Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2008
Distinct Columnar and Lamellar Liquid Crystalline Phases Formed by New Bolaamphiphiles with Linear and Branched Lateral Hydrocarbon Chains Marko Prehm, [a,b] Claudia Enders, [a] Maryam Yahyaee Anzahaee, [a] Benjamin Glettner, [a] Ute Baumeister, [b] and Carsten Tschierske*,[a] [a] Organic Chemistry, Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Germany; Fax: +49 345 552 7346; Tel: +49 345 552 5664; E-mail: carsten.tschierske@chemie.uni-halle.de [b] Physical Chemistry, Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, Mühlpforte, D-06108 Halle, Germany. S1
1. Additional Figures and Tables (a) (b) (c) (d) Figure S1. (a, b) Textures (color versions of Figure 4a,e) and (c,d) X-ray diffraction patterns (wide angle region) obtained from surface-aligned samples of the mesophases of Lin18: (a) Col hex(6)cyl-6 /p6mm-phase at T = 125 C, (c) at T = 121 C; (b) Col rec(6)cyl-8 /c2mm-phase at T = 115 C, (d) at T = 90 C. (a) (b) Figure S2. Textures of the mesophases of Tmp and Ada: (a) Col hex(6)cyl-6 /p6mm-phase of Tmp at T = 92 C; (b) Col hex(6)cyl-6 /p6mm-phase of Ada at T = 70 C. S2
1200 d 10 = 3.04 nm 1050 900 I / a.u. 750 600 d 20 = 1.52 nm 450 0.45 nm 300 5 10 15 20 25 2θ / Figure S3. Powder diffraction pattern of the Col hex -phase of Tmp at T = 92 C with d-values for the observed reflections and for the maximum of the diffuse outer scattering. 2250 d 10 = 3.06 nm 2000 1750 I / a.u. 1500 1250 d 11 = 1.80 nm 1000 750 d 20 = 1.53 nm 0.50 nm 500 5 10 15 20 25 2θ / Figure S4. Powder diffraction pattern of the Col hex -phase of Ada at T = 64 C with d-values for the observed reflections and for the maximum of the diffuse outer scattering. (a) (b) Figure S5. Col rec(6)cyl-8 /c2mm phase of Ment*: (a) Texture of the mesophases at T = 100 C (color version of Figure 7a); (b) X-ray diffraction pattern of an aligned sample at 95 C, small angle region with indexation. S3
(a) (b) Figure S6. Textures of the mesophases of Chol*11: (a) Lam Iso phase at T = 138 C; (b) Lam phase at T = 130 C (color versions of Figure 9a,c). (a) (b) 2.2 2.0 I rel / I a.u. 1.8 1.6 1.4 100 150 200 250 χ / Figure S7. Compound Bra22: (a) X-ray diffraction pattern of a partially aligned sample at T = 95 C; (b) distribution of the wide-angle scattering along? (black line) with maxima at 180 [I rel = I(95 C) / I(107 C, Iso)] in comparison with the? position of the layer reflections (red line). 2500 d 10 = 4.04 nm 2000 1500 I / a.u. 1000 500 0.45 nm 0 5 10 15 20 25 2θ / Figure S8. Powder diffraction pattern of the Lam Sm -phase of Benz6/1 at T = 80 C with d-value for the layer reflection and for the maximum of the diffuse outer scattering. S4
(a) (b) 16000 d 10 = 4.70 nm 14000 12000 10000 I / a.u. 8000 6000 4000 2000 0 0.49 nm 0 7 14 21 Figure S9. X-ray diffraction pattern of a partially aligned sample of Benz6/2 in the Lam N - phase at T = 100 C: (a) 2D pattern, (b)?-scan of the diffraction pattern with the d-values. 2θ / (a) (b) 16000 d 10 = 4.29 nm 14000 12000 10000 I / a.u. 8000 6000 4000 2000 0.47 nm 0 0 5 10 15 20 25 Figure S10. X-ray diffraction pattern of an aligned sample of Benz6/3 in the Col hex -phase at T = 112 C: (a) 2D pattern, (b)?-scan of the diffraction pattern with the d-values. 2θ / (a) (b) 10000 d 10 = 5.25 nm 8000 I / a.u. 6000 4000 2000 0 d 20 = 2.62 nm d 30 = 1.76 nm 0.47 nm 0 5 10 15 20 25 Figure S11. X-ray diffraction pattern of a partially aligned sample of Benz11/3 in the Lam N - phase at T = 90 C: (a) 2D pattern, (b)?-scan of the diffraction pattern with the d-values. 2θ / S5
Table S1. Crystallographic data (θ obs : experimental scattering angle; d obs : experimental and d calc : calculated d spacing; hk/n: assigned indices for 2D phases (Col rec, Col hex )/ order of reflection for Lam Sm phases, Parameter used: Lattice parameters or d values used to calculate d calc with an error of the calculated parameters in the order of 0.1 nm) Comp. T ( C) Phase Plane Group θ obs d obs hk/n d calc d obs - d calc Parameter used (nm) Lin9 86 Col rec 1.095 4.03 11 4.00 0.03 a = 5.78 p2gg 1.505 2.94 20 2.89 0.05 b = 5.55 1.740 2.54 21 2.56-0.02 Lin10 98 Col rec 1.233 3.58 11 3.88-0.30 a = 5.65 p2gg 1.563 2.83 20 2.83 0.00 b = 5.32 1.660 2.66 02 2.66 0.00 1.753 2.52 21 2.50 0.02 1.825 2.42 12 2.41 0.01 Lin11 105 Col hex 1.435 3.08 10 a = 3.55 Lin12 100 Col hex 1.440 3.07 10 3.12-0.05 a = 3.60 2.425 1.82 11 1.80 0.02 2.815 1.57 20 1.56 0.01 Lin14 125 Col hex 1.436 3.08 10 3.15-0.07 a = 3.64 2.430 1.82 11 1.82 0.00 2.781 1.59 20 1.58 0.01 Lin16 109 Col hex 1.415 3.12 10 3.12 0.00 a = 3.60 2.464 1.79 11 1.80-0.01 2.852 1.55 20 1.56-0.01 Lin18 124 Col hex 1.422 3.11 10 3.14-0.03 a = 3.63 2.433 1.82 11 1.82 0.00 2.854 1.55 20 1.57-0.02 101 Col rec 0.922 4.79 02 4.79 0.00 a = 3.60 c2mm 1.311 3.37 11 3.37 0.00 b = 9.58 1.818 2.43 04 2.40 0.03 2.547 1.73 20 1.80-0.07 S6
