Synthesis of (-) -Swainsonine and Optically Active 3, 4-Dihydroxy-2-Hydroxymethylpyrrolidines

Indolizidine and quinolizidine alkaloids

“…l 7 A non-carbohydrate route (Scheme 3) to ( -)-swainsonine (8) by Ikota and Hanaki18 proceeds by way of face-selective osmylation of the optically active butenolide (1 7), available by a literature procedure from (R)-glutamic acid. The cis-diol portion of the product was protected as the dioxolan, after which successive reduction, mesylation, and displacement with azide ion provided the azido-mesylate (18). The pyrrolidine ring was set up with the correct relative stereochemistry at three of the target molecule's four stereogenic centres after reduction of the azide group and cyclization.…”

A Practical Synthesis of (−)-Swainsonine

“…Apparently, there is still no cost-effective way to either isolate swainsonine from natural sources or to prepare it synthetically. While a great deal of effort has been expended on developing synthetic routes to swainsonine, there is still a need for a practical synthesis of this important alkaloid. Perhaps the most practical routes developed to date are those reported by the research groups of Fleet 11m,r and Cha 11n…”

“…Perhaps the most practical routes developed to date are those reported by the research groups of Fleet 11m,r and Cha 11n11o. Recent efforts in our laboratories directed toward preparing analogs of swainsonine have led to the development of a practical route to this important alkaloid.…”

“…Palladium-catalyzed hydrogenolysis of 8 to the amine followed by filtration of the catalyst and treatment of the filtrate with sodium methoxide caused cyclization to the known crystalline bicyclic lactam 9 in 75% yield. Reduction of 9 with borane−methyl sulfide complex gave a 94% yield of crystalline 10 , also a known compound, 11h,k,n,s which was hydrolyzed to swainsonine ( 1 ) in 96% yield. While not the shortest synthesis,11o this route involves simple, reproducible steps that work well on a substantial scale.…”

Synthesis of polyhydroxylated alkaloids via allene cyclisation

“…Amongst the chiral synthons utilised for the synthesis of DAB-1, commercially available (S)-pyroglutamic acid 3.16 (Scheme 3.3) was considered to be an appropriate starting point for two separate groups. 166,167 This could be attributed to the structural features of (S)-pyroglutamic acid: a pyrrolidinone motif bearing the requisite chiral centre α-to the nitrogen. As such, it was envisioned that reduction of the α-carboxylic acid, followed by installation of the trans diol and subsequent reduction of the lactam, would lead to an expedient synthesis of DAB-1.…”