Stereoselective Chemoenzymatic Cascade Synthesis of the bis-THF Core of Acetogenins

Matthijs J. van Lint, Mélanie Hall, Kurt Faber, Rob J.M. van Spanning, Eelco Ruijter, Romano V.A. Orru

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

bis-Tetrahydrofuran acetogenins are a class of natural products displaying highly potent and selective anti-tumor activity. Herein we report a new route to precursors of these natural products, utilizing the pseudo C2-symmetry in the central bis-tetrahydrofuran fragment. Key steps of our stereoselective chemoenzymatic strategy include the epoxide hydrolase-mediated desymmetrization of meso-epoxides and a cascade cyclization in either “inside-out” or “outside-in” direction, providing stereoselective access to the cores of both bullatacin- and rolliniastatin 1-type acetogenins with 6 stereocenters each from a common mono-epoxide precursor.

Original languageEnglish
Pages (from-to)1092-1101
Number of pages10
JournalEuropean Journal of Organic Chemistry
Volume2019
Issue number5
DOIs
Publication statusPublished - 7 Feb 2019

Fingerprint

Acetogenins
epoxy compounds
Epoxy Compounds
Biological Products
cascades
tetrahydrofuran
Epoxide Hydrolases
Cyclization
synthesis
Tumors
products
tumors
routes
fragments
symmetry
bullatacin

Keywords

  • Acetogenins
  • Chemoenzymatic synthesis
  • Epoxide hydrolases
  • Natural products
  • Stereoselective synthesis

Cite this

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title = "Stereoselective Chemoenzymatic Cascade Synthesis of the bis-THF Core of Acetogenins",
abstract = "bis-Tetrahydrofuran acetogenins are a class of natural products displaying highly potent and selective anti-tumor activity. Herein we report a new route to precursors of these natural products, utilizing the pseudo C2-symmetry in the central bis-tetrahydrofuran fragment. Key steps of our stereoselective chemoenzymatic strategy include the epoxide hydrolase-mediated desymmetrization of meso-epoxides and a cascade cyclization in either “inside-out” or “outside-in” direction, providing stereoselective access to the cores of both bullatacin- and rolliniastatin 1-type acetogenins with 6 stereocenters each from a common mono-epoxide precursor.",
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Stereoselective Chemoenzymatic Cascade Synthesis of the bis-THF Core of Acetogenins. / van Lint, Matthijs J.; Hall, Mélanie; Faber, Kurt; van Spanning, Rob J.M.; Ruijter, Eelco; Orru, Romano V.A.

In: European Journal of Organic Chemistry, Vol. 2019, No. 5, 07.02.2019, p. 1092-1101.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Stereoselective Chemoenzymatic Cascade Synthesis of the bis-THF Core of Acetogenins

AU - van Lint, Matthijs J.

AU - Hall, Mélanie

AU - Faber, Kurt

AU - van Spanning, Rob J.M.

AU - Ruijter, Eelco

AU - Orru, Romano V.A.

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AB - bis-Tetrahydrofuran acetogenins are a class of natural products displaying highly potent and selective anti-tumor activity. Herein we report a new route to precursors of these natural products, utilizing the pseudo C2-symmetry in the central bis-tetrahydrofuran fragment. Key steps of our stereoselective chemoenzymatic strategy include the epoxide hydrolase-mediated desymmetrization of meso-epoxides and a cascade cyclization in either “inside-out” or “outside-in” direction, providing stereoselective access to the cores of both bullatacin- and rolliniastatin 1-type acetogenins with 6 stereocenters each from a common mono-epoxide precursor.

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KW - Chemoenzymatic synthesis

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