Table S1. continued Comp. T ( C) Phase Plane Group θ obs d obs hk/n d calc d obs - d calc Parameter used (nm) Lin20 95 Col rec 0.913 4.84 02 4.85-0.01 a = 3.70 c2mm 1.277 3.46 11 3.48-0.02 b = 9.70 1.820 2.43 04 2.43 0.00 2.306 1.92 20 1.85 0.07 2.619 1.69 22 1.73-0.04 Lin22 119 Lam Sm 1.212 3.64 1 3.64 0.00 d = 3.64 2.423 1.82 2 1.82 0.00 106 Col rec 0.916 4.82 02 4.82 0.00 a = 3.86 c2mm 1.252 3.53 11 3.58-0.05 b = 9.64 1.841 2.40 04 2.41-0.02 2.286 1.93 20 1.93 0.00 2.463 1.79 22 1.79 0.00 Ada 64 Col hex 1.445 3.06 10 3.06 0.00 a = 3.53 2.455 1.80 11 1.77 0.03 2.890 1.53 20 1.53 0.00 Tmp 92 Col hex 1.452 3.04 10 3.04 0.00 a = 3.51 2.911 1.52 20 1.52 0.00 Ment* 95 Col rec 0.927 4.76 02 4.76 0.00 a = 3.73 c2mm 1.284 3.44 11 3.47-0.03 b = 9.52 1.849 2.39 13 2.42-0.03 2.371 1.86 20 1.87-0.01 2.548 1.73 22 1.74-0.01 Chol*11 136 Lam Iso 0.880 5.02 1 5.02 0.00 d = 5.02 1.785 2.47 2 2.51-0.04 125 Lam 0.990 4.46 1 4.46 0.00 d = 4.46 1.961 2.25 2 2.23 0.02 Bra22 95 Lam Sm 1.625 2.72 1 2.72 0.00 d = 2.72 3.195 1.38 2 1.36 0.02 S7
Table S1. continued Comp. T ( C) Phase Plane Group θ obs d obs hk/n d calc d obs - d calc Parameter used (nm) Benz6/1 80 Lam Sm 1.095 4.04 1 d = 4.04 Benz6/2 100 Lam N 0.940 4.70 1 4.70 0.00 d = 4.70 2.742 1.61 3 1.57 0.04 Benz6/3 112 Col hex 1.030 4.29 10 a = 4.95 Benz11/3 90 Lam N 0.841 5.25 1 5.25 0.00 d = 5.25 1.687 2.62 2 2.63-0.01 2.513 1.76 3 1.75 0.01 Table S2. Calculations of molecular volume (V mol ), volume of the hypothetical unit cells (V cell ) and number of molecules in these unit cells (n cell ). a Comp. Phase V cell [nm 3 ] V mol [nm 3 ] n cell,cryst n cell,liq n cell Lin9 Col rec 14.436 0.645 22.4 17.6 20.0 Lin10 Col rec 13.526 0.670 20.2 15.9 18.1 Lin11 Col hex 4.911 0.694 7.1 5.6 6.4 Lin12 Col hex 5.050 0.720 7.0 5.5 6.3 Lin14 Col hex 5.164 0.769 6.7 5.3 6.0 Lin16 Col hex 5.050 0.819 6.2 4.9 5.6 Lin18 Col hex 5.135 0.869 5.9 4.6 5.3 Col rec 15.520 17.9 14.1 16.0 Lin20 Col rec 16.151 0.918 17.6 13.8 15.7 Lin22 Col rec 16.745 0.968 17.3 13.6 15.5 Ada Col hex 4.856 0.939 5.2 4.1 4.7 Tmp Col hex 4.801 0.903 5.3 4.2 4.8 Ment* Col rec 15.979 0.963 16.6 13.0 14.8 Benz6/3 Col hex 21.220 b 1.631 13.0 10.2 11.6 a V cell = volume of the unit cell defined by the dimensions a x b x 0.45 nm for rectangular phases and a 2 x sin(60 ) x 0.45 nm for hexagonal phases; V mol = volume for a single molecule as calculated using the crystal volume increments; [1] n cell,cryst = number of molecules in the unit cell, calculated according to n cell = V cell /V mol (average packing coefficient in the crystal is k = 0.7; [2] n cell,liq = number of molecules in the unit cell of an isotropic liquid with an average S8
packing coefficient k = 0.55, calculated according to n cell,liq = 0.55/0.7 x n cell,cryst ; n cell = in the LC phase estimated as the average of that in the n cell,cryst and n cell,liq ; b for the Col hex -phase of this compound the volume of the unit cell was calculated using a 2 x sin(60 ) x h assuming a height of h = 1.8 nm corresponding to the average stacking distance along the columns. 2. Syntheses and Analytical Data 2.1 Compounds Linn 2-Benzyloxyphenol (1) [3] To a stirred suspension of 1,2-dihydroxybenzene (50 g, 0.45 mol) and potassium hydroxide (25.2 g, 0.45 mol) in dry methanol (500 ml) was slowly added benzyl chloride (52 ml, 0.45 mol). The resulting mixture was stirred for 1 h at room temperature and thereafter 4 h under reflux. After cooling to room temperature potassium hydroxide solution in water (100 ml, 1 M) was added and the dibenzylated side product was extracted with diethyl ether (2 x 50 ml). The aqueous phase was acidified with HCl (2M) and extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with water and brine and dried over anhydrous Na 2 SO 4. After filtration the solvent was removed under reduced pressure, the crude product was dissolved in chloroform and filtered through a plug of silica gel. The product was obtained after removing the solvent and purification by distillation in vacuo as a colorless liquid. Yield: 40.2 g (44 %); bp 115-117 C at 1.5 10-2 mbar. (lit., 108-120 C at 5 10-2 mbar). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.43-7.34 (m, 5H, Ar-H), 6.97-6.81 (m, 4H, Ar-H), 5.68 (bs, 1H, OH), 5.10 (s, 2H, OCH 2 Ph). 2-Benzyloxy-4-bromophenol (2) [4] A solution of 2-benzyloxyphenol (1) (27.8 g, 0.14 mol) in CH 2 Cl 2 /acetic acid (210 ml, 2:1, v/v) was cooled to 0 C and bromine (22.4 g, 0.14 mol) dissolved in acetic acid (70 ml) was added within 10 min. After stirring at this temperature for 10 min, water (300 ml) was added and the reaction mixture was extracted with chloroform (2 x 100 ml). The combined organic layers were washed with saturated Na 2 SO 3 solution in water, water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent the crude product was purified by column chromatography (silica gel, chloroform) and crystallization from diethyl ether/pe (1:1, v/v). Colorless solid; Yield: 30 g (77 %); mp 66-68 C. 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.41-7.34 (m, 5H, Ar-H), 7.05 (d, 4 J(H,H) = 2.2, 1H, Ar-H), 7.00 (dd, 3 J(H,H) = 8.4, 4 J(H,H) = 2.2, 1H, Ar-H), 6.81 (d, 3 J(H,H) = 8.5, 1H, Ar-H), 5.58 (s, 1H, OH), 5.06 (s, 2H, OCH 2 Ph). 3-[4 -(2,3-Dihydroxypropoxy)-3-hexyloxybiphenyl-4-yloxy]propane-1,2-diol Lin6 1 H NMR (acetone-d 6, J/Hz, 400 MHz): d 7.52 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 7.18 (s, 4 J(H,H) = 2.1, 1H, Ar-H), 7.09 (dd, 3 J(H,H) = 8.3, 4 J(H,H) = 2.2, 1H, Ar-H), 7.02 (d, 3 J(H,H) = 8.4, 1H, Ar-H), 6.98 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 4.10-3.94 (m, 6H, OCH, OCH 2 ), 3.74-3.61 (m, 6H, OCH 2 ), 1.79 (quint, 3 J(H,H) = 7.0, 2H, OCH 2 CH 2 ), 1.54-1.47 (m, 2H, CH 2 ), 1.39-1.32 (m, 4H, CH 2 ), 0.89 (t, 3 J(H,H) = 7.1, 3H, CH 3 ). 13 C NMR (methanol-d 4, J/Hz, 100 MHz): d S9
