Institution: | 1. Organisch-Chemisches Institut, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany;2. Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081 Aviano, Italy;3. Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081 Aviano, Italy
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari, Campus Scientifico Via Torino 155, 30174 Venezia-Mestre, Italy;4. Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari, Campus Scientifico Via Torino 155, 30174 Venezia-Mestre, Italy;5. Dipartimento di Scienze Chimiche, Università degli studi di Padova, via Marzolo 1, 35131 Padova, Italy |
Abstract: | Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones. |