A Generalized Approach to Sarpagine Alkaloids

Seminar series
Organic Colloquium
Wed, Mar 9 1:00pm
Cram Conference Room – 3440 Molecular Sciences Bldg
Speaker Professor Tanja Gaich
Universität Konstanz
Department of Chemistry

Organic Colloquium

“A Generalized Approach to Sarpagine Alkaloids”

Abstract.  Sarpagine alkaloids comprise a large family of natural products consisting of more than 90 individual congeners. A generalized synthetic access to sarpagine alkaloids via a joint-synthetic sequence has been accomplished. Its applicability is showcased by the enantioselective total syntheses of vellosimine (1), N-methylvellosimine (2), and 10-methoxyvellosimine (3). The joint-synthetic sequence is very concise (8 steps) from known compound 8, and requires no protecting groups. The indole heterocycle was introduced in the last step. This strategy was crucial to access all family members via a shared synthetic route, and led to precursor 4, which we term "privileged intermediate". Starting from this intermediate, all sarpagines can be synthesized using phenylhydrazines with different substitution patterns (5-7). Our approach brings about the advantage that synthesis optimization only needs to be carried out once for many natural products. The key features of the synthesis are 1) a [5+2]-cycloaddition, and 2) a ring enlargement.