159.3, 150.6, 149.2, 135.4, 134.2, 128.3 (2C), 119.7, 116.3, 115.7 (2C), 113.6, 72.5, 71.4, 71.3, 70.5, 69.9, 64.5, 64.2, 32.3, 30.2, 26.5, 23.3, 14.2. EA calc. for C 24 H 34 O 7 0.5H 2 O: C 64.99%, H 7.95 %; found: C 65.31 %, H 8.05 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-octyloxybiphenyl-4-yloxy]propane-1,2-diol Lin8 1 H NMR (methanol-d 4, J/Hz, 400 MHz): d 7.46 (d, 3 J(H,H) = 8.6, 2H, Ar-H), 7.11 (s, 1H, Ar- H), 7.07 (d, 3 J(H,H) = 8.2, 1H, Ar-H), 7.00-6.97 (m, 2H, Ar-H), 4.09-4.03 (m, 4H, OCH, OCH 2 ), 4.01-3.96 (m, 4H, OCH 2 ), 3.75-3.63 (m, 4H, OCH 2 ), 1.79 (quint, 3 J(H,H) = 7.0, 2H, OCH 2 CH 2 ), 1.53-1.45 (m, 2H, CH 2 ), 1.39-1.28 (m, 8H, CH 2 ), 0.91-0.87 (m, 3H, CH 3 ). 13 C NMR (methanol-d 4, J/Hz, 100 MHz): d 159.6, 150.6, 149.3, 136.1, 134.9, 128.6 (2C), 120.3, 116.4, 115.9 (2C), 114.1, 72.4, 71.8 (2C), 70.7, 70.5, 64.5, 64.2, 32.9, 30.5, 30.4, 30.3, 27.1, 23.6, 14.3. EA calc. for C 26 H 38 O 7 0.25H 2 O: C 66.86%, H 8.31 %; found: C 67.06 %, H 8.36 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-nonyloxybiphenyl-4-yloxy]propane-1,2-diol Lin9 1 H NMR (methanol-d 4, J/Hz, 400 MHz): d 7.48 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 7.13 (d, 4 J(H,H) = 2.0, 1H, Ar-H), 7.09 (dd, 3 J(H,H) = 8.4, 4 J(H,H) = 2.1, 1H, Ar-H), 7.02 (d, 3 J(H,H) = 8.4, 1H, Ar-H), 6.99 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 4.10-4.06 (m, 4H, OCH, OCH 2 ), 4.03-3.96 (m, 4H, OCH 2 ), 3.75-3.63 (m, 4H, OCH 2 ), 1.81 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.54-1.48 (m, 2H, CH 2 ), 1.40-1.28 (m, 10H, CH 2 ), 0.89 (t, 3 J(H,H) = 7.1, 3H, CH 3 ). 13 C NMR (methanol-d 4, J/Hz, 100 MHz): d 159.5, 150.5, 149.3, 136.1, 134.8, 128.5 (2C), 120.3, 116.3, 115.8 (2C), 114.0, 72.42, 71.8 (2C), 70.7, 70.5, 64.4, 64.2, 33.0, 30.6, 30.5 (2C), 30.3, 27.1, 23.7, 14.4. EA calc. for C 27 H 40 O 7 0.5H 2 O: C 66.78%, H 8.51 %; found: C 66.73 %, H 8.42 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-decyloxybiphenyl-4-yloxy]propane-1,2-diol Lin10 1 H NMR (methanol-d 4, J/Hz, 400 MHz): d 7.47 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.13 (d, 4 J(H,H) = 2.1, 1H, Ar-H), 7.09 (dd, 3 J(H,H) = 8.3, 4 J(H,H) = 2.1, 1H, Ar-H), 7.02 (d, 3 J(H,H) = 8.4, 1H, Ar-H), 6.99 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 4.10-4.05 (m, 4H, OCH, OCH 2 ), 4.03-3.96 (m, 4H, OCH 2 ), 3.75-3.63 (m, 4H, OCH 2 ), 1.81 (quint, 3 J(H,H) = 7.0, 2H, OCH 2 CH 2 ), 1.55-1.47 (m, 2H, CH 2 ), 1.41-1.28 (m, 12H, CH 2 ), 0.89 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 158.9, 150.1, 149.0, 134.6, 133.7, 127.9 (2C), 119.4, 115.5, 115.3 (2C), 113.3, 72.3, 71.3 (2C), 70.9, 69.4, 64.4, 64.2, 31.9, 29.7, 29.6, 29.6, 29.5, 29.3, 26.2, 22.7, 14.0. EA calc. for C 28 H 42 O 7 0.25H 2 O: C 67.92%, H 8.65 %; found: C 68.09 %, H 8.70 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-undecyloxybiphenyl-4-yloxy]propane-1,2-diol Lin11 1 H NMR (methanol-d 4, J/Hz, 400 MHz): d 7.47 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.12 (d, 4 J(H,H) = 2.1, 1H, Ar-H), 7.09 (dd, 3 J(H,H) = 8.3, 4 J(H,H) = 2.0, 1H, Ar-H), 7.02 (d, 3 J(H,H) = 8.4, 1H, Ar-H), 6.99 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 4.10-4.06 (m, 4H, OCH, OCH 2 ), 4.04-3.96 (m, 4H, OCH 2 ), 3.75-3.63 (m, 4H, OCH 2 ), 1.81 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.55-1.47 (m, 2H, CH 2 ), 1.40-1.26 (m, 14H, CH 2 ), 0.89 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.2, 150.4, 149.3, 134.9, 134.1, 128.3 (2C), S10
124.1, 123.0, 119.7, 115.8, 115.6 (2C), 113.6, 72.7, 71.7 (2C), 71.3, 69.9, 64.8, 64.6, 32.3, 30.1 (4C), 29.9, 29.8, 26.7, 23.2, 14.5. EA calc. for C 29 H 44 O 7 0.25H 2 O: C 68.41%, H 8.81 %; found: C 68.39 %, H 8.84 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-dodecyloxybiphenyl-4-yloxy]propane-1,2-diol Lin12 1 H NMR (methanol-d 4, J/Hz, 400 MHz): d 7.47 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.12 (d, 4 J(H,H) = 2.1, 1H, Ar-H), 7.08 (dd, 3 J(H,H) = 8.3, 4 J(H,H) = 2.1, 1H, Ar-H), 7.01 (d, 3 J(H,H) = 8.3, 1H, Ar-H), 6.99 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 4.10-4.05 (m, 4H, OCH, OCH 2 ), 4.03-3.96 (m, 4H, OCH 2 ), 3.75-3.63 (m, 4H, OCH 2 ), 1.81 (quint, 3 J(H,H) = 7.0, 2H, OCH 2 CH 2 ), 1.55-1.47 (m, 2H, CH 2 ), 1.40-1.25 (m, 16H, CH 2 ), 0.89 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.2, 150.4, 149.3, 134.9, 134.1, 128.3 (2C), 124.0, 119.8, 115.9, 115.6 (2C), 113.7, 72.8, 71.7 (2C), 71.3, 69.9, 64.6, 64.6, 32.3, 30.2, 30.1 (4C), 29.9, 29.8, 26.7, 23.2, 14.5. EA calc. for C 30 H 46 O 7 0.25H 2 O: C 68.87%, H 8.96 %; found: C 69.03 %, H 9.00 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-tetradecyloxybiphenyl-4-yloxy]propane-1,2-diol Lin14 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.68 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.40 (s, 1H, Ar- H), 7.25 (s, 2H, Ar-H), 7.21-7.19 (m, 2H, Ar-H, overlapped by pyridine), 4.65-4.44 (m, 6H, OCH, OCH 2 ), 4.33-4.22 (m, 4H, OCH 2 ), 4.12 (t, 3 J(H,H) = 6.6, 2H, OCH 2 CH 2 ), 1.81 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.52-1.45 (m, 2H, CH 2 ), 1.25 (bs, 20H, CH 2 ), 0.86 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.1, 150.2, 149.2, 134.7, 133.9, 128.2, 119.6, 115.5, 115.5 (2C), 113.3, 72.5, 71.5, 71.5, 71.1, 69.6, 64.6, 64.4, 32.2, 30.0 (2C), 30.0, 30.0 (2C), 29.9, 29.9, 29.8, 29.6, 26.5, 23.0, 14.3. EA calc. for