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Synthesis 2009(20): 3449-3459  
DOI: 10.1055/s-0029-1216972
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Chemo- and Product-selective Electrooxidation of 3-(Arylthiomethyl)-Δ³-cephems

Hideo Tanaka*a, Yoshihisa Tokumarua,c, Ken-ichi Fukuia, Manabu Kuroboshia, Sigeru Toriia,d, Anny Jutandb, Christian Amatore*b
a Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima-naka 3-1-1, Okayama 700-8530, Japan
Fax: +81(86)2518079; e-Mail: tanaka95@cc.okayama-u.ac.jp;
b Ecole Normale Supérieure, Département de Chimie, UMA CNRS 8640, 24, Rue Lhomond, 75231 Paris Cedex 5, France
c Otsuka Chemical Co. Ltd., 463 Kagasuno, Kawauti-cho, Tokushima 771-0193, Japan
d The Institute of Creative Chemistry Co., Musa 874-5, Okayama 701-2141, Japan
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Received 13 April 2009
Publikationsdatum:
28. August 2009 (online)

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Abstract

Electrolysis of 3-arylthiomethyl-Δ³-cephems possessing various substituents on the arylthio moiety undergo chemoselective and product-selective electrooxidation to give several different products. These include isomeric mixtures of the corresponding methoxylated cephems, a bis[(Δ³-cephem-3-yl)methyl]disulfide or a 3-dimethoxymethyl-Δ³-cephem. The selectivity of the oxidation is highly dependent on the nature of the substituents on the arylthio moiety which suggests that both steric and electronic effects play an important role in the electrooxidation of 3-arylthiomethyl-Δ³-cephems.

