The Witkop reaction: A Photochemical C-H-activation/cyclization and its Strategic Application in the Total Synthesis of Dichomine and related Alkaloids
Final Report Abstract
The goal of this project was the total synthesis of dichomine via a photochemical macrocyclization namely the Witkop cyclization. Although the target compound 1 could not be obtained, six other alkaloids four of which iboga alkaloids – to which dichomine also belongs – were synthesized. These compounds velbanamine, isovelbanamine, cleavamine, 20R-1,2-dehydropseudoaspidospermidine, 20R-dihydrocleavamine, and 20S-hydroxy-1,2-dehydropseudoaspidospermidine were accessed via three structurally slightly different Witkop precursors. The synthetic route to these three key intermediates followed a generalized scheme with minor amendments required for the individual structures. The Witkop cyclization was successfully applied to all three key precursors in moderate to very good yields. It is thus fair to state, that the six alkaloids were synthesized following a generalized synthetic scheme. Oxidation reactions applied to the macrocyclic structures of two of these iboga alkaloids led to the synthesis of two aspidosperma alkaloids. However, the oxidation cascade leading to dichomine did not result in the desired outcome. The total syntheses of isovelbanamine and 20S-hydroxy-1,2-dehydropseudoaspidospermidine were published. The remaining four natural products are still unpublished and will be reported in due course together with the efforts to dichomine which are still ongoing in our laboratory and will hopefully be completed successfully soon.
Publications
- Total synthesis of (±)-20S-Hydroxy-1,2-dehydro-pseudoaspidospermidine via a C-H activation/transannular cyclization strategy. Chem. Commun. 2017, 53 (54), 7451–7453
C. Leitner, T. Gaich
(See online at https://doi.org/10.1039/C7CC02699D)