C 32 H 50 O 7 0.25H 2 O: C 69.72%, H 9.23 %; found: C 69.92 %, H 9.47 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-hexadecyloxybiphenyl-4-yloxy]propane-1,2-diol Lin16 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.67 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.39 (s, 1H, Ar- H), 7.24 (s, 2H, Ar-H), 7.20-7.18 (m, 2H, Ar-H, overlapped by pyridine), 6.89 (bs, 1H, OH), 6.76 (bs, 1H, OH), 6.49 (bs, 1H, OH), 6.38 (bs, 1H, OH), 4.61-4.43 (m, 6H, OCH, OCH 2 ), 4.32-4.23 (m, 4H, OCH 2 ), 4.11 (t, 3 J(H,H) = 6.6, 2H, OCH 2 CH 2 ), 1.80 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.50-1.46 (m, 2H, CH 2 ), 1.26-1.25 (m, 28H, CH 2 ), 0.85 (t, 3 J(H,H) = 6.8, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.1, 150.3, 149.2, 134.8, 134.0, 128.2 (2C), 119.7, 115.7, 115.6 (2C), 113.5, 72.7, 71.7 (2C), 71.2, 69.8, 64.7, 64.5, 34.0, 32.3, 30.2, 30.2 (2C), 30.1 (2C), 30.1 (2C), 30.1, 29.9, 29.8, 26.6, 23.1, 14.5. EA calc. for C 34 H 54 O 7 : C 71.05 %, H 9.47 %; found: C 70.98 %, H 9.47 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-icosyloxybiphenyl-4-yloxy]propane-1,2-diol Lin20 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.68 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.40 (s, 1H, Ar- H), 7.25 (s, 2H, Ar-H), 7.21-7.19 (m, 2H, Ar-H, overlapped by pyridine), 4.64-4.44 (m, 6H, OCH, OCH 2 ), 4.33-4.22 (m, 4H, OCH 2 ), 4.12 (t, 3 J(H,H) = 6.6, 2H, OCH 2 CH 2 ), 1.81 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.50-1.47 (m, 2H, CH 2 ), 1.29-1.25 (m, 32H, CH 2 ), 0.86 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.1, 150.3, 149.3, 134.9, 134.0, 128.2 (2C), 119.7, 115.8, 115.6 (2C), 113.6, 72.7, 71.7 (2C), 71.2, 69.8, 64.7, S11
64.5, 32.3, 30.2 (4C), 30.2 (2C), 30.2, 30.2, 30.2, 30.1, 30.1 (2C), 30.1, 29.9, 29.8, 26.6, 23.1, 14.5. EA calc. for C 38 H 62 O 7 : C 72.34 %, H 9.91 %; found: C 72.35 %, H 9.84 %. 3-[4 -(2,3-Dihydroxypropoxy)-3-docosyloxybiphenyl-4-yloxy]propane-1,2-diol Lin22 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.67 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.40 (s, 1H, Ar- H), 7.24 (s, 2H, Ar-H), 7.20-7.18 (m, 2H, Ar-H, overlapped by pyridine), 4.64-4.44 (m, 6H, OCH, OCH 2 ), 4.33-4.22 (m, 4H, OCH 2 ), 4.12 (t, 3 J(H,H) = 6.5, 2H, OCH 2 CH 2 ), 1.81 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.50-1.46 (m, 2H, CH 2 ), 1.30-1.25 (m, 36H, CH 2 ), 0.86 (t, 3 J(H,H) = 6.7, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.1, 150.3, 149.2, 134.8, 133.9, 128.2 (2C), 119.6, 115.7, 115.5 (2C), 113.5, 72.5, 71.5 (2C), 71.1, 69.7, 64.6, 64.4, 32.1, 30.0 (6C), 30.0 (4C), 30.0, 30.0, 30.0, 29.9, 29.9, 29.7, 29.6, 26.5, 23.0, 14.3. EA calc. for C 40 H 66 O 7 : C 72.91 %, H 10.10 %; found: C 72.80 %, H 10.03 %. 2.2 Synthesis of Ada 11-Bromoundecyl adamantane-1-carboxylate Admantane-1-carboxylic acid (1,1g, 6.1 mmol), bromoundecane-1-ol (1.4 g, 5.5 mmol), DCC (2.3g, 5.5 mmol) and DCC (25.2 g, 0.45 mol) were dissolved in anhydrous CH 2 Cl 2 (50 ml) and stirred at room temperature for 24 h. The reaction mixture was then filtered trough silica gel. After evaporation of the solvent the crude product was crystallized from EtOAc. Colorless solid; Yield: 1.8 g (80 %); mp 115-117 C. 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 4.16 (t, 3 J(H,H) = 6.6, 2H, COOCH 2 ), 3.38 (t, 3 J(H,H) = 6.9, 2H, CH 2 Br), 1.99 (bs, 2H, CH 2 ), 1.87-1.79 (m, 8H, CH 2 ), 1.74-1.65 (m, 6H, CH 2 ), 1.62-1.55 (m, 3H, CH), 1.44-1.37 (m, 2H, CH 2 ), 1.33-1.25 (m, 12H, CH 2 ). 4,4 -Bis(2,2-dimethyl-1,3-dioxolan-4-ylmethoxy)biphenyl-3-yloxyundecyl adamantane-1- carboxylate 6/ada A mixture of 5 (170 mg, 0.39 mmol), 11-bromoundecyl adamantane-1-carboxylate (196 mg, 0.47 mmol), K 2 CO 3 (272 mg, 1.97 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless oil; Yield: 170 mg (57 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.43 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 7.03-7.01 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.9, 3H, Ar-H), 4.47 (quint, 3 J(H,H) = 5.9, 2H, OCH), 4.18-4.05 (m, 4H, OCH 2 ), 4.03-3.88 (m, 8H, OCH 2, COOCH 2 ), 1.98 (bs, 2H, CH 2 ), 1.87-1.86 (m, 6H, CH 2 ), 1.84-1.77 (m, 2H, CH 2 ), 1.73-1.64 (m, 6H, CH 2 ), 1.62-1.55 (m, 3H, CH), 1.49-1.42 (m, 2H, CH 2 ), 1.46 (m, 3H, CH 3 ), 1.45 (m, 3H, CH 3 ), 1.39 (s, 3H, CH 3 ), 1.38 (s, 3H, CH 3 ), 1.35-1.26 (m, 12H, CH 2 ). S12
4,4 -Bis(2,3-dihydroxypropyloxy)biphenyl-3-yloxyhexyl adamantane-1-carboxylate Ada A mixture of 6/Ada (170 mg, 0.22 mmol) and 10% HCl (5 ml) in MeOH (20 ml) was heated to reflux for 3 h. The progress of the reaction was monitored by TLC. The solvent was evaporated and sat. aq. NaHCO 3 (20 ml) was added to the resulting mixture to obtain a precipitate. The precipitate was filtered off and washed with water and petroleum ether. The crude product was purified by repeated crystallization from EtOAc. Colorless solid; Yield: 90 mg (60 %). 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.68 (d, 3 J(H,H) = 8.6, 2H, Ar-H), 7.40 (s, 1H, Ar-H), 7.25 (s, 2H, Ar-H), 7.21-7.18 (m, 2H, Ar-H, overlapped by pyridine), 4.64-4.44 (m, 6H, OCH, OCH 2 ), 4.30-4.22 (m, 4H, OCH 2 ), 4.16 (t, 3 J(H,H) = 6.6, 2H, OCH 2 CH 2 ), 4.12 (t, 3 J(H,H) = 6.5, 2H, CH 2 COO), 1.98 (d, 3 J(H,H) = 2.9, 6H, CH 2 ), 1.90 (s, 3H, CH 2 ), 1.80 (quint, 3 J(H,H) = 7.1, 2H, OCH 2 CH 2 ), 1.51-1.44 (m, 2H, CH 2 ), 1.36-1.20 (m, 10H, CH 2 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 177.2, 159.1, 150.3, 149.3, 134.9, 134.0, 128.2 (2C), 119.7, 115.8 (2C), 115.6, 113.5, 72.7, 71.7 (2C), 71.2, 69.8, 64.8, 64.5, 64.5, 41.2, 39.5 (2C), 36.9 (2C), 30.1, 30.0, 30.0, 29.9, 29.7, 29.3, 28.6, 26.6, 26.4. EA calc. for C 40 H 58 O 9 0.25H 2 O: C 69.89 %, H 8.58 %; found: C 69.89 %, H 8.50%. 