Sustainable construction of value-added naphthoquinones for pharmaceuticals

Abstract

The most crucial and essential ongoing global research is to convert the abundantly available feedstock into materially and medicinally valuable scaffolds in a greener mode. This requires the proper selection of feedstock and the development of systematic green synthetic strategies to convert it into valuable entities. One of the most attractive and abundant feedstocks is lawsones. However, the selective removal of the enolic hydroxy group from the dynamic tautomers of lawsones to access 1,2- and/or 1,4-naphthoquinones, which have plenty of synthetic applications, remains a challenge. Herein, we report metal-free, chemo-/regio-selective high-yielding hydrodehydroxylation (HDH) and hydrodechlorination (HDC) strategies in which the abundantly available 3-alkyllawsones were treated with aqueous HI in AcOH under microwave irradiation for a few minutes to access a vast library of materially and medicinally important 1,2- and 1,4-naphthoquinones. We also reported the short total synthesis of medicinally important drug molecules, such as deoxyneocryptotanshinone, miltirone, and vitamin-K₃ (menadione) and their analogues, using the currently developed HDH as a key reaction. The commercial/easy availability of the feedstock lawsone and 3-alkyllawsones, bio-friendly nature of aqueous hydriodic acid and acetic acid, complete chemo-/regio-selectivity of hydrodehydroxylation of the enolic-hydroxy groups, huge substrate scope, quantitative yields, large synthetic applications, and the short synthesis of medicinal molecules are the key attractions of this work compared to the previous synthesis of 1,2-naphthoquinones.