PDF herunterladen
Synlett 2008(16): 2417-2420  
DOI: 10.1055/s-2008-1078170
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Cross-Metathesis Approach to the Synthesis of Key Precursor of the Macrolide Core of Rhizoxin D [¹]

Srinivas Padakantia,b, Bukkapattanam R. Sreekantha, Velisoju Mahendara, Manojit Pala, Khagga Mukkantib, Javed Iqbala, Parthasarathi Das*a
a Discovery Research, Dr. Reddy’s Laboratories Ltd., Bollaram Road, Miyapur, Hyderabad 500049, AP, India
Fax: +91(40)23045438; e-Mail: parthasarathi@drreddys.com;
b Chemistry Division, Institute of Science & Technology, JNT University, Kukatpally, Hyderabad 500072, AP, India
Weitere Informationen

Publikationsverlauf

Received 15 April 2008
Publikationsdatum:
10. September 2008 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

The synthesis of key precursor 5 of the macrolide core of rhizoxin D has been achieved by cross metathesis between two olefinic fragments 6 and 7. Both the olefinic fragments are easily synthesized in a diastereoselective manner from the common precursor 1-benzyloxy-2-methylhex-5-ene-3-ol (8).

Keywords

rhizoxin D - Keck allylation - Crimmins aldol - Takai ­olefination - cross metathesis

1

DRL Publication No. 691.

