Glycerophosphoinositols: Total Synthesis of the First Fluorescent Probe Derivative

Abstract

The first fluorescent glycerophosphoinositol probe was synthesized in moderate good yield (37%). The total synthesis applied a convergent synthetic strategy involving two successive coupling reactions between the three key moieties: myo-inositol, glycerol, and NBD-aminohexanoic acid.

Key words

coupling - chromophores - allylation - glycerophosphoinositol - fluorescent probe

• References and Notes

• 1 Corda D, Iurisci C, Berrie CP. Biochim. Biophys. Acta 2002; 1582: 52
• 2a Filippi BM, Mariggiò S, Pulvirenti T, Corda D. Biochim. Biophys. Acta 2008; 1783: 2311
• 2b Iacovelli L, Falasca M, Valitutti S, D’Arcangelo D, Corda D. J. Biol. Chem. 1993; 268: 20402
• 3a Buccione R, Baldassarre M, Trapani V, Catalano C, Pompeo A, Brancaccio A, Giavazzi R, Luini A, Corda D. Eur. J. Cancer 2005; 41: 470
• 3b Corda D, Zizza P, Varone A, Bruzik KS. Mariggiò S. Biochem. Soc. Trans. 2012; 40: 101
• 4a Berrie CP, Iurisci C, Piccolo E, Bagnati R, Corda D. Methods Enzymol. 2007; 434: 187
• 4b Berrie CP, Dragani LK, van der Kaay J, Iurisci C, Brancaccio A, Rotilio D, Corda D. Eur. J. Cancer 2002; 38: 2463
• 5a Rasmussen JA. M, Hermetter A. Prog. Lipid Res. 2008; 47: 436
• 5b Gonçalves MS. T. Chem. Rev. 2009; 109: 190
• 6a Chen J, Profit AA, Prestwich GD. J. Org. Chem. 1996; 61: 6305
• 6b Sureshan KM, Riley AM, Potter BV. L. Tetrahedron Lett. 2007; 48: 1923
• 7 Novotný J, Pospechová K, Hrabálek A, Cáp R, Vávrová C. Bioorg. Med. Chem. Lett. 2009; 19: 6975
• 8a Pietrusiewicz KM, Salamonczyk GM, Bruzik KS, Wieczorek W. Tetrahedron 1992; 26: 5523
• 8b Bruzik KS, Salamonczyk GM. Carbohydr. Res. 1989; 195: 67
• 8c Xu Y, Sculimbrene BR, Miller SJ. J. Org. Chem. 2006; 71: 4919
• 8d Leung LW, Bittman R. Carbohydr. Res. 1998; 305: 171
• 8e Ling L, Ozaki S. Carbohydr. Res. 1994; 256: 49
• 9a Boseggia E, Gatos M, Lucatello L, Mancin F, Moro S, Palumbo M, Sissi C, Tecilla P, Tonellato U, Zagotto G. J. Am. Chem. Soc. 2004; 126: 4543
• 9b Mazu TK, Etukala JR, Zhu XY, Jacob MR, Khan SI, Walker LA, Ablordeppey SY. Bioorg. Med. Chem. 2011; 19: 524
• 10 Sureshan KM, Shashidhar MS, Praveen T, Das T. Chem. Rev. 2003; 103: 4477
• 11 Elie CJ. J, Dreef CE, Verduyn R, Van Der Mare GA, Van Boom JH. Tetrahedron 1989; 45: 3477