Key words

antibiotics - chemoselective - electrooxidation - radical cation

    References

  • 1a Torii S. Electroorganic Syntheses: Methods and Applications. Part 1, Oxidations   Wiley-VCH; Weinheim: 1985. 
  • 1b Baciocchi E. Rol C. Scamosci E. Sebastiani GV. J. Org. Chem.  1991,  56:  5498 
    Suche in Google Scholar
  • 2a Henning L. Hammerich O. Organic Electrochemistry   4th ed.:  Marcel Dekker; New York: 2001. 
    Suche in Google Scholar
  • 2b Amatore C. Jutand A. Mallet JM. Meyer G. Sinay P. J. Chem. Soc., Chem. Commun.  1990,  718 
  • 2c Balavoine G. Gref A. Fischer JC. Lubineau A. Tetrahedron Lett.  1990,  31:  5761 
    Suche in Google Scholar
  • 2d Narizuka S. Fuchigami T. J. Org. Chem.  1993,  58:  4200 
    Suche in Google Scholar
  • 2e Nokami J. Ryokume K. Inada J. Tetrahedron Lett.  1995,  36:  6099 
    Suche in Google Scholar
  • 2f Mitsudo K. Kawaguchi T. Miyahatra S. Matsuda W. Kuroboshi M. Tanaka H. Org. Lett.  2005,  7:  4649 
    Suche in Google Scholar
  • 2g Mitsudo K. Matsuda W. Miyahara S. Tanaka H. Tetrahedron Lett.  2006,  47:  5147 
    Suche in Google Scholar
  • 2h Nokami J. Hatate M. Wakabayashi S. Okawara R. Tetrahedron Lett.  1980,  21:  2557 
    Suche in Google Scholar
  • 3a Mobashery S. Lemer SA. Johnston M. J. Am. Chem. Soc.  1986,  108:  1685 
    Suche in Google Scholar
  • 3b Brown RF. Kinnick MD. Morin JM. Vasileff RT. Counter F. Davidson EO. Ensminger PW. Eudaly JA. Kasher JS. Katner AS. Koehler RE. Kurz KD. Lindstrom TD. Lunn WHW. Preston DA. Ott JL. Quay JF. Shadle JK. Steinberg MI. Stucky JF. Swartzendruber JK. Turner JR. Webber JA. Wright WE. Zimmerman KM. J. Med. Chem.  1990,  33:  2114 
    Suche in Google Scholar
  • 3c Nakayama E. Fujimoto K. Muramatsu S. Miyakuchi M. Watanabe K. Ide J. J. Antibiot.  1991,  44:  854 
    Suche in Google Scholar
  • 3d Jungheim LN. Shepherd TA. Meyer DL. J. Org. Chem.  1992,  57:  2334 
    Suche in Google Scholar
  • 3e Pilik J. Synth. Commun.  1994,  24:  243 
    Suche in Google Scholar
  • 3f Negi S. Yamanaka M. Sugiyama I. Komatsu Y. Sasho M. Tsuruoka A. Kamada A. Tsuda I. Hiruma R. Katsu K. Machida Y. J. Antibiot.  1994,  47:  1507 
    Suche in Google Scholar
  • 4 Topics in Antibiotics Chemistry   Vol. 4:  Sammes PG. Ellis Horwood; Chichester: 1980. 
  • 5 Cefpodoxime proxetil, bearing a methoxymethyl moiety at the C-3 position of cephalosporin derivatives, has been used as an orally active drug. Its precursor, 3-methoxymethyl-Δ³-cephem was prepared by methoxylation of the correspond-ing 3-acetoxymethyl-Δ³-cephem derivative using CaCl2 in aq MeOH, see: Fujimoto K. Ishihara S. Yanagisawa H. Ide J. Nakayama E. Nakao H. Sugawara S. Iwata M. J. Antibiot.  1987,  40:  370 
    Suche in Google Scholar
  • 6a Recent Advances in the Chemistry of β-Lactam Antibiotics   Special Publication No. 38:  Gregory GI. The Royal Society of Chemistry; London: 1980. 
  • 6b Webber JA. Huffman GW. Koehler RE. Murphy CF. Ryan CW. Van Heyningen EM. Vasileff RT. J. Med. Chem.  1971,  14:  113 
    Suche in Google Scholar
  • 6c Animati F. Botta M. De Angelis F. Dorigo A. Grgurina I. Nicoletti R. J. Chem. Soc., Perkin Trans. 1  1983,  2281 
  • 6d Koyama Y. Huang S.-P. Keda D. Kondo S. Synlett  1990,  389 
  • 7 GCLE® is commercially available from Otsuka Chemical Co., Ltd., see: Taniguchi M. Misawa T. Shiroi T. Torii S. Tanaka H. Nippon Kagaku Kaishi  1995,  577 
  • 8 For a report on non-electrochemical oxidation and nucleo-philic substitution of 2-(ceph-3-em-3-ylmethylthio)pyridine N-oxide with CuCl2 in MeOH, see: Ochiai M. Aki O. Morimoto A. Okada T. Kaneko T. Tetrahedron Lett.  1972,  23:  2345 
    Suche in Google Scholar
  • 9a Prasada R. Korrapati VV. Dandala R. Handa VK. Subramanyeswara K. Anand G. Rao IV. Rani A. Naidu A. J. Heterocycl. Chem.  2007,  44:  1513 
    Suche in Google Scholar
  • 9b Sendo Y. Yoshioka M. Nagata W. Heterocycles  1982,  17:  231 
    Suche in Google Scholar
  • 12a Yoshida J. Takada K. Ishichi Y. Isoe S. J. Chem. Soc., Chem. Commun.  1994,  2361 
  • 12b Yoshida J. J. Synth. Org. Chem. Jpn.  1995,  53:  53 
    Suche in Google Scholar
  • 12c Yoshida J. Sugawara M. Kise N. Tetrahedron Lett.  1996,  37:  3157 
    Suche in Google Scholar
  • 12d Yoshida J. Sugawara M. Tatsumi M. Kise N. J. Org. Chem.  1998,  63:  5950 
    Suche in Google Scholar
  • 13 Buchanan GW. Reyes-Zamora C. Cheung C. J. Org. Chem.  1975,  40:  2537 
    CrossrefSuche in Google Scholar
  • 14 Baliah V. Uma M. Tetrahedron  1963,  19:  455 
    Suche in Google Scholar
10

Isomerization of 3-exo-methylene-4-methoxycepham 3c into 3-methoxymethyl-Δ³-cephem 3a was accomplished in MeOH containing HCl.8

11

Tanaka, H.; Yoshida, M.; Torii, S. unpublished results.