Antisense Gapmers with LNA-Wings and (S)-5′-C-Aminopropyl-2′-arabinofluoro-nucleosides Could Efficiently Suppress the Expression of KNTC2

Previously reported (S)-5′-C-aminopropyl-2′-arabinofluoro-thymidine (5ara-T) and newly synthesized (S)-5′-C-aminopropyl-2′-arabinofluoro-5-methyl-cytidine (5ara-^MeC) analogs were incorporated into a series of antisense gapmers containing multiple phosphorothioate (PS) linkages and locked nucleic acids (LNAs) in their wing regions. The functional properties of the gapmers were further evaluated in vitro. Compared with the positive control, for the LNA-wing full PS gapmer without 5ara modification, it was revealed that each gapmer could have a high affinity and be thermally stable under biological conditions. Although the cleavage pattern was obviously changed; gapmers with 5ara modification could still efficiently activate E. coli RNase H1. In addition, incorporating one 5ara modification into the two phosphodiester linkages could reverse the destabilization in enzymatic hydrolysis caused by fewer PS linkages. In vitro cellular experiments were also performed, and the Lipofectamine^® 2000 (LFA)+ group showed relatively higher antisense activity than the LFA-free group. KN5ara-10, which contains fewer PS linkages, showed similar or slightly better antisense activity than the corresponding full PS-modified KN5ara-3. Hence, KN5ara-10 may be the most promising candidate for KNTC2-targeted cancer therapy.     

Pyrazinium Di(hydrogen sulfate) as a Novel,Highly Efficient and Homogeneous Catalyst for the Condensation of Enolizable Ketones with Aldehydes,Acetonitrile and Acetyl Chloride

A highly efficient protocol for the synthesis of β‐acetamido ketone or ester derivatives in the presence of pyrazinium di(hydrogen sulfate) {Py(OSO₃H)₂} as a novel, green and homogeneous solid acid catalyst at room temperature is described. One‐pot multi‐component condensation of enolizable ketones or alkyl acetoacetates with aldehydes, acetonitrile and acetyl chloride affords the title compounds in high to excellent yields and in relatively short reaction times. In this work, the efficiency of our recently reported solid acid catalyst, saccharin sulfonic acid (Sa‐SO₃H), in the synthesis of β‐acetamido ketones/esters is also studied. Moreover, in this research, some new β‐acetamido ketones and esters (i.e. one complex structure) are prepared.     

2‐(1H‐Benzotriazole‐1‐yl)‐1,1,3,3‐Tetramethyluronium Tetrafluoro Borate (TBTU) as an Efficient Coupling Reagent for the Esterification of Carboxylic acids with Alcohols and Phenols at Room Temperature

Esterification of carboxylic acids with alcohols and phenols by using 2‐(1H‐benzotriazole‐1‐yl)‐1,1,3,3‐tetramethyluronium tetrafluoroborate (TBTU) in the presence of triethylamine as a base proceeded smoothly under mild conditions to afford the corresponding esters in good to high yields in acetonitrile at room temperature.