Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Effect of different ventilation modalities on the early prognosis of patients with sleep apnea after acute ischemic stroke---protocol for a prospective, open-label and randomised controlled trial.

BACKGROUND: Sleep apnea is highly prevalent after acute ischemic stroke (AIS) and has increased stroke-related mortality and morbidity. The conventional sleep apnea treatment is continuous positive airway pressure (CPAP) ventilation. However, it is poorly tolerated by patients and is not used in all stroke patients. This protocol describes the impact of high-flow nasal cannula (HFNC) oxygen therapy compared to nasal continuous positive airway pressure (nCPAP) ventilation or usual care on the early prognosis of patients with sleep apnea after AIS. METHODS: This randomised controlled study will be conducted in the intensive care unit of the Department of Neurology at the Wuhan Union Hospital. According to the study plan, 150 patients with sleep apnea after AIS will be recruited. All patients are randomly allocated in a 1:1:1 ratio to one of three groups: the nasal catheter group (standard oxygen group), the HFNC group, and the nCPAP group. Patients receive different types of ventilation after admission to the group, and their tolerance while using the different ventilation is recorded. Patients will be followed up by telephone three months after discharge, and stroke recovery is recorded. The primary outcomes were 28-day mortality, the incidence of pulmonary infection and endotracheal intubation. DISCUSSION: This study analyses different ventilation modalities for early interventions in patients with sleep apnea after AIS. We will investigate whether nCPAP and HFNC reduce early mortality and endotracheal intubation rates and improve distant neurological recovery in patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05323266; 25 March 2022).

Antinociceptive C19-diterpenoid alkaloids from the roots of Aconitum nagarum.

Three new C19-diterpenoid alkaloids, nagarumines A-C (1-3), together two known alkaloids, deoxyaconitine (4) and N-deethyldeoxyaconitine (5), were isolated from the roots of Aconitum nagarum. The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as high resolution mass spectrometry. The in vivo pharmacological studies revealed that nagarumine C (3) possessed comparable antinociceptive activity (ED50 = 76.0 µmol/kg) with the positive control drugs aspirin and acetaminophen.

Antinociceptive diterpenoid alkaloids from the roots of Aconitum austroyunnanense.

A phytochemical investigation on the roots of Aconitum austroyunnanense afforded three undescribed aconitine-type C19-diterpenoid alkaloids, austroyunnanines A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. The isolated alkaloids were tested in vivo for their antinociceptive properties. Consequently, austroyunnanine B (2) exhibited significant antinociceptive effect and its ID50 value (48.0 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Antibacterial lanostane triterpenoids from Ganoderma tsugae.

A phytochemical investigation on the 80% EtOH extract of the fruiting bodies of Ganoderma tsugae resulted into the isolation of two previously undescribed lanostane triterpenoids, 7,11-dioxo-3ß-acetyloxy-26,27-dihydroxy-lanosta-8,24-diene (1) and 7,20-dioxo-3ß-acetyloxy-11ß,15α-dihydroxy-22,23,24,25,26,27-hexanorlanosta-8-ene (2), togeher with one known lanostane triterpenoid ganodermanontriol (3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the triterpenoids were in vitro evaluated for their antibacterial activities against six pathogenic microorganisms. Compound 3 exhibited some activities against three Gram positive bacteria with MIC values less than 30 µg/ml.

Enantioselective Total Synthesis of Spirotryprostatin A.

In this paper, we disclosed a novel enantioselective total synthesis of spirotryprostatin A (1) in 15 steps with a 7.4% total yield from commercially available 2-iodo-5-methoxyaniline and γ-butyrolactone. The key step features of this synthesis include the copper-catalyzed cascade reaction of o-iodoaniline derivatives with alkynone to introduce the quaternary carbon stereocenter and an aza-Michael tandem reaction to construct the spiro[pyrrolidine-3,3'-oxindole] moiety.

Antinociceptive C19-diterpenoid alkaloids from the root of Aconitum episcopale.

A chemical investigation on the roots of Aconitum episcopale afforded three undescribed aconitine-type C19-diterpenoid alkaloids, episcopalines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vivo for their antinociceptive properties. As a result, episcopaline B (2) showed potent antinociceptive effect and its ID50 value (55.0 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Antinociceptive C19-diterpenoid alkaloids isolated from Aconitum pseudostapfianum.

Phytochemical investigation on the roots of Aconitum pseudostapfianum resulted in the isolation of three new aconitine-type C19-diterpenoid alkaloids, pseudostapines A-C (1-3). Their structures were determined by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, NOESY and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vivo for their antinociceptive potential. As a result, pseudostapine C (3) showed 2-fold more potent antinociceptive effect (ID50 = 60.3 µmol/kg) than the positive control drugs aspirin and acetaminophen.

[C_(19)-diterpenoid alkaloids from Aconitum austroyunnanense].

