Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole
Wen Ren,
Qian Zhao,
Chuan Zheng,
Qiong Zhao,
Li Guo,
Wei Huang
Affiliations
Wen Ren
Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Qian Zhao
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Chuan Zheng
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Qiong Zhao
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Li Guo
Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Wei Huang
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures.
