Synthesis 2007(5): 749-753  
DOI: 10.1055/s-2007-965925
PAPER
© Georg Thieme Verlag Stuttgart · New York

Syntheses of 2-Pyrones via Electrophilic Substitutions at C7 of 4-Hydroxy-6-methyl-2-pyrone through Mono- or Dianion Formation

Xuejun Zhang, Michael McLaughlin, R. Lizeth P. Muñoz, Richard P. Hsung*, Jiashi Wang, Jacob Swidorski
Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Rennebohm Hall, 777 Highland Avenue, Madison­, WI 53705, USA
Fax: +1(608)2625345; e-Mail: rhsung@wisc.edu;
Further Information

Publication History

Received 27 October 2006
Publication Date:
08 February 2007 (online)

Abstract

Electrophilic substitution protocols useful for functionalizations at C7 of 4-hydroxy-6-methyl-2-pyrone, or triacetic acid, are described here. This method was applied to the synthesis of annularin E.

    References

  • 1 For a review, see: Romines KR. Chrusciel RA. Curr. Med. Chem.  1995,  2:  825 
  • For recent reports, see:
  • 2a Fors KS. Gage JR. Heier RF. Kelly RC. Perrault WR. Wicnienski N. J. Org. Chem.  1998,  63:  7348 
  • 2b Vara Prasad JVN. Tummino PJ. Ferguson D. Saunders J. Vander Roest S. McQuade TJ. Heldsinger A. Reyner EL. Stewart BH. Guttendorf RJ. Para KS. Lunney EA. Gracheck SJ. Domagala JM. Biochem. Biophys. Res. Commun.  1996,  221:  815 
  • 3a Schwartz TM. Bundy GL. Strohbach JW. Thaisrivongs S. Johnson PD. Skulnick HI. Tomich PK. Lynn JC. Chong K.-T. Hinshaw RR. Raub TJ. Padbury GE. Toth LN. Bioorg. Med. Chem. Lett.  1997,  7:  399 
  • 3b Thaisrivongs S. Janakiraman MN. Chong K.-T. Tomich PK. Dolak LA. Turner SR. Strohbach JW. Lynn JC. Horng M.-M. Hinshaw RR. Watenpaugh KD. J. Med. Chem.  1996,  39:  2400 
  • 3c Thaisrivongs S. Watenpaugh KD. Howe WJ. Tomich PK. Dolak LA. Chong K.-T. Tomich CSC. Tomasselli AG. Turner SR. Strohbach JW. Mulichak AM. Janakiraman MN. Moon JB. Lynn JC. Horng M.-M. Hinshaw RR. Curry KA. Rothrock DJ. J. Med. Chem.  1995,  38:  3624 
  • 4 For isolation, see: Shu Y.-Z. Ye Q. Li H. Kadow KF. Hussain RA. Huang S. Gustavson DR. Lowe SE. Chang LP. Pirnik DM. Kodukula K. Bioorg. Med. Chem. Lett.  1997,  7:  2295 
  • For recent synthetic efforts toward orevactaene, see:
  • 5a Organ MG. Bratovanov S. Tetrahedron Lett.  2000,  41:  6945 
  • 5b Organ MG. Bilokin YV. Bratovanov S. J. Org. Chem.  2002,  67:  5176 
  • For isolation, see:
  • 6a Otoguro K. Kuno F. Õmura S. Pharmacol. Ther.  1997,  76:  45 
  • 6b Otoguro K. Shiomi K. Yamaguchi Y. Arai N. Sunazuka T. Masuma R. Iwai Y. Õmura S. J. Antibiot.  2000,  53:  5 
  • 7 For a recent review on synthetic efforts toward arisugacin A, see: Cole KP. Hsung RP. In Strategies and Tactics in Organic Synthesis   Vol.4:  Harmata M. Pergamon Press; Oxford: 2004.  p.41-70  
  • For our total synthesis efforts, see:
  • 8a Hsung RP. J. Org. Chem.  1997,  62:  7904 
  • 8b Zehnder LR. Hsung RP. Wang J.-S. Golding GM. Angew. Chem. Int. Ed.  2000,  39:  3876 
  • 8c Cole KP. Hsung RP. Tetrahedron Lett.  2002,  43:  8791 
  • 8d Cole KP. Hsung RP. Yang X.-F. Tetrahedron Lett.  2002,  43:  3341 
  • 8e Hsung RP. Cole KP. Zehnder LR. Wang J. Wei LL. Yang X.-F. Coverdale HA. Tetrahedron  2003,  59:  311 
  • For isolation, see:
  • 9a Nair MSR. Carey ST. Tetrahedron Lett.  1975,  16:  3617 
  • 9b Nair MSR. Phytochemistry  1976,  15:  1090 
  • 10 Shimizu T. Hiranuma S. Wantanabe T. Heterocycles  1993,  36:  2445 
  • 11 For a leading reference, see: Katritzky AR. Wang Z. Wang M. Hall CD. Suzuki K. J. Org. Chem.  2005,  70:  4854 
  • For some examples, see:
  • 12a Organ MG. Wang J. J. Org. Chem.  2003,  68:  5568 
  • 12b Hagiwara H. Kobayashi K. Hoshi T. Suzuki T. Ando M. Tetrahedron  2001,  57:  5039 
  • 12c Lokot IP. Pashkovsky FS. Lakhvich FA. Tetrahedron  1999,  55:  4783 
  • 13 Douglas CJ. Sklenicka HM. Shen HC. Golding GM. Mathias DS. Degen SJ. Morgan CD. Shih RA. Mueller KL. Seurer LM. Johnson EW. Hsung RP. Tetrahedron  1999,  55:  13683 
  • 14a For an earlier report on generating the dianion from triacetic acid, see: Wachter MP. Harris TM. Tetrahedron  1970,  26:  1685 
  • For C7 alkylations, see:
  • 14b Shimo T. Matsuzaki S. Somekawa K. J. Heterocycl. Chem.  1994,  31:  387 
  • 14c Groutas WC. Stanga MA. Brubaker MJ. Huang TL. Moi MK. Carroll RT. J. Med. Chem.  1985,  28:  1106 
  • 14d Poulton GA. Cyr TD. Can. J. Chem.  1982,  60:  2821 
  • For an addition to aldehyde, see:
  • 14e Oikawa H. Kobayashi T. Katayama K. Suzuki Y. Ichihara A. J. Org. Chem.  1998,  63:  8748 
  • For C7 oxidation, see:
  • 14f Suzuki E. Hamajima R. Inoue S. Synthesis  1975,  192 
  • 14g Bacardit R. Moreno-Mañas M. Pleixats R. J. Heterocycl. Chem.  1982,  19:  157 
  • For bromination, see:
  • 14h Jones RCF. Patience JM. Tetrahedron Lett.  1989,  30:  3217 
  • 15 For an application of its utility, see: McLaughlin MJ. Hsung RP. Cole KC. Hahn JM. Wang J. Org. Lett.  2002,  4:  2017 
  • 16 Li C. Nitka MV. Gloer JB. J. Nat. Prod.  2003,  66:  1302 
  • For some other recently isolated related 2-pyrone containing natural products, see:
  • 17a Cutignano A. Fontana A. Renzulli L. Cimino G. J. Nat. Prod.  2003,  66:  1399 
  • 17b Pedras MSC. Chumala PB. Phytochemistry  2005,  66:  81 
  • 18 For an application of its utility, see: Swidorski JJ. Wang J. Hsung RP. Org. Lett.  2006,  8:  777