• 12 d-1-O-Allyl-3,4,5,6-tetra-O-benzyl-2-O-(N-benzyloxycarbonyl-6-aminohexyl)-myo-inositol (7) ¹H NMR (400 MHz, CDCl₃): δ = 1.24–1.62 (m, 8 H, CH₂), 3.14–3.22 (m, 3 H, CH ₂NHCbz, H₁), 3.32 (dd, J = 9.8, 2.3 Hz, 1 H, H₅), 3.42 (app t, J = 9.2 Hz, 1 H, H₃), 3.72 (app t, J = 6.5 Hz, 1 H, CH₂O), 3.84 (app t, J = 2.3 Hz, 1 H, H₂), 3.90–4.00 (m, 2 H, H₆, H₄), 4.12–4.13 (m, 2 H, OCH ₂CHCH₂), 4.68–4.70 (m, 2 H, CH₂Ph), 4.77–4.90 (m, 6 H, CH₂Ph), 5.08 (s, 2 H, NHCOOCH ₂Ph), 5.16 (dd, J = 10.4, 1.7 Hz, 1 H, OCH₂CHCH ₂), 5.29 (dd, J = 17.2, 1.7 Hz, 1 H, OCH₂CHCH ₂) 5.91 (tdd, J = 17.2, 10.4, 5.7 Hz, 1 H, OCH₂CHCH₂), 7.27–7.37 (m, 25 H, CH, Ar). ¹³C NMR (100 MHz, CDCl₃): δ = 25.8 (C₃′), 26.6 (C₄′), 30.3 (C₅′), 31.1 (C₂′), 41.2 (C₆′), 66.7 (NHCOCH₂Ph), 71.7 (C₁′), 72.9 (OCH₂Ph) 73.3 (OCH₂Ph), 75.6 (C₃), 76.0 (C₅), 76.1 (CH₂CH=CH₂), 80.7 (C₂), 81.0 (C₁), 81.8 (C₆), 83.7 (C₄), 116.9 (CH₂CH=CH₂), 127.7, 128.1, 128.2, 128.05, 128.6 (CH, Ar), 135.1 (CH₂ CH=CH₂), 136.8, 138.6, 138.9, 139.0 (C, Ar), 156.5 (CO). Anal. Calcd for C₅₁H₅₉NO₈: C, 75.2; H, 7.3; N, 1.7. Found: C, 75.4; H, 7.4; N, 1.6.
• 13a Kawato HC, Nakayama K, Inagaki H, Ohta T. Org. Lett. 2001; 3: 3451
• 13b Russell MG. N, Baker R, Billington DC. Carbohydr. Res. 1992; 234: 263
• 14 Chandrasekhar S, Reddy R, Rao RJ. Tetrahedron 2001; 57: 3435
• 15 d-3,4,5,6-Tetra-O-benzyl-2-O-(N-benzyloxycarbonyl-6-aminohexyl)-myo-inositol (8) ¹H NMR (400 MHz, CDCl₃): δ = 1.25–1.40 (m, 6H, CH₂), 1.45–1.50 (m, 2 H, CH₂), 2.27 (br s, 1 H, OH), 3.17 (dd, J = 12.7, 6.2 Hz, 2 H, CH ₂NHCbz), 3.39–3.48 (m, 3 H, H₁, H₃, H₅), 3.60 (dd, J = 15.6, 6.5 Hz, 1 H, CH₂O), 3.74 (app t, J = 9.4 Hz, 1 H, H₆), 3.84–3.98 (m, 3 H, H₄, H₂, CH₂O), 4.69 (s, 2 H, CH₂Ph), 4.78–4.84 (m, 3 H, CH₂Ph), 4.89–4.93 (m, 3 H, CH₂Ph), 5.08 (s, 2 H, NHCOOCH ₂Ph), 7.27–7.35 (m, 25 H, CH, Ar). ¹³C NMR (100 MHz, CDCl₃): δ = 25.8 (C₃′), 26.6 (C₄′), 30.0 (C₅′), 30.3 (C₂′), 41.1 (C₆′), 66.7 (NHCOCH₂Ph), 72.4 (C₁′), 73.0 (OCH₂Ph), 73.4 (OCH₂Ph), 75.7 (C₃), 75.9 (C₅), 81.3 (C₂), 82.0 (C₁), 82.4 (C₆), 83.7 (C₄), 127.7, 128.1, 128.2, 128.5, 128.6 (CH, Ar), 136.8, 138.4, 138.7, 139.0 (C, Ar), 156.5 (CO). Anal. Calcd for C₄₈H₅₅NO₈: C, 74.5; H, 7.2; N, 1.8. Found: C, 74.8; H, 7.1; N, 1.9.
• 16 Ainge GD, Parlane NA, Denis M, Dyer BS. J. Org. Chem. 2007; 72: 5291
