Privileged Biorenewable Secologanin-Based Diversity-Oriented Synthesis for Pseudo-Natural Alkaloids: Uncovering Novel Neuroprotective and Antimalarial Frameworks

Huajian Zhu, Yunrui Cai, Shijia Ma, Yushi Futamura, Jinbiao Li, Wen Zhong, Xiangnan Zhang, Hiroyuki Osada, Hongbin Zou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Bioprivileged molecules hold great promise for supplementing petrochemicals in sustainable organic synthesis of a diverse bioactive products library. Secologanin, a biorenewable monoterpenoid glucoside with unique structural elements, is the key precursor for thousands of natural monoterpenoid alkaloids. Inspired by its inherent highly congested functional groups, a secologanin-based diversity-oriented synthesis (DOS) strategy for novel pseudo-natural alkaloids was developed. All the reactive units of secologanin were involved in these operation simplicity protocols under mild reaction conditions, including the one-step enantioselective transformation of exocyclic C8, C8/C11, and C8/C9/C10 as well as the chemoenzymatic manipulation of endocyclic C2/C6 via the attack by various nucleophiles. A combinatory scenario of the aforementioned reactions further provided diverse polycyclic products with multiple chiral centers. Preliminary activity screening of these newly constructed molecules led to the discovery of antimalarial and highly potent neuroprotective skeletons. The application of green biorenewable secologanin in diversity-oriented pseudo-natural monoterpenoid alkaloid synthesis might encourage the pursuit of valuable bioactive frameworks.

Original languageEnglish
Pages (from-to)5320-5327
Number of pages8
JournalChemSusChem
Volume14
Issue number23
DOIs
Publication statusPublished - 2021 Dec 6
Externally publishedYes

Keywords

  • alkaloids
  • diversity-oriented synthesis
  • renewable resources
  • secologanin
  • sustainable chemistry

ASJC Scopus subject areas

  • Environmental Chemistry
  • Chemical Engineering(all)
  • Materials Science(all)
  • Energy(all)

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