Download PDF
Synlett 2003(10): 1399-1402
DOI: 10.1055/s-2003-40834
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Glycosylated ortho-Carboranyl Amino Acid

Christian Thimona,b, Luigi Panzab, Christophe Morin*a
a Laboratoire d’Etudes Dynamiques et Structurales de la Sélectivité (associé au CNRS, UMR 5616), Départment de Chimie, Université Joseph Fourier, B.P. 53-X, 38041 Grenoble, France
Fax: +33(476)514927; e-Mail: christophe.morin@ujf-grenoble.fr;
b Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Viale Ferrucci 33, 28100 Novara, Italy
Further Information

Publication History

Received 24 May 2003
Publication Date:
24 July 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The preparation of an ortho-carborane derivative bearing both carbohydrate and amino acid substituents is presented; opening of a glucofuranuro-γ-lactone derivative with propargylamines, cycloaddition of decaborane to an acetylenic bond and amidation with a N-Fmoc-glutamate derivative are the key-steps in this synthesis.

Key words

amino acids - boron - carbohydrates - carboranes - cyclo­additions

    References

  • 1 Bregadze VI. Chem. Rev.  1992,  92:  209 
    CrossrefGoogle Scholar
  • 2 Valliant JF. Guenther KJ. King AS. Morel P. Schaffer P. Sogbein OO. Stephenson KA. Coord. Chem. Rev.  2002,  232:  173 
    CrossrefGoogle Scholar
  • For examples in the meta-carborane series, see:
  • 3a Das BC. Kabalka GW. Srivastava RR. Bao W. Das S. Li G. J. Orgmet. Chem.  2000,  614-615:  255 
    CrossrefGoogle Scholar
  • 3b Das BC. Das S. Li G. Bao W. Kabalka GH. Synlett  2001,  1417 
    CrossrefGoogle Scholar
  • 3c Kabalka GW. Das BC. Das S. Li G. Srivastava RR. Natarajan N. Khan MK. Coll. Czech. Chem. Commun.  2002,  67:  836 
    CrossrefGoogle Scholar
  • 4 Kane RR. Pak RH. Hawthorne FW. J. Org. Chem.  1993,  58:  991 
    Google Scholar
  • 5a Holman GD. Rees WD. Biochim. Biophys. Acta  1982,  685:  78 
    Google Scholar
  • 5b Joost H.-G. Thorens B. Mol. Membr. Biol.  2001,  18:  247 
    Google Scholar
  • 5c Dwyer DS. Vannucci SJ. Simpson IA. Int. Rev. Neurobiol.  2002,  51:  159 
    Google Scholar
  • 5d Medina RA. Owen GI. Biol. Res.  2002,  35:  9 
    Google Scholar
  • 6a Gomez FA. Hawthorne MF. J. Org. Chem.  1992,  57:  991 
    Google Scholar
  • 6b Vinas C. Benakki R. Texidor F. Casabo J. Inorg. Chem.  1995,  34:  991 
    Google Scholar
  • 7 Heying TL. Ager JW. Clark SL. Mangold DJ. Goldstein HJ. Hillman M. Polak RJ. Szymanski JW. Inorg. Chem.  1963,  2:  1089 
    CrossrefGoogle Scholar
  • 8 Kitahara T. Ogawa T. Naganuma T. Masui M. Agric. Biol. Chem.  1974,  38:  2189 
    Google Scholar
  • 9 Bleriot Y. Veighey CR. Smelt KH. Cadefeau J. Stalmans W. Biggadike K. Lane AL. Muller M. Watkin DJ. Fleet GWJ. Tetrahedron: Asymmetry  1996,  7:  2761 
    Google Scholar
  • 10a Owen LN. Peat S. Jones WGJ. J. Chem. Soc.  1941,  339 
    Google Scholar
  • 10b Abbadi M. Holman GD. Morin C. Rees WD. Yang J. Tetrahedron Lett.  1999,  40:  5861 
    Google Scholar
  • 12a

    4-Hydroxy-but-2-ynamine was prepared by overnight stirring of a solution of 4-tosyloxybut-2-yn-1-ol in ammonium hydroxide, followed by evaporation and treatment of the crude solid with Dowex 1X8 R3N+Cl- pre-washed with 4% NaOH aq solution. The brown oil thus obtained should be used without delay.
  • 12b For more information on 4-hydroxy-but-2-ynamine, see: Marszak-Fleury A. Laroche J. Bull. Soc. Chim. Fr.  1963,  1270 
    Google Scholar
  • 12c For more information on synthetic procedure, see: Dumez E. Faure R. Dulcere J.-P. Eur. J. Org. Chem.  2001,  2577 
    Google Scholar
  • 12d

