Enantioselective Total Syntheses of the Proposed and Revised Structures of Methoxystemofoline: A Stereochemical Revision.

This article describes the full details of our synthetic efforts toward the enantioselective total synthesis of the complex alkaloid methoxystemofoline. The enantioselective construction of the tetracyclic core features: (1) the Keck allylation at the N-α bridgehead carbon to forge the tetrasubstituted stereocenter; (2) an olefin cross-metathesis reaction for the side-chain elongation that is amenable for the synthesis of congeners and analogues; and (3) a regioselective aldol addition reaction with methyl pyruvate that ensured the subsequent regioselective cyclization reaction to construct the fourth ring. Overman's method was employed to install the 5-(alkoxyalky1idene)-3-methyl-tetronate moiety. In the last step, a nonstereoselective reaction resulted in the formation of both the proposed structure of methoxystemofoline and its E-stereoisomer, the natural product (revised structure), in a 1:1 ratio. We suggest to rename the natural product as isomethoxystemofoline, and report for the first time the complete 1H NMR data for this natural product.

Design and Synthesis of New Circularly Polarized Thermally Activated Delayed Fluorescence Emitters.

This work describes the first thermally activated delayed fluorescence material enabling circularly polarized light emission through chiral perturbation. These new molecular architectures obtained through a scalable one-pot sequential synthetic procedure at room temperature (83% yield) display high quantum yield (up to 74%) and circularly polarized luminescence with an absolute luminescence dissymmetry factor, |glum|, of 1.3 × 10(-3). These chiral molecules have been used as an emissive dopant in an organic light emitting diode exhibiting external quantum efficiency as high as 9.1%.

Toward the total synthesis of haliclonin†A: construction of a tricyclic substructure.

Three keys to success: A concise method for the construction of a tricyclic substructure (2) of haliclonin A (1) in racemic form is described (see figure). This synthesis features a new Pd-mediated chemoselective carbonyl-enone coupling reaction, an organocatalytic reaction, and a ring-closing metathesis reaction for the construction of the macrocyclic ring as key steps.

Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4­induced liver fibrosis using RNA­sequencing.

Pien Tze Huang (PZH), a common hepatoprotective Traditional Chinese Medicine that has been found to be an effective treatment for carbon tetrachloride­induced hepatic damage, including liver fibrosis. Circular RNAs (circRNAs) serve a crucial role in regulating gene expression levels via circRNA/micro (mi)RNA/mRNA networks in several human diseases and biological processes. However, whether circRNAs are involved in the underlying mechanism of the therapeutic effects of PZH on liver fibrosis remains unclear. Therefore, the aim of the present study was to investigate these effects using circRNA expression profiles from PZH­treated fibrotic livers in model mice. A case­control study on >59,476 circRNAs from CCl4­induced (control group, n=6) and PZH­treated (case group, n=6) mice was performed using circRNA sequencing in liver tissues. PZH treatment resulted in the differential expression of 91 circRNAs, including 58 upregulated and 33 downregulated circRNAs. Furthermore, the construction of competing endogenous networks also indicated that differentially expressed circRNAs acted as miRNA sponges. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of miRNA targets demonstrated that PZH­affected circRNAs were mainly involved in biological processes such as 'positive regulation of fibroblast proliferation', 'cellular response to interleukin­1' and 'regulation of DNA­templated transcription in response to stress' and in a number of important pathways, such as 'TNF signaling pathway', 'PI3K­Akt signaling pathway', 'IL­17 signaling pathway' and 'MAPK signaling pathway'. To further validate the bioinformatics data, reverse transcription­-quantitative PCR was performed on seven miRNA targets in a human hepatic stellate LX­2 cell model. The results suggested that seven of the miRNAs exhibited regulatory patterns that were consistent with those of the transcriptome sequencing results. Kaplan­Meier survival analysis demonstrated that the expression levels of dihydrodiol dehydrogenase and solute carrier family 7, member 11 gene were significantly associated with patient survival, 269 patients with liver hepatocellular carcinoma from The Cancer Genome Atlas database. To the best of our knowledge, this was the first study to provide evidence that PZH affects circRNA expression levels, which may serve important roles in PZH­treated fibrotic liver through the regulation of functional gene expression. In conclusion, the present study provided new insights into the mechanism underlying the pathogenesis of liver fibrosis and identified potential novel, efficient, therapeutic targets against liver injury.

Enantioselective total syntheses of (+)-stemofoline and three congeners based on a biogenetic hypothesis.

The powerful insecticidal and multi-drug-resistance-reversing activities displayed by the stemofoline group of alkaloids render them promising lead structures for further development as commercial agents in agriculture and medicine. However, concise, enantioselective total syntheses of stemofoline alkaloids remain a formidable challenge due to their structural complexity. We disclose herein the enantioselective total syntheses of four stemofoline alkaloids, including (+)-stemofoline, (+)-isostemofoline, (+)-stemoburkilline, and (+)-(11S,12R)-dihydrostemofoline, in just 19 steps. Our strategy relies on a biogenetic hypothesis, which postulates that stemoburkilline and dihydrostemofolines are biogenetic precursors of stemofoline and isostemofoline. Other highlights of our approach are the use of Horner-Wadsworth-Emmons reaction to connect the two segments of the molecule, an improved protocol allowing gram-scale access to the tetracyclic cage-type core, and a Cu-catalyzed direct and versatile nucleophilic alkylation reaction on an anti-Bredt iminium ion. The synthetic techniques that we developed could also be extended to the preparation of other Stemona alkaloids.

Genome Sequences of Six Cluster N Mycobacteriophages, Kevin1, Nenae, Parmesanjohn, ShrimpFriedEgg, Smurph, and SpongeBob, Isolated on Mycobacterium smegmatis mc2155.

The annotation of six cluster N Mycobacterium smegmatis phages (Kevin1, Nenae, Parmesanjohn, ShrimpFriedEgg, Smurph, and SpongeBob) reveals regions of genomic diversity, particularly within the central region of the genome. The genome of Kevin1 includes two orphams (genes with no similarity to other phage genes), with one predicted to encode an AAA-ATPase.

Ruthenium-catalyzed hydrogen isotope exchange of C(sp3)-H bonds directed by a sulfur atom.

We present here the first example of C(sp3)-H activation directed by a sulfur atom. Based on this transformation catalyzed by Ru/C, we have developed a hydrogen isotope exchange reaction for the deuterium and tritium labelling of thioether substructures in complex molecules.

Enantioselective total synthesis of (+)-methoxystemofoline and (+)-isomethoxystemofoline.

The first enantioselective total synthesis of (+)-methoxystemofoline (2) and (+)-isomethoxystemofoline (3) has been reported. The synthesis employed the halide-assisted bromotropanonation method that we developed recently to construct the core structure, and Overman's strategy for the implementation of the butenolide moiety. Through this work, the structure of methoxystemofoline was revised as with an E-alkene, and its absolute configuration was established.

Versatile construction of functionalized tropane ring systems based on lactam activation: enantioselective synthesis of (+)-pervilleine B.

The halo-assisted intramolecular addition of silyl enol ethers with in situ activated lactams yielded (hydroxylated) 1-halo-8-azabicyclo[3,2,1]octane and 1-halo-9-azabicyclo[3,3,1]nonane ring systems, which provided an easy enantioselective access to 6ß-silyloxytropane-3-one, 3α,6ß-dihydroxytropane, and pervilleine B. The absolute configuration of the natural (-)-pervilleine B was determined to be 1R,3R,5S,6R.