Synthesis, Spectroscopic and Semiempirical Studies of New Quaternary Alkylammonium Conjugates of Sterols

Abstract

New quaternary alkylammonium conjugates of steroids were obtained by two step reaction of sterols (ergosterol, cholesterol, dihydrocholesterol) with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with a long chain tertiary alkylamine. The structures of products were confirmed by spectral ( 1 H-NMR, 13 C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods. The pharmacotherapeutic potential of synthesized compounds has been estimated on the basis of Prediction of Activity Spectra for Substances (PASS).

Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies

“…In turn, Rao and co-workers isolated six other aminosterols (43)(44)(45)(46)(47)(48) from the liver of the dogfish shark ( Figure 4) [15]. The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI).…”

“…The unsymmetrical bisquaternary ammonium salts (92-101) demonstrate a bacteriostatic activity that depends on the alkyl chain length. Brycki and co-workers obtained the series of quaternary alkylammonium conjugates of ergosterol, cholesterol, and cholestanol [48]. The conjugates were synthesized by two-step reactions.…”

“…The synthesis and physicochemical properties of quaternary N,N-dimethyl-3-phthalimidopropylammonium conjugates of ergosteryl 3β-bromoacetate, cholesteryl 3β-bromoacetate, and dihydrocholesteryl 3β-bromoacetate, as well as methyl litocholate 3α-bromoacetate, methyl deoxycholate 3α-bromoacetate, and methyl cholate 3α-bromoacetate with N,N-dimethyl-3-phthalimidopropylamine in acetonitrile were investigated and described. Brycki and co-workers obtained the series of quaternary alkylammonium conjugates of ergosterol, cholesterol, and cholestanol [48]. The conjugates were synthesized by two-step reactions.…”

“…The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI). The antimicrobial activity of aminosterols (43)(44)(45)(46)(47)(48) and squalamine (1) Great efforts have also been made to synthesize squalamine. Okumura et al synthesized squalamine from a derivative of desmosterol via 12 steps with 7.4% of the total yield [38].…”

“…The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI). The antimicrobial activity of aminosterols (43)(44)(45)(46)(47)(48) and squalamine (1) is summarized in Synthesis of 6β-hydroxy-3-α-(or β-)aminosterols (53-58) from hyodeoxycholic acid (49) has been presented by Jones et al (Scheme 3) [44]. The modification of hyodeoxycholic acid was carried out by the esterification of the carboxyl group and oxidation of both hydroxyl groups to ketones, followed by a conversion of the A/B ring system from cis to trans by acid-catalyzed isomerization.…”