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Synlett 2008(19): 2969-2972  
DOI: 10.1055/s-0028-1083625
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of the C9-C21 Fragment of Geldanamycin via a Diastereoselective Substrate-Controlled Hydrogenation

Tony Horneff, Thorsten Bach*
Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
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Publication History

Received 12 August 2008
Publication Date:
12 November 2008 (online)

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Abstract

An Ir-catalyzed diastereoselective hydrogenation was employed to establish the stereogenic center at carbon atom C14 of a C9-C21 fragment of geldanamycin. The fragment was stereoselectively synthesized from d-mannitol in 18 steps.

Key words

ansamycins - diastereoselectivity - hydrogenation - protecting groups - quinones - stereoselective synthesis

    References and Notes

  • 2a De Boer C. Meulman PA. Wnuk RJ. Peterson DH. J. Antibiot.  1970,  23:  442 
    Google Scholar
  • 2b Sasaki K. Rinehart KL. Slomp G. Grostic MF. Olson EC. J. Am. Chem. Soc.  1970,  92:  7591 
    Google Scholar
  • 3a Whitesell L. Mimnaugh EG. De Costa B. Myers CE. Neckers LM. Proc. Natl. Acad. Sci. U. S. A.  1994,  91:  8324 
    Google Scholar
  • 3b Stebbins CE. Russo AA. Schneider C. Rosen N. Hartl FU. Pavletich NP. Cell  1997,  89:  239 
    Google Scholar
  • 3c Roe SM. Prodromou C. O’Brien R. Ladbury JE. Piper PW. Pearl LH. J. Med. Chem.  1999,  42:  260 
    Google Scholar
  • 4a Ferrarini M. Heltai S. Zocchi MR. Rugarli C. Int. J. Cancer  1992,  51:  613 
    Google Scholar
  • 4b For recent reviews, see: Whitesell L. Lindquist SL. Nat. Rev. Cancer  2005,  5:  761 
    Google Scholar
  • 5a Supko JG. Hickman RL. Grever MR. Malspeis L. Cancer Chemother. Pharmacol.  1995,  36:  305 
    Google Scholar
  • 5b Dikalov S. Landmesser U. Harrison DG. J. Biol. Chem.  2002,  277:  25480 
    Google Scholar
  • 6a Andrus MB. Meredith EL. Hicken EJ. Simmons BL. Glancey RR. Ma W. J. Org. Chem.  2003,  68:  8162 
    Google Scholar
  • 6b Qin H.-L. Panek JS. Org. Lett.  2008,  10:  2477 
    Google Scholar
  • Selected examples:
  • 7a Schnur RC. Corman ML. Gallaschun RJ. Cooper BA. Dee MF. Doty JL. Muzzi ML. Moyer JD. DiOrio CI. Barbacci EG. Miller PE. O’Brien AT. Morin MJ. Foster BA. Pollack VA. Savage DM. Sloan DE. Pustilnik LR. Moyer MP. J. Med. Chem.  1995,  38:  3806 
    Google Scholar
  • 7b Schnur RC. Corman ML. Gallaschun RJ. Cooper BA. Dee MF. Doty JL. Muzzi ML. DiOrio CI. Barbacci EG. Miller PE. Pollack VA. Savage DM. Sloan DE. Pustilnik LR. Moyer JD. Moyer MP. J. Med. Chem.  1995,  38:  3813 
    Google Scholar
  • 7c Kuduk SD. Zheng FF. Sepp-Lorenzino L. Rosen N. Danishefsky SJ. Bioorg. Med. Chem. Lett.  1999,  9:  1233 
    Google Scholar
  • 7d Kuduk SD. Harris CR. Zheng FF. Sepp-Lorenzino L. Ouerfelli Q. Rosen N. Danishefsky SJ. Bioorg. Med. Chem. Lett.  2000,  10:  1303 
    Google Scholar
  • 7e Kasuya Y. Lu Z.-R. Kopeèková P. Kopeèek J. Bioorg. Med. Chem. Lett.  2001,  11:  2089 
    Google Scholar
  • 7f Hargreaves R. David CL. Whitesell L. Skibo EB. Bioorg. Med. Chem. Lett.  2003,  13:  3075 
    Google Scholar
  • 7g Rastelli G. Tian Z.-Q. Wang Z. Myles D. Liu Y. Bioorg. Med. Chem. Lett.  2005,  15:  5016 
    Google Scholar
  • 8a Schill G. Merkel C. Zürcher C. Justus Liebigs Ann. Chem.  1977,  288 
    Google Scholar
  • 8b Davis CJ. Moody CJ. Synlett  2002,  1874 
    Google Scholar
  • 8c McErlean CSP. Proisy N. Davis CJ. Boland NA. Sharp SY. Boxall K. Slawin AMZ. Workman P. Moody CJ. Org. Bioorg. Chem.  2007,  531 
    Google Scholar
  • 9a Bach T. Lemarchand A. Synlett  2002,  1302 
    Google Scholar
  • 9b Lemarchand A. Bach T. Tetrahedron  2004,  60:  9659 
    Google Scholar
  • 9c Lemarchand A. Bach T. Synthesis  2005,  1977 
    Google Scholar
  • For reviews, see:
  • 10a Gradillas A. Pérez-Castells J. Angew. Chem. Int. Ed.  2006,  45:  6086 
    Google Scholar
  • 10b Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed.  2005,  44:  4490 
    Google Scholar
  • 10c Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 
    Google Scholar
  • 11 Racherla US. Brown HC. J. Org. Chem.  1991,  56:  401 
    CrossrefGoogle Scholar
  • 12a Wrona IE. Gabarda AE. Evano G. Panek JS. J. Am. Chem. Soc.  2005,  127:  15026 
    Google Scholar
  • 12b Belardi JK. Micalizio GC. Org. Lett.  2006,  8:  2409 
    Google Scholar
  • 12c Canova S. Bellosta V. Bigot A. Mailliet P. Mignani S. Cossy J. Org. Lett.  2007,  9:  145 
    Google Scholar
  • 13 Nicolaou KC. Picopio AD. Bertinato P. Chakraborty TK. Minowa N. Koide K. Chem. Eur. J.  1995,  1:  318 
    Google Scholar
  • 14 House HO. Rasmusson GR. J. Org. Chem.  1961,  26:  4278 
    CrossrefGoogle Scholar
  • 15 Treadwell EM. Cermak SC. Wiemer DF. J. Org. Chem.  1999,  64:  8718 
    CrossrefGoogle Scholar
  • 16 Review: Hoffmann RW. Chem. Rev.  1989,  89:  1841 
    CrossrefGoogle Scholar
  • 17 Crabtree R. Acc. Chem. Res.  1979,  12:  331 
    Google Scholar
  • 18 For an example of the ability of a methoxy group to direct an Ir-catalyzed hydrogenation, see: Crabtree RH. Davis MW. J. Org. Chem.  1986,  51:  2655 
    Google Scholar
  • 19a Hartmann C. Meyer V. Ber. Dtsch. Chem. Ges.  1893,  26:  1727 
    Google Scholar
  • 19b Frigerio M. Santagostino M. Sputore S. J. Org. Chem.  1999,  64:  4537 
    Google Scholar
  • 19c More JD. Finney NS. Org. Lett.  2002,  4:  3001 
    Google Scholar
  • 20 Roush WR. Ando K. Powers DB. Palkowitz AD. Halterman RL. J. Am. Chem. Soc.  1990,  112:  6339 
    CrossrefGoogle Scholar
  • 21 Horneff T. Herdtweck E. Randoll S. Bach T. Biomol. Med. Chem.  2006,  14:  6223 
    Google Scholar
  • 22 Boger DL. Garbaccio RM. J. Org. Chem.  1999,  64:  8350 
    CrossrefGoogle Scholar
  • 23a Lalancette JM. Frêche A. Monteux R. Can. J. Chem.  1968,  46:  2754 
    Google Scholar
  • 23b Lalancette JM. Frêche A. Brindel JR. Laliberté M. Synthesis  1972,  526 
    Google Scholar
1