Eight C_(19)-diterpenoid alkaloids( 1-8) were isolated from the ethyl acetate soluble fraction of 95% ethanol extract of the ground roots of Aconitum austroyunnanense through various column chromatographies on silica gel,ODS,Sephadex LH-20 and MCI gel.Their structures were elucidated as 14α-benzoyloxy-13ß,15α-dihydroxy-1α,6α,8ß,16ß,18-pentamethoxy-19-oxoaconitan( 1),N-deethylaconitine( 2),spicatine B( 3),leucanthumsine A( 4),acofamine B( 5),macrorhynine B( 6),aconitilearine( 7),and ambiguine( 8) based on their chemical and physicochemical properties and spectroscopic data. Compound 1 was a new compound and alkaloids 2-8 were isolated from this plant for the first time. Some isolated alkaloids were tested in vitro for cytotoxic potential by employing the MTT method. As a result,alkaloid 1 exhibited weak cytotoxic activity against three tested tumor cell lines( A-549,He La,and Hep G2) with IC_(50) values less than 20 µmol·L~(-1).

[Amaryllidaceae alkaloids from Lycoris radiata].

Three aporphine-type alkaloids (1-3), three lycorine-type alkaloids (4-6), two crinane type alkaloids (7, 8) and one phenanthridine-type alkaloid (9) were isolated from the chloroform soluble fraction of 70% ethanol extract of the bulbs of Lycoris radiata through various column chromatographies over silica gel, ODS, Sephadex LH-20 and MCI. Their structures were elucidated as (+)-N-methoxylcarbonyl-1,2-methylenedioxyl-isocorydione (1), isocorydione (2), 8-demethyl-dehydrocrebanine (3), (+)-3-hydroxy-anhydrolycorine N-oxide (4), vasconine (5), pancratinine D (6), yemenine A (7), 11-O-acetylhaemanthamine (8), and 5,6-dihydro-5-methyl-2-hydroxyphenanthridine (9) based on their chemical and physicochemical properlies and spectroscopic data. Compound 1 was a new compound and alkaloids 2-9 were isolated and identified from this plant for the first time.

A risk-predictive model for obstructive sleep apnea in patients with chronic obstructive pulmonary disease.

Background: Obstructive sleep apnea syndrome (OSA) is increasingly reported in patients with chronic obstructive pulmonary disease (COPD). Our research aimed to analyze the clinical characteristics of patients with overlap syndrome (OS) and develop a nomogram for predicting OSA in patients with COPD. Methods: We retroactively collected data on 330 patients with COPD treated at Wuhan Union Hospital (Wuhan, China) from March 2017 to March 2022. Multivariate logistic regression was used to select predictors applied to develop a simple nomogram. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the value of the model. Results: A total of 330 consecutive patients with COPD were enrolled in this study, with 96 patients (29.1%) confirmed with OSA. Patients were randomly divided into the training group (70%, n = 230) and the validation group (30%, n = 100). Age [odds ratio (OR): 1.062, 1.003-1.124], type 2 diabetes (OR: 3.166, 1.263-7.939), neck circumference (NC) (OR: 1.370, 1.098-1,709), modified Medical Research Council (mMRC) dyspnea scale (OR: 0.503, 0.325-0.777), Sleep Apnea Clinical Score (SACS) (OR: 1.083, 1.004-1.168), and C-reactive protein (CRP) (OR: 0.977, 0.962-0.993) were identified as valuable predictors used for developing a nomogram. The prediction model performed good discrimination [AUC: 0.928, 95% confidence interval (CI): 0.873-0.984] and calibration in the validation group. The DCA showed excellent clinical practicability. Conclusion: We established a concise and practical nomogram that will benefit the advanced diagnosis of OSA in patients with COPD.

Development and validation of a predictive model for new-onset atrial fibrillation in sepsis based on clinical risk factors.

Objective: New-onset atrial fibrillation (NOAF) is a common complication and one of the primary causes of increased mortality in critically ill adults. Since early assessment of the risk of developing NOAF is difficult, it is critical to establish predictive tools to identify the risk of NOAF. Methods: We retrospectively enrolled 1,568 septic patients treated at Wuhan Union Hospital (Wuhan, China) as a training cohort. For external validation of the model, 924 patients with sepsis were recruited as a validation cohort at the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China). Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses were used to screen predictors. The area under the ROC curve (AUC), calibration curve, and decision curve were used to assess the value of the predictive model in NOAF. Results: A total of 2,492 patients with sepsis (1,592 (63.88%) male; mean [SD] age, 59.47 [16.42] years) were enrolled in this study. Age (OR: 1.022, 1.009-1.035), international normalized ratio (OR: 1.837, 1.270-2.656), fibrinogen (OR: 1.535, 1.232-1.914), C-reaction protein (OR: 1.011, 1.008-1.014), sequential organ failure assessment score (OR: 1.306, 1.247-1.368), congestive heart failure (OR: 1.714, 1.126-2.608), and dopamine use (OR: 1.876, 1.227-2.874) were used as risk variables to develop the nomogram model. The AUCs of the nomogram model were 0.861 (95% CI, 0.830-0.892) and 0.845 (95% CI, 0.804-0.886) in the internal and external validation, respectively. The clinical prediction model showed excellent calibration and higher net clinical benefit. Moreover, the predictive performance of the model correlated with the severity of sepsis, with higher predictive performance for patients in septic shock than for other patients. Conclusion: The nomogram model can be used as a reliable and simple predictive tool for the early identification of NOAF in patients with sepsis, which will provide practical information for individualized treatment decisions.

