Dimethyl Sulfide → 2,3-O-Isopropylidene-D-erythronolactone

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Reaction Steps

Removal of the silyl protecting group from (5a) gave the diol (6), which was smoothly converted to the crystalline dimesylate (7). Selective displacement of the less hindered mesylate of (7) with sodium azide afforded (8). 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 (see Setoi, H.; et al J. Org. Chem. 1985, 50, 3948-3950; Bashyal, B. P.; et al Tetrahedron 1987, 43, 3083; Bennett, R. B.; et al J. Am. Chem. Soc. 1989, 111, 2580-2582; and Naruse, M.; et al J. Org. Chem. 1994, 59, 1358-1364) which was hydrolyzed to swainsonine (1) in 96% yield. While the reduction of (9) to (10) has been reported by Fleet using BH3.Me2S (see: Carpenter, N. M.; et al Tetrahedron Lett. 1989, 30, 7261-7264) their procedure involves isolation of the borane complex of (10). The present procedure is adapted from a similar one by Keck which was used to make an epimer of swainsonine, see: Keck, G. E.; Romer, D. R. J. Org. Chem. 1993, 58, 6083-6089. While not the shortest synthesis, this route involves simple, reproducible steps that work well on a substantial scale. Using this method, 4.5 g of swainsonine was be prepared in 20% overall yield from the lactone (2), requiring 11 steps involving three chromatographic separations and five crystallizations.

Provenance & Evidence