    Analytical data for the tosylate salt: mp 94-96 °C. 1H NMR (300 MHz, D2O) 7.60 (d, 2 H, J = 7.1 Hz, ArH), 7.27 (d, 2 H, J = 7.1 Hz, ArH), 4.18 (s, 2 H, H-4), 3.77 (s, 2 H, H-1), 2.30 (s, 3 H, CH3). 13C NMR 140.0 (Cquat Ar), 137.9 (Cquat Ar); 127.2 (CH Ar), 123.1 (CH Ar), 82.5 and 73.8 (C-2, C-3), 47.1 and 27.0 (C-1, C-4), 18.3 (CH3).
  • 12e Similarly, but-2-yn-1,4-diamine was prepared from 1,4-bis-mesyloxy-but-2-yne, see: Haslinger H. Soloway AH. J. Med. Chem.  1966,  9:  792 
    Google Scholar
  • 12f

    Analytical data for its bis mesylate salt: mp 160 (dec.) 1H NMR (300 MHz, D2O) 3.77 (s, 4 H, H-1/H-4), 2.58 (s, 6 H, CH3). 13C NMR 79.1 (C-2/
    C-3), 39.2 (CH3), 29.8 (C-1/C-4).
  • 13 Such a derivative could be useful in the preparation of bis-glycosyl-carboranes (Panza, L. et al., manuscript in preparation), see: Giovenzana GB. Lay L. Monti D. Palmisano G. Panza L. Tetrahedron  1999,  55:  14123 
    CrossrefGoogle Scholar
  • 14 Fein M. Grafstein D. Paustian JE. Bobinski J. Lichstein BM. Myes N. Schwartz NS. Cohen MS. Inorg. Chem.  1963,  2:  1115 
    CrossrefGoogle Scholar
  • 15 Bagget N. Smithson A. Carbohydr. Res.  1982,  108:  59 
    CrossrefGoogle Scholar
  • 16 Blériot Y. Masaguet CF. Charlwood J. Winchester BG. Lane AL. Crook S. Watkin DJ. Fleet GWJ. Tetrahedron  1997,  53:  15135 
    CrossrefGoogle Scholar
  • 17 Barili PL. Berti G. Catelani G. Colonna F. Marra A. Tetrahedron Lett.  1986,  27:  2307 
    CrossrefGoogle Scholar
  • 20 Cundari S. Dalpozzo R. De Nino A. Procopio A. Sindona G. Athanassopulos K. Tetrahedron  1999,  55:  10155 
    CrossrefGoogle Scholar
  • 21 Nabakka JM. Harwell DE. Knobler CB. Hawthorne MF. J. Organomet. Chem.  1998,  550:  423 
    Google Scholar
  • 25 For a synthesis of 10B enriched decaborane, see: Adams L. Tomlison S. Wang J. Hosmane SN. Maguire JA. Hosmane NS. Inorg. Chem. Commun.  2002,  5:  765 
    CrossrefGoogle Scholar
  • For some reviews about ‘chemistry and BNCT’, see:
  • 26a Hawthorne MF. Angew. Chem., Int. Ed. Engl.  1993,  32:  950 
    CrossrefPubMedGoogle Scholar
  • 26b Morin C. Tetrahedron  1994,  50:  12521 
    CrossrefPubMedGoogle Scholar
  • 26c Soloway AH. Tjarks W. Barnum BA. Rong F.-G. Barth RF. Codogni IW. Wilson JG. Chem. Rev.  1998,  98:  1515 
    CrossrefPubMedGoogle Scholar
11