Diagnostic Value of Rapid On-Site Evaluation for CT-Guided Percutaneous Fine Needle Aspiration in the Diagnosis of Pulmonary Occupying Lesions.

OBJECTIVE: Rapid on-site evaluation (ROSE) is an effective and efficient auxiliary examination, but its value for CT-guided percutaneous fine-needle aspiration (FNA) in the diagnosis of pulmonary occupying lesions is unclear. This study is aimed at evaluating the clinical utility of ROSE for CT-guided percutaneous FNA. METHODS: We reviewed 234 patients from September 2018 to April 2019. The result using ROSE was compared with the final pathological diagnosis of CT-guided percutaneous FNA, and we also compared the complications between the ROSE group and the NO-ROSE group. The final pathological diagnosis results served as the gold standard. We also analyzed the diagnostic rate of FNA and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of malignancy. The correlation between diverse pathological types of lung cancer was also taken into consideration. RESULTS: In total, 132 patients underwent CT-guided percutaneous FNA with ROSE (ROSE group), and 102 did not (NO-ROSE group). The diagnostic rate, sensitivity, specificity, PPV, and NPV of the ROSE group were 91.6%, 89.1%, 94.1%, 93.4%, and 90.1%, respectively. The complication rates of the ROSE group and the NO-ROSE group were 8.33% and 16.67%, respectively. This difference was not statistically significant (P > 0.05). In subsets of adenocarcinoma (AC) and small cell lung cancer (SCLC) patients, the ROSE result was highly consistent with the final pathological result. CONCLUSION: CT-guided percutaneous FNA combined with ROSE has a high diagnostic rate, sensitivity, and specificity for pulmonary occupying lesions and an acceptable rate of complications. This method is worthy of wide use given its high efficiency and safety.

Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086.

A new benzamide (1) and four known compounds (2-5) were isolated from endophytic Streptomyces YIM67086, and their structures were determined as 2-amino-3,4-dihydroxy-5-methoxybenzamide (1), 4-hydroxy-3-methoxybenzoic acid (2), phenylacetic acid (3), N-acetyltyramine (4) and p-hydroxytruxinic acid (5). Compound 5 was first found in the microorganism. The antimicrobial activities of compounds 1-5 and antioxidant activity of compound 1 were investigated.

Metabolites of Streptomyces sp., an endophytic actinomycete from Alpinia oxyphylla.

Four known compounds had been isolated from the Streptomyces sp. YIM66017, and their structures were elucidated by spectral analysis as 2,6-dimethoxy terephthalic acid (1), yangjinhualine A (2), α-hydroxyacetovanillone (3) and cyclo(Gly-Trp) (4). Compound 1 was isolated from natural resources for the first time, and compounds 2-4 were isolated from streptomycetes for the first time. The 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assays showed that 1 showed higher activity than rutin with IC50 of 4.61 µg/mL and 2 showed the activity with IC50 of 57.12 µg/mL.

Medelamine C, a new omega-hydroxy alkylamine derivative from endophytic Streptomyces sp. YIM 66142.

A new alkylamine derivative and a common fatty acid were isolated from Streptomyces sp. YIM 66142. On the basis of spectral data, including HRMS, NMR and 2D NMR, their structures were determined as medelamine C (1) and isomyristic acid (2). The omega-hydroxyl group in structure 1 is rare in a natural alkylamine. The possible biosynthetic pathway in the genus Streptomyces from isomyristic acid (2) to medelamines is proposed. Compound 1 showed no obvious cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, SW480 cell lines. The omega-hydroxyl and the acetyl at NH in compound 1 decreased its cytotoxicity in comparison with that of medelamine.

Alkaloids from an endophytic streptomyces sp. YIM66017.

Three alkaloids, flavensomycinoic acid (1), a linear polyketide, alpiniamide (2), and cyclo (L-Trp-L-Ala) (3), were isolated from the culture filtrate of endophytic Streptomyces sp. YIM66017 from Alpinia oxyphylla. Their structures were elucidated by spectroscopic analysis and the structure of 1 was confirmed by X-ray crystallographic analysis. Compound 1 was isolated from a natural source for the first time, and compound 2 is a new compound. Compound 1 showed cytotoxicity to MCF-7 with an IC50 value of 17.0 microM.

A new cyclopeptide from endophytic Streptomyces sp. YIM 64018.

One new cyclopeptide, cyclo(L-Phe-L-Ala-L-Phe-Gly), named as vinaceuline (1) and three known cyclodipeptides, cyclo (Phe-Gly), cyclo (Phe-4-hydroxyl-Pro) and cyclo (Phe-Ile) were isolated from broth culture of endophytic Streptomyces YIM 64018 associated with Paraboea sinensis. The planar structure of the new compound was assigned on the basis of 1D and 2D NMR spectroscopic techniques, while t he a bsolute configurations of the amino acid residueswere determined by application of the advanced Marfey method. Cyclotetrapeptides are rarely found as Streptomycete metabolites.