Dendritic Biomimicry
979±986
(CH2Cl2/EtOAc 90:10); 1H NMR (500 MHz, CDCl3): d 7.61 (d,
3J(H,H) 8.0 Hz, 1H; ArH), 7.22 (d, 3J(H,H) 8.0 Hz, 1H; ArH), 7.16
chemistry. S.K. was supported by the Erasmus/Socrates programme and the
Â
Conseil Regional dꢁAlsace. L.M. was supported by the Erasmus pro-
3
3
(t, J(H,H) 7.5 Hz, 1H; ArH), 7.05 (t, J(H,H) 7.5 Hz, 1H; ArH), 6.83
gramme. We thank the NMR service of the University of York for
measurement of 500 MHz NMR spectra and T. Dransfield (University of
York) for mass spectral analysis.
(s, 1H; ArH), 5.31 (s, 1H; NH), 5.16 (s, 1H; NH), 4.23 (s, 1H; CHNH), 3.67
(s, 3H; NCH3), 3.10 (m, 1H; CH2CHNH), 1.37 (s, 9H; (CH3)3CO), 1.06 (s,
13
9H; (CH3)3CNH); C NMR (125 MHz, CDCl3): d 170.6 (C O), 155.6
(C O), 137.1, 128.0, 127.9, 121.9, 119.3, 119.2, 109.6, 109.3 (all Ar), 79.88
((CH3)3CO), 55.53 (CHCO), 51.10 ((CH3)3CN), 32.67 (NCH3), 28.66
(CH2CHCO), 28.48 (C(CH3)3), 28.37 (C(CH3)3); IR (KBr) nÄ 3341m,
3055w, 2973m, 2930m, 1658s, 1543s, 1475m, 1454m, 1391m, 1365m, 1323w,
1303w, 1270m, 1250m, 1224w, 1175m, 1056w, 1013w, 863w, 738m cm 1. MS
[1] a) M. R. Eftink, Methods Biochem. Anal. 1991, 35, 127 ± 205, and
references therein; b) P. R. Callis, Methods Enzymol. 1997, 278, 113 ±
150, and references therein; c) D. Creed, Photochem. Photobiol. 1984,
39, 537 ± 562, and references therein.
[2] P. R. Callis, B. K. Burgess, J. Phys. Chem. B, 1997, 101, 9429 ± 9432, and
references therein.
(CI): m/z: 374 (100) [MH] , 318 (65) [MH C(CH3)3] , 274 (100)
[MH CONHC(CH3)3] , 171 (41), 144 (31) [indole CH2] ; HRMS
(FAB) (C21H32N3O3 H) [MH] : calculated 374.2444, found 374.2446.
[3] For some selected examples see: a) H. Lami, N. Glasser, J. Chem.
Compound G1(NMe): Method as for G1(NH), only with dry THF as
solvent and 6 as carboxylic acid. Work-up: when reaction was complete
(44 h), the mixture was filtered under gravity and the solvent was
evaporated. CH2Cl2 (15 mL) was added to the yellow oil residue, which
was then washed with sat. aq. NaHCO3 (2 Â 15 mL) and H2O (2 Â 15 mL).
The organic layer was dried over MgSO4, filtered under gravity and
evaporated (rotary evaporation and vacuum line) to give the crude product
as a viscous yellow oil. Purification by column chromatography (SiO2,
CH2Cl2/MeOH 90:10) gave the pure product as a viscous yellow oil. Yield:
46%; Rf 0.80 (CH2Cl2/MeOH 90:10); 1H NMR (500 MHz, CDCl3): d
7.62 (d, 3J(H,H) 7.5 Hz, 1H; ArH), 7.19 (d, 3J(H,H) 8.0 Hz, 1H; ArH),
7.12 (t, 3J(H,H) 7.8 Hz, 1H; ArH), 7.03 (t, 3J(H,H) 7.8 Hz, 2H; ArH),
6.90 (s, 1H; ArH), 5.95 (s, 1H; NH), 5.22 (s, 1H; NH), 4.31 (m, 1H;
CHNH), 3.60 ± 3.40 (m, 24H; CH2O, CO2CH3, NCH3), 3.10 (m, 2H;
CH2CHNH), 2.39 (t, 3J(H,H) 6.5 Hz, 6H; CH2CO2Me), 1.30 (s, 9H;
(CH3)3CO); 13C NMR (125 MHz, CDCl3): d 172.0 (CO2Me), 171.5
Â
Phys. 1986, 84, 597 ± 604; b) L. Serrano-Andres, B. O. Roos, J. Am.
