PDF herunterladen
Synthesis 2007(15): 2397-2403  
DOI: 10.1055/s-2007-983768
PAPER
© Georg Thieme Verlag Stuttgart · New York

Selective Synthesis of ent-15-epi-F 2t -Isoprostane and a Deuterated Derivative

Manami Shizuka, Marc L. Snapper*
Department of Chemistry, Eugene F. Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA
Fax: +1(617)5521442; e-Mail: marc.snapper@bc.edu;
Weitere Informationen

Publikationsverlauf

Received 8 March 2007
Publikationsdatum:
12. Juli 2007 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Isoprostanes are an emerging class of lipid metabolites whose physiological properties are not well understood. The selective synthesis of ent-15-epi-F2t-isoprostane, an isomer active in a preliminary screening assay is described. The synthesis features a regioselective cross-metathesis on an enantiomerically enriched divinyl cyclopentyl intermediate to selectively differentiate the side-chains of the target. The route provides the isoprostane, as well as a d 4-labeled analogue, in 14 steps from readily available starting material­s.

Key words

asymmetric synthesis - metathesis - olefination - lipids

    References

  • For free radical peroxidation of arachidonic acid, see:
  • 1a Morrow JD. Hill KE. Burk RF. Nammour TM. Badr KF. Roberts LJ. Proc. Nat. Acad. Sci. U.S.A.  1990,  87:  9383 
    CrossrefGoogle Scholar
  • 1b Morrow JD. Awad JA. Boss HJ. Blair IA. Roberts LJ. Proc. Natl. Acad. Sci. U.S.A.  1992,  89:  10721 
    CrossrefGoogle Scholar
  • 1c Morrow JD. Minton TA. Mukundan CR. Campbell MD. Zackert WE. Daniel VC. Badr KF. Blair IA. Roberts LJ. J. Biol. Chem.  1994,  269:  4317 
    CrossrefGoogle Scholar
  • 1d Harrison KA. Murphy RC. J. Biol. Chem.  1995,  270:  17273 
    CrossrefGoogle Scholar
  • 1e Morrow JD. Awad JA. Wu A. Zackert WE. Daniel VC. Roberts LJ. J. Biol. Chem.  1996,  271:  23185 
    CrossrefGoogle Scholar
  • 1f Basu S. Prostaglandins, Leukotrienes Essent. Fatty Acids  1998,  58:  319 
    CrossrefGoogle Scholar
  • 1g Roberts LJ. Fessel JP. Chem. Phys. Lipids  2004,  128:  173 
    CrossrefGoogle Scholar
  • 1h See also: Wang D. DuBois RN. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  415 
    CrossrefGoogle Scholar
  • 2a Natarajan R. Lanting L. Gonzales N. Nadler J. Am. J. Physiol.  1996,  271:  E159 
    CrossrefGoogle Scholar
  • 2b Kunapuli P. Lawson JA. Rokach JA. Meinkoth JL. FitzGerald GA. J. Biol. Chem.  1998,  273:  22442 
    CrossrefGoogle Scholar
  • 3a Leitinger N. Blazek I. Sinzinger H. Thrombosis Res.  1997,  86:  337 
    CrossrefGoogle Scholar
  • 3b Cranshaw JH. Evans TW. Mitchell JA. Brit. J. Pharm.  2001,  132:  1699 
    CrossrefGoogle Scholar
  • 3c For review, see: Csiszar A. Stef G. Pacher P. Ungvari Z. Prostaglandins, Leukotrienes Essent. Fatty Acids  2002,  66:  557 
    CrossrefGoogle Scholar
  • 4a Morrow JD. Zackert WE. Van Der Ende DS. Reich EE. Terry ES. Cox B. Sanchez SC. Montine TJ. Roberts LJ. Oxidative Stress Disease  2002,  8:  57 
    CrossrefGoogle Scholar
  • 4b For a recent review, see: Milne GL. Morrow JD. Antioxid. Redox Signal.  2006,  8:  1379 
    CrossrefGoogle Scholar
  • 4c Yin H. Musiek ES. Morrow JD. J. Biol. Sci.  2006,  6:  469 
    CrossrefGoogle Scholar
  • 4d Morrow JD. Curr. Pharmaceut. Design  2006,  12:  895 
