A Chemo-Enzymatic Expeditious Route to Racemic Dihexanoyl (2<i>R</i>*,3<i>R</i>*,4<i>R</i>*)-Dehydroxymethylepoxyquinomycin (DHMEQ), the Precursor for Lipase-Catalyzed Synthesis of the Potent Nuclear Factor-κB Inhibitor, (2<i>S</i>,3<i>S</i>,4<i>S</i>)-DHMEQ

Abstract

In order to synthesize the potent nuclear factor (NF)-κB inhibitor, (2S,3S,4S)-dehydroxymethylepoxyquinomycin (DHMEQ), in a large scale, a new route for its corresponding racemic precursor, dihexanoyl (2R*,3R*,4R*)-DHMEQ, was developed. By employing both hydroquinone and benzoquinone intermediates, the total yield, reproducibility, and synthetic steps were improved and the synthetic cost was reduced.

Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ

“…An alternative route to serve this substrate efficiently for lipase-catalyzed kinetic resolution was developed. In this synthesis, crude DHMEQ was directly acylated and racemic, but a distereomerically pure form of dihexanoate was obtained [11]. We also found an effective way of (+)-DHMEQ preparation with Burkholderia cepacia lipase-catalyzed hydrolysis of structurally modified precursor [12].…”

An entry to indole quinones using in situ generated nitrobenzoquinone

“…4 Previous uses of nitroquinones in organic synthesis include the innovative synthesis of indolequinone by Parker and Sworin 5 Our approach to the synthesis of indole containing quinones began with nitrohydroquinone (3), which was readily available from demethylation of 2,5-dimethoxynitrobenzene. 7 The corresponding quinone is unstable to storage, but it can be generated in situ using an oxidant such as silver oxide or MnO2 and readily reacted with nucleophiles. 8 To the best of our knowledge this is the first report of the reaction of nitrobenzoquinone with indoles.…”