Total synthesis of solamargine

An alternative total synthesis of solamargine

“…In our previous method [8], although treatment of solasodine 3 with a partially protected glycosyl donor 2 in dry methylene dichloride in the presence of AgOTf and N-iodosuccinimide (NIS) at 50 °C afforded the desired key saponin 4 in an optimized yield around 65% (Scheme 1), significantly simplifying the solamargine synthesis, a large amount of expensive donor 2 was quickly consumed in the presence of cyclic amine (oxaza-spiro structure). Based on the phenomenon, herein we explored a new method for the total synthesis of solamargine 1 as shown in Scheme 2.…”

“…PMB (p-methoxybenzyl) in Schmidt reagent 5 was selected as the protecting groups, as it not only enhances the reactivity of the sugar moiety, but also improves the selectivity in the final deprotection step. Thus, the known compound 2 [8] was first acetylated with acetic anhydride in pyridine, which was further converted into trichloroacetim- idate 5. Treatment of compound 6 [8] with HF/Py complex provided acceptor 7.…”

“…Thus, the known compound 2 [8] was first acetylated with acetic anhydride in pyridine, which was further converted into trichloroacetim- idate 5. Treatment of compound 6 [8] with HF/Py complex provided acceptor 7. After coupling of glycosyl donor 5 and aglycone precursor 7 in anhydrous methylene chloride with mild catalyst AgOTf [9], key intermediate 8 was obtained in 94% isolated yield.…”

“…After coupling of glycosyl donor 5 and aglycone precursor 7 in anhydrous methylene chloride with mild catalyst AgOTf [9], key intermediate 8 was obtained in 94% isolated yield. Selective reduction of 16-ketone 8 with NaBH 4 /i-PrOH [10] (9), followed by reductive cyclization with Ph 3 P/THF/H 2 O under refluxing (10) and removal of the acetyl group with NaOMe in MeOH, afforded acceptor 11 in 53% overall yield for three steps [8]. Condensation of 11 and rhamnopyranosyl bromide 12 using AgOTf and 2,6-lutidine as catalysts [11] afforded trisaccharide alkaloid 13 in excellent yield (90%).…”

“…Recently, we reported the total synthesis of solamargine using partially protected glucopyranosyl donor and an oxaza-spiro moiety in 13 steps in a 10.5% overall yield. The synthetic solamargine exhibited good cytotoxic activities against tumor cells HeLa, A549, MCF-7, K562, HCT116, U87, and HepG2 with IC50 ranging from 2.1 to 8.0 µM [8]. To further investigate the preclinical potential, we need a practical method toward large scale preparation of solamargine.…”