• 17 d-3,4,5,6-Tetra-O-benzyl-2-O-(N-benzyloxycarbonyl-6-aminohexyl)-1-{benzyl[(R)-1,2-isopropylidene-sn-glycerol-3-yl]phospho}-myo-inositol (10) ¹H NMR (400 MHz, CDCl₃): δ = 1.27–1.57 (m, 14 H), 3.10–3.18 (m, 2 H, CH ₂NH), 3.34–3.52 (m, 2 H), 3.52–3.58 (m, 1 H), 3.72–3.81 (m, 3 H), 3.81–3.88 (m, 4 H), 4.10–4.25 (m, 3 H), 4.58–4.70 (m, 3 H, CH₂Ph), 4.76–4.91 (m, 7 H, CH₂Ph), 5.07 (s, 2 H, CH ₂OCONH), 7.24–7.30 (m, 30 H, CH, Ar). ¹³C NMR (100 MHz, CDCl₃,): δ = 25.4, 25.7, 26.8, 29.9, 30.1, 31.0, 41.2, 63.1, 65.8, 66.8, 67.9, 69.5, 72.8, 73.6, 74.0, 75.9, 76.2, 78.8, 80.2, 80.5, 81.5, 83.2, 109.9, 128.1, 128.5, 128.6, 128.7, 135.8, 136.8, 138.5, 138.8, 156.5. ³¹P NMR (101 MHz, CDCl₃): δ = –1.7. Anal. Calcd for C₆₁H₇₂NO₁₃P: C, 69.2; H, 6.8; N, 1.3. Found: C, 69.3; H, 6.9; N, 1.3.
• 18 d-2-O-(6-Aminohexyl)-1-{[(R)-1,2-isopropylidene-sn-glycerol-3-yl]phospho}-myo-inositol (11) ¹H NMR (400 MHz, D₂O): δ = 1.32–1.42 (m, 7 H, CCH ₃, CH₂), 1.45 (s, 3 H, CCH ₃), 1.56–1.70 (m, 4 H, CH₂), 2.94–3.06 (m, 2 H, CH ₂NH₂), 3.25–3.28 (m, 1 H), 3.51–3.65 (m, 2 H), 3.70–3.75 (m, 2 H, CH₂O), 3.81–3.96 (m, 5 H), 4.02 (s, 1 H), 4.13–4.17 (m, 1 H), 4.39–4.45 (m, 1 H). ¹³C NMR (100 MHz, D₂O): δ = 23.1, 24.0, 24.5, 25.4, 28.8, 39.3, 46.8, 65.1, 65.4, 70.9, 71.5, 72.5, 73.7, 73.9, 74.5, 76.3, 79.4, 110.0. ³¹P NMR (101 MHz, CDCl₃): δ = –1.3. Anal. Calcd for C₁₈H₃₆NO₁₁P: C, 45.7; H, 7.6; N, 2.9. Found: C, 45.8; H, 7.3; N, 2.8.
• 19 Vishwakarma RA, Vehring S, Mehta A, Sinha A, Pomorski T, Herrmann A, Menon AK. Org. Biomol. Chem. 2005; 3: 1275
• 20 d-1-[(R)-sn-Glycerol-3-phospho]-2-O-{6-(6-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino] hexanamido)hexyl}-myo-inositol (12) ¹H NMR (400 MHz, D₂O): δ = 1.20–1.27 (m, 5 H, CH₂), 1.38–1.45 (dd, J = 13.4, 6.8 Hz, 3 H, CH₂), 1.51–1.56 (dd, J = 13.7, 6.9 Hz, 2 H, CH₂), 1.62–1.68 (dd, J = 14.5, 7.1 Hz, 2 H, CH₂), 1.76–1.83 (dd, J = 14.5, 6.9 Hz, 2 H, CH₂), 2.25 (app t, J = 7.1 Hz, 2 H, CH ₂CONH), 3.10 (app t, J = 6.8 Hz, 2 H, CH ₂NHCO), 3.28 (t, J = 9.2 Hz, 1 H, CH ₂NH-NBD), 3.53–3.62 (m, 5 H), 3.64–3.67 (m, 1 H), 3.69–3.76 (m, 3 H), 3.79–3.85 (m, 1 H), 3.88–3.98 (m, 4 H) 4.04 (app t, J = 2.6 Hz, 1 H, H₁), 6.38 (d, J = 9.0 Hz, 1 H, CH, NBD), 8.50 (d, J = 9.0 Hz, 1 H, CH, NBD). ³¹P NMR (101 MHz, CDCl₃): δ = –2.1. Anal. Calcd for C₂₇H₄₄N₅O₁₅P: C, 45.7; H, 6.2; N, 9.9. Found: C, 45.6; H, 6.2; N, 9.7.
• 21 Kim JH, Yang MS, Lee WS, Park KH. J. Chem. Soc., Perkin Trans. 1 1998; 2877