A flexible carbanionic approach to protected trans-(2R,3S)-2-substituted 3-aminopyrrolidines: application to the asymmetric synthesis of (+)-absouline

Based on the use of phenyl thioether (3S)-7 as a synthetic equivalent to the N- and alpha-dianions (3S)-2a, a new carbanionic approach to trans-(2R,3S)-2-substituted 3-aminopyrrolidines (10) is described. Application of the method to the asymmetric synthesis of 1-aminopyrrolizidine alkaloid (+)-absouline is also reported

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

INTRODUCTION: The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model. RESULTS: Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27). CONCLUSIONS: The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy

Studies towards the Total Asymmetric Synthesis of the Pentacyclic Indole Alkaloid Arboflorine: Asymmetric Synthesis of a Key Intermediate

The synthesis of a plausible key intermediate for a biomimetic asymmetric synthesis of indole alkaloid arboflorine is described. The method featured the use of Ellman's sulfinamide chemistry for the establishment of the first chiral center, and the Polonovski-Potier reaction for the formation of the alpha-aminonitrile moiety.NSF of China[20832005]; NFFTBS[J1030415]; National Basic Research Program (973 Program) of China[2010CB833200

The first enantioselective synthesis of cytotoxic marine natural product palau'imide and assignment of its C-20 stereochemistry

Methyl tetramate derivative 6 has been developed as a new building block for the flexible and racemization-free synthesis of methyl 5-benzyl-3-methyltetramate via alkylation, and used in the first asymmetric synthesis of palau'imide (1). This allowed the establishment of the hitherto unknown stereochemistry at the C-20 of palau'imide as S.NSF of China [20832005]; National Basic Research Program (973 Program) of China [2010CB833200

The ISApl12 Dimer Circular Intermediate Participates in mcr-1 Transposition

Objectives: The mobile colistin resistance gene mcr-1 is a serious threat to global human and animal health. The composite transposon Tn6330 and its circular intermediate were proposed to be involved in the spread of mcr-1 but their roles remain poorly understood.Methods: To further explore the intermediates during the transposition of Tn6330, we engineered Escherichia coli strains that carry an intact Tn6330 transposon or its deletion derivatives. PCR assays were performed to detect IR-IR junctions and possible circular intermediates. We carried out transposition experiments to calculate transposition frequency. The transposition sites were characterized by whole genome sequence and ISMapper-based analyses.Results: The presence of an intact Tn6330 was demonstrated to be essential for the successful transposition of mcr-1, although both Tn6330 and Tn6330-ΔIR could form circular intermediates. The insertion sequence junction structure was observed in all constructed plasmids but the ISApl1 dimer was only formed in one construct containing an intact Tn6330. The average frequency of mcr-1 transposition in an E. coli strain possessing an intact Tn6330 was ∼10-6 per transformed cell. We identified 27 integration sites for the Tn6330 transposition event. All the transposition sites were flanked by 2 bp target duplications and preferentially occurred in AT-rich regions.Conclusion: These results indicate that mcr-1 transposition relies on the presence of an intact Tn6330. In addition, formation of the tandem repeat ISApl12 could represent a crucial intermediate. Taken together, the current investigations provide mechanistic insights in the transposition of mcr-1

A new approach to 3-hydroxyprolinol derivatives by samarium diiodide-mediated reductive coupling of chiral nitrone with carbonyl compounds

A flexible diastereoselective approach to trans-(3S)-hydroxyprolinol derivatives is described, which is based on the samarium diiodide-mediated reductive coupling of the chiral 1-pyrroline N-oxide (nitrone)(S)-10 with carbonyl compounds. The reductive hydroxyalkylation of nitrone 10 with ketones and aromatic aldehydes is highly diastereoselective in establishing the C-2 chiral center of the pyrrolidine ring.NSF of China [20832005]; Innovative Research Team in Science & Technology (University) in Fujian Province and the Program for New Century Excellent Talents in Xiamen Universit

Physicochemical and Structural Properties of Pre-digested Puffed Rice Flours with Different Dextrose Equivalent Values

In the present study, pre-digested puffed rice flours with different dextrose equivalent (DE) values were prepared by using enzymatic pretreatment and extrusion, and their gelatinization characteristics, physicochemical and structural properties were analyzed. The results showed that compared with puffed rice flour, the water solubility index of pre-digested puffed rice flour increased by up to about 1.5 times with an increase in DE value, the water absorption index decreased by up to 76%, the slip angle decreased, the Carr index and Hausner ratio increased, and the reconstitutability and fluidity improved obviously. Moreover, the final viscosity and setback value of pre-digested puffed rice flour decreased with increasing DE value, decreasing by up to 37.79% and 94.87%, respectively. Moreover, after enzymatic pretreatment and extrusion, the soluble protein content of pre-digested puffed rice flour decreased, and the content of rapidly digestible starch increased significantly, while the secondary structure of protein and the crystalline structure of starch did not change significantly. The results provide a theoretical basis for the application of pre-digested puffed rice flour instead of maltodextrin in foods for special medical purpose