Chem. Soc. 1996, 118, 185 ± 195; c) Y. Chen, M. D. Barkley, Biochem-
istry, 1998, 37, 9976 ± 9982; d) B. S. Hudson, Acc. Chem. Res. 1999, 32,
297 ± 300; e) A. Smolyar, C. F. Wong, J. Mol. Struct. (THEOCHEM)
1999, 488, 51 ± 67; f) J. R. Lombardi, J. Phys. Chem. A, 1999, 103,
6335 ± 6338.
[4] a) G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic Molecules:
Concepts, Syntheses, Perspectives, VCH, Weinheim, 1996; b) H.-F.
Chow, T. K.-K. Mong, M. F. Nongrum, C.-W. Wan, Tetrahedron, 1998,
54, 8543 ± 8660; c) O. A. Matthews, A. N. Shipway, J. F. Stoddart, Prog.
Polym. Sci. 1998, 23, 1 ± 56; d) M. Fischer, F. Vögtle, Angew. Chem.
1999, 111, 934 ± 955; Angew. Chem. Int. Ed. 1999, 38, 884 ± 905.
[5] D. K. Smith, F. Diederich, Chem. Eur. J. 1998, 4, 1353 ± 1361, and
references therein.
Â
[6] C. J. Hawker, K. L. Wooley, J. M. J. Frechet, J. Am. Chem. Soc. 1993,
115, 4375 ± 4376.
(C O), 155.4 (C O), 137.0, 128.3, 128.1, 121.7, 119.3, 119.1, 109.6, 109.1,
(all Ar), 79.56 ((CH3)3CO), 69.10 (CH2O), 66.72 (CH2O), 59.66
(NHC(CH2)3), 55.53 (CHCO) 51.68 (CO2CH3) 34.70 (CH2CO2Me), 32.67
(NCH3), 28.73 (CH2CHCO) 28.34 (CH3CO); IR (neat) nÄ 3369m, 2953m,
2880m, 1738s, 1679s, 1620m, 1515s, 1485s, 1439s, 1367s, 1328m, 1252s, 1198s,
[7] a) P. J. Dandliker, F. Diederich, M. Gross, C. B. Knobler, A. Louati,
E. M. Sanford, Angew. Chem. 1994, 106, 1821 ± 1824; Angew. Chem.
Int. Ed. Engl. 1994, 33, 1739 ± 1742; b) P. J. Dandliker, F. Diederich, J.-
P. Gisselbrecht, A. Louati, M. Gross, Angew. Chem. 1995, 107, 2906 ±
2909; Angew. Chem. Int. Ed. Engl. 1995, 34, 2725 ± 2728; c) P. J.
Dandliker, F. Diederich, A. Zingg, J.-P. Gisselbrecht, M. Gross, A.
Louati, E. Sanford, Helv. Chim. Acta, 1997, 80, 1773 ± 1801; d) P.
Weyermann, J.-P. Gisselbrecht, C. Boudon, F. Diederich, M. Gross,
Angew. Chem. 1999, 111, 3400 ± 3405; Angew. Chem. Int. Ed. 1999, 38,
3215 ± 3219.
[8] K. W. Pollak, J. W. Leon, J. M. J. Frechet, M. Maskus, H. D. Abruna,
Chem. Mater. 1998, 10, 30 ± 38.
[9] a) C. M. Cardona, A. E. Kaifer, J. Am. Chem. Soc. 1998, 120, 4023 ±
4024; b) C. M. Cardona, T. D. McCarley, A. E. Kaifer, J. Org. Chem.
2000, 65, 1857 ± 1864; c) D. K. Smith, J. Chem. Soc. Perkin Trans. 2,
1999, 1563 ± 1565.
[10] Dendritic effects on redox chemistry (see also refs. [7] and [9]):
a) C. B. Gorman, Adv. Mater. 1997, 9, 1117 ± 1119; b) C. B. Gorman,
B. L. Parkhurst, W. Y. Su, K.-Y. Chen, J. Am. Chem. Soc. 1997, 119,
1141 ± 1142; c) C. Gorman, Adv. Mater. 1998, 10, 295 ± 309.
[11] Dendritic effects on optical properties: a) J. Issberner, F. Vögtle, L.
de Cola, V. Balzani, Chem. Eur. J. 1997, 3, 706 ± 712; b) C. Devadoss, P.
Bharathi, J. S. Moore, Angew. Chem. 1997, 109, 1706 ± 1709; Angew.
Chem. Int. Ed. Engl. 1997, 36, 1633 ± 1635; c) F. Vögtle, M. Plevoets,
M. Nieger, G. C. Azzellini, A. Credi, L. de Cola, V. de Marchis, M.
Venturi, V. Balzani, J. Am. Chem. Soc. 1999, 121, 6290 ± 6298; d) D.-L.
Jiang, T. Aida, Nature, 1997, 388, 454 ± 456; e) M. Kawa, J. M. J.