General procedure for opening of lactone 2 with amines (5-15 mmole scale): To a solution of lactone in acetonitrile (10 mL/mmole) was added an excess of amine (2-4 equiv) and the mixture was stirred overnight after which time volatiles were removed. Compound 4 was obtained quantitatively without purification while isolation of pure 6 (87%) and 7 (98%) was performed by flash chromatography on silica gel (eluent:CH2Cl2/CH3OH, 95:5). 4: 1H NMR (300 MHz,, CDCl3): 7.38 (t, J = 5.4 Hz, 1 H, NH); 5.97 (d, J 1,2 = 3.6 Hz, 1 H, H-1); 4.84-4.07 (m, 8 H); 2.32 (t, J 1 ′,3 ′ = 2.5 Hz, 1 H, H-3′); 1.48 (s, 3 H, CH3); 1.31 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): 172.3 (C-6); 112.2 (C-1); 105.2 [C(CH3)2]; 85.1; 80.8; 79.1 (C-3′); 75.2; 72.0 (C-2′); 69.7; 29.2 (C-1′); 26.8 (CH3); 26.2 (CH3). 6: 1H NMR (300 MHz,, CDCl3): 5.96 (d, J 1,2 = 3.5 Hz, 1 H, H-1); 4.76-4.43 (m, 4 H); 4.10-3.82 (m, 3 H); 3.40-3.10 (m); 3.16 (s, H-1′′); 3.09 (s, H-1); 2.32 (t, J 1 ′-3 ′ = 2.4 Hz, H-3′); 2.26 (t, J 1 ′-3 ′ = 2.4 Hz, H-3′); 1.46 (s, 3 H, CH3); 1.31 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): 172.9 and 172.8 (C-6); 112.1 [C(CH3)2]; 112.0 [C(CH3)2]; 105.6 (C-1); 84.5; 82.7*; 77.9; 75.7; 75.6; 73,3; 72.7; 65.9; 39.0 (C-1′); 37.6 (C-1′); 34.6 (C-1′′); 34.1 (C-1′); 26.9 (CH3); 26.3 (CH3). 7 1H NMR (300 MHz, CD3OD): 5.90 (d, J 1,2 = 3.6 Hz, 1 H, H-1); 4.47 (d, J 1,2 = 3.6 Hz, 1 H, H-2); 4.34-4.37 (dapp, J app = 6.0 Hz, 1 H,); 4.26-4.16 (m, 4 H); 4.08-4.05 (tapp, J app = 1.9 Hz, 2 H,); 1.44 (s, 3 H, CH3); 1.29 (s, 3 H,CH3). 13C NMR (75 MHz, CD3OD): 174.3 (C-6); 112.9 [C(CH3)2]; 106.4 (C-1); 86.4; 82.3; 81.9; 81.3; 75.9; 71.0; 50.7 (C-4′); 29.6 (C-1′); 271 (CH3); 264 (CH3). [α]20 D -13 (c 6; MeOH).

18

To a solution of 7 (1g; 3.3 mmol) in acetone (30 mL) were added under stirring 2,2- dimethoxypropane (20 mL, 164 mmol; 50 equiv) and camphorsulfonic acid (77 mg, 0.33 mmol; 0.1 equiv). After 24 h stirring, NaHCO3 (2 g) was added and after further 15 min stirring the mixture was filtered on celite. The oil (crude 11) obtained after evaporation of the volatiles was dissolved in methanol (50 mL) containing AcOH (170 µL of 60% aqueous solution) and stirred at 50 °C for 80 min then cooled rapidly to r.t. Sodium hydrogen carbonate (2 g) was added and the solution was stirred for 15 min before filtration. Compound 12 (1.010 g, 3 mmol 90%) was obtained pure after column chromatography (silica gel, CH2Cl2/CH3OH: 95/5) as a white foam 1H NMR (300 MHz, CDCl3): 6.57 (l s, 1 H, NH); 6.04 (d, J 1,2 = 3.7 Hz, 1 H, H-1); 4.60-4.50 (m, 2 H); 4.30-4.11 (m, 6 H); 1.49 (s, 3 H, CH3); 1.42 (s, 3 H, CH3); 1.39 (s, 3 H, CH3); 1.32 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): 169.3 (C-6); 112.1 [C(CH3)2)]; 107.8 (C-1); 101.0 [C(CH3)2]; 83.0; 82.2; 80.3 (C-2′, C-3′); 78.6; 74.2; 71.2; 50.3 (C-4′); 28.8 (C-1′); 26.5 (CH3); 26.0 (CH3); 23.9 (CH3); 23.2 (CH3).

19

Mesylate 13 was obtained conventionally (triethylamine, mesyl chloride, 2.2 equiv each, in CH2Cl2, 2 h, 98%). 1H NMR (300 MHz, CDCl3): 6.53 (s l, 1 H, NH); 6.04 (d, J 1,2 = 3.7 Hz, 1 H, H-1); 4.90-4.85 (m, 2 H, W1/2 = 33 Hz); 4.60-4.50 (m, 2 H); 4.10-4.25 (m, 4 H); 3.12 (s, 3 H, H-1′′); 1.49 (s, 3 H, CH3); 1.43 (s, 3 H, CH3); 1.40 (s, 3 H, CH3); 1.32 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): 169.8 (C-6); 112.4 [C(CH3)2]; 106.5 (C-1); 101.3 [C(CH3)2]; 85.6 (CCH2); 83.6; 79.3; 75.6 (CCH2); 74.9; 71.9; 57.6 (C-4′); 39.1 (C-1′′); 28.9 (C-1′); 27.2 (CH3); 26.6 (CH3); 24.6 (CH3); 23.9 (CH3).

