NMR-Assisted Structure Elucidation of an Anticancer Steroid-β-Enaminone Derivative

Abstract

The fortuitous modification of a quinoline-proline-piperazine side chain linked to a steroid in the presence of lithium (trimethylsilyl) acetylide has generated an unknown product that is more active than its precursor. After having characterized two β-enaminones (two-carbon homologation compounds) that were generated from a simplified model side chain, we have identified the unknown product as being the β-enaminone steroid derivative 1. NMR analysis, especially two-dimensional (2D) experiments (correlation spectroscopy (COSY), NOE spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC)) provided crucial information that was found essential in the characterization of enaminone 1. We also proposed a mechanism to rationalize the formation of this biologically active compound.

Keywords

• enaminone
• steroid
• NMR
• ethynylation
• rearrangement
• anti-cancer agent