Potent adjuvant effect elicited for tumor immunotherapy by a liposome conjugated pH-sensitive polymer and dendritic cell-targeting Toll-like-receptor ligand.

The generation of DCs with augmented functions is a strategy for obtaining satisfactory clinical outcomes in tumor immunotherapy. We developed a novel synthetic adjuvant comprising a liposome conjugated with a DC-targeting Toll-like-receptor ligand and a pH-sensitive polymer for augmenting cross-presentation. In an in vitro study using mouse DCs, these liposomes were selectively incorporated into DCs, significantly enhanced DC function and activated immune responses to present an epitope of the incorporated antigen on the major histocompatibility complex class I molecules. Immunization of mice with liposomes encapsulating a tumor antigen significantly enhanced antigen-specific cytotoxicity. In tumor-bearing mice, vaccination with liposomes encapsulating a tumor antigen elicited complete tumor remission. Furthermore, vaccination significantly enhanced cytotoxicity, targeting not only the vaccinated antigen but also the other antigens of the tumor cell. These results indicate that liposomes are an ideal adjuvant to develop DCs with considerably high potential to elicit antigen-specific immune responses; they are a promising tool for cancer therapy with neoantigen vaccination.

Trifluoromethanesulfonyl hypervalent iodonium ylide for copper-catalyzed trifluoromethylthiolation of enamines, indoles, and ß-keto esters.

A novel electrophilic-type trifluoromethylthiolation reagent, a trifluoromethanesulfonyl hypervalent iodonium ylide, was designed and reacted well with various nucleophiles to afford the desired CF3S-substituted products. In situ reduction of the trifluoromethanesulfonyl group to give the trifluoromethylthio group, which is the key step in this process, was realized in the presence of copper(I) chloride.

Remote anionic Fries rearrangement of sulfonates: regioselective synthesis of indole triflones.

An unusual NaH-mediated remote anionic 1,5-thia-Fries rearrangement reaction was developed. This method provides an efficient approach for the regioselective synthesis of not only 2-(2-hydroxyphenyl)-3-indole triflones but also related 3-sulfonylindoles.

Synthesis of indole and biindolyl triflones: trifluoromethanesulfonylation of indoles with Tf2O/TTBP (2,4,6-tri-tert-butylpyridine) system.

A convenient synthesis of indole triflones is reported. N-Alkyl, aryl and N-H indole triflones were obtained in 82-96% yields by the Tf(2)O/TTBP System. Biindolyl triflones were accessed in 51-81% yields for the first time by simple treatment of the resulting indole triflones with a base and without any use of organometallic chemistry. An environmentally friendly solvent, Solkane 365/227, can be substituted for this process without any loss of efficiency.