22

Amine 15 was obtained by reaction of mesylate 13 with 25% aq. ammonia/dioxane (5/1) 35 °C, 80 min Yield: 95%. 1H NMR (300 MHz, CDCl3): 6.56 (s l, 1 H, NH); 6.04 (d, J 1-2 = 3.7 Hz, 1 H, H-1); 4.59-4.55 (m, 2 H); 4.24-4.08 (m, 4 H); 3.46-3.44 (m, 2 H, J app = 2 Hz); 1.70 (s l, 2 H, NH2); 1.48 (s, 3 H, CH3); 1.43 (s, 3 H, CH3); 1.39 (s, 3 H, CH3); 1.32 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): 169.5 (C-6); 112.3 [C(CH3)2]; 106.4 (C-1); 101.1 [C(CH3)2]; 84.3; 83.6; 79.1; 74.8; 71.8 (C-2, C-3, C-4, C-5); 67,1; 31.6 (C-4′); 29.1 (C-1′); 27.1 (CH3); 26.6 (CH3); 24.6 (CH3); 23.8 (CH3).

23

N-Fmoc amino acid 16: Condensation of amine 15 in CH2Cl2 with commercially available benzyl ester of N-Fmoc glutamic acid in the presence of 1 equiv of DCC: 82%. 1H NMR (300 MHz, CDCl3): 7.75-7.26 (m, 13 H, H ar); 6.71 (s l, 1 H, NH); 6.59 (s l, 1 H, NH); 6.04 (dapp, J app = 7.95 Hz, NH); 6.00 (dapp, J app = 3.7 Hz, 1 H, H-1); 5.15 [s, 2 H, CH2 (Bn)];.4.58-3.98 (m, 12 H); 2.50-1.50 (m l, 4 H); 1.44 (s, CH3); 1.38 (s, CH3); 1.34 (s, CH3); 1.29 (s, CH3). 13C NMR (75 MHz, CDCl3): 171.9 (C-5′′); 169.7 (C-6); 156.3 [OC(O)NH]; 143.9, 143.7, 141.3 (Cquat Fmoc); 135.2 (OCH2C); 128.6; 128.5; 128.3; 127.7; 127.1; 125.1; 120.0; 112.3 [C(CH3)2]; 106.3 (C-1); 101.2 [C(CH3)2]; 83.5; 79.4; 79.3; 78.2; 77.6; 74.8; 71.8; 67,.2 (OCH2CH); 67.0 (OCH2CH); 53.7 (C-2′′); 47.1 (OCH2CH); 32.0; 29.2; 28.9; 27.9; 27.0 (CH3); 26.5 (CH3); 24.4 (CH3); 23.7 (CH3).

24

Carborane 17: Under argon, a solution of decaborane (20 mg; 0.17 mmol, 1.3 equiv) in toluene (2 mL) and acetonitrile (68 µL; 1.3 mmol, 10 equiv) was heated at 110 °C for 1 h then cooled to r.t. before the addition of 16 (100 mg; 0.13 mmol). The mixture was stirred at reflux for 5 h and methanol (0.5 mL) was added to destroy the excess of decaborane. After evaporation of the volatiles, column chromatography on silica gel (CH2Cl2/EtOAc: 8.5/1.5) gave carborane 17 (50 mg, 46%) as a white powder. 1H NMR (300 MHz, CDCl3): 7.74 (dapp, J app = 7.5 Hz, 2 H); 7.58 (dapp, J app = 7.2 Hz, 2 H); 7.5-7.2 (m, 11 H); 6.00 (d, J = 3.6 Hz, 1 H, H-1); 5.87 (d, J = 7.9 Hz, 1 H, NH); 5.17 (s l, 2 H, CCH2O); 4.55-4.08 (m, 12 H); 2.28-2.02 (m); 1.44 (s, CH3); 1.39 (s, CH3); 1.36 (s, CH3); 1.28 (s, CH3). 13C NMR
(75 MHz, CDCl3): 172.4 (C-1′′); 171.7 (NHCO); 170;6 (NHCO); 156.6 [OC(O)NH]; 143.9; 143.7; 141.4 (Cquat Fmoc); 135.2 (OCH2C); 128.7; 128.6; 128.4; 127.8; 127.2; 125.2; 120.1; 112.6 [C(CH3)2]; 106.5 (C-1); 101.6 [C(CH3)2]; 83.5; 81.0 (CB); 79.7; 78.2; 75.1; 71.8; 67.5 (OCH2CH); 67.2 (OCH2CH); 53.6 (C-2′′); 47.2 (OCH2CH); 42.0 (CH2N); 41.1 (CH2N); 32.0; 28.4; 27.1 (CH3); 26.6 (CH3); 24.2 (CH3); 23.7 (CH3). Anal. C43H57B10N3O11-0.25 CH2Cl2. Calcd.: C 56.39, H 6.29, B 11.73, N 4.56; found C 56.48, H 6.35, B 11.75, N 4.55. MS (electrospray):
(M + Na)+ centered at m/z = 923.5 (cluster from m/z = 919.5 to 926.5 with relative intensities matching the calculated spectrum for C43H57B10N3O11).