The synthesis of 3α- and 3β-dihydrocadambine from secologanin

Abstract

Secologanin, protected as the dimethyl acetal of its tetraacetate, had previously been dihydroxylated at the vinyl side chain with high stereoselectivity to provide the glycol (4) of the correct configuration for the synthesis of 3α- and 3β-dihydrocadambine. The glycol was converted to the cyclic acetal 5 to protect the secondary alcohol, the primary alcohol was oxidized to provide the aldehyde 6, and this was reductively coupled with tryptamine. Treatment of the coupled intermediate (8) with 90% formic acid followed by deacetylation of the glycoside led to the formation of a mixture of 3α- and 3β-dihydrocadambine (40% and 33%, respectively). The synthesis confirms the structure assigned to these alkaloids, and establishes the configuration, relative and absolute, at all centres except C-3 (where it provides no new stereochemical information).