Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

Vilotijević, Ivan; Jamison, Timothy F.

doi:10.1002/9783527634606.ch15

“…[13,14] There have been a few attempts to construct MLPs in a single step as described in the Nakanishi hypothesis. [15] For example, in 1997, Murai's group reported that two fused sixmembered rings can be obtained by a tandem epoxide-toepoxonium ring-opening cyclization (Figure 1c-1). [16] In 2004, McDonald's group found that when the terminal hydroxyl group of a polyepoxy alcohol is replaced with a carbonate or carbamate group, a Lewis acid-catalyzed epoxide ring-opening cascade gives four fused seven-membered-ring polyether fragments (Figure 1c-2).…”

Section: Introductionmentioning

confidence: 99%

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo‐Selective Epoxide‐to‐Epoxonium Ring‐Opening Cascades

Xiao,

Li,

Ren

et al. 2024

Angewandte Chemie

0

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Marine ladder polyethers have attracted the attention of chemists and biologists because of their potent biological activities. Synthetic chemists have attempted to construct their polyether frameworks by epoxide ring‐opening cascades, as Nakanishi hypothesis describes. However, Baldwin’s rules of ring closure state that exo‐selective intramolecular cyclization of epoxy alcohols is preferred over endo‐selective cyclization. Herein, we investigated epoxide ring‐opening cascades of polyepoxy alcohols in [EMIM]BF4/PFTB (1‐ethyl‐3‐methylimidazolium tetrafluoroborate /perfluoro‐tert‐butyl alcohol) and found that all‐endo products were formed via epoxide‐to‐epoxonium ring‐opening cyclizations (not restricted by Baldwin’s rules, which only apply to intramolecular hydroxyl‐to‐epoxide cyclizations). We determined that the key factor enabling polyepoxy alcohols to undergo a high proportion of all‐endo‐selective cyclizations was inhibition of exo‐selective hydroxyl‐to‐epoxide cyclization starting from the terminal hydroxyl group of a polyepoxy alcohol. By introducing a slow‐release protecting group to the terminal hydroxyl group, we could markedly increase the cyclization yields of polyether fragments with hydrogen atoms at the ring junctions. For the first time, we constructed consecutively fused six‐membered‐ring and fused seven‐, eight‐, and nine‐membered‐ring polyether fragments by epoxide‐to‐epoxonium ring‐opening cyclizations through the addition of a suitable Lewis acid. We also suggest that the biosynthesis of marine ladder polyethers may proceed via epoxide‐to‐epoxonium ring‐opening cyclization of polyepoxide.

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“…[13,14] There have been a few attempts to construct MLPs in a single step as described in the Nakanishi hypothesis. [15] For example, in 1997, Murai's group reported that two fused sixmembered rings can be obtained by a tandem epoxide-toepoxonium ring-opening cyclization (Figure 1c-1). [16] In 2004, McDonald's group found that when the terminal hydroxyl group of a polyepoxy alcohol is replaced with a carbonate or…”

Section: Introductionmentioning

confidence: 99%

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo‐Selective Epoxide‐to‐Epoxonium Ring‐Opening Cascades

Xiao,

Li,

Ren

et al. 2024

Angew Chem Int Ed

0

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Marine ladder polyethers have attracted the attention of chemists and biologists because of their potent biological activities. Synthetic chemists have attempted to construct their polyether frameworks by epoxide ring‐opening cascades, as Nakanishi hypothesis describes. However, Baldwin’s rules of ring closure state that exo‐selective intramolecular cyclization of epoxy alcohols is preferred over endo‐selective cyclization. Herein, we investigated epoxide ring‐opening cascades of polyepoxy alcohols in [EMIM]BF4/PFTB (1‐ethyl‐3‐methylimidazolium tetrafluoroborate /perfluoro‐tert‐butyl alcohol) and found that all‐endo products were formed via epoxide‐to‐epoxonium ring‐opening cyclizations (not restricted by Baldwin’s rules, which only apply to intramolecular hydroxyl‐to‐epoxide cyclizations). We determined that the key factor enabling polyepoxy alcohols to undergo a high proportion of all‐endo‐selective cyclizations was inhibition of exo‐selective hydroxyl‐to‐epoxide cyclization starting from the terminal hydroxyl group of a polyepoxy alcohol. By introducing a slow‐release protecting group to the terminal hydroxyl group, we could markedly increase the cyclization yields of polyether fragments with hydrogen atoms at the ring junctions. For the first time, we constructed consecutively fused six‐membered‐ring and fused seven‐, eight‐, and nine‐membered‐ring polyether fragments by epoxide‐to‐epoxonium ring‐opening cyclizations through the addition of a suitable Lewis acid. We also suggest that the biosynthesis of marine ladder polyethers may proceed via epoxide‐to‐epoxonium ring‐opening cyclization of polyepoxide.

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Asymmetric Epoxidation

2017

Asymmetric Synthesis of Three‐Membered Rings

5

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Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

Cited by 4 publications

References 220 publications

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo‐Selective Epoxide‐to‐Epoxonium Ring‐Opening Cascades

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo‐Selective Epoxide‐to‐Epoxonium Ring‐Opening Cascades

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo‐Selective Epoxide‐to‐Epoxonium Ring‐Opening Cascades

Asymmetric Epoxidation

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