2.3 Synthesis of Tmp 2-(12-Bromododecyloxy)-1,3,5-trimethylbenzene A mixture of 2,4,6-trimethylphenol (1.5 g, 11 mmol), 1,12-dibromododecane (5.4 g, 16.5 mmol), K 2 CO 3 (7.6 g, 55 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by crystallization from methanol. Colorless oil; Yield: 1.9 g (45 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 6.79 (s, 2H, Ar-H), 3.70 (t, 3 J(H,H) = 6.6, 2H, OCH 2 ), 3.39 (t, 3 J(H,H) = 6.9, 2H, CH 2 Br), 2.22 (s, 9H, CH 3 ), 1.88-1.73 (m, 4H, CH 2 ), 1.51-1.24 (m, 16H, CH 2 ). 2,2-Dimethyl-4-[4 -(2,2-dimethyl-1,3-dioxolan-4-yloxymethyl)]-2-(12- mesityloxydodecyloxy)biphenyl-1,3-dioxolane 6/Tmp A mixture of 5 (240 mg, 0.64 mmol), 2-(12-bromododecyloxy)-1,3,5-trimethylbenzene (250 mg, 0.58 mmol), K 2 CO 3 (400 mg, 2.9 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless oil; Yield: 320 mg (75 %); mp. 63-65 C. 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.44 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.04-7.02 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.9, 3H, Ar-H), 4.50-4.45 (m, 2H, OCH), 4.18-4.06 (m, 4H, OCH 2 ), 4.03-3.89 (m, 6H, OCH 2 ), 3.70 (t, 3 J(H,H) = 6.6, 2H, OCH 2 ), 2.21 (s, 9H, CH 3 ), 1.84-1.72 (m, 4H, S13
CH 2 ), 1.50-1.43 (m, 4H, CH 2 ), 1.46 (m, 3H, CH 3 ), 1.45 (m, 3H, CH 3 ), 1.40 (s, 3H, CH 3 ), 1.39 (s, 3H, CH 3 ), 1.36-1.27 (m, 12H, CH 2 ). 3-[4 -(2,3-Dihydroxypropoxy)-3-(12-mesityloxydodecyloxy)biphenyl-4-yloxy]propane- 1,2-diol Tmp A mixture of 6/Tmp (310 mg, 0.42 mmol) and 10% HCl (5 ml) in MeOH (20 ml) was heated to reflux for 3 h. The progress of the reaction was monitored by TLC. The solvent was evaporated and sat. aq. NaHCO 3 (20 ml) was added to the resulting mixture to obtain a precipitate. The precipitate was filtered off and washed with water and petroleum ether. The crude product was purified by repeated crystallization from methanol. Colorless solid; Yield: 140 mg (51 %). 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.68 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.40 (s, 1H, Ar-H), 7.25 (s, 2H, Ar-H), 7.21-7.18 (m, 2H, Ar-H, overlapped by pyridine), 6.82 (s, 2H, Ar-H), 4.64-4.44 (m, 6H, OCH, OCH 2 ), 4.33-4.22 (m, 4H, OCH 2 ), 4.12 (t, 3 J(H,H) = 6.5, 2H, OCH 2 CH 2 ), 3.72 (t, 3 J(H,H) = 6.5, 2H, OCH 2 CH 2 ), 2.30 (s, 6H, CH 3 ), 2.19 (s, 3H, CH 3 ), 1.85-1.76 (m, 4H, OCH 2 CH 2 ), 1.54-1.45 (m, 4H, CH 2 ), 1.34-1.23 (m, 12H, CH 2 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.1, 154.5, 150.3, 149.2, 134.8, 134.0, 132.8, 130.6 (2C), 129.8 (4C), 128.2 (2C), 119.6, 115.5, 113.5, 72.6, 72.6, 71.6 (2C), 71.2, 69.7, 64.7, 64.5, 31.0, 30.1, 30.1, 30.1 (2C), 30.0, 29.9, 26.7, 26.6, 20.8, 16.5 (3C), EA calc. for C 39 H 56 O 8 0.25H 2 O: C 71.26 %, H 8.66 %; found: C 71.02 %, H 8.41 %. 2.4 Synthesis of Ment* (1R,2S,4S)-2-(12-Bromododecyloxy)-1-isopropyl-4-methylcyclohexane A mixture of (1S,2R,5S)-2-isopropyl-5-methylcyclohexane-1-ol (1.0 g, 6.40 mmol), 1,12- dibromododecane (4.2 g, 12.8 mmol) and NaH (0.18 g, 7.68 mmol) in dioxane (50 ml) was stirred under reflux for 4 h. After cooling to room temperature water (20 ml) was added dropwise and the aq. layer was extracted by diethyl ether (2 x 50 ml). The combined organic layers where washed with sat. aq. NaHCO 3, water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless liquid; Yield: 1.4 g (74 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 3.61-3.55 (m, 1H, OCH 2 ), 3.38 (t, 3 J(H,H) = 6.8, 2H, CH 2 Br), 3.25-3.20 (m, 1H, OCH 2 ), 2.97 (dt, 1H, 3 J(H,H) = 10.5, 4 J(H,H) = 4.1, OCH), 2.24-2.16 (m, 1H, CH), 2.09-2.04 (m, 1H, CH), 1.83 (quint, 3 J(H,H) = 7.1, 2H, CH 2 CH 2 O), 1.65-1.46 (m, 5H, CH, CH 2 ), 1.42-1.22 (m, 18H, CH, CH 2 ), 0.89 (d, 3 J(H,H) = 6.5, 3H, CH 3 ), 0.87 (d, 3 J(H,H) = 7.1, 3H, CH 3 ), 0.75 (d, 3 J(H,H) = 7.0, 3H, CH 3 ). 4,4 -Bis(2,2-dimethyl-1,3-dioxolane-4-ylmethoxy)-3-[12-(1R,2S,4S)- menthyloxydodecyloxy]biphenyl 6/Ment* A mixture of 5 (200 mg, 0.46 mmol), (1R,2S,4S)-2-(12-bromododecyloxy)-1-isopropyl-4- methylcyclohexane (197 mg, 0.49 mmol), K 2 CO 3 (318 mg, 2.3 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) S14
and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless oil; Yield: 260 mg (75 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.43 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.03-7.01 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.6, 3H, Ar-H), 4.47 (quint, 3 J(H,H) = 5.9, 2H, OCH), 4.18-4.05 (m, 4H, OCH 2 ), 4.03-3.88 (m, 6H, OCH 2 ), 3.61-3.20 (m, 1H, OCH 2 ), 2.96 (dt, 1H, 3 J(H,H) = 10.5, 4 J(H,H) = 4.1, OCH), 2.24-2.16 (m, 1H, CH), 2.09-2.04 (m, 1H, CH), 1.80 (quint, 3 J(H,H) = 7.1, 2H, CH 2 CH 2 O), 1.69-1.50 (m, 5H, CH, CH 2 ), 1.46 (s, 3H, CH 3 ), 1.45 (s, 3H, CH 3 ), 1.39 (s, 3H, CH 3 ), 1.38 (s, 3H, CH 3 ), 1.35-1.25 (m, 15H, CH, CH 2 ), 0.89 (d, 3 J(H,H) = 6.6, 3H, CH 3 ), 0.87 (d, 3 J(H,H) = 7.1, 3H, CH 3 ), 0.74 (d, 3 J(H,H) = 7.0, 3H, CH 3 ). 