    References and Notes

  • 2a Iwasaki S. Kobayashi H. Furukawa J. Namikoshi M. Okuda S. J. Antibiot.  1984,  37:  354 
    Google Scholar
  • 2b Iwasaki S. Namikoshi M. Kobayashi H. Furukawa J. Okuda S. Chem. Pharm. Bull.  1986,  34:  1387 
    Google Scholar
  • 3 Kiyoto S. Kawai Y. Kawakita T. Kino E. Okuhara M. Uchida I. Tanaka H. Hashimoto M. Terano H. Kohsaka M. Aoki H. Imanaka H. J. Antibiot.  1986,  39:  762 
    CrossrefPubMedGoogle Scholar
  • 4 Graham MA. Bissett D. Setanoians A. Hamilton T. Kerr DJ. Henrar R. Kaye SB. J. Natl. Cancer Inst.  1992,  84:  494 
    CrossrefPubMedGoogle Scholar
  • 5 Takahasi M. Iwasaki S. Kobayashi H. Murai T. Sato Y. Haraguchi-Hiraoka T. Nagano H. J. Antibiot.  1987,  40:  66 
    CrossrefPubMedGoogle Scholar
  • 6a Keck GE. Wager CA. Wager TT. Savin KA. Covel JA. McLaws MD. Krishnamurthy D. Cee VJ. Angew. Chem. Int. Ed.  2001,  40:  231 
    Google Scholar
  • 6b Mitchell IS. Pattenden G. Stonehouse JP. Tetrahedron Lett.  2002,  43:  493 
    Google Scholar
  • 6c White JD. Blakemore PR. Green NJ. Hauser EB. Holobski MA. Keown LE. Nylund Kolz CS. Phillips BW. J. Org. Chem.  2002,  67:  7750 
    Google Scholar
  • 6d Lafontaine JA. Provencal DP. Gardelli C. Leahy JW. J. Org. Chem.  2003,  68:  4215 
    Google Scholar
  • 6e Jiang Y. Hong J. Burke SD. Org. Lett.  2004,  6:  1445 
    Google Scholar
  • 6f Mitchell IS. Pattenden G. Stonehouse J. Org. Biomol. Chem.  2005,  3:  4412 
    Google Scholar
  • 6g N’zoutani M.-A. Lensen N. Pancrazi A. Ardisson J. Synlett  2005,  491 
    Google Scholar
  • 7a Rama Rao AV. Sharma GVM. Bhanu MN. Tetrahedron Lett.  1992,  33:  3907 
    Google Scholar
  • 7b Rama Rao AV. Bhanu MN. Sharma GVM. Tetrahedron Lett.  1993,  34:  707 
    Google Scholar
  • 7c Boger DL. Curran TT. J. Org. Chem.  1992,  57:  2235 
    Google Scholar
  • 7d Keck GE. Park M. Krishnamurthy D. J. Org. Chem.  1993,  58:  3787 
    Google Scholar
  • 7e Lafontaine JA. Leahy JW. Tetrahedron Lett.  1995,  36:  6029 
    Google Scholar
  • 7f Provencal DP. Gardelli C. Lafontaine JA. Leahy JW. Tetrahedron Lett.  1995,  36:  6033 
    Google Scholar
  • 7g Davenport RJ. Regan AC. Tetrahedron Lett.  2000,  41:  7619 
    Google Scholar
  • 8 Chatterjee AK. Choi TL. Sanders DP. Grubbs RH. J. Am. Chem. Soc.  2003,  125:  11360 
    CrossrefGoogle Scholar
  • 9a Pfeiffer MWB. Phillips AJ. J. Am. Chem. Soc.  2005,  127:  5334 
    Google Scholar
  • 9b Kim S. Ko H. Lee T. Kim D. J. Org. Chem.  2005,  70:  5756 
    Google Scholar
  • 9c Mehta G. Shinde HM. Chem. Commun.  2005,  3703 
    Google Scholar
  • 9d Nicolaou KC. Harisson ST. Angew. Chem. Int. Ed.  2006,  45:  3256 
    Google Scholar
  • 9e Virolleaud M.-A. Menant C. Fenet B. Piva O. Tetrahedron Lett.  2006,  47:  5127 
    Google Scholar
  • 10a Saibaba V. Das P. Mukkanti K. Iqbal J. Tetrahedron Lett.  2006,  47:  7927 
    Google Scholar
  • 10b Saibaba V. Sampath A. Mukkanti K. Iqbal J. Das P. Synthesis  2007,  2797 
    Google Scholar
  • 11 Srinivas P. Pal M. Mukkanti K. Iqbal J. Tetrahedron Lett.  2006,  47:  5969 
    CrossrefGoogle Scholar
  • 12 Keck GE. Park M. Krishnamurthy D. J. Org. Chem.  1993,  58:  3787 
    CrossrefGoogle Scholar
  • 13a Crimmins MT. Bryan WK. Tabet EA. Kaleem C. J. Org. Chem.  2001,  66:  894 
    Google Scholar
  • 13b Crimmins MT. Caussanel F. J. Am. Chem. Soc.  2006,  128:  3128 
    Google Scholar
  • 13c Narasimhulu C. Iqbal J. Mukkanti K. Das P. Tetrahedron Lett.  2008,  49:  3185 
    Google Scholar
  • 14 Phukan P. Sasmal S. Maier ME. Eur. J. Org. Chem.  2003,  1733 
    CrossrefGoogle Scholar
  • 15 Saibaba V. Das P. Mukkanti K. Iqbal J. Tetrahedron Lett.  2006,  47:  6083 
    Google Scholar
  • 16 Phukan P. Bauer M. Maier ME. Synthesis  2003,  1324 
    Artikel in Thieme ConnectGoogle Scholar
  • 18 Takai K. Nitta K. Utimoto K. J. Am. Chem. Soc.  1986,  108:  7408 
    CrossrefGoogle Scholar
1

DRL Publication No. 691.

17

Crystal Data for Fragment 17
C40H50O4Si1, M = 622.92, monoclinic, space group P2 1 , a = 14.79 (2) Å, b = 9.29 (1) Å, c = 15.09 (2) Å, β = 102.33 (2)˚, V = 2026 (4) ų, Z = 2, D c = 1.021 g cm-³, reflections collected = 20735, unique reflections = 4637, [R int = 0.0682], final R indices [I > 2σ(I)]: R 1 = 0.065, wR 2 = 0.114, CCDC-662327 contains the supplementary crystallographic data for this letter. These data can be obtained free of charge from The Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk./data_request/cif.

