Abstract
Cyst nematodes are troublesome parasites that live on, and destroy, a range of important host vegetable plants. Damage caused by the potato cyst nematode has now been reported in over 50 countries. One approach to eliminating the problem is to stimulate early hatching of the nematodes, but key hatching stimuli are not naturally available in sufficient quantities to do so. Here, we report the first chemical synthesis of solanoeclepin A, the key hatch-stimulating substance for potato cyst nematode. The crucial steps in our synthesis are an intramolecular cyclization reaction for construction of the highly strained tricyclo[5.2.1.01,6]decane skeleton (DEF ring system) and an intramolecular Diels–Alder reaction of a furan derivative for the synthesis of the ABC carbon framework. The present synthesis has the potential to contribute to addressing one of the critical food issues of the twenty-first century.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tsutsumi, M. & Sakurai, K. Influence of root diffusates of several host and non-host plants on the hatching of the soybean cyst nematode, Heterodera glycines. Jpn J. Appl. Entomol. Zool. 10, 129–137 (1966).
Stone, A. R. Recent developments and some problems in the taxonomy of cyst-nematodes, with a classification of the heteroderoidea. Nematologica 23, 273–288 (1977).
Clarke, A. J. & Perry, R. N. Hatching of cyst-nematodes. Nematologica 23, 350–368 (1977).
Shepherd, A. M. & Clarke, A. J. Molting and hatching stimuli, in Plant Parasitic Nematodes Vol. 2 (eds Zuckerman, B. M., Mai, W. F. & Rohde, R. A.) 267–287 (Academic, 1971).
Okada, T. Hatching stimulants for the cyst nematodes. Jpn J. Nematol. 5, 1–9 (1975).
Masamune, T., Anetai, M., Takasugi, M. & Katsui, N. Isolation of a natural hatching stimulus, glycinoeclepin A, for the soybean cyst nematode. Nature 297, 495–496 (1982).
Fukuzawa, A., Furusaki, A., Ikura, M. & Masamune, T. Glycinoeclepin A, a natural hatching stimulus for the soybean cyst nematode. J. Chem. Soc. Chem. Commun. 222–224 (1985).
Mulder, J. G., Diepenhorst, P., Plieger, P. & Bruggemann-Rotgans, I. E. M. Hatching agent for the potato cyst nematode. CT Int. Appl. WO 93 02 083 (1992) (Chem. Abstr. 118, 185844z).
Schenk, H. et al. Elucidation of the structure of solanoeclepin A, a natural hatching factor of potato and tomato cyst nematodes, by single-crystal X-ray diffraction. Croat. Chem. Acta 72, 593–606 (1999).
Murai, A., Tanimoto, N., Sakamoto, N. & Masamune, T. Total synthesis of glycinoeclepin A. J. Am. Chem. Soc. 110, 1985–1986 (1988).
Mori, K. & Watanabe, H. Recent results in the synthesis of semiochemicals: synthesis of glycinoeclepin A. Pure Appl. Chem. 61, 543–546 (1989).
Corey, E. J. & Houpis, I. N. Total synthesis of glycinoeclepin A. J. Am. Chem. Soc. 112, 8997–8998 (1990).
Watanabe, H. & Mori, K. Triterpenoid total synthesis. Part 2. Synthesis of glycinoeclepin A, a potent hatching stimulus for the soybean cyst nematode. J. Chem. Soc. Perkin Trans. 1 2919–2934 (1991).
Shiina, Y., Tomata, Y., Miyashita, M. & Tanino, K. Asymmetric total synthesis of glycinoeclepin A: generation of a novel bridgehead anion species. Chem. Lett. 39, 835–837 (2010).
Blaauw, R. H. et al. Intramolecular [2+2] photocycloadditions as an approach towards the bicyclo[2.1.1]hexane substructure of solanoeclepin A. Chem. Commun. 1463–1464 (2000).
Blaauw, R. H. et al. Intramolecular photochemical dioxenone-alkene [2+2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A. J. Org. Chem. 66, 233–242 (2001).
Blaauw, R. H. et al. Intramolecular [2+2] photocycloadditions as an approach towards the right-hand side of solanoeclepin A. J. Chem. Soc. Perkin Trans. 1 2250–2256 (2001).
