Stereoselective total synthesis of pyrrolizidine alkaloid bases: (-)-rosmarinecine and (-)-isoretronecanol

Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 9. Synthesis of (−)-Rosmarinecine

“…The simpler necines such as isoretronecanol have served as common targets to demonstrate new synthetic methodology, as witnessed by the myriad of synthetic approaches on record. , (−)-Rosmarinecine, on the other hand, is structurally one of the more complex necines bases, with four stereogenic centers on the eight atoms that form the 1-azabicyclo[3.3.0]octane ring system. It is, therefore, not very surprising that, prior to our effort, there was only one synthesis of this natural product, reported by Tatsuta et al, who prepared (−)-rosmarinecine in 17 steps from d -glucosamine …”

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

“…Previous methods include synthesis from a furanose derivative, obtaining a higher yield of 18% but in 10 total steps, and intramolecular cycloaddition methods, obtaining the same 15% yield but in 8 steps. [64][65][66][67] N-Oxide 76 was shown to partially racemise and so the group attempted to develop a DKR. Higher yields could be obtained with a slight decrease in enantioselectivity, however the enantioselectivity was higher than that that would be obtained if no racemization were occurring.…”

Total syntheses of bioactive natural products from carbohydrates

“…The methodology to use glycosamine would enable to construct nitrogen-containing polyhydroxy compounds frequently seen in natural products. The utility of glycosamines in syntheses of optically active compounds has been developed in our laboratory [60,61]. Herein, we describe the novel methodology to use amino sugars, which includes the specific reaction of glucosamines.…”

“…Until total syntheses of (À)-rosmarinecine (42) (Fig. 2) in our laboratory [61], there had not been reported on completely stereoselective syntheses of optically active pyrrolizidine alkaloids [62][63][64][65]. The stereoselective synthesis of (À)-rosmarinecine (42) was converted to the triol 51, which contained already felicitously placed functional groups and an anomeric carbon of potential value for the stereoselective introduction of hydroxyl groups and carbon chain.…”