3-{4 -(2,3-Dihydroxypropoxy)-3-[12-(1R,2S,4S)-menthyloxydodecyloxy]biphenyl-4- yloxy}propane-1,2-diol Ment* A mixture of 6/Ment* (250 mg, 0.33 mmol) and 10% HCl (5 ml) in MeOH (20 ml) was heated to reflux for 3 h. The progress of the reaction was monitored by TLC. The solvent was evaporated and the residue was taken up in EtOAc (50 ml). After washing with sat. aq. NaHCO 3, water and brine the solvent was evaporated and the crude product was purified by repeated crystallization from EtOAc. Colorless solid; Yield: 120 mg (54 %). 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.67 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.39 (s, 1H, Ar-H), 7.24 (s, 2H, Ar-H), 7.20-7.19 (m, 2H, Ar-H, overlapped by pyridine), 4.63-4.43 (m, 6H, OCH, OCH 2 ), 4.32-4.19 (m, 4H, OCH 2 ), 4.11 (t, 3 J(H,H) = 6.5, 2H, PhOCH 2 CH 2 ), 3.67-3.25 (m, 1H, OCH 2 ), 3.01 (dt, 1H, 3 J(H,H) = 10.5, 4 J(H,H) = 4.2, OCH), 2.43-2.36 (m, 1H, CH), 2.16-2.10 (m, 1H, CH), 1.80 (quint, 3 J(H,H) = 5.6, 2H, CH 2 CH 2 O), 1.66-1.39 (m, 8H, CH, CH 2 ), 1.305-1.23 (m, 13H, CH, CH 2 ), 0.89 (d, 3 J(H,H) = 6.7, 3H, CH 3 ), 0.88 (d, 3 J(H,H) = 6.1, 3H, CH 3 ), 0.84 (d, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (methanol-d 4, J/Hz, 125 MHz): d 159.1, 150.3, 149.2, 134.8, 134.0, 128.2 (2C), 119.7, 115.7, 115.5 (2C), 113.5, 79.2, 72.7, 71.6 (2C), 71.2, 69.8, 68.5, 64.7, 64.5, 49.0, 41.1, 35.1, 31.8, 31.0, 30.1, 30.1, 30.1 (2C), 30.0, 29.9, 26.9, 26.6, 26.3, 24.1, 24.1, 22.7, 21.4, 17.0. [a] D 20 = -26.2 (THF, 4.0 mg ml -1 ). EA calc. for C 40 H 64 O 8 0.5H 2 O: C 70.45 %, H 9.61 %; gef.: C 70.62 %, H 9.77 %. 2.5 Synthesis of Chol*n Cholest-5-en-3ß-tosylate [5] To a solution of cholest-5-en-3ß-ol (5.0 g, 12.9 mmol) in pyridine (30 ml) was added 4- methylbenzenesulfonyl chloride (4.93 g, 25.8 mmol) under an argon atmosphere. The solution was left standing overnight at room temperature. Diethylether was added (100 ml) and the resulting solution was washed with water (3 x 50 ml). After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent the crude product was purified by crystallization from acetone. Colorless solid; Yield: 4.5 g (65 %); mp 130-132 C (lit., [5] 132-134 C). 1 H NMR (CDCl 3, J/Hz, 200 MHz) d 7.77 (d, 3 J(H,H) = 8.4, 2H, Ar-H), 7.30 (d, 3 J(H,H) = 8.0, 2H, Ar- H), 5.29-5.26 (m, 1H, CH=C), 4.30 (quint, 3 J(H,H) = 5.6, 1H, OCH), 2.42 (s, 3H, PhCH 3 ), S15
2.29-2.19 (m, 2H, CH 2 ), 2.02-1.69 (m., 6H, CH 2 ), 1.53-0.82 (m, 33H, CH, CH 2, CH 3 ), 0.63 (s, 3H, CH 3 ). 6-Brom-1-(cholest-5-en-3ß-oxy)hexane [6] A solution of cholest-5-en-3ß-tosylate (2.5 g, 4.62 mmol) and 6-bromhexane-1-ol (2.32 g, 23.1 mmol) in anhydrous dioxane (30 ml) was stirred for 4 h at reflux. The solvent was evaporated under reduced pressure, the residue was taken up in diethyl ether (100 ml) and washed with sat. aq. NaHCO 3, water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent the crude product was purified by column chromatography (silica gel, chloroform) and crystallization from EtOAc. Colorless solid; Yield: 0.43 g (17 %); mp 96-98 C. 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 5.33-5.32 (m, 1H, CH=C), 3.43 (t, 3 J(H,H) = 6.7, 2H, OCH 2 ), 3.39 (t, 3 J(H,H) = 6.8, 2H, BrCH 2 ), 3.14-3.06 (m, 1H, OCH), 2.35-2.13 (m, 2H, CH 2 ), 2.03-1.76 (m., 7H, CH 2 ), 1.59-1.20 (m, 18H, CH,CH 2 ), 1.17-0.83 (m, 22H, CH, CH 2, CH 3 ), 0.66 (s, 3H, CH 3 ). 4,4 -Bis(2,2-dimethyl-1,3-dioxolane-4-ylmethoxy)-3-[6-(cholest-5-en-3ß-oxy)hexyloxy]- biphenyl 6/Chol* A mixture of 5 (170 mg, 0.41 mmol), 6-brom-1-(cholest-5-en-3ß-oxy)hexane (228 mg, 0.41 mmol), K 2 CO 3 (272 mg, 1.97 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless oil; Yield: 320 mg (91 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.43 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 7.03-7.01 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.8, 3H, Ar-H), 5.32-5.31 (m, 1H, CH=C), 4.51-4.44 (m, 2H, OCH), 4.18-4.06 (m, 4H, OCH 2 ), 4.03-3.88 (m, 6H, OCH 2 ), 3.44 (t, 3 J(H,H) = 6.6, 2H, OCH 2 ), 3.14-3.06 (m, 1H, OCH), 2.36-2.31 (m, 1H, CH), 2.20-2.13 (m, 1H, CH), 2.01-1.91 (m, 2H, CH 2 ), 1.89-1.76 (m, 5H, CH, CH 2 ), 1.61-0.98 (m, 41H, CH,CH 2, CH 3 ), 0.90 (d, 3 J(H,H) = 6.5, 4H, CH, CH 3 ), 0.85 (dd, 3 J(H,H) = 6.6, 4 J(H,H) = 1.7, 6H, CH 3 ), 0.66 (s, 3H, CH 3 ). 3-{3-[6-(Cholest-5-en-3ß-oxy)hexyloxy]-4 -(2,3-dihydroxypropoxy)biphenyl-4- yloxy}propane-1,2-diol Chol*6 A mixture of 6/Chol* (300 mg, 0.33 mmol) and 10% HCl (5 ml) in MeOH (20 ml) was heated to reflux for 3 h. The progress of the reaction was monitored by TLC. The solvent was evaporated and the residue was taken up in EtOAc (50 ml). After washing with sat. aq. NaHCO 3, water and brine the solvent was evaporated and the crude product was purified by repeated crystallization from EtOAc. Colorless solid; Yield: 180 mg (66 %). 1 H NMR (pyridine-d 5, J/Hz, 400 MHz): d 7.68 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.39 (s, 1H, Ar-H), 7.25 (s, 2H, Ar-H), 7.21-7.19 (m, 2H, Ar-H, overlapped by pyridine), 5.45-5.44 (m, 1H, CH=C), 4.64-4.44 (m, 6H, OCH, OCH 2 ), 4.30-4.23 (m, 4H, OCH 2 ), 4.10 (t, 3 J(H,H) = 6.5, 2H, OCH 2 ), 3.51-3.47 (m, 2H, OCH 2 ), 3.28-3.20 (m, 1H, CH), 2.58-2.53 (m, 1H, CH), 2.40-2.33 S16
