Synthesis, Spectral Characterization, andIn VitroCytotoxicity of N-2′-Hydroxyethyl-Substituted Azacholestanes Prepared from 6-Oxocholestanes by Modified Schmidt Reaction

Abstract

The present paper reports the synthesis and spectroscopic characterization of few N-2′-hydroxyethyl-substituted azacholestanes using BF3-OEt2, TiCl4, SnCl4, and H2SO4as catalysts in moderate yields by a modified version of Schmidt reaction. A notable feature is the passivity of SnCl4in case of 3β-acetoxy-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one and 3β-chloro-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one. However, the reaction was unsuccessful in case of N-2′-Hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one. Another striking aspect is the attainment of high yield in case of H2SO4as catalyst. The semisolid compounds are characterized using various spectroscopic techniques such as FT-IR,1H-NMR and mass spectra, and microanalytical data. A reaction mechanism has been proposed on the basis of previous studies. Moreover, the compounds have also been screened for theirin vitrocytotoxicity against human colon carcinoma cell line, HCT116, and human liver hepatocellular carcinoma cell line, HepG2, using doxorubicin as standard. On the basis of IC50values, 3β-chloro-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one (5) was found to inhibit the cancer cells most effectively.