Synthesis of 16α-amino-pregnenolone derivatives via ionic liquid-catalyzed aza-Michael addition and their evaluation as C 17,20 -lyase inhibitors

The Use of Switchable Polarity Solvents for the Synthesis of 16‐Arylidene Steroids via Claisen–Schmidt Condensation

“…As part of our ongoing interest in using sustainable methods for the synthesis of steroid derivatives, our goal was the synthesis of 16‐substituted androstane and estrane derivatives including promising 17β‐HSD1 inhibitors mentioned above through a green approach, replacing traditionally used inorganic bases to a switchable polarity solvent mixture as catalyst and reaction medium.…”

Synthesis of Steroidal Thioethers via [HDBU][OAc]‐Mediated Michael Addition of Thiols to 16‐Dehydropregnenolone

“…This clearly shows the catalytic activity of [HDBU][OAc] and the necessity of using a catalyst in these reactions. It should be mentioned that in contrast to the aza‐Michael reaction of steroids carried out in the same ionic liquid, [40] no hydrolysis of the ester functionality of substrate 1 was observed. Addition of other thiols ( 3 b‐3 d ) to 16‐dehydropregnenolone acetate ( 1 ) (entries 5, 7, 10) and reactions of 16‐dehydropregnenolone ( 2 ) (entries 4, 6, 9, 12) led to the corresponding thioether derivatives with similar results.…”

“…As a comparison, the application of other ILs such as 2hydroxyethylammonium formate [36] and [HDBU][Lac] (Lac: lactate) [40] was also considered. As our previous studies on ILcatalyzed reactions [28,40,[44][45][46] of steroidal substrates have shown that a temperature higher than 60 °C is necessary to dissolve the substrates in IL solvents, the use of imidazolium ILs, susceptible to decomposition and leading to side reactions in the presence of basic anions [37] was excluded.…”

“…Although 2-HEAF was found to be an efficient catalyst in the addition of thiophenols, no conversion of aliphatic derivatives was observed. [36] Based on these considerations and the suitability of [HDBU][OAc] in the aza-Michael reactions of steroidal substrates [40] , the applicability of this IL in the thiol-Michael reaction of pregnenolone derivatives was investigated in the present work. It should be mentioned that [HDBU][OAc] was also found to be an excellent promoter in other C-S bond forming reactions, such as in sulfenylation of indoles using sulfonyl hydrazides as thiol surrogates [41] , or in the coppercatalyzed cross-coupling reaction of aryl-halides with sulfonyl hydrazides [42] .…”

Mechanistic Investigation of DBU-Based Ionic Liquids for Aza-Michael Reaction: Mass Spectrometry and DFT Studies of Catalyst Role

“…[16][17][18][19][20][21][22] Notably, 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)-based ILs has exhibited a high catalytic activity in the aza-Michael reactions compared to conventional catalysts and with imidazole-based ILs. 1,[23][24][25][26][27] However, the effective role of catalysis by DBU-based ILs has not been completely investigated and to know the catalytic model is very important for designing and developing ionic liquids with excellent catalytic properties.…”