(m, 1H, CH), 2.02-1.93 (m, 3H, CH, CH 2 ), 1.84-1.77 (m, 4H, CH 2 ), 1.66-1.39 (m, 16H, CH, CH 2, CH 3 ), 1.27-0.93 (m, 17H, CH, CH 2, CH 3 ), 0.90 (s, 3H, CH 3 ), 0.88 (s, 3H, CH 3 ), 0.67 (s, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz) d 159.1, 149.2, 141.4, 134.9, 134.9, 134.0, 128.2 (2C), 121.7, 119.7, 115.8, 115.6 (2C), 113.6, 79.3, 72.7, 71.6 (2C), 71.2, 69.7 (2C), 68.1, 64.7, 64.5 (2C), 57.1, 56.7, 50.7, 42.8, 40.3, 40.0, 40.0, 37.8, 37.4, 36.7, 36.2, 32.5, 32.4, 30.9, 30.0, 29.3, 28.7, 28.4, 26.6, 26.5, 24.8, 24.4, 23.1, 22.9, 21.6, 19.8, 19.2, 12.3, 7.6. [a] D 20 = -8.6 (THF, 2.9 mg ml -1 ). EA calc. for C 51 H 78 O 8 0.25H 2 O: C 74.37 %, H 9.61 %; found C 74.33 %; H 9.99 %. 3-{3-[11-(Cholest-5-en-3ß-oxy)undecyloxy]-4 -(2,3-dihydroxypropoxy)biphenyl-4- yloxy}propane-1,2-diol Chol*11 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.44 (d, 3 J(H,H) = 8.5, 2H, Ar-H), 7.04-7.02 (m, 2H, Ar-H), 6.95 (d, 3 J(H,H) = 8.8, 3H, Ar-H), 5.32 (bs, 1H, CH=C), 4.21-4.01 (m, 8H, OCH, OCH 2 ), 3.87-3.73 (m, 4H, OCH 2 ), 3.42 (t, 3 J(H,H) = 6.8, 2H, OCH 2 ), 3.13-3.07 (m, 1H, OCH), 2.35-2.32 (m, 1H, CH), 2.20-2.16 (m, 1H, CH), 2.00-1.81 (m, 8H, CH, CH 2 ), 1.56-1.41 (m, 12H, CH, CH 2, CH 3 ), 1.36-1.27 (m, 18H, CH, CH 2, CH 3 ), 1.15-1.02 (m, 8H, CH, CH 2, CH 3 ), 0.98 (s, 3H, CH 3 ), 0.89 (d, 3 J(H,H) = 6.3, 3H, CH 3 ), 0.84 (d, 3 J(H,H) = 6.5, 6H, CH 3 ), 0.65 (s, 3H, CH 3 ). 13 C NMR (CDCl 3, J/Hz, 100 MHz): d 157.8, 149.8, 147.6, 141.2, 135.5, 134.2, 127.9 (2C), 121.3, 119.3, 116.3, 114.9 (2C), 112.3, 79.0, 73.3, 70.4, 70.0 (2C), 69.5, 69.2 (2C), 68.1, 64.0, 63.7 (2C), 56.9, 56.3, 50.4, 42.4, 39.9, 39.6, 39.3, 37.4, 37.0, 36.3, 35.8, 32.0, 30.3, 29.6, 29.5, 29.5, 29.3, 28.6, 28.2, 28.0, 26.2, 26.0, 24.3, 23.9, 22.8, 22.5, 21.2, 19.4, 18.8, 11.9. [a] D 20 = -11.2 (THF, 3.5 mg ml -1 ). EA calc. for C 56 H 88 O 8 : C 75.63 %, H 9.97 %; found C 75.91 %; H 9.93 %. 2.6 3-[4'-(2,3-Dihydroxypropoxy)-3-(2-decyldodecyloxy)biphenyl-4-yloxy]propane-1,2- diol Bra22 The synthesis of this compound will be described in a separate Paper. [7] 1 H NMR (pyridined 5, J/Hz, 400 MHz): d = 7.69 (d, 3 J(H,H) = 8.4, 2H, Ar-H), 7.48 (s, 1H, Ar-H), 7.19 (m, 4H, Ar-H), 6.87 (d, 3 J(H,H) = 4.80, 1H, OH), 6.67 (d, 3 J(H,H) = 5.2, 1H, OH), 6.48 (t, 3 J(H,H) = 5.6, 1H, OH), 6.36 (t, 3 J(H,H) = 5.6, 1H, OH), 4.64-4.45 (m, 6H, OCH, OCH 2 ), 4.35-4.21 (m, 4H, OCH 2 ), 4.13 (d, 3 J(H,H) = 5.6, 2H, OCH 2 CH 2 ), 1.96 (m, 1H, CH), 1.66-1.53 (m, 2H, CH 2 ), 1.44 (m, 4H, CH 2 ), 1.24 (m, 30H, CH 2 ), 0.85 (t, 3 J(H,H) = 6.9, 3H, CH 3 ). 13 C NMR (pyridine-d 5, J/Hz, 100 MHz): d 159.2, 150.7, 149.3, 135.0, 134.0, 128.3 (2C), 119.7, 115.9, 115.6 (2C), 113.5, 72.8, 72.6, 71.7, 71.7, 71.2, 64.7, 64.5, 38.9, 32.3 (2C), 32.1 (2C), 30.6 (2C), 30.2 (2C), 30.1 (2C), 30.1 (2C), 29.8 (2C), 27.5 (2C), 23.2 (2C), 14.5 (2C). EA calc. for C 40 H 66 O 7 0.5H 2 O: C 71.92 %, H 10.11 %; found C 71.98 %; H 10.06 %. 2.7 Synthesis of Benzn/m 6-Bromohexyl 4-dodecyloxybenzoate 4-Dodecyloxybenzoic acid (2.0 g, 6.53 mmol), 6-bromohexane-1-ol (1.3 g, 7.18 mmol), DCC (1.48 g, 7.18 mmol) and DMAP (0.05 g, 0.72 mmol) were dissolved in anhydrous CH 2 Cl 2 (50 S17
ml) and stirred at room temperature for 24 h. The reaction mixture was then filtered trough silica gel. After evaporation of the solvent the crude product was purified by column chromatography (silica gel, chloroform) and crystallization from petroleum ether. Colorless solid; Yield: 2.02 g (66 %); mp 36-38 C. 1 H NMR (CDCl 3, J/Hz, 400 MHz) d 7.95 (d, 3 J(H,H) = 8.4, 2H, Ar-H), 6.88 (d, 3 J(H,H) = 8.4, 2H, Ar-H), 4.27 (t, 3 J(H,H) = 6.5, 2H, COOCH 2 ), 3.98 (d, 3 J(H,H) = 6.6, 4H, OCH 2 ), 3.40 (t, 3 J(H,H) = 6.8, 2H, CH 2 Br), 1.88 (quint, 3 J(H,H) = 6.9, 2H, CH 2 CH 2 Br), 1.77 (quint, 3 J(H,H) = 7.3, 4H, OCH 2 CH 2, COOCH 2 CH 2 ), 1.54-1.40 (m, 6H, CH 2 ), 1.35-1.20 (m, 18H, CH 2 ), 0.87 (t, 3 J(H,H) = 6.8, 3H, CH 3 ). 4,4 -Bis(2,2-dimethyl-1,3-dioxolane-4-ylmethoxy)biphenyl-3-yloxyhexyl 4-dodecyloxybenzoate A mixture of 4,4 -bis(2,2-dimethyl-1,3-dioxolane-4-ylmethoxy)biphenyl-3-ol 5 (250 mg, 0.58 mmol), 6-bromohexyl 4-dodecyloxybenzoate (268 mg, 0.61 mmol), K 2 CO 3 (401 mg, 2.90 mmol) and tetrabutylammonium iodide (5 mg) in anhydrous DMF (50 ml) was stirred at 80 C for 6 h. After cooling to room temperature, the reaction mixture was poured into ice-water (50 ml) and the aqueous layer was extracted with diethyl ether (3 x 50 ml). The combined organic layers were washed with sat. aq. LiCl water and brine. After drying over anhydrous Na 2 SO 4, filtration and evaporation of the solvent, the crude product was purified by preparative thin layer chromatography (silica gel, petroleum ether/chloroform, 1:2, v/v). Colorless liquid; Yield: 430 mg (91 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz) d 7.95 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 7.44 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.04-7.02 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.7, 3H, Ar-H), 6.86 (d, 3 J(H,H) = 8.9, 2H, Ar-H), 4.51-4.45 (m, 2H, OCH), 4.28 (t, 3 J(H,H) = 6.6, 2H, COOCH 2 ), 4.18-3.88 (m, 12H, OCH 2 ), 1.88-1.82 (m, 2H, COOCH 2 CH 2 ), 1.81-1.74 (m, 4H, OCH 2 CH 2 ), 1.60-1.50 (m, 4H, CH 2 ), 1.46 (m, 3H, CH 3 ), 1.45 (m, 3H, CH 3 ), 1.40 (m, 3H, CH 3 ), 1.38 (s, 3H, CH 3 ), 1.35-1.22 (m, 18H, CH 2 ), 0.87 (t, 3 J(H,H) = 6.8, 3H, CH 3 ). 