1176s, 1113m, 1074m, 1024m, 892w, 849m, 782w, 743m cm 1; MS (electro-
spray): m/z: 702 (100) [MNa] , 703 (31); HRMS (FAB): (C33H49N3O12
Na) [MNa] : calculated 702.3214, found 702.3215.
Compound G2(NMe): The synthesis was as for G2(NH), only with dry
THF as solvent and 6 as carboxylic acid. The reaction was followed by GPC
and pushed to completion by adding several portions of Boc-protected
methyltryptophan and coupling agents (HOBt and DCC) dissolved in THF.
After 4 days the precipitate contained in the mixture was removed by
filtration under gravity. The solvent was rotary evaporated; the pale yellow
residue was dissolved in CH2Cl2 (15 mL) and washed with sat. aq. NaHCO3
(2 Â 15 mL) and H2O (2 Â 15 mL). The organic phase was dried (MgSO4),
filtered under gravity and rotary evaporated to give the crude product as a
viscous pale yellow oil. The product was purified by GPC to afford a viscous
pale yellow oil. Yield: 32%; Rf 0.70 (CH2Cl2/MeOH 90:10); 1H NMR
(500 MHz, CD3OD) peaks in 1H NMR spectrum were broadenedÐ
presumably due to conformational effects: d 7.50 (brd, 3J(H,H) 8.0 Hz,
1H; ArH), 7.18 (brd, 3J(H,H) 8.0 Hz, 1H; ArH), 7.03 (m, 1H; ArH),
6.93 ± 6.88 (m, 2H; ArH), 4.50 ± 4.40 (brm, 1H; CHNH), 3.80 ± 3.60 (m,
75H; CO2CH3, CH2O, NCH3), 3.25 ± 3.10 (m, 2H; CH2CHNH), 2.38 (t,
3J(H,H) 7.0 Hz, 18H; CH2CO2Me), 2.36 (t, 3J(H,H) 7.0 Hz, 6H;
CH2CONH), 1.42 (s, 9H; (CH3)3CO); 13C NMR (125 MHz, CD3OD):
Â
Ä
d 174.1 (CONH Â 1), 173.9 (CO2Me), 173.6 (CONH Â 3), 157.3 (C O),
138.5, 129.5, 129.2, 122.5, 120.0, 119.9, 110.8, 110.2 (all Ar), 80.54
((CH3)3CO), 70.14 (CH2O Â 3), 69.98 (CH2O Â 9), 68.80 (CH2O Â 3),
67.98 (CH2O Â 9), 61.39 (NHC(CH2)3), 57.06 (CHCO), 52.20 (CO2CH3),
38.04 (CH2CONH), 35.66 (CH2COOMe), 32.89 (NCH3), 28.76 (CH3CO),
26.04 (CH2CHCO); IR (neat) nÄ 3327brs, 2952s, 2928s, 2875s, 1737s, 1674s,
1625m, 1560m, 1438m, 1366m, 1270m, 1198s, 1176s, 1111s, 1074m,
Â
Frechet, Chem. Mater. 1998, 10, 286 ± 296; f) D. K. Smith, Chem.
Commun. 1999, 1685 ± 1686; g) S. A. Vinogradov, D. F. Wilson, Chem.
Eur. J. 2000, 6, 2456 ± 2461;
[12] Dendritic effects on catalysis: a) H. Brunner, J. Organomet. Chem.
1995, 500, 39 ± 46; b) P. Bhyrappa, J. K. Young, J. S. Moore, K. S.
Suslick, J. Am. Chem. Soc. 1996, 118, 5708 ± 5711; c) C. C. Mak, H.-F.
Chow, Macromolecules, 1997, 30, 1228 ± 1230; d) H.-F. Chow, C. C.
Mak, J. Org. Chem. 1997, 62, 5116 ± 5127; e) P. Bhyrappa, G.
Vaijayanthimala, K. S. Suslick, J. Am. Chem. Soc. 1999, 121, 262 ±
263; f) T. Habicher, F. Diederich, V. Gramlich, Helv. Chim. Acta,
1999, 82, 1066 ± 1095; g) Q.-H. Fan, Y.-M. Chen, X.-M. Chen, D.-Z.
Jiang, F. Xi, A. S. C. Chan, Chem. Commun. 2000, 789 ± 790.
[13] For a review of dendritic effects on molecular recognition see: a) D. K.
Smith, F. Diederich, Top. Curr. Chem. 2000, 210, 183 ± 227; for specific
1025w cm 1; MS (electrospray): m/z: 1744 (100) [MNa] , 1745 (87)
[MNaH] , 1746 (33), [M{13C1}NaH] .
Acknowledgements
D.K.S. acknowledges the University of York for financial assistance in
setting up a research program to explore supramolecular dendrimer
Chem. Eur. J. 2001, 7, No. 5
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