Thieme Chemistry Best Paper Awards: Synthesis of Securinega Alkaloids and Beyond - presented by Prof Sunkyu Han and Dr Jeanne Therese Andres | Stabilizing Soluble Acenes and Azaacenes - presented by Dr. Jan Freudenberg | γ-Selective C–H functionalization of tertiary alkylamines using α-ammonio radical - presented by Prof Yota Sakakibara | Catalytic synthesis of nitrogen-containing molecules and plant chemical biology - presented by Prof Kei Murakami

Thieme Chemistry Best Paper Awards

Dr. Jan FreudenbergProf Kei MurakamiProf Sunkyu HanProf Yota Sakakibara
Slide at 11:45
KAIST Securinega Alkaloids: Source of Inspiration Our distinct approach: Post modification of the securinega framework Sunkyu Han (KAIST) Rauhut-Currier-type flueggenine C dimers Jeon, S.; Han, S. J. Am. Chem. Soc. 2017, 139, 6302. flueggenine C flueggenine D Jeon, S.; Lee, J.; Park, S.; Han, S. Chem. Sci. 2020, 11, 10928. securinega framework flueggenine A For a review on dimeric securinega alkaloids synthesis: Jeon, S.; Park, J.; Han, S. Synlett 2017, 28, 2353. Seo, S.; Han, S. For a review on high-oxidation state securinega alkaloids synthesis: unpublished results Kang, G.; Park. S.; Han, S. Eur. J. Org. Chem. 2021, 2021, 1508.
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References
  • 1.
    S. Jeon and S. Han (2017) An Accelerated Intermolecular Rauhut–Currier Reaction Enables the Total Synthesis of (−)-Flueggenine C. Journal of the American Chemical Society
  • 2.
    S. Jeon et al. (2020) Total synthesis of dimeric Securinega alkaloids (−)-flueggenines D and I. Chemical Science
  • 3.
    S. Han et al. (2017) Syntheses of Dimeric Securinega Alkaloids. Synlett
  • 4.
    S. M. Seo et al. (2025) Total synthesis of (−)-flueggenine A and (−)-15′-epi-flueggenine D. Chemical Science
  • 5.
    G. Kang et al. (2021) The Chemistry of High‐Oxidation State Securinega Alkaloids. European Journal of Organic Chemistry
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Summary (AI generated)

The structure of the securinega monomer features a saturated α, β, γ, δ moiety on the right side. This configuration classifies it as a microceptor, enabling it to undergo Rauhut-Currier type dimerization. We successfully synthesized various dimeric securinega alkaloids through this reaction; however, I will focus on the left side of the structure, which contains a heterocyclic piperidine with a tertiary amine moiety.

One notable reactivity of tertiary amines is their ability to oxidize into amine oxides. Further oxidation of these amine oxides can yield nitro compounds. Nitro compounds can react with nitrile oxides via a 3+2 cycloaddition reaction. Intramolecularly, this can produce compounds A and B, as reported in actual syntheses. Intermolecularly, an isoxazolidine ring can form through the 3+2 cycloaddition between a nitrone and an alkene.

Additionally, the Meisenheimer rearrangement is a significant reaction that will be elaborated on in later slides. This rearrangement can lead to the formation of epoxy amino isoxazolidine. An interesting structural motif arises from the deprotonation and elimination of this epoxy amino compound. If we can induce dehydro elimination at the 2 and 3 positions, we believe it will lead to many natural products that are biogenetically derived from the 2,3-dihydro securinega framework. Our focus is on accessing this intermediate to facilitate the synthesis of more complex congeners of securinega alkaloids. After forming the anoxide molecule, the typical reaction that follows is the Polonovsky reaction, which activates the anoxide and induces an elimination reaction.