Synthesis of Bis-Strychnos Alkaloids (–)-Sungucine, (–)-Isosungucine, and (–)-Strychnogucine B from (–)-Strychnine

Abstract

It was developed a concise synthetic route resulting in the first syntheses of bis-Strychnos alkaloids (-)-sungucine, (-)-isosungucine, and (-)-strychnogucine B from commercially available (-)-strychnine. Employing a highly convergent synthetic strategy, it was demonstrated that both Strychnos monomers could be efficiently prepared from commercially available (-)-strychnine. The venerable Mannich reaction was enlisted to join the two Strychnos monomers in a biomimetic fashion. Subsequent epimerization and olefin isomerization yielded (-)-strychnogucine B. Functional group manipulation transformed (-)-strychnogucine B into (-)-sungucine and (-)-isosungucine. Computational chemistry was employed to rationalize the regiochemical course of key steps en route to the bis-Strychnos targets.

Synthesis of (−)-Melodinine K: A Case Study of Efficiency in Natural Product Synthesis

“…In 2016, our lab reported the first chemical syntheses of bis- Strychnos alkaloids (−)-sungucine and (−)-isosungucine in nine steps (longest linear sequence) and 11 steps (total) from commercially available (−)-strychnine. , Application of the principle of minimum chemical distance was key to recognizing that both monoterpene indole fragments comprising the sungucines could be readily prepared from commercially available (−)-strychnine. Accordingly, we looked for natural and sustainable sources of (−)-tabersonine ( 6 ) for our synthesis of 1 .…”