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. 2006 Apr 13;8(8):1609-12.
doi: 10.1021/ol0602811.

De novo asymmetric synthesis of D- and L-swainsonine

Haibing Guo  1 , George A O'Doherty
Affiliations

De novo asymmetric synthesis of D- and L-swainsonine

Haibing Guo et al. Org Lett. .

Abstract

[reaction: see text] The enantioselective syntheses of both enantiomers of the indolizidine natural product swainsonine have been achieved in 13 steps from furan. The indolizidine ring system is installed by a one-pot hydrogenolysis of both an azide and an O-Bn group along with an intramolecular reductive amination reaction. The asymmetry of swainsonine was introduced by Noyori reduction of an acylfuran. This route relies upon an Achmatowicz rearrangement, a diastereoselective palladium-catalyzed glycosylation, Luche reduction, and a dihydroxylation reaction.

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Figures

Figure 1
Figure 1
Swainsonine (1) and L-enantiomer (ent-1)
Scheme 1
Scheme 1
Retrosynthetic analysis of swainsonine (1)
Scheme 2
Scheme 2
Key reductive cyclization to swainsonine (1)
Scheme 3
Scheme 3
Enantioselective synthesis of pyranone (ent)-8
Scheme 4
Scheme 4
Palladium catalyzed C-1 protection
Scheme 5
Scheme 5
Palladium catalyzed C-4 azide incorporation
Scheme 6
Scheme 6
Diastereoselective C-2/3 dihydroxylation and reductive cyclization to L-swainsonine (ent-1)
Scheme 7
Scheme 7
Synthesis of swainsonine (ent)-1 via a protected swainsonine (29)
See this image and copyright information in PMC

References

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