19

Spectral Data for 6
[α]D ²³ -21.6 (c 0.5, CHCl3). IR (neat): 2918, 1722, 1614, 1514 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.92 (d, 3 H, J = 6.8 Hz), 1.72 (ddd, 1 H, J = 14.0, 10.4, 3.6 Hz), 1.77 (d, 3 H, J = 1.2 Hz), 1.89 (ddd, 1 H, J = 12.0, 9.6, 2.4 Hz), 2.14 (ddd, 1 H, J = 11.6, 6.4, 4.8 Hz), 3.29 (dd, 1 H, J = 9.2, 6.4 Hz), 3.46 (dd, 1 H, J = 10.0, 6.4 Hz), 3.78 (s, 3 H), 3.82 (dd, 1 H, J = 9.2, 4.0 Hz), 4.11 (d, 1 H, J = 10.8, Hz), 4.30 (d, 1 H, J = 10.8 Hz), 4.46 (m, 2 H), 5.29 (ddd, 1 H, J = 7.2, 4.8, 2.4 Hz), 5.79 (dd, 1 H, J = 10.4, 1.6 Hz), 6.05 (dd, 1 H, J = 17.2, 10.4 Hz), 6.20 (s, 1 H), 6.34 (dd, 1 H, J = 17.2, 1.2 Hz), 6.83 (d, 2 H, J = 8.8 Hz), 7.22 (d, 2 H, J = 8.4 Hz), 7.28 (m, 5 H). ¹³C NMR (50 MHz, CDCl3): δ = 13.0, 19.1, 35.7, 37.3, 55.2, 70.3, 71.9, 72.6, 72.9, 79.2, 80.0, 113.8, 127.4, 127.5, 128.3, 129.4, 129.6, 130.0, 130.5, 138.4, 148.0, 159.1, 165.5. ESI-HRMS: m/z calcd for C27H33IO5Na [M + Na]+: 587.1270; found: 587.1277.

20

Synthetic Procedure and Spectroscopic Data of 5
A mixture of a solution of 6 (0.035 g, 0.06 mmol) and 7 (0.024 g, 0.123 mmol) in DCE (0.3 mL) was treated with Grubbs second-generation catalyst (5.25 mg, 0.0056 mmol) and the dark purple solution stirred at reflux temperature for 48 h. The reaction mixture was then loaded directly on top of a wet column packed with SiO2 and purified by flash chromatography (EtOAc-hexane, 1:3) to afford the product 5 (0.036 g, 80%) as light brown oil; [α]D ²³ -22.0 (c 0.1, CHCl3). IR (neat): 3468, 2924, 1712, 1414, 1247 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.92 (d, 3 H, J = 6.8 Hz), 0.97 (d, 3 H, J = 7.2 Hz), 1.42 (m, 1 H), 1.72 (m, 1 H), 1.77 (s, 3 H), 1.88 (m, 2 H), 2.18 (m, 6 H), 2.71 (dd, 1 H, J = 12.0, 2.0 Hz), 3.30 (dd, 1 H, J = 9.2, 6.4 Hz), 3.45 (dd, 1 H, J = 9.6, 6.4 Hz), 3.62 (dd, 1 H, J = 10.4, 5.2 Hz), 3.71 (dd, 1 H, J = 10.8, 7.6 Hz), 3.78 (s, 3 H), 3.82 (dd, 1 H, J = 8.8, 4.4 Hz), 4.12 (m, 2 H), 4.30 (d, 1 H, J = 10.8), 4.57 (s, 2 H), 5.26 (ddd, 1 H, J = 7.2, 4.8, 2.8 Hz), 5.81 (d, 1 H, J = 15.6 Hz), 6.20 (s, 1 H), 6.79 (m, 1 H), 6.83 (d, 2 H, J = 8.4 Hz), 7.21 (d, 2 H, J = 8.8 Hz), 7.38 (m, 5 H). ¹³C NMR (50 MHz, CDCl3): δ = 10.4, 12.4, 19.0, 30.9, 32.0, 35.4, 35.9, 37.2, 38.5, 39.6, 55.1, 63.9, 70.2, 71.9, 72.6, 72.8, 79.3, 80.0, 80.2, 113.7, 123.9, 127.4, 128.2, 129.2, 129.5, 129.9, 138.3, 144.5, 147.8, 159.0, 165.4, 170.9. ESI-HRMS: m/z calcd for C36H47IO8Na [M + Na]+: 757.2213; found: 757.2210.