A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α‐cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)‐strictosidine, which is an important intermediate in biosynthesis. This two‐step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)‐strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)‐strictosamide, (−)‐neonaucleoside A, (−)‐cymoside, and (−)‐3α‐dihydrocadambine.

A trienamine-mediated asymmetric Diels− Alder reaction using a 5-nitro-2,3-dihydro-4-pyridone derivative as a dienophile in the presence of a secondary amine organocatalyst derived from cis-hydroxyproline was discovered. The reaction provides optically active octahydroquinolines through an endo-selective [4 + 2] cyclization pathway. The following stereoselective denitration, isomerization, and/ or hydrogenation generated divergent stereoisomers of decahydroquinolines, which are useful synthons for the total synthesis of Lycopodium alkaloids. Letter pubs.acs.org/OrgLett

A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α‐cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)‐strictosidine, which is an important intermediate in biosynthesis. This two‐step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)‐strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)‐strictosamide, (−)‐neonaucleoside A, (−)‐cymoside, and (−)‐3α‐dihydrocadambine.

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