Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 24:138:154980.
doi: 10.1016/j.tetlet.2024.154980. Epub 2024 Feb 24.

An attempted oxidative coupling approach to the scholarinine A framework

Kerry E Jones  1 , Fernando Martínez Lara  1 , Blane P Zavesky  2 , Richmond Sarpong  1
Affiliations

An attempted oxidative coupling approach to the scholarinine A framework

Kerry E Jones et al. Tetrahedron Lett. .

Abstract

In this manuscript, an oxidative carbon-carbon bond forming reaction to construct the framework of alkaloids such as scholarinine A is explored using a constrained substrate. Instead of the desired carbon-carbon bond formation between an indole C3 position and a malonate group, a competing carbon-nitrogen bond between the malonate and indole C3 position was observed to form. This work adds to the growing body of substrates for oxidative carbon-carbon bond formation and importantly, demonstrates that these reactions are challenging for some conformationally constrained substrates.

Keywords: Alkaloids’ akuammiline; Indole; Oxidative coupling; Scholarinine A; Total synthesis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Selected akuammiline alkaloids and the structurally related 6.
Scheme 1.
Scheme 1.
(A) Retrosynthesis plan to scholarinine A (1). (B) Precedent for oxidative enolate-indole oxidative C—C bond formation from Baran (Ref. 11) and Ma (Ref. 10).
Scheme 2.
Scheme 2.
(A) Retrosynthesis plan for the preparation of tryptophol-based substrate 13. (B) Synthesis of ene-piperidone 14.
Scheme 3.
Scheme 3.
Synthesis of N-phenethyl tryptophol malonate substrate 22a.
Scheme 4.
Scheme 4.
(A) Syntheses of tryptophol-derived substrates 24 and 25. (B) Depiction of the anticipated major conformers of 22a/b, 24, and 25.
Scheme 5.
Scheme 5.
Proposed mechanism for the oxidative C—C bond formation/furanoindoline formation.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Zhan R, Du S-Z, Duan Z-H, Nian Y, Chen Y-G, Scholarinine a, a N3 T-type caged-monoterpene indole alkaloid as Cav3.1 T-type Calcium Channel inhibitor from alstonia scholaris, Tetrahedron Lett. 61 (2020) 151354.
    1. Sparks TC, Lorsbach BA, Perspectives on the agrochemical industry and agrochemical discovery, Pest Manag. Sci. 73 (2017) 672–677. - PubMed
    1. King GF, Escoubas P, Nicholson GM, Peptide toxins that selectively target insect nav and cav channels, Channels 2 (2008) 100–116. - PubMed
    1. Kopecky BJ, Liang R, Bao J, T-type Calcium Channel blockers as neuroprotective agents, Pflüg. Arch.-Eur. J. Physiol. 466 (2014) 757–765. - PMC - PubMed
    1. Krishnan P, Mai C-W, Yong K-T, Low Y-Y, Lim K-H, Alstobrogaline, an unusual pentacyclic monoterpenoid indole alkaloid with aldimine and aldimine-N-oxide moieties from alstonia scholaris, Tetrahedron Lett. 60 (2019) 789–791;
    2. Wang Z, Xiao Y, Wu S, Chen J, Li A, Tatsis EC, Deciphering and reprogramming the cyclization regioselectivity in bifurcation of indole alkaloid biosynthesis, Chem. Sci. 13 (2022) 12389–12395. - PMC - PubMed