Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents.

Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel®.

Cationic cyclization reactions with alkyne terminating groups: a useful tool in biomimetic synthesis.

Cyclization reactions through cationic intermediates have become a highly valuable tool in organic synthesis. The use of alkynes as the terminating group in this type of cationic process offers wide synthetic possibilities because this group can serve as a precursor of different functionalities. This article shows relevant examples of cationic cyclization reactions with alkynes as terminating groups with the intention of demonstrating the potential of this type of process, particularly in the context of biomimetic synthesis of natural products.

Generation of alkoxysulfonyl radicals from chlorosulfates and their intramolecular capture with alkynes to obtain sultones.

An unprecedented radical-mediated reaction of alkyne-containing chlorosulfates to synthesize sultones has been established. The reaction leads to the formation and subsequent capture of alkoxysulfonyl radicals, which are species known for a long time but not studied for synthetic purposes.

Synthesis of Spirocyclic Compounds by a Ring-Expansion/Cationic Cyclization Cascade Reaction of Chlorosulfate Derivatives.

A novel cascade reaction to prepare spirocarbocyclic compounds from chlorosulfate derivatives has been developed. The process involves an unusual thermal elimination of the chlorosulfate moiety, a ring-expansion reaction, and a subsequent cationic cyclization reaction. Despite the relatively complex skeletal rearrangement, the reaction described here is featured by its operational simplicity, being just a thermal process that does not require additional reagents, catalysts, or additives.