Copper-catalyzed aerobic oxidative radical alkoxycyclization of tryptamines to access 3-alkoxypyrroloindolines

We report a copper-catalyzed alkoxycyclization of tryptamine derivatives with O₂ as the sole oxidant, leading to a variety of C3a-alkoxypyrroloindolines in good yields with high diastereoselectivities. This reaction involves an interesting double catalytic cycle in which copper-catalyzed carboamination cyclization is favored to form the C-3 radical pyrrolidinoindoline intermediate, then a copper-catalytic radical alkoxylation reaction proceeds smoothly.

An oxazoline/copper-catalyzed cascade carboamination alkoxylation of substituted tryptamine under mild eco-friendly O₂ oxidation conditions was reported.

Pyrrolidino[2,3-b]indoline is an important heterocyclic core skeleton that exists in numerous biologically active natural products and pharmaceutical molecules.¹ Cyclotryptamine type molecules which are oxygenated at the C3a position are especially outstanding due to their prominent bioactivity profiles,² various applications in biological probes³ and chiral catalysts.⁴As direct access to these complex products, the development of C3a-oxygenation/cyclization reactions of tryptamine or tryptophan derivatives has attracted extensive interest from synthetic chemists. Recently, some remarkable efforts have contributed to the one-step assembly of 3-hydroxyl,⁵ acetoxyl,⁶ peroxyl⁷ and other oxygenated⁸ pyrroloindolines through oxidative cyclization of tryptophan substrates. However, by utilizing a similar strategy, the direct synthesis of 3-alkoxyl pyrroloindolines remains less developed. In 2020, Zhong et al.⁹ reported the first example of alkoxycyclization of tryptamine derivatives using molecular iodine catalyst with tert-butyl hydroperoxide as the oxidant. None of the other studies, like using transition-metal catalysts, have been described yet.Copper salts, which are inexpensive and easily accessible, have been widely used in organic synthesis as catalysts. Copper(ii)-promoted radical intramolecular carboamination of alkene has proven to be an effective means toward the synthesis of N-fused heterocycles.¹⁰ Recent reports have utilized this strategy toward the cyclization and radical alkylation, aromatization and aminooxygenation of alkene.¹⁰ However, due to the difficulty in homolytic breakage of the oxygen–hydrogen bond in alcohols with a high bond dissociation energy (BDE is ca.105 kcal mol⁻¹),¹¹ the related direct cyclization and radical alkoxylation of carbon–carbon double bond with copper catalysts is still unknown. Inspired by the relevant research of copper-catalyzed radical alkoxylation reaction,¹² we assume that if the catalytic carboamination and radical alkoxylation tandem reaction could be realized by a single copper catalyst, which will represent as a new effective protocol for the direct construction of alkoxyl-containing N-fused heterocycles. Herein, we report an oxazoline/copper-catalyzed cascade carboamination alkoxylation of substituted tryptamine under mild eco-friendly O₂ oxidation conditions, which facilitate the construction of the 3-alkoxyl pyrroloindolinese motif in good yield with good to excellent levels of diastereoselectivity (Scheme 1).Open in a separate windowScheme 1Copper-catalyzed cyclization and alkoxylation of tryptamines.In our studies, the commercial easily available N-methyl tryptamine 1a was chosen as model substrate. Initially, 10 mol% of metal salt CuBr₂ was used as catalyst, the 3-alkoxylation product 2a was obtained as 38% yield with 14/1 dr (

Near-infrared tunable surface plasmon resonance sensors based on graphene plasmons via electrostatic gating control

A tunable near-infrared surface plasmon resonance sensor based on graphene plasmons via electrostatic gating control is investigated theoretically. Instead of the traditional refractive index sensing, the sensor can respond sensitively to the change of the chemical potential in graphene caused by the attachment of the analyte molecules. This feature can be potentially used for biological sensing with high sensitivity and high specificity. Theoretical calculations show that the chemical potential sensing sensitivities under wavelength interrogation patterns are 1.5, 2.21, 3, 3.79, 4.64 nm meV⁻¹ at different wavebands with centre wavelengths of 1100, 1310, 1550, 1700, 1900 nm respectively, and the full width half maximum (FWHM) is also evaluated to be 10, 25.5, 43, 55.5, 77 nm at these different wavebands respectively. It can be estimated that the theoretical limit of detection (LOD) in DNA sensing of the proposed sensor can reach the femtomolar level, several orders of magnitude superior to that of noble metal-based SPR sensors (nanomolar or subnanomolar scale), and is comparable to that of noble metal-based SPR sensors with graphene/Au-NPs as a sensitivity enhancement strategy. The FWHM is much smaller than that of the noble metal-based SPR sensors, making the proposed sensor have a potentially higher figure of merit (FOM). This work provides a new way of thinking to detect in an SPR manner the analyte that can cause chemical potential change in graphene and provides a beneficial complement to refractive index sensing SPR sensors.

A tunable near-infrared surface plasmon resonance sensor based on graphene plasmons via electrostatic gating control is investigated theoretically.     

