A-ring functionalization of cholestane with highly substituted pyrans and 2-aminoisophthalonitriles

Abstract

Following our ongoing interest on modified steroidal compounds for biological purposes, herein we endeavor the two-step regioselective synthesis of three-substituted pyran-cholestane fused compounds (6 examples, yields up to 83%) at C-2:C-3 A-ring side of the steroid scaffold. In the presence of higher amounts of malononitrile, the intermediate α,β-unsaturated carbonyl substrates give rise to competing reactions leading to the formation of the corresponding 2-aminoisophthalonitrile fused compounds (2 examples, up to 37% yield).

Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors

“…The most recognizable steroidal compound is cholesterol (cholest-5-en-3β-ol), which is considered a lipid-type molecule, being one of the most important structural components of cell membranes [ 59 , 60 ]. Following our ongoing interest in modified steroidal compounds for biological purposes, such as protein aggregation inhibitors, we used the MW-assisted regioselective synthesis of cholestane-fused compounds 46 and 47 ( Scheme 15 ) [ 61 ]. In classical heating conditions, the reaction of α,β-unsaturated carbonyl substrates 45 with malononitrile is difficult to control, leading to complex reaction mixtures of several unidentified compounds.…”

“…Upon application of MW irradiation, we managed to drive the reaction in different directions, carefully controlling the amount of malononitrile. This strategy allowed the efficient synthesis of pyran- 46 and 2-aminoisophthalonitrile-cholestane 47 -fused compounds, in 65–83% and 30–37% yield, respectively ( Scheme 15 ) [ 61 ].…”