Ruthenium-Catalyzed C–H Arylation of Aromatic Acids with <i>ortho</i>-Haloaniline To Access Phenanthridinones

Phenanthridinone is a significant moiety in pharmaceutical and material science; thus, it is highly desirable to develop an efficient and robust method to construct phenanthridinone from readily available starting materials. Herein, we report a Ru-catalyzed C–H arylation of aromatic carboxylic acids with ortho-haloanilines, followed by intramolecular dehydration to afford phenanthridinones in high yields

2‑Acetylthienopyridine Synthesis via Thiolation and Copper-Catalyzed Cyclization of <i>o</i>‑Propynol Fluoropyridine Using Xanthate as a Thiol Surrogate

2-Acylthienopyridines and related heterocycles are readily prepared in moderate to good yields under mild conditions by a nucleophilic thiolation, copper-catalyzed cyclization, and an oxidation cascade process using potassium xanthate as the thiol source. Moreover, excellent chemoselectivity, broad substrate scope, and good functional group tolerance are prominent features of this transformation

Annexin V‑Conjugated Mixed Micelles as a Potential Drug Delivery System for Targeted Thrombolysis

To alleviate the hemorrhagic side effect of thrombolysis therapy, a thrombus targeted drug delivery system based on the specific affinity of Annexin V to phosphatidylserine exposed on the membrane surface of activated platelet was developed. The amphiphilic and biodegradable biomaterial, polycaprolactone-<i>block</i>-poly­(2-(dimethylamino)­ethyl methacrylate)-<i>block</i>-poly­(2-hydroxyethyl methacrylate) (PCL-<i>b</i>-PDMAEMA-<i>b</i>-PHEMA (PCDH)) triblock polymer, was synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) to use as the nanocarriers of thrombolytic drug. In order to conjugate Annexin V to the polymer, PCDH was modified by succinic anhydride via ring-opening reaction to introduce the carboxyl group (PCDH-COOH). After preparation of PCDH/PCDH-COOH (9/1, m/m) mixed micelles, Annexin V was coupled with the micelles using carbodiimide chemistry. The blood clot lysis assay in vitro confirmed that lumbrokinase-loaded targeted micelles (LKTM) had stronger thrombolysis potency than free lumbrokinase (LK) and LK-loaded nontargeted micelles (LKM, <i>P</i> < 0.05). In vivo thrombolytic assay, multispectral, optoacoustic tomography (MSOT) was used to assess the target ability of LKTM. The results of MSOT images indicated the fluorescence intensity of the LKTM group located in the blood clot position were significantly stronger than the LKM group. A 5 mm of carotid artery containing blood clot was cut out 24 h later after administration to assess the degree of thrombolysis. The results of thrombolytic assay in vivo were consistent with the assay in vitro, which the differences between LK, LKM, and LKTM groups were both statistically significant. All the results of thrombolysis assays above proved that the capacity of thrombolysis in the LKTM group was optimal. It suggested that Annexin V-conjugated micelles will be a potential drug delivery system for targeted thrombolysis