3-(2-Azidoethyl)oxindoles: Advanced Building Blocks for One-Pot Assembly of Spiro[pyrrolidine-3,3′-oxindoles]

A new synthetic approach to biologically relevant spiro[pyrrolidine-3,3'-oxindoles] was developed on the basis of the cascade transformation of 3-(2-azidoethyl)-oxindoles via Staudinger/aza-Wittig/Mannich reactions. The parent azides were readily synthesized through a nudeophilic ring opening of spiro[cyclopropane-1,3'-oxindoles] with the azide ion. A series of new spiro[pyrrolidine-3,3'-oxindoles] with various (het)aryl substituents at the C2 and C5 positions of the pyrrolidine ring were synthesized. In vitro experiments revealed their high crotoxicity toward LNCaP and PC-3 tumor cell lines.