• Concise Syntheses of bis‐Strychnos Alkaloids (−)‐Sungucine, (−)‐Isosungucine, and (−)‐Strychnogucine B from (−)‐Strychnine

      Zhao, Senzhi; Chen, Heng; Sirasani, Gopal; Dobereiner, Graham; Andrade, Rodrigo B.; Teijaro, Christiana; Vaddypally, Shivaiah; Zdilla, Michael; 0000-0001-5375-0241; 0000-0001-6203-9689; 0000-0003-0212-2557; 0000-0001-6885-2021 (2016-06-15)
      The first chemical syntheses of complex, bis‐Strychnos alkaloids (−)‐sungucine (1), (−)‐isosungucine (2), and (−)‐strychnogucine B (3) from (−)‐strychnine (4) is reported. Key steps included (1) the Polonovski–Potier activation of strychnine N‐oxide; (2) a biomimetic Mannich coupling to forge the signature C23−C5′ bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3CN‐mediated reduction to fashion the ethylidene moieties in 1–3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners.
    • Synthesis of Bis-Strychnos Alkaloids (–)-Sungucine, (–)-Isosungucine, and (–)-Strychnogucine B from (–)-Strychnine

      Zhao, Senzhi; Teijaro, Christiana; Chen, Heng; Sirasani, Gopal; Vaddypally, Shivaiah; O'Sullivan, Owen; Zdilla, Michael; Dobereiner, Graham; Andrade, Rodrigo B.; 0000-0001-5375-0241; 0000-0001-6203-9689; 0000-0003-0212-2557; 0000-0001-6885-2021 (2019-03)
      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.