过氧化氢酶对溃疡性结肠炎大鼠肠黏膜内细胞因子表达和NF-κB激活的影响

目的 观察过氧化氢酶（CAT）对大鼠溃疡性结肠炎（UC）的预防作用。方法 用5％葡聚糖硫酸钠（DSS）制备大鼠UC模型;CAT灌肠,观察UC的症状和组织学变化;采用RT-PCR技术检测UC大鼠肠黏膜内TNF-α、IL-1β、IL-8的表达水平;应用免疫电泳迁移率改变分析（EMSA）法检测UC大鼠肠黏膜细胞NF-κB的激活情况。结果 CAT预防组UC的症状、组织损害均较CAT治疗组、模型组明显减轻,同时TNF-α、IL-1β、IL-8的表达较CAT治疗组、模型组降低（P〈0．05）,NF-κB的核结合活性也降低,但较正常对照组仍明显升高。结论 CAT对UC的发生有预防作用。     

Sister Mary Joseph nodule as cutaneous manifestations of metastatic ovarian cancer: A case report and review of the literature

Rationale:The Sister Mary Joseph''s nodule is an umbilical nodule resulting from the metastasis of malignant tumors in the pelvic and/or abdominal cavity. Sister Mary Joseph''s nodules are very rare, and the morphology of the skin lesions is not specific and is easily misdiagnosed. Here, we report a case of cutaneous manifestations of metastatic ovarian cancer.Patient concerns:The patient was admitted to our hospital because of abdominal distention, and a nodule was found in the umbilicus. A computerized tomography scan of the entire abdomen showed nodular soft tissue in the subcutaneous fat space of the umbilical area and multiple pelvic masses, which were suspected metastases of peritoneal and omentum ovarian cancer.Interventions:To confirm the pathological diagnosis, posterior fornix puncture was performed. Pathological biopsy showed adenocarcinoma. Histological examination revealed a mass arising from high-grade serous carcinoma of the ovary. The patient received 2 cycles of chemotherapy with paclitaxel liposomes and carboplatin and underwent interval debulking surgery. Postoperative pathology was consistent with high-grade serous carcinoma of the ovary. Cancer involvement was observed in umbilical lesions. After the operation, the patient was given 6 cycles of chemotherapy with paclitaxel liposomes and carboplatin.Outcomes:The patient underwent follow-up until October 2020. A computerized tomography scan of the entire abdomen showed that the lymph nodes in the abdominal cavity were larger than before, suggesting a platinum-sensitive relapse. After receiving the same regimen of chemotherapy, carbohydrate antigen 125 dropped to the normal range, and consolidated treatment was administered for 3 cycles. Owing to her BRCA1 mutations, olaparib was administered for maintenance treatment. Until now, she had been in the outpatient clinic for regular follow-up visits.Lessons:The umbilicus remains an infrequently examined area, which cannot be underestimated and warrants careful clinical follow-up and histological evaluation, as appropriate.     

422例锁骨下中心静脉穿刺置管术并发症临床分析

目的 分析、探讨锁骨下中心静脉穿刺置管术并发症和改进技术.方法 对2001年1月～2007年5月422例应用锁骨下中心静脉穿刺置管术患者进行回顾性分析,研究相关的并发症和技术问题.结果 422例锁骨下中心静脉穿刺置管术总并发症发生率为6.40%,其中局部渗血、血肿8例(1.90%),误穿动脉6例(1.42%),气胸3例(0.71%),局部红肿感染5例(1.18%),心律失常2例(0.47%).结论 锁骨下中心静脉穿刺置管术具有一定的风险,需从多方面、多环节分析原因,预防并发症的发生.     

A new way to reduce the pain of ultherapy treatment

This article describes a case of using intravenous sufentanil in treatment of ultherapy to achieve satisfactory analgesic effect. Further rearchis need to find a convenient, safe and practical method to solve the problem of pain caused by ultherapy treatment.     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

Magnesium intake and primary liver cancer incidence and mortality in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratio_{tertile 3 vs. 1}: 0.44; 95% confidence interval: 0.24, 0.80; p_trend = 0.0065) and mortality (subdistribution hazard ratio_{tertile 3 vs. 1}: 0.37; 95% confidence interval: 0.19, 0.71; p_trend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all p_nonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.     

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose–response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HR_{Tertile 3 vs. 1} 2.05; 95% confidence interval [CI] 1.23–3.41) and death from this disease (SHR_{Tertile 3 vs. 1} 1.97; 95% CI 1.13–3.41). Similar results were obtained for DII score from food only. A nonlinear dose–response pattern was identified for the aforementioned associations (all p_nonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.     

基于弥散张量成像技术的双相障碍患者脑白质纤维束异常分析

目的探讨抑郁期双相障碍患者脑白质纤维束的变化。方法选取42例未用药双相障碍抑郁期患者(患者组)和年龄、性别及右利手与之相匹配的59名对照者(对照组)进行DTI检查,根据约翰霍普金斯大学人类白质纤维束图谱,将大脑白质组织分割为20条公认存在的粗大纤维束,应用PANDA软件计算每个被试者每条白质纤维束的4项平均弥散属性,采用非参数置换检验比较2组在20条白质纤维束上弥散指标的差异,将差异有统计学意义的脑白质纤维束弥散指标与临床指标进行Pearson相关分析。结果患者组左侧钩束各向异性分数(fractional anisotropy,FA)值低于对照组(0.40±0.01与0.41±0.01,P=0.001);胼胝体辐射线额部FA值低于对照组(0.36±0.02与0.38±0.02,P<0.001);左侧钩束径向弥散率(radial diffusivity,RD)值高于对照组(6.57×10^-4±2.41×10^-5与6.40×10^-4±2.42×10^-5,P=0.0017)。Pearson相关分析显示,2组弥散指标差异有统计学意义的白质纤维束与临床指标之间均无相关性。结论抑郁期双相障碍患者钩束及胼胝体辐射线额部存在脑白质完整性破坏。