4,4 -Bis(2,3-dihydroxypropyloxy)biphenyl-3-yloxyhexyl 4-dodecyloxybenzoate Benz6/1 A mixture of 4,4 -Bis(2,2-dimethyl-1,3-dioxolane-4-ylmethoxy)biphenyl-3-yloxyhexyl 4- dodecyloxybenzoate (430 mg, 0.52 mmol) and 10% HCl (5 ml) in MeOH (20 ml) was heated to reflux for 3 h. The progress of the reaction was monitored by TLC. The solvent was evaporated and sat. aq. NaHCO 3 (20 ml) was added to the resulting mixture to obtain a precipitate. The precipitate was filtered off and washed with water and petroleum ether. The crude product was purified by repeated crystallization from EtOAc/petroleum ether. Colorless solid; Yield: 230 mg (59 %). 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.95 (d, 3 J(H,H) = 8.4, 2H, Ar-H), 7.43 (d, 3 J(H,H) = 8.5, 2H, Ar-H), 7.04-7.01 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.3, 3H, Ar-H), 6.86 (d, 3 J(H,H) = 8.5, 2H, Ar-H), 4.29 (t, 3 J(H,H) = 6.6, 2H, COOCH 2 ), 4.19-4.02 (m, 8H, OCH, OCH 2 ), 3.97 (t, 3 J(H,H) = 6.5, 2H, OCH 2 CH 2 ), 3.86-3.75 (m, 4H, OCH, OCH 2 ), 3.24 (bs, 1H, OH), 2.63 (bs, 2H, OH), 2.05 (bs, 1H, OH), 1.89-1.73 (m, 6H, CH 2 ), 1.62-1.52 (m, 6H, CH 2 ), 1.45-1.41 (m, 2H, CH 2 ), 1.35-1.23 (m, 14H, CH 2 ), 0.86 (d, 3 J(H,H) = 6.5, 3H, CH 3 ). 13 C NMR (CDCl 3, J/Hz, 100 MHz): d 166.5, 162.8, 157.7, 149.4, 147.3, 135.3, 134.1, 131.4 (2C), 127.9 (2C), 122.5, 119.2, 115.7, 114.8 (2C), 114.0 (2C), 111.8, S18
73.1, 70.4, 69.9, 69.4, 68.8, 68.3, 64.5, 64.0, 63.7, 32.0, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4, 29.2 (2C), 28.7, 26.1, 25.8, 25.8, 22.8, 14.2. EA calc. for C 43 H 62 O 10 0.25H 2 O: C 69.47 %, H 8.47 %; found: C 69.40 %, H 8.88 %. 4,4 -Bis(2,3-dihydroxypropyloxy)biphenyl-3-yloxyhexyl 3,4-didodecyloxybenzoate Benz6/2 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.60 (dd, 3 J(H,H) = 8.5, 4 J(H,H) = 2.0, 1H, Ar-H), 7.51 (d, 4 J(H,H) = 1.9, 1H, Ar-H), 7.43 (d, 3 J(H,H) = 8.8, 2H, Ar-H), 7.05-7.02 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.7, 3H, Ar-H), 6.82 (d, 3 J(H,H) = 8.5, 1H, Ar-H), 4.29 (t, 3 J(H,H) = 6.7, 2H, COOCH 2 ), 4.13-3.99 (m, 12H, OCH, OCH 2 ), 3.84-3.73 (m, 4H, OCH, OCH 2 ), 1.84-1.76 (m, 8H, CH 2 ), 1.60-1.51 (m, 6H, CH 2 ), 1.48-1.41 (m, 6H, CH 2 ), 1.35-1.22 (m, 28H, CH 2 ), 0.86 (d, 3 J(H,H) = 6.7, 6H, CH 3 ). 13 C NMR (CDCl 3, J/Hz, 100 MHz): d 166.5, 157.6, 153.1, 149.4, 148.4, 147.3, 135.3, 134.1, 127.9 (2C), 123.4, 122.6, 119.2, 115.7, 114.8, 114.4 (2C), 112.0, 111.8, 73.1, 70.4, 69.9, 69.4 (2C), 69.0, 68.8, 64.6, 64.0, 63.7, 32.0 (2C), 29.8 (2C), 29.7 (2C), 29.7 (2C), 29.7 (2C), 29.5, 29.5 (2C), 29.4, 29.3 (2C), 29.2, 29.2, 28.7, 26.1, 26.1, 25.8, 22.8 (2C), 14.2 (2C). EA calc. for C 55 H 86 O 11 : C 71.55 %, H 9.39 %; found: C 71.69 %, H 9.51 %. 4,4 -Bis(2,3-dihydroxypropyloxy)biphenyl-3-yloxyhexyl 3,4,5-tridodecyloxybenzoate Benz6/3 1 H NMR (CDCl 3, J/Hz, 400 MHz): d 7.42 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.24-7.23 (m, 2H, Ar-H), 7.04-7.02 (m, 2H, Ar-H), 6.93 (d, 3 J(H,H) = 8.7, 3H, Ar-H), 4.29 (t, 3 J(H,H) = 6.8, 2H, COOCH 2 ), 4.19-3.96 (m, 14H, OCH, OCH 2 ), 3.86-3.73 (m, 4H, OCH, OCH 2 ), 1.88-1.69 (m, 10H, CH 2 ), 1.60-1.41 (m, 12H, CH 2 ), 1.34-1.20 (m, 46H, CH 2 ), 0.86 (d, 3 J(H,H) = 6.8, 9H, CH 3 ). 13 C NMR (CDCl 3, J/Hz, 100 MHz): d 166.5, 157.7, 152.7 (2C), 149.4, 147.3, 142.4, 135.3, 134.0, 127.9 (2C), 124.9, 119.2, 115.7, 114.8 (2C), 111.8, 108.1, 73.5, 73.1 (2C), 70.4, 69.9, 69.4, 69.3 (2C), 68.8, 64.9, 64.0, 63.7 (2C), 32.0, 32.0, 30.4, 29.8, 29.8, 29.8, 29.8, 29.8, 29.8, 29.7, 29.7, 29.5, 29.5, 29.5, 29.3, 28.8, 26.2, 26.2, 25.8, 25.8, 22.8, 14.2 (3C). EA calc. for C 67 H 110 O 12 : C 72.66 %, H 10.01 %; found: C 72.94 %, H 10.11 %. 4,4 -Bis(2,3-dihydroxypropyloxy)biphenyl-3-yloxyundecyl 3,4,5-tridodecyloxybenzoate Benz11/3 1 H-NMR (CDCl 3, J/Hz, 400 MHz): d 7.43 (d, 3 J(H,H) = 8.7, 2H, Ar-H), 7.23 (s, 2H, Ar-H), 7.04-7.02 (m, 2H, Ar-H), 6.94 (d, 3 J(H,H) = 8.7, 3H, Ar-H), 4.26 (t, 3 J(H,H) = 6.8, 2H, COOCH 2 ), 4.21-3.97 (m, 14H, OCH, OCH 2 ), 3.87-3.77 (m, 4H, OCH 2 ), 3.25 (bs, 1H, OH), 2.65 (bs, 1H, OH), 2.53 (bs, 1H, OH), 2.07 (s, 1H, OH), 1.84-1.68 (m, 10H, OCH 2 CH 2, COOCH 2 CH 2 ), 1.49-1.41 (m, 8H, CH 2 ), 1.35-1.24 (m, 60H, CH 2 ), 0.86 (t, 3 J(H,H) = 6.8, 9H, CH 3 ). 13 C NMR (CDCl 3, J/Hz, 100 MHz): d 166.3, 157.6, 152.6 (2C), 149.5, 147.2, 142.3, 135.3, 134.0, 127.9 (2C), 124.9, 119.1, 115.8, 114.7 (2C), 111.8, 108.0 (2C), 73.5, 73.3 (2C), 70.3, 69.8, 69.3, 69.2 (2C), 69.0, 65.1, 64.0, 63.6 (2C), 32.0, 30.4, 29.8, 29.8, 29.8, 29.8, 29.8, 29.8, 29.7, 29.7, 29.6, 29.6, 29.6, 29.5, 29.5, 29.5, 29.4, 29.4, 28.9, 26.2, 26.2, 26.1, 22.8, 14.2 (3C). EA calc. for C 72 H 120 O 12 0.25H 2 O: C 73.15 %, H 10.27 %; found: C 72.97 %, H 10.02 %. S19
3. References [1] A. Immirzi and B. Perini, Acta Cryst. Sect. A, 1977, 33, 216-218. [2] A. I. Kitaigorodski, in Molekülkristalle, Akademieverlag Berlin, 1979. [3] B. Chen, U. Baumeister, G. Pelzl, M.K. Das, X. B. Zeng, G. Ungar, C. Tschierske, J. Am. Chem. Soc. 2005, 127, 16578-16591. [4] Z. Xin, G. Liu, C. Abad-Zapatero, Z. Pei, B. G. Szczepankiewicz, X. Li, T. Zhang, C. W. Hutchins, P. J. Hajduk, S. J. Ballaron, M. A. Stashko, Bioorg. Med. Chem. Lett. 2003, 13, 3947-3950. [5] H. J. Buchanan, P. J. Cox, S. M. S. V. Doidge-Harrison, R. A. Howie, M. Jaspars, J. L. Wardell, J. Chem. Soc. Perkin Trans. 1 1997, 24, 3657-3664. [6] Y. Krishnan-Ghosh, R. S. Gopalan, G. U. Kulkarni, S. Bhattacharya, J. Mol. Struct. 2001, 560, 345-356. [7] M. Prehm, X. Cheng, C. Enders, S. Diele, M. K. Das, U. Baumeister, F. Liu, X. Zeng, G. Ungar, C. Tschierske manuscript in preparation. S20