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Synthesis 2003(12): 1803-1808
DOI: 10.1055/s-2003-41027
PAPER
© Georg ThiemeVerlag Stuttgart · New York

A Short and Efficient TotalSynthesis of the Naturally Occurring Coumarins Siderin, Kotanin,Isokotanin A and Desertorin C

Wolfgang Hüttela, Martin Niegerb, Michael Müller*a
a Institut für Biotechnologie 2, Forschungszentrum Jülich GmbH, 52425Jülich
Fax: +49(2461)613870; e-Mail: mi.mueller@fz-juelich.de;
b Institut für Anorganische Chemie, Rheinische Friedrich-Wilhelms-Universität, 53121 Bonn
Further Information

Publication History

Received 25 June 2003
Publication Date:
13 August 2003 (online)

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Abstract

Starting from methyl 2-hydroxy-4-methoxy-6-methylbenzoate (6) and its regioisomeric dehydrodimers 7-9,readily available by an oxidative coupling reaction of 6, the naturally occurring coumarins siderin(1), kotanin (2),isokotanin A (3) and desertorin C (4) were synthesized in a novel and highlyefficient three-step transformation. In the case of kotanin (2) both atropisomers were prepared fromthe pure atropisomers of 7.

Key words

atropisomerism - biaryls - oxidative phenoliccoupling - natural coumarins

    References

  • 1 Bringmann G. Günther C. Ochse M. Schupp O. Tasler S. Prog.Chem. Org. Nat. Prod.  2001,  82:  1 
    Google Scholar
  • 2 Stothers JB. Stoessl A. Can. J. Chem.  1988,  66:  2816 
    CrossrefGoogle Scholar
  • 3a Büchi G. Luk KC. Kobbe B. Townsend JM. J. Org.Chem.  1977,  42:  244 
    Google Scholar
  • 3b

    See also Refs. [2] [4b] [7a]

  • 4a Laakso JA. Narske ED. Gloer JB. Wicklow DT. Dowd PF. J.Nat. Prod.  1994,  57:  128 
    CrossrefGoogle Scholar
  • 4b Nozawa K. Nakajima S. Kawai K.-I. Udagawa SI. Miyaji M. Phytochemistry  1994,  35:  1049 
    CrossrefGoogle Scholar
  • 5 Nozawa K. Seyea H. Nakajima S. Udagawa SI. Kawai KI. J. Chem. Soc., Perkin Trans. 1  1987,  1735 
    CrossrefGoogle Scholar
  • Siderin(1):
  • 6a Venturella P. Bellino A. Piozzi F. TetrahedronLett.  1974,  15:  979 
    Google Scholar
  • 6b Chexal KK. Fouweather C. Holker JSE. J. Chem. Soc., Perkin Trans. 1  1974,  554 
    Google Scholar
  • 6c Ahluwalia VK. Kumar D. Indian J. Chem.,Sect. B  1976,  14:  589 
    Google Scholar
  • Kotanin(2)
  • 7a Racemic: Büchi G. Klaubert DH. Shank RC. Weinreb SM. Wogan GN. J.Org. Chem.  1971,  36:  1143 
    CrossrefGoogle Scholar
  • 7b Stereoselective: Lin G.-Q. Zhong M. Tetrahedron:Asymmetry  1997,  8:  1369 
    CrossrefGoogle Scholar
  • Isokotanin A(3)
  • 8a Racemic: Lin G.-Q. Zhong M. Acta Chim.Sin.  1997,  55:  97 ; Chem. Abstr. 1997, 126, 211942
    Google Scholar
  • 8b Stereoselective: Lin G.-Q. Zhong M. TetrahedronLett.  1996,  37:  3015 
    Google Scholar
  • 8c Stereoselective: Bringmann G. Hinrichs J. Henschel P. Kraus J. Peters K. Peters E.-M. Eur.J. Org. Chem.  2002,  1096 
    Google Scholar
  • Desertorin C(4)
  • 9a Racemic: Rizzacasa MA. Sargent MV. J. Chem. Soc., PerkinTrans. 1  1988,  2425 
    Google Scholar
  • 9b Stereoselective: Kyasnoor RV. Sargent MV. Chem. Commun.  1998,  2713 
    Google Scholar
  • 9c Steroselective: Baker RW. Kyasnoor RV. Sargent MV. Skelton BW. White AH. Aust.J. Chem.  2000,  53:  487 
    Google Scholar
  • 11a Drochner D. Hüttel W. Nieger M. Müller M. Angew. Chem.Int. Ed.  2003,  42:  931 ; Angew. Chem. 2003, 115, 961
    Google Scholar
  • 11b

    Drochner, D.; Karl,U.; Nieger, M., Müller, M.; Steglich, W., manuscript inpreparation.

  • 12 Similar reactions are reported inthe literature. However, yields are low and reaction conditionscannot be applied to substrate 6., e.g.: Connor DT. Sorenson RJ. J. Heterocycl. Chem.  1981,  18:  587 
    CrossrefGoogle Scholar
  • 13 Long RS. J.Am. Chem. Soc.  1947,  69:  990 
    CrossrefGoogle Scholar
  • 14 Basiski W. Polish J. Chem.  1995,  69:  376 ; Chem. Abstr. 1995, 123, 32908
    Google Scholar
  • 15 Szabó V. Borda J. Theisz E. ActaChim. Acad. Sci. Hung.  1980,  103:  271 ; Chem. Abstr. 1981, 94, 103116
    Google Scholar
  • 16a Suzuki E. Katsuragawa B. Inoue S. Synthesis  1978,  144 
    Article in Thieme ConnectGoogle Scholar
  • 16b See also Refs.
    Article in Thieme Connect
  • 20a Chiarello J. Joullié MM. Tetrahedron  1988,  44:  41 
    Google Scholar
  • 20b Sala T. Sargent MV. J. Chem. Soc., Perkin Trans.Trans.1  1981,  855 
    Google Scholar
10

The total syntheses of the three biarylcoumarins 2-4 require ca.25 steps according to the literature.

17

This was demonstrated for the 6,8′-bisaminochromenone 15, which was converted to desertorin C(4) in a single step. Hence, the hydrolyticmixture was dehydrated chemically with dimethyl carbonate afterno starting material could be detected (TLC). Acetyl chloride wasadded to generate additional HCl. The yield (34%) is comparableto the overall yield of the two-step procedure (36%).

18

The low yield in the case of M-(-)-2 ismainly due to a nonoptimized reaction time for acidic hydrolysis.

19

The isomers of kotanin(2)were erroneously mismatched in a previous publication. [11a]

21

Crystallographic data (excluding structurefactors) for the structures reported in this paper have been depositedwith the Cambridge Crystallographic Data Centre as supplementary publicationno. CCDC-215646. Copies of the data can be obtained free of chargeat www.ccdc.cam.ac.uk/conts/retrieving.html [orfrom the Cambridge Crystallographic Data Centre, 12 Union Road,Cambridge CB2 1EZ, UK; Fax: int. code+44-1223/336-033;e-mail: deposit@ccdc.cam.ac.uk].