Briere, J.-F. et al. Synthesis of the right-hand substructure of solanoeclepin A. Eur. J. Org. Chem. 2371–2377 (2001).
Hue, B. T. B. et al. Synthesis of the cyclobutanone core of solanoeclepin A via intramolecular allene butenolide photocycloaddition. Org. Biomol. Chem. 1, 4364–4366 (2003).
Hue, B. T. B. et al. Synthesis of the tricyclic core of solanoeclepin A through intramolecular [2+2] photocycloaddition of an allene butenolide. Eur. J. Org. Chem. 127–137 (2006).
Benningshof, J. C. J. et al. Studies towards the total synthesis of solanoeclepin A: synthesis of the 7-oxabicyclo[2.1.1]heptane moiety and attempted seven-membered ring formation. J. Chem. Soc. Perkin Trans. 1 1693–1700 (2002).
Benningshof, J. C. J. et al. Studies toward the total synthesis of solanoeclepin A: synthesis and potato cyst nematode hatching activity of analogues containing the tetracyclic left-hand substructure. J. Chem. Soc. Perkin Trans. 1 1701–1713 (2002).
Tojo, S. & Isobe, M. Stereocontrolled synthesis of the oxabicyclo[2.1.1]heptane segment of solanoeclepin A. Synthesis 1237–1244 (2005).
Stork, G. & Cohen, J. F. Ring size in epoxynitrile cyclization. A general synthesis of functionally substituted cyclobutanes. Application to (±)-grandisol. J. Am. Chem. Soc. 96, 5270–5272 (1974).
Tanino, K., Tomata, Y., Shiina, Y. & Miyashita, M. A novel cyclopenetene annulation method based on conjugate addition reactions of α-cyano carbanion species. Eur. J. Org. Chem. 328–334 (2006).
Charette, A. B., Juteau, H., Lebel, H. & Molinaro, C. Enantioselective cyclopropanation of allylic alcohols with dioxaborolane ligands: scope and synthetic applications. J. Am. Chem. Soc. 120, 11943–11952 (1998).
Kuwajima, I. & Urabe, H. Regioselective arylation of silyl enol ethers of methyl ketones with aryl bromides. J. Am. Chem. Soc. 104, 6831–6833 (1982).
Acknowledgements
The authors thank Prof. T. Inabe (Hokkaido University) for X-ray diffraction measurements. This research was partly supported by the Global COE Program (project no. B01: Catalysis as the basis for innovation in materials science) and a Grant-in-Aid for Scientific Research on Innovative Areas (project no. 2105: Organic synthesis based on reaction integration) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Author information
Authors and Affiliations
Contributions
K.T. and M.M. conceived the experiments and analysed the results. M.T., Y.T. and H.T. performed the laboratory experiments and optimized the reaction conditions. T.U. and T.N. performed biological testing and evaluation of synthetic solanoeclepin A. K.T. and M.M. wrote the paper.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary information
Supplementary information (PDF 7749 kb)
Supplementary information
Crystallographic data for compound 35 (CIF 38 kb)
Supplementary information
Crystallographic data for compound S18 (CIF 23 kb)
Rights and permissions
About this article
Cite this article
Tanino, K., Takahashi, M., Tomata, Y. et al. Total synthesis of solanoeclepin A. Nature Chem 3, 484–488 (2011). https://doi.org/10.1038/nchem.1044
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchem.1044
This article is cited by
-
Catalytic 4-exo-dig carbocyclization for the construction of furan-fused cyclobutanones and synthetic applications
Nature Communications (2023)
-
Impact of the genetic diversity of three cyst nematodes on the effectiveness of root exudates to induce hatching
European Journal of Plant Pathology (2021)
-
The hatching-stimulation activity of solanoeclepin A toward the eggs of Globodera (Tylenchida: Heteroderidae) species
Applied Entomology and Zoology (2021)
-
UPLC-MS/MS analysis and biological activity of the potato cyst nematode hatching stimulant, solanoeclepin A, in the root exudate of Solanum spp.
Planta (2021)
-
An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations
Nature Chemistry (2015)