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. 2009;48(21):3802-5.
doi: 10.1002/anie.200806292.

A stereoselective synthesis of the bromopyrrole natural product (-)-agelastatin A

Paul M Wehn  1 , J Du Bois
Affiliations

A stereoselective synthesis of the bromopyrrole natural product (-)-agelastatin A

Paul M Wehn et al. Angew Chem Int Ed Engl. 2009.

Abstract

Weaving an intricate web: A stereoselective synthesis of (-)-agelastatin A has been developed, which requires 11 steps from commercially available starting material. The application of a Rh-catalyzed intramolecular olefin aziridination reaction and the subsequent manipulation of the resulting tricyclic intermediate (see scheme) punctuate this study.

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Figures

Figure 1
Figure 1
The agelastatin family of natural products.
Figure 2
Figure 2
Rh-catalyzed aziridination: a versatile method for assembling polyfunctionalized amines.
Figure 3
Figure 3
Retrosynthetic analysis of (–)-agelastatin A.
Figure 4
Figure 4
Homoallylic sulfamate synthesis from commercial lactam.
Figure 5
Figure 5
Catalytic aziridination and regioselective ring-opening affords the desired oxathiazepane heterocycle 8. Rh2(esp)2 = Rh2(α,α,α’,α’-1,3-benzenediproprionate)2.
Figure 6
Figure 6
Oxathiazepane 8 activation and ring opening.
Figure 7
Figure 7
Rearrangement of allylic azide 11 necessitates strategic modification.
Figure 8
Figure 8
Paal-Knorr condensation installs pyrrole unit.
Scheme 1
Scheme 1
a) Me3P, THF/H2O; then MeNCO, 81%; b) m-CPBA, DCE, 0 °C; then Et3N, 80 °C, 89%; c) 2.5 mol % OsO4, NaIO4, THF/H2O, 45 °C, 81%; d) KOtBu, tAmOH, 45 °C, 77%; e) NBS, THF/MeOH, 0→25 °C, 75%. m-CPBA = meta-chloroperbenzoic acid, NBS = N-bromosuccinimide.
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References

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