Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin

Lim, Boram; Yeo, Huisu; Han, Seunghyo; Kim, Dabin; Lee, Hansuk; Koo, Sangho

doi:10.3390/app15031438

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Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin

by

Boram Lim

^1,*,

Huisu Yeo

²,

Seunghyo Han

²,

Dabin Kim

²,

Hansuk Lee

² and

Sangho Koo

^2,*

¹

College of Bangmok Basic Education, Myongji University, Myongji-Ro 116, Cheoin-Gu, Yongin 17058, Gyeonggi-Do, Republic of Korea

²

Department of Chemistry, Myongji University Myongji-Ro 116, Cheoin-Gu, Yongin 17058, Gyeonggi-Do, Republic of Korea

^*

Authors to whom correspondence should be addressed.

Appl. Sci. 2025, 15(3), 1438; https://doi.org/10.3390/app15031438

Submission received: 4 January 2025 / Revised: 28 January 2025 / Accepted: 29 January 2025 / Published: 30 January 2025

(This article belongs to the Special Issue Research on Organic and Medicinal Chemistry)

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Featured Application: Total synthesis of phenolic compounds containing terpenoid chains.

Abstract

The total synthesis of biologically and pharmacologically important phenolic isoprenoids, grifolin and neogrifolin, was developed through simple allylation and cyclization procedures using only ethyl acetoacetate, ethyl crotonate, and farnesyl bromide as substrates. The regioisomeric terpenophenols, which consist solely of orcinol and farnesyl moieties, cannot be synthesized purely by direct coupling between the units. The regioselectivity issue was solved by controlling the timing of the allylation of β-ketoester with farnesyl bromide and the cyclization with ethyl crotonate. 2-Farnesyl-5-methyl-cyclohexane-1,3-dione and 6-farnesyl-5-methyl-cyclohexane-1,3-dione were prepared in a highly regioselective manner from ethyl acetoacetate in overall yields of 43% and 40%, respectively. The oxidative aromatization of the regioisomeric cyclohexane-1,3-diones produced grifolin and neogrifolin, respectively.

Keywords: aromatization; cyclization; Dieckman condensation; total synthesis; phenol; terpenoid

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MDPI and ACS Style

Lim, B.; Yeo, H.; Han, S.; Kim, D.; Lee, H.; Koo, S. Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin. Appl. Sci. 2025, 15, 1438. https://doi.org/10.3390/app15031438

AMA Style

Lim B, Yeo H, Han S, Kim D, Lee H, Koo S. Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin. Applied Sciences. 2025; 15(3):1438. https://doi.org/10.3390/app15031438

Chicago/Turabian Style

Lim, Boram, Huisu Yeo, Seunghyo Han, Dabin Kim, Hansuk Lee, and Sangho Koo. 2025. "Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin" Applied Sciences 15, no. 3: 1438. https://doi.org/10.3390/app15031438

APA Style

Lim, B., Yeo, H., Han, S., Kim, D., Lee, H., & Koo, S. (2025). Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin. Applied Sciences, 15(3), 1438. https://doi.org/10.3390/app15031438

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Regioselective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin

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