Catalyst-Free, Room-Temperature Accessible Regioselective Synthesis of Spiroquinolines and Their Antioxidant Study

Abstract

An efficient, regioselective, and environmentally benign approach was established using the multicomponent reaction-based synthesis of novel antioxidant spiroquinoline derivatives such as spiro[dioxolo[4,5-<i>g</i>]quinoline], spiro[dioxino[2,3-<i>g</i>]quinoline], and spiro[pyrazolo[4,3-<i>f</i>]quinoline] by reaction of aryl aldehyde, Meldrum's acid, and amine derivatives under an additive-free reaction in aqueous ethanol. Here, two asymmetric carbon centers, three new C-C bonds, and one C-N bond are developed in the final motif. This synthetic methodology offers excellent yields with an easy workup procedure, high diastereoselectivity [d.r. >50:1 (<i>cis</i>/<i>trans</i>)], admirable atom economy, and low <i>E</i>-factor values. Synthesized spiro compounds were investigated for their in vitro antioxidant activity by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In the ABTS radical scavenging assay, compounds <b>4d</b>, <b>4f</b>, and <b>4l</b> exhibit excellent potency, and in the DPPH radical scavenging assay, compounds <b>4a</b>, <b>4d</b>, <b>4f</b>, and <b>4g</b>, exhibit excellent potency.