UC Berkeley

A unified approach to the total synthesis of Lycopodium alkaloids belonging to the miscellaneous class has been developed, wherein a single tetracyclic amine is employed as a common intermediate in synthetic studies toward several alkaloids.

An overview of Lycopodium alkaloids is presented, including their structural classification, isolation and biological activity. The biosynthesis of alkaloids in the miscellaneous group is discussed in depth. A summary of previous synthetic work focusing on miscellaneous Lycopodium alkaloids is presented, including total syntheses of luciduline, lyconadins A and B and nankakurines A and B. A model study of spirolucidine is discussed.

A biomimetic route to access spirolucidine and nankakurine B has been investigated. In this study, a tetracyclic amine that is a key intermedite in the total synthesis of lyconadin A previously developed in our laboratory is elaborated into a tertiary alcohol that mimics the proposed biosynthetic precursor of nankakurine B. A biomimetic ring-contractive α-hydroxyimine rearrangement to generate nankakurine B has been extensively investigated and found to be disfavored.

The conversion of a tricyclic ketone (first synthesized en route to lyconadin A) to the tetracyclic core of serratezomine D has been investigated. The core of this molecule was inaccessible via methods employed in the studies toward lyconadin A.

The total synthesis of 1'-epi-dihydrolycolucine from the key common tetracyclic amine intermediate has been achieved. Studies toward the synthesis of serratezomine E served as a platform to develop this method and to determine the stereochemical outcome of this reaction.