxicity of PFOS toxicity in aquatic animals and environments.

CT-based radiographic measurements and effectiveness estimates of full-endoscopic surgery in thoracic myelopathy caused by ossification of ligamentum flavum.

BACKGROUND: Evaluate the effectiveness of posterior percutaneous full-endoscopic technique for patients with thoracic myelopathy caused by ossification of ligamentum flavum (TOLF). METHODS: A prospective study was conducted for 16 patients with TOLF, who were treated with posterior endoscopic technique from 2017 to 2019. The sagittal and cross-sectional CT images are used to measure the area of ossified ligamentum and evaluate the decompression of surgery, respectively. The effectiveness was evaluated with visual analog scale (VAS), modified Japanese Orthopedic Association scale (mJOA), The Oswestry Disability Index (ODI), and Macnab efficacy evaluation. RESULTS: The average area of TOLF on sagittal and cross-sectional CT images in the 16 patients was (116.62 ± 32.72) mm2 and (141.59 ± 27.25) mm2 preoperatively, (15.99 ± 12.54) mm2 and (11.72 ± 8.64) mm2 at 3 days after the operation, (16.78 ± 11.49) mm2 and (10.82 ± 7.57) mm2 postoperative 1 year, respectively. The invasive proportion of spinal canal at preoperative sagittal and cross-sectional CT images was (48.10 ± 10.04) % and (57.58 ± 11.37) %, which decreased to (6.83 ± 4.48) % and (4.40 ± 3.01) % at the final follow-up. The average score of mJOA, VAS and ODI improved. The excellent and good rate was 87.50% according to Macnab evaluation. Compared with preoperative, differences in areas of TOLF, proportions of spinal canal, and clinical assessments of postoperative 3 days and 1 year were all statistically significant. Two cases of dural tear were observed. CONCLUSION: Endoscopic surgery has a good clinical effect on TOLF, which has the advantage of less trauma to the paraspinal muscles and no impact on the spinal structure. The CT-based radiographic measurements can quantitatively evaluate the degree of spinal canal stenosis in TOLF.

Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.

Background: Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. Methods: We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. Results: CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. Conclusion: This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.

Lewis Base-Catalyzed Trifluoromethylsulfinylation of Allylic Alcohols: Stability-Oriented Divergent Synthesis.

A novel strategy is demonstrated for Lewis base-activated trifluoromethylsulfinylation of allylic alcohols. Controllable synthesis of structurally varied allylic trifluoromethanesulfones via sigmatropic rearrangements was performed, and trifluoromethanesulfinate esters were achieved. This metal-free, catalytic divergent transformation features good functional group tolerance and late-stage modification of bioactive molecules. Mechanistic studies suggested that Lewis bases interact with N-(trifluoromethylsulfinyl)phthalimide to generate an ion pair adduct followed by O-trifluoromethylsulfinylation with allylic alcohols.