Efficient Synthesis of Solasodine, O‐Acetylsolasodine, and Soladulcidine as Anticancer Steroidal Alkaloids

Abstract

An efficient synthesis of the steroidal alkaloids solasodine (1), O-acetylsolasodine (2), and soladulcidine (3) starting from easily available diosgenin and tigogenin in five or six steps (overall yield 25, 24, and 28%, resp.) is described. Moreover, our synthetic route provides a selective modification at C(3) of 1 and related compounds in order to carry out lead optimization on these natural antitumor steroidal alkaloids.

Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic effects on human cancer cells

“…Solasodine 1 (Scheme 1) was synthesized using five straightforward sequential reactions as reported previously (22). Six glycosyl bromide 10-15 (Scheme 1) was then employed to assemble a small library of solasodine glycosides using classic Koenigs-Knorr glycosylation.…”

Convergent Synthesis of Solamargine and Analogues Thereof: Structural Revision of 16‐epi‐Solamargine and Cytotoxic Evaluation

“…Thus changing the ratio of PhCF 3 /tBuCN/CH 2 Cl 2 to 5:1:3 (v/v/v) improved the solubility of 3a and enhanced the yield and stereoselectivity of the reaction ( Table 2, entry 5). To our pleasure, the HB(C 6 F 5 ) 4 -catalyzed coupling of azide 3b, [16] prepared from tosylate 3a,w ith imidate 4 performed well and furnished the desired glycosides in 75 %y ield and at an excellent ratio of b isomer 2/ a isomer 12 = 13.1:1 (Table 2, entry 6).…”

“…Our retrosynthetic analysiso fs olamargine 1 is outlined in Scheme1.T he plan featured the late-stage formationo fa no xaazaspirodecane system on pseudodiosgenyl glycosides 2, which was envisaged to be available by stereoselective glyco- sylation of tosylate 3a [13,15] or azide 3b [16] as the acceptor andc hacotriosyl trichloroacetimidate 4 [13] as the donor. 3a or azide 3b in turn could be prepared from diosgenin( 5), ar eadily availables pirostanol.…”

“…Trimethylsilyli odide (TMSI) [26] generated in situ from trimethylsilylc hloride (TMSCl) and NaI in CH 3 CN is ap owerful reagent to reduce azides to amines, and has been adopted in the synthesis of solasodine, [16,27] the aglycone of solamargine. With glycoside 2 secured, formation of oxaazaspirodecane wasc onducted by treating 2 with TMSI (2.0 equiv., Scheme 2).…”

A facile and efficient method for the synthesis of solasodine from diosgenin

“…Recently, Sun and Tian groups, respectively, gave a method for the synthesis of solasodine from diosgenin (five steps, 25% overall yield; nine steps, 21% overall yield, respectively). 8,9 However, these methods so suffer from one or more drawbacks, such as harsh reaction conditions, cumbersome workup procedures, and long reaction time. Furthermore, these methods are not economical to prepare abundant solasodine derivatives due to low yields.…”