Synthesis and biological activity of certain amino-derivatives of 5α-steroids

Abstract

Certain 17β-aminoderivatives of 5α-steroids based on tigogenin were synthesized and their antitumor activity was studied. The structures of the synthesized compounds were confirmed by NMR and IR spectroscopy and mass spectrometry.We previously reported the synthesis and biological activity of certain derivatives of 17-amino alcohols of the 5α-androstane type and demonstrated their effect on the CNS [1] and radioprotective properties [2]. We synthesized 17β-amino-5α-androstane, a compound known to have anti-inflammatory and fungicidal activity [3]. In order to explain the antitumor activity, we synthesized certain derivatives of 17-aminosteroids.The starting material for the synthesis of the amine derivatives of 5α-androstanes was tigogenin (1), which was isolated from Yucca gloriosa cultivated in Georgia. Tigogenin was transformed into epiandrosterone acetate (2) and then into the 17β-aminoderivatives (3-9) by the literature method [1-3]. Thus, 17β-amino-5α-androstan-3β-ol (3) was prepared from 2 by Leuckart-Wallach amination [4]; 17α-amino-5α-androstan-3β-ol (4), by a modified Streitweiser-Schaeffer method [5]. The product of the Leuckart-Wallach reaction was reduced by an excess of LiAlH 4 in THF to give the 17β-methylamino derivative (5) [1].3: R = OH, R 1 = NH 2 , R 2 = H; 4: R = OH, R 1 = H, R 2 = NH 2 ; 5: R = OH, R 1 = CH 3 N, R 2 = H 6: R = OH, R 1 = NHCOOCH 3 , R 2 = H; 7: R = OCOOCH 3 , R 1 = NHCOOCH 3 , R 2 = H 8: R = OH, R 1 = H, R 2 = NHCOOCH 3 ; 9: R = OCOOCH 3 , R 1 = H, R 2 = NHCOOCH 3 10: R = OH, R 1 = CH 3 NCH 2 CONH 2 , R = H; 11: R = OH, R 1 = CH 3 NCH 2 CH 2 NH 2 , R 2 = H 12: R = O; 13: R = NOH The carbamoyl derivatives 6-9 were synthesized by treatment of 3 and 4 with an excess of Cl(CO)OCH 3 in pyridine. The mixture formed by this of the mono-and diacylated compounds (6, 7, and 8, 9, respectively) was separated by chromatography over a silica-gel column with elution successively by mixtures of petroleum ether and ethylacetate (20:1 and 10:1) [1]. Diaminoderivative 11 was prepared by reaction of 17β-methylamine (5) with chloroacetamide in the presence of Na 2 CO 3 in DMF at 80-90°C with subsequent reduction of amide 10 by an excess of LiAlH 4 in 1,4-dioxane. We also synthesized 17β-amino-5α-androst-2-ene (14) according to the previously published scheme [3] from epiandrosterone acetate (2) by forming 5α-androst-2-en-17-one (12) and reduction of its oxime 13 by metallic Na in n-propanol.

Steroids: partial synthesis in medicinal chemistry

“…A long-range effect of the substituents on ring A has been reported 83 on the stereochemistry of cyanohydrin formation from C-17 ketones. 17b-Amino steroids have been prepared 84 as potential anti-tumour agents. The diphenylphosphinyl moiety has been introduced both onto ring D at C-16 85 and attached 86 to the ethynyl side chain in a mifepristone analogue 26.…”

Antimicrobial Activity of Nitrogen-Containing 5-α-Androstane Derivatives: In Silico and Experimental Studies

“…Thus, the purpose of our study was in silico evaluation of the antimicrobial potential of thirty-one nitrogen-containing 5-α-androstane derivatives and further experimental testing of their antibacterial and antifungal activity, including action on the resistant strains. Thirty-one amino-, amido-, hydroximino-, phtalimido-, d-homo-, and azido-steroidal derivatives 1-27, that we synthesized earlier [21,[32][33][34][35][36][37][38][39][40][41][42][43], were prepared and evaluated for antimicrobial actions.…”

Synthesis from Tigogenin of 17β-Amino-5α-Androstan-3β-Ol Peptide Derivatives

“…Saturated and unsaturated 17E-aminosteroids are used as intermediates to synthesize biologically active derivatives [5,6]. Peptide analogs of amidosteroids, among which compounds with various physiological activities such as anti-arrhythmic and antitumor have been found, were prepared by adding amino acids to aminosteroids [7,8].…”