    CrossrefGoogle Scholar
  • 5a Quinn JF. Montine KS. Moore M. Morrow JD. Kaye JA. Montine TJ. J. Alzheimer’s Dis.  2004,  6:  93 
    Google Scholar
  • 5b Nishio T. Miyadera R. Sakai R. Abe K. Kanazawa H. Fukui K. Urano S. J. Clin. Biochem. Nutr.  2006,  38:  161 
    Google Scholar
  • 5c For a review, see: Montine TJ. Quinn JF. Kaye JA. Morrow JD. Oxidative Stress Disease  2006,  22:  147 
    Google Scholar
  • 6a For recent review, see: Giovanni D. Falco A. Patrono C. Chem. Phys. Lipids  2004,  128:  149 
    CrossrefGoogle Scholar
  • 6b See also: Boyne MS. Sargeant LA. Bennett FI. Wilks RJ. Cooper RS. Forrester TE. Diabetes Res. Clin. Pract.  2007,  76:  149 
    CrossrefGoogle Scholar
  • 7a Camphausen K. Menard C. Sproull M. Goley E. Basu S. Coleman CN. Int. J. Radiat. Oncol. Biol. Phys.  2004,  58:  1536 
    CrossrefGoogle Scholar
  • 7b Rossner P. Gammon MD. Terry MB. Agrawal M. Zhang FF. Teitelbaum SL. Eng SM. Gaudet MM. Neugut AI. Santella RM. Cancer Epidem. Biomar.  2006,  15:  639 
    CrossrefGoogle Scholar
  • For reviews, see:
  • 8a Taber DF. Hoerner SR. Herr JR. Gleave MD. Kanai K. Pina R. Jiang Q. Xu M. Chem. Phys. Lipids  2004,  128:  57 
    CrossrefGoogle Scholar
  • 8b Quan LG. Cha JK. Chem. Phys. Lipids  2004,  128:  3 
    CrossrefGoogle Scholar
  • 8c Rokach J. Kim S. Bellone S. Lawson JA. Pratico D. Powell WS. FitzGerald GA. Chem. Phys. Lipids  2004,  128:  35 
    CrossrefGoogle Scholar
  • For early references, see:
  • 8d Corey EJ. Shih NY. Shimoji K. Tetrahedron Lett.  1984,  25:  5013 
    CrossrefGoogle Scholar
  • 8e O’Connor DE. Mihelich ED. Coleman MC. J. Am. Chem. Soc.  1984,  106:  3577 
    CrossrefGoogle Scholar
  • 8f Rondot B. Durand T. Girard JP. Rossi JC. Schio L. Khanapure SP. Rokach J. Tetrahedron Lett.  1993,  34:  8245 
    CrossrefGoogle Scholar
  • 8g Hwang SW. Adiyama M. Khanapure S. Schio L. Rokach J. J. Am. Chem. Soc.  1994,  116:  10829 
    CrossrefGoogle Scholar
  • 8h Larock RC. Lee NH. J. Am. Chem. Soc.  1991,  113:  7815 
    CrossrefGoogle Scholar
  • 8i See also: Roland A. Durand T. Egron D. Vidal JP. Rossi JC. J. Chem. Soc., Perkin Trans. 1  2000,  245 
    CrossrefGoogle Scholar
  • 8j Durand T. Guy A. Vidal JP. Rossi JC. J. Org. Chem.  2002,  67:  3615 
    CrossrefGoogle Scholar
  • 8k Jacobo SH. Chang C.-T. Lee G.-J. Lawson JA. Powell WS. Pratico D. FitzGerald GA. Rokach J. J. Org. Chem.  2006,  71:  1370 
    CrossrefGoogle Scholar
  • 8l Jung ME. Berliner A. Angst D. Yue D. Koroniak L. Watson AD. Li R. Org. Lett.  2005,  7:  3933 
    CrossrefGoogle Scholar
  • 8m Pinot E. Guy A. Guyon A.-L. Rossi J.-C. Durand T. Tetrahedron: Asymmetry  2005,  16:  1893 
    CrossrefGoogle Scholar
  • 9 Schrader TO. Snapper ML. J. Am. Chem. Soc.  2002,  124:  10998 
    CrossrefGoogle Scholar
  • 10a Schrader TO. Snapper ML. Tetrahedron Lett.  2000,  41:  9685 
    CrossrefGoogle Scholar
  • For earlier studies on ring-opening cross-metathesis of cyclobutenes, see:
  • 10b Randall ML. Tallarico JA. Snapper ML. J. Am. Chem. Soc.  1995,  117:  9610 
    CrossrefGoogle Scholar
  • 10c Tallarico JA. Bonitatebus PJ. Snapper ML. J. Am. Chem. Soc.  1997,  119:  7157 
    CrossrefGoogle Scholar
  • 10d Snapper ML. Tallarico JA. Randall ML. J. Am. Chem. Soc.  1997,  119:  1478 
