Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 2: The Final Phase and Completion.

The final phase of the total synthesis of (-)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson-Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (-)-spirochensilide A (1) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis.

BACKGROUND: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure. METHOD: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods. RESULTS: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors. CONCLUSION: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Carrier phase shifted SPWM based on current sourced multi-modular converter for active power filter.

A novel current-source active power filter (APF) based on multi-modular converter with carrier phase-shifted SPWM (CPS-SPWM) technique is proposed. With this technique, the effect of equivalent high switching frequency converter is obtained with low switching frequency converter. It is very promising in current-source APF that adopt superconducting magnetic energy storage component.