PDF herunterladen
Synlett 2013; 24(12): 1545-1548
DOI: 10.1055/s-0033-1338961
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (S,5Z,8E,10E)-12-Hydroxyheptadeca-5,8,10-trienoic Acid (12S-HHT) and its Analogues

Toshifumi Tojo
a   Department of Bioengineering, Tokyo Institute of Technology, Box B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan   Fax: +81(45)9245789   eMail: ykobayas@bio.titech.ac.jp
,
Qian Wang
a   Department of Bioengineering, Tokyo Institute of Technology, Box B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan   Fax: +81(45)9245789   eMail: ykobayas@bio.titech.ac.jp
,
Toshiaki Okuno
b   Department of Biochemistry, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan
,
Takehiko Yokomizo
b   Department of Biochemistry, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan
,
Yuichi Kobayashi*
a   Department of Bioengineering, Tokyo Institute of Technology, Box B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan   Fax: +81(45)9245789   eMail: ykobayas@bio.titech.ac.jp
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 09. April 2013

Accepted after revision: 10. Mai 2013

Publikationsdatum:
14. Juni 2013 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

Natural 12S-HHT and its analogues were synthesized for study of structure and activity relationship toward the BLT2 receptor. The Suzuki–Miyaura coupling was used for construction of the 8E,10E-diene moiety of 12S-HHT and analogues of (12R)- and 12-keto-types, whereas Wittig reaction was used for the synthesis of (8Z)- and (8Z,12R)-isomers.

Key words

asymmetric synthesis - cross-coupling - HHT - Wittig reaction - Suzuki–Miyaura coupling
 

  • References and Notes

  • 3 Okuno T, Iizuka Y, Okazaki H, Yokomizo T, Taguchi R, Shimizu T. J. Exp. Med. 2008; 205: 759
    CrossrefSuche in Google Scholar
    • 4a Iizuka Y, Yokomizo T, Terawaki K, Komine M, Tamaki K, Shimizu T. J. Biol. Chem. 2005; 280: 24816
      CrossrefSuche in Google Scholar
    • 4b Yasuda D, Okuno T, Yokomizo T, Hori T, Hirota N, Hashidate T, Miyano M, Shimizu T, Nakamura M. FASEB J. 2009; 23: 1470
      CrossrefSuche in Google Scholar
    • 4c Iizuka Y, Okuno T, Saeki K, Uozaki H, Okada S, Misaka M, Sato T, Toh H, Fukayama M, Takeda N, Kita Y, Shimizu T, Nakamura A, Yokomizo T. FASEB J. 2010; 24: 4678
      CrossrefSuche in Google Scholar
    • 6a Suzuki M, Noyori R. J. Am. Chem. Soc. 1982; 104: 2024
      CrossrefSuche in Google Scholar
    • 6b Suzuki M, Ohtake H, Kameya Y, Hamanaka N, Noyori R. J. Org. Chem. 1989; 54: 5292
      CrossrefSuche in Google Scholar
    • 6c Russell SW, Pabon HJ. J. J. Chem. Soc., Perkin Trans. 1 1982; 545
      Crossref
    • 6d Greé R, Tourbah H, Carrié R. Tetrahedron Lett. 1986; 27: 4983
      CrossrefSuche in Google Scholar
    • 6e De Montarby L, Tourbah H, Greé R. Bull. Chim. Soc. Fr. 1989; 419
    • 6f Nicolaou KC, Stylianides NA, Ramphal JY. J. Chem. Soc., Perkin Trans. 1 1989; 2131
  • 10 Matsumura K, Hashiguchi S, Ikariya T, Noyori R. J. Am. Chem. Soc. 1997; 119: 8738
    CrossrefSuche in Google Scholar
  • 11 Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
    Suche in Google Scholar
  • 12 Kitano Y, Matsumoto T, Wakasa T, Okamoto S, Shimazaki T, Kobayashi Y, Sato F. Tetrahedron Lett. 1987; 28: 6351
    CrossrefSuche in Google Scholar
  • 13 The Noyori reduction of acetylene ketone i afforded alcohol ii with 96% ee by chiral HPLC of the derived benzoate. However, hydrostannation of the TBDPS ether iii under radical- (AIBN) or PdCl2(PPh3)2-catalyzed conditions followed by iodination gave a mixture of (S)-7, the cis-isomer, and the regioisomer (Scheme 3).
  • 14 12S-HHT (1): 1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H), 1.14–1.80 (m, 10 H), 2.00–2.20 (m, 2 H), 2.37 (t, J = 7.5 Hz, 2 H), 2.83 (t, J = 6.0 Hz, 2 H), 2.60–4.00 (br s, 2 H), 4.12 (q, J = 6.0 Hz, 1 H), 5.30–5.52 (m, 2 H), 5.55–5.73 (m, 2 H), 6.04 (dd, J = 15.0, 10.5 Hz, 1 H), 6.18 (dd, J = 15.0, 10.5 Hz, 1 H). (8Z)-Isomer 3: 1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.18–1.81 (m, 10 H), 2.00–2.26 (m, 2 H), 2.36 (t, J = 7.0 Hz, 2 H), 2.87 (dt, J = 16.0, 7.0 Hz, 1 H), 3.03 (dt, J = 16.0, 7.0 Hz, 1 H), 3.20–4.00 (br s, 2 H), 4.26 (q, J = 6.0 Hz, 1 H), 5.32–5.52 (m, 3 H), 5.69 (dd, J = 15.0, 6.0 Hz, 1 H), 5.98 (t, J = 11.0 Hz, 1 H), 6.58 (dd, J = 15.0, 11.0 Hz, 1 H). 12-Keto isomer 5: 1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.23–1.42 (m, 5 H), 1.57–1.82 (m, 4 H), 2.08–2.22 (m, 2 H), 2.38 (t, J = 7.0 Hz, 2 H), 2.55 (t, J = 7.5 Hz, 2 H), 2.94 (t, J = 5.0 Hz, 2 H), 5.40–5.55 (m, 2 H), 6.05–6.26 (m, 3 H), 7.13 (dd, J = 16.0, 10.0 Hz, 1 H).