Current address: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

24

Analytical Data of 2
[α]D ²0 -14.5 (c 1.89, Et2O). ¹H NMR (360 MHz, CDCl3): δ = -0.01 (s, 3 H), 0.01 (s, 3 H), 0.76 (d, J = 6.6 Hz, 3 H), 0.82-0.92 (m, 9 H), 1.05 (d, J = 6.8 Hz, 3 H), 1.15 (ddd, J = 14.2, 10.3, 2.0 Hz, 1 H), 1.26 (d, J = 7.3 Hz, 6 H), 1.28 (d, J = 6.6 Hz, 6 H), 1.61 (ddd, J = 14.2, 10.7, 3.5 Hz, 1 H), 1.99-2.12 (m, 1 H), 2.18-2.28 (m, 1 H), 2.50 (dd, J = 12.8, 8.3 Hz, 1 H), 2.55 (dd, J = 12.8, 6.7 Hz, 1 H), 3.19 (ddd, J = 10.7, 2.4, 2.0 Hz, 1 H), 3.23 (s, 3 H), 3.55 (dd, J = 7.9, 2.4 Hz, 1 H), 3.79 (s, 3 H), 4.07 (sept, J = 6.6 Hz, 1 H), 4.48-4.62 (m, 1 H), 4.90-5.04 (m, 2 H), 5.20 (s, 2 H), 5.68 (ddd, J = 17.2, 10.3 Hz, 8.5 Hz, 1 H), 7.13 (s, 1 H), 7.30-7.45 (m, 5 H), 7.60 (s, 1 H). ¹³C NMR (90.6 MHz, CDCl3): δ = -4.8, -4.0, 17.7, 18.5, 19.3, 22.2, 22.3, 22.5, 22.5, 26.1, 29.8, 33.6, 36.3, 41.9, 57.1, 60.5, 66.7, 70.9, 76.1, 76.3, 81.1, 104.2, 114.2, 127.6, 128.0, 128.1, 128.8, 136.4, 138.8, 141.7, 141.7, 144.5, 146.9, 153.3. IR (neat): 3432, 2971, 2928, 1738, 1602, 1514, 1471, 1436, 1382, 1372, 1224, 1196, 1111, 1069, 1030, 834, 776 cm-¹. MS (ES+): m/z (%) = 732 (89), 690 (36), 672 (100). HRMS (ES+): m/z calcd for C38H62NO7Si [M + H]+: 672.4290; found: 672.4276.