Synthesis of Demissidine and Solanidine

Abstract

Demissidine and solanidine, two steroidal alkaloids, are synthesized in eight steps from tigogenin acetate and diosgenin acetate, respectively, which involve the replacement of three C-O bonds with C-N bonds. Key transformations include a cascade ring-switching process of furostan-26-acid, an epimerization of C25, an intramolecular Schmidt reaction, and an imine reduction/intramolecular aminolysis process.

Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives

“…The lactam moiety of 3a could also be stereoselectively reduced by BH 3 ·THF to afford the secondary amine product 7 in good yield with a slight increase of the optical purity . Both of the Bz protecting groups could be removed with the assistance of Red-Al, and the corresponding amide 8 could be formed in 78% yield with retention of the enantioselectivity . Lactam 8 could be further reduced by BH 3 ·THF and give the diamine product 9 in good yield with an excellent er value (Scheme ).…”

“…18 Both of the Bz protecting group could be removed with the assistance of Red-Al and the corresponding amide 8 could be formed in 78% yield with retention of the enantioselectivity. 19 Lactam 8 could be further reduced by BH3 . THF and give the diamine product 9 in good yield with excellent er value (Scheme 5).…”

Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates

“…In the solanidine analogue synthesis reported by Uhle [ 37 ], the imine was obtained in 20% yield from kryptogenin 16-(2,4-dinitrophenyl)hydrazone and transformed into 25-episolanidine by refluxing with KOH in ethylene glycol in 65% yield. In 2016, Tian and coworkers [ 18 ] developed a new way to synthesize solanidine and demissidine using diosgenin or tigogenin as a starting material, respectively. In the method proposed by the Chinese group, 26-methyl ester 22-imine was prepared in five steps and further transformed into the desired alkaloid by the selective reduction of the imine moiety to pyrrolidine, spontaneous intramolecular aminolysis of the obtained amino-ester to lactam, and reduction.…”

“…So far, eight syntheses of solanidine and demissidine have been described, four of them in the last decade, and the latest one was reported last year [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Although recently invented methods brought a significant improvement, the described methods suffer from several drawbacks, such as multi-step procedures or unsatisfactory yields.…”

Photocatalytic C-N addition amination of olefin

“…Amines widely exist in nature, wherein some of cyclic amines have crucially biological and physiological activities [1,2]. They are also the basic blocks for the syntheses of important intermediates, raw materials or fine chemicals such as pharmaceuticals, pesticides and dyes [4][5][6].…”