Divergent Synthesis of Methylene Lactone- and Methylene Lactam-Based Spiro Compounds: Utility of Amido-Functionalized γ-Hydroxylactam as a Precursor for Cytotoxic N,O- and N,N-Spiro Compounds.

Abstract

Pharmaceutically attractive methylene lactone- and methylene lactam-based spiro compounds have been synthesized by employing amido-functionalized γ-hydroxylactam as a common intermediate. Development of a new route for bifurcated synthesis of two types of N,O-spiro compounds was accomplished by treatment of the intermediate under acidic conditions, leading to potent cytotoxic methylene lactone-based spiro compounds. New methylene lactam-based N,N-spiro compounds could be delivered via N-tert-butyloxycarbonyl protection of the terminal amide moiety of the intermediate followed by lactam cyclization under basic conditions.