Crystalline Sponge Gallery

G011 · Synthetic intermediate

Asnovolin synthesis intermediate 6

C25H40O4 · 404.59 g mol−1

First crystal structure · Nature Chemistry 2025 · compound 6 →

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INTERACTIVE 3D STRUCTURE

Explore Asnovolin synthesis intermediate 6 in its crystalline sponge

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CHONCage
2D chemical structure of Asnovolin synthesis intermediate 6
Asnovolin synthesis intermediate 6 · 2D chemical structure
3D crystal structure of Asnovolin synthesis intermediate 6 determined by the crystalline-sponge method
Asnovolin synthesis intermediate 6 · crystalline-sponge guest structure
Asnovolin synthesis intermediate 6 inside a crystalline sponge coordination cage
Asnovolin synthesis intermediate 6 · coordination-cage host–guest structure

Synthetic intermediate 6 resolved by the crystalline-sponge method.

A stereochemically dense waypoint in the total-synthesis landscape of the asnovolin spiromeroterpenoids.

Molecular formula
C25H40O4
Molecular weight
404.59 g mol−1
CCDC accession
2357199 ↗
Host
Pd6L4 cage
Study
Nat. Chem. 2025
Compound in publication
6

MOLECULAR HISTORY

From fungal meroterpenoids to a crystallographically defined synthesis intermediate

The asnovolins are compact, highly oxygenated spiromeroterpenoids. Their crowded ring systems make stereochemical control—and direct structural verification of advanced intermediates—central problems in synthesis.

  1. 2016

    Asnovolins A–G isolated

    A family of meroterpenoids with unusual carbon skeletons was isolated from Aspergillus novofumigatus, defining a new target class for biosynthetic and synthetic studies.1

  2. 2018

    The related biosynthetic network mapped

    Pathway reconstruction in the same fungus elucidated novofumigatonin biosynthesis and identified the oxidative enzymes that generate its highly oxygenated, orthoester-containing framework.2

  3. 2022

    First asymmetric total syntheses

    A unified fragment-coupling strategy delivered the first asymmetric total syntheses of the asnovolins and related spiromeroterpenoids, creating advanced intermediates for structural study.3

  4. 2025

    Intermediate 6 receives its first crystal structure

    A minute sample from the asnovolin synthesis program was analysed inside a symmetry-mismatched coordination cage, resolving its fused rings and oxygenated substituents without requiring crystals of the intermediate itself.4

WHY THIS STRUCTURE MATTERS

Advanced synthesis intermediates are often scarce, conformationally flexible and reluctant to crystallize. This structure shows how the crystalline-sponge method can turn such an analytical bottleneck into direct three-dimensional evidence.

References

  1. Ishikawa, K.; Sato, F.; Itabashi, T.; et al. “Asnovolins A–G, Spiromeroterpenoids Isolated from the Fungus Aspergillus novofumigatus, and Suppression of Fibronectin Expression by Asnovolin E.” J. Nat. Prod. 2016, 79, 2167–2174. DOI 10.1021/acs.jnatprod.6b00013 ↗
  2. Matsuda, Y.; Bai, T.; Phippen, C. B. W.; et al. “Novofumigatonin Biosynthesis Involves a Non-Heme Iron-Dependent Endoperoxide Isomerase for Orthoester Formation.” Nat. Commun. 2018, 9, 2587. DOI 10.1038/s41467-018-04983-2 ↗
  3. Yang, F.; Porco, J. A., Jr. “Unified, Asymmetric Total Synthesis of the Asnovolins and Related Spiromeroterpenoids: A Fragment Coupling Approach.” J. Am. Chem. Soc. 2022, 144, 12970–12978. DOI 10.1021/jacs.2c05366 ↗
  4. He, W. et al. “Supramolecular Coordination Cages as Crystalline Sponges through a Symmetry Mismatch Strategy.” Nat. Chem. 2025, 17, 1051–1058. DOI 10.1038/s41557-025-01750-x ↗

SOURCE PUBLICATION

Supramolecular coordination cages as crystalline sponges through a symmetry mismatch strategy

Nature Chemistry 2025

DOI 10.1038/s41557-025-01750-x ↗