Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

Establishment of FAP-overexpressing Cells for FAP-targeted Theranostics.

OBJECTIVE: Fibroblast activation protein (FAP) has been widely studied and exploited for its clinical applications. One of the difficulties in interpreting reports of FAP-targeted theranostics is due to the lack of accurate controls, making the results less specific and less confirmative. This study aimed to establish a pair of cell lines, in which one highly expresses FAP (HT1080-hFAP) and the other has no detectable FAP (HT1080-vec) as control, to accurately evaluate the specificity of the FAP-targeted theranostics in vitro and in vivo. METHODS: The cell lines of the experimental group (HT1080-hFAP) and no-load group (HT1080-vec) were obtained by molecular construction of the recombinant plasmid pIRES-hFAP. The expression of hFAP in HT1080 cells was detected by PCR, Western blotting and flow cytometry. CCK-8, Matrigel transwell invasion assay, scratch test, flow cytometry and immunofluorescence were used to verify the physiological function of FAP. The activities of human dipeptidyl peptidase (DPP) and human endopeptidase (EP) were detected by ELISA in HT1080-hFAP cells. PET imaging was performed in bilateral tumor-bearing nude mice models to evaluate the specificity of FAP. RESULTS: RT-PCR and Western blotting demonstrated the mRNA and protein expression of hFAP in HT1080-hFAP cells but not in HT1080-vec cells. Flow cytometry confirmed that nearly 95% of the HT1080-hFAP cells were FAP positive. The engineered hFAP on HT1080 cells had its ability to retain enzymatic activities and a variety of biological functions, including internalization, proliferation-, migration-, and invasion-promoting activities. The HT1080-hFAP xenografted tumors in nude mice bound and took up 68GA-FAPI-04 with superior selectivity. High image contrast and tumor-organ ratio were obtained by PET imaging. The HT1080-hFAP tumor retained the radiotracer for at least 60 min. CONCLUSION: This pair of HT1080 cell lines was successfully established, making it feasible for accurate evaluation and visualization of therapeutic and diagnostic agents targeting the hFAP.