Synthesis and Computational Studies of 2-nitro-3-phenyl-3- (phenylthio)propan-1-ol and their Derivatives

Nitro-olefins acts as excellent Michael acceptors. The nitro group and hetetro atom nucleophiles of sulfur anions acts as nucleophiles due to the strong electron deficiency exhibited by them. When concerning about the catalytic addition of thiols to nitro-olefin, DABCO is considered to be the catalyst of great choice as it has drawn a boundless attention in the recent years of research interest. Hence in this study, Michael addition of thiols to nitro-olefins was performed in Lewis base DABCO (1,4-diazabicyclo[2.2.2]octane) with tetrahydrofuran (THF) at room temperature. 2-nitro-3- phenyl-3-(phenylthio)propan-1-ol derivatives 6a-6f were obtained at appreciable purity of compounds which was ascertained by melting point and thin-layer chromatography and was characterized by 1H – 13C NMR. The synthesized compounds were subjected to molecular docking studies through commercial software using Discovery Studio 4.0. Further the pharmacokinetics properties were studied by ADMET. DMol3 properties and B3LYP functions were also studied. Among the six derivative compound 6b showed the higher docking energy of the score -88.1382 and promising molecular interaction against the target protein cytochrome P450 17A1 (steroid 17 alpha - hydroxylase / 17, 20 lyase) which is primarily involved in the steroid biosynthesis pathway. The synthesized compounds of 2-nitro-3-phenyl-3-(phenylthio)propan-1-ol derivatives were explored against the target 3SWZ (CYP17A1). The compound 6b “3-(4-ethylphenyl)-2-nitro-3-(phenylthio)propan-1-ol” exhibited desirable pharmacokinetic and higher reactivity, hence could be proposed for further in vitro anticancer activity.