    CrossrefGoogle Scholar
  • 10e Tallarico JA. Randall ML. Snapper ML. Tetrahedron  1997,  53:  16511 
    CrossrefGoogle Scholar
  • 11 Schrader TO. Ph.D. Thesis   Boston College; Chestnut Hill Massachusetts: 2002. 
    Google Scholar
  • 12 Theil F. Schick H. Winter G. Reck G. Tetrahedron  1991,  47:  7569 
    CrossrefGoogle Scholar
  • 13 Gosh AK. Liu W. J. Org. Chem.  1997,  62:  7908 
    CrossrefPubMedGoogle Scholar
  • 14 For a more recent and convenient approach to this intermediate, see: Zhao Y. Rodrigo J. Hoveyda AH. Snapper ML. Nature (London)  2006,  443:  67 
    CrossrefGoogle Scholar
  • 15a Buchi G. Burgess EM. J. Am. Chem. Soc.  1960,  82:  4333 
    CrossrefGoogle Scholar
  • 15b Eaton PE. Tetrahedron Lett.  1964,  3695 
    CrossrefGoogle Scholar
  • 15c Serebryakov EP. Kulomzina-Pletneva SD. Margaryan AK. Tetrahedron  1979,  35:  77 
    CrossrefGoogle Scholar
  • 16 Cho JH. Kim BM. Org. Lett.  2003,  5:  531 
    CrossrefGoogle Scholar
  • 18 Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 
    CrossrefPubMedGoogle Scholar
  • 20 Einhorn J. Einhorn C. Ratajczak F. Pierre J.-L. J. Org. Chem.  1996,  61:  7452 
    CrossrefPubMedGoogle Scholar
  • 21 This isotopically labeled isoprostane could be used as an alternative standard for metabolic studies as shown in: Kim S. Powell WS. Lawson JA. Jacobo SH. Pratico D. FitzGerald GA. Maxey K. Rokach J. Bioorg. Med. Chem. Lett.  2005,  15:  1613 
    CrossrefGoogle Scholar
  • 22 Williams JM. Jobson RB. Yasuda N. Marchesini G. Dolling U.-J. Grabowski EJJ. Tetrahedron Lett.  1995,  36:  5461 
    Google Scholar
  • For selected examples of GC/MS studies for the analysis of isoprostanes, see:
  • 23a Roberts LJ. Morrow JD. In Methods in Biological Oxidative Stress   Hensley K. Floyd RA. Humana Press; Totawa NJ: 2003.  Chap. 4. p.33-39  
    CrossrefGoogle Scholar
  • 23b Morrow JD. Harris TM. Roberts LJ. Anal. Biochem.  1990,  184:  1 
    CrossrefGoogle Scholar
  • 23c Wang Z. Ciabattoni G. Creminon C. Lawson J. FitzGerald GA. Patrono C. Maclouf J. J. Pharmacol. Exp. Ther.  1995,  275:  94 
    CrossrefGoogle Scholar
  • 23d Bachi A. Zuccato E. Baraldi M. Fanelli R. Chiabrando C. Free Radic. Biol. Med.  1996,  20:  619 
    CrossrefGoogle Scholar
  • 23e Waugh RJ. Murphy RC. J. Am. Soc. Mass Spectrom.  1996,  7:  490 
    CrossrefGoogle Scholar
  • 23f Patrignani P. Santini G. Panara MR. Sciulli M. Greco A. Rotondo MT. diGiamberardino M. Maclouf J. Ciabattoni G. Patrono C. Br. J. Pharmacol.  1996,  118:  1285 
    CrossrefGoogle Scholar
  • 25 Garber SB. Kingsbury JS. Gray BL. Hoveyda AH. J. Am. Chem. Soc.  2000,  122:  8168 
    Google Scholar
  • 26 Theil F. Schick H. Winter G. Reck G. Tetrahedron  1991,  47:  7569 
    CrossrefGoogle Scholar
17

Regioselectivity was determined by COSY NMR.

19

Selectivity was determined by 1H NMR (estimated detection limits of 20:1) by comparison with authentic samples of each diastereomer.

24

More details on the setup and results of the GC/MS detection assay may be obtained by contacting the authors.

27

Data shown for a 74% yield reaction. Yields range from
70-90%, depending on catalyst purity.

28

This compound is the major isomer; however, it is in a mixture of isomers of lower deuterium incorporation.