ABSTRACT
Herein, we report an efficient strategy for the rapid construction of 1,4-oxazines starting from simple α-amino ketones and diazo pyruvates under mild reaction conditions. This transformation is efficiently catalyzed by RuCl3 through a tandem N-H insertion/cyclization sequence via an enol formation. This reaction shows broad functional group tolerance, and the resulting 1,4-oxazine products show promising anticancer activities toward HCT116.
ABSTRACT
A series of polysubstituted pyrrolidines obtained via ruthenium-catalyzed cascade cyclization of diazo pyruvates and anilines as well as their corresponding pyrrole analogs obtained via dehydration were evaluated for their antiproliferation activities. Pyrrolidines 3h and 3k showed good proliferation inhibitory effects toward 10 cancer cell lines with IC50 values ranging from 2.9 to 16 µM. Furthermore, pyrrolidine 3k induced cell cycle arrest at the G0/G1 phase and time- and dose-dependent cellular apoptosis in both HCT116 and HL60 cells, suggesting that this type of pyrrolidine structure might be a good candidate for future anticancer therapies.
Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Pyrroles/pharmacology , Pyrrolidines/pharmacology , A549 Cells , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Proliferation , Dose-Response Relationship, Drug , Drug Design , Drug Screening Assays, Antitumor , HCT116 Cells , HL-60 Cells , HeLa Cells , Humans , Inhibitory Concentration 50 , Jurkat Cells , Molecular Structure , Neoplasms/pathology , PC-3 Cells , Pyrroles/chemical synthesis , Pyrrolidines/chemical synthesis , Structure-Activity Relationship , Time FactorsABSTRACT
An unprecedented synthesis of polysubstituted pyrrolidines from anilines and diazo pyruvates by ruthenium catalysis under mild reaction conditions is reported. An enol intermediate derived from the N-H insertion of aniline toward the ruthenium carbene species as well as an imine ester intermediate generated by SET-mediated oxidation of enol were proposed as the key intermediates. This strategy provides various pyrrolidines containing four contiguous stereocenters in good efficiency with high diastereoselectivities.
ABSTRACT
A highly diastereoselective approach for the rapid construction of an isochroman skeleton was achieved by the copper(ii)-catalyzed transformation of alcohol-tethered enones and diazo compounds. This transformation was proposed to proceed through the intramolecular Michael-type trapping of an in situ generated oxonium ylide intermediate. The copper(ii) catalyst may play a dual role in catalyzing diazo decomposition as well as activating the enone unit. With this method, a series of 3,4-substituted isochromans were obtained with excellent diastereoselectivities under very mild reaction conditions.
