Total Synthesis of (+)-Muricatetrocin B via a Late-Stage Co-Catalyzed Hartung-Mukaiyama Cyclization.

Convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against the HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. Our synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung-Mukaiyama cyclization for convergent assembly of the 2,5-trans-substituted tetrahydrofuran ring.

Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease.

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25-45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied. Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance. Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.

Prognostic nutritional index as a predictor of mortality in nontuberculous mycobacterial lung disease.

BACKGROUND: Although the association between nontuberculous mycobacterial lung disease (NTM-LD) and malnutrition is known, there are a few reports on the association between the nutritional score and death in patients with NTM-LD. This study investigated the association between the nutrition data at the time of NTM-LD diagnosis and death. METHODS: A retrospective study was conducted for patients with NTM-LD who visited the Maebashi Red Cross Hospital from January 2014 to December 2018. The patients were divided into the survival and death groups and analyzed statistically. RESULTS: The diagnostic criteria for NTM-LD were met by 150 patients. The median age was 70 years (range, 20-94 years). There were 51 (34.0%) men and 99 (66.0%) women. In the death group, the body mass index was significantly low, and there were significantly more patients with asthma. Further, computed tomography at the first visit revealed significantly fewer cases of the nodular bronchiectasis type. In the hematologic examination at the time of NTM-LD diagnosis, the white blood cell, neutrophil, and platelet counts and C-reactive protein and serum calcium levels were significantly higher in the death group, while the serum albumin level was significantly lower. In the death group, the prognostic nutritional index (PNI), calculated from the hematologic findings, was significantly lower, while the Glasgow Prognostic Score (GPS) was significantly higher. A logistic regression analysis was performed on items with significant differences, and the PNI and platelet count were independent factors predicting death. CONCLUSIONS: PNI might be effective as a prognostic factor for NTM-LD.

Tandem Three-Component Synthesis of syn-1,2- and syn-1,3-Diol Derivatives.

The development of efficient methods for stereocontrolled synthesis of polyol derivatives has been of continuing interest for the synthetic community. We describe herein tandem olefin cross-metathesis/hemiacetalization/intramolecular oxa-Michael addition of allylic/homoallylic alcohols, α,ß-unsaturated ketones, and aldehydes, which enabled the synthesis of syn-1,2- and syn-1,3-diol derivatives in a step-economical manner. A series of differentially protected polyol derivatives could be obtained in subsequent transformations via chemoselective/regioselective cleavage of the acetal moiety of the tandem reaction products.

A palladium-catalyst stabilized in the chiral environment of a monoclonal antibody in water.

We report the first preparation of a monoclonal antibody (mAb) that can immobilize a palladium (Pd)-complex. The allylic amination reaction using a supramolecular catalyst consisting of the Pd-complex and mAb selectively gives the (R)-enantiomer product with an enantiomeric excess (ee) of 98 ± 2%. This is in sharp contrast to the reaction catalyzed by a conventional Pd-catalyst (ee < 2%).

Stereoselective Tandem Synthesis of syn-1,3-Diol Derivatives by Integrating Olefin Cross-Metathesis, Hemiacetalization, and Intramolecular Oxa-Michael Addition.

Stereoselective tandem synthesis of syn-1,3-diol motifs, abundantly present in polyketide natural products and relevant pharmaceuticals, was achieved from homoallylic alcohols, α,ß-unsaturated ketones, and aldehydes. Olefin cross-metathesis of homoallylic alcohols with α,ß-unsaturated ketones, hemiacetalization of the resultant alcohols with aldehydes, and subsequent intramolecular oxa-Michael addition of the derived hemiacetals furnished syn-1,3-dioxane derivatives in good to excellent yields without isolation of any intermediates. The acetal moiety of the resultant syn-1,3-dioxanes could be cleaved chemoselectively/regioselectively under mild conditions in subsequent transformations.

Possible Serological Markers to Predict Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Background and objectives: Idiopathic pulmonary fibrosis (IPF) has a particularly poor prognosis, and most IPF-related deaths are due to acute exacerbation (AE) of this condition. Few reports about biomarkers to predict prognosis of AE-IPF have been published since the release of the new AE-IPF criteria in 2016. The present study investigated relationships between serological markers and in-hospital mortality after the onset of AE-IPF. Methods: Demographic, serological, and imaging data from patients hospitalized at the Maebashi Red Cross Hospital (Gunma, Japan) between 1 January 2013, and 31 December 2017, were retrospectively reviewed. Subjects fulfilling the diagnostic criteria for AE-IPF were divided into those who survived or died; statistical analysis of risk factors was performed using data from these two groups. Results: Diagnostic criteria for AE-IPF were fulfilled by 84 patients (59 males (70.2%)), with a median age of 78 years (range, 56-95 years). IPF was diagnosed before hospitalization in 50 (59.5%) patients and 38 (45.2%) died in hospital. Among the serological markers at hospitalization in the deceased group, C-reactive protein (CRP) was significantly higher than in the survivor group (p = 0.002), while total serum protein (p = 0.031), albumin (p = 0.047) and total cholesterol (p = 0.039) were significantly lower. Cox hazard analysis of factors predicting mortality, corrected for age, sex and BMI, revealed the following: CRP (hazard ratio (HR) 1.080 (95% confidence interval (CI) 1.022-1.141); p = 0.006), LDH (HR 1.003 (95% CI 1.000-1.006); p = 0.037), and total cholesterol (HR 0.985 (95% CI 0.972-0.997); p = 0.018). Conclusions: Our data suggest that CRP, LDH, and total cholesterol may be biomarkers predicting mortality in patients with AE-IPF. However, only prospective controlled studies can confirm or not our observation as a generalizable one.

Small Cell Lung Cancer with Sarcoidosis in Spontaneous Remission: A Case Report.

A 69-year-old woman was diagnosed with sarcoidosis, which was not treated with corticosteroid therapy. Her levels of angiotensin converting enzyme decreased significantly over 4 years and a mass lesion was detected near the lower part of her left main bronchus, and diagnosed as small cell lung cancer (SCLC). Treatment of the SCLC with a series of chemotherapeutic agents produced excellent results. The pulmonary sarcoidosis did not show any deterioration despite the frequent use of amrubicin, which is known to be a cause of interstitial pneumonia. This is a case report of SCLC complicated with sarcoidosis in a stage of spontaneous remission, possibly suggesting an association between sarcoidosis and tumor immunity, since recent reports have suggested that immune checkpoint inhibitors might be involved in the development of sarcoidosis.

Accumulation of periostin in acute exacerbation of familial idiopathic pulmonary fibrosis.

Periostin, an extracellular matrix molecule, is associated with idiopathic pulmonary fibrosis (IPF). It is known that the frequency of familial IPF (FIPF) ranges from 0.5% to 2.2% among IPF cases. However, the relationship between periostin and FIPF has not been previously described. We report the first case of periostin accumulation in the lungs of a patient with an acute exacerbation of FIPF. A 72-year-old woman, diagnosed with FIPF, had been followed up for 5 years. The patient experienced increased dyspnea within a 1-month period and was referred to our hospital. The patient was hypoxic, and chest computed tomography showed rapidly expanding bilateral reticular shadows. Despite pulse-steroid and intravenous-cyclophosphamide therapy, the patient died 25 days after admission. On admission, serum periostin levels were not significantly elevated, while serum fibrotic marker levels were elevated. Immunohistochemical analysis of the lungs on autopsy showed marked accumulation of periostin in the active fibrotic lesions, whereas intact and burned-out areas did not show significant expression of periostin. This case might provide insight into the role of periostin in acute exacerbation of IPF.