Rf = 0; IR: νmax (KBr discs)/cmϪ1 3700w, 3456s, 3301m, 3074w,
2954w, 2928m, 2859m, 1723m, 1646s, 1575m, 1533m, 1490w,
1447m, 1312w, 1261m, 1185w, 1101w, 1026w, 800w, 694m,
667w; [α]D ϩ5.6 (c = 1, MeOH). Significant differences in data
2 (a) D. K. Smith and F. Diederich, Chem. Eur. J., 1998, 4, 1353–1361;
(b) A. E. Barron and R. N. Zuckermann, Curr. Opin. Chem. Biol.,
1999, 3, 681–687.
3 Dendrimers based on -lysine are detailed in references 9–19. This
reference lists examples of other dendritic peptides. Some of these
are based on naturally occurring branched amino acids, such as
-glutamic or -aspartic acids, whilst others are based on modified
amino acid type building blocks. (a) J. Kress, A. Rosner and
A. Hirsch, Chem. Eur. J., 2000, 6, 247–257; (b) B. Buschhaus,
W. Bauer and A. Hirsch, Tetrahedron, 2003, 59, 3899–3915;
(c) Y. Kim, F. W. Zeng and S. C. Zimmerman, Chem. Eur. J., 1999, 5,
2133–2138; (d ) A. J. Brouwer, S. J. E. Mulders and R. M. J. Liskamp,
Eur. J. Org. Chem., 2001, 1903–1915; (e) E. Bellis, T. Markidis and
G. Kokotos, Synthesis, 2002, 1359–1364; ( f ) A. Ritzén and T. Frejd,
Eur. J. Org. Chem., 2000, 3771–3782; (g) L. Twyman, A. E. Beezer
and J. C. Mitchell, Tetrahedron Lett., 1994, 35, 4423–4424; (h) L. J.
Twyman, A. E. Beezer, R. Esfand, B. T. Mathews and J. C. Mitchell,
J. Chem. Res. (S), 1998, 758–759; (i) S. J. E. Mulders, A. J. Brouwer
and R. M. J. Liskamp, Tetrahedron Lett., 1997, 38, 3085–3088;
(j) D. Ranganathan and S. Kurur, Tetrahedron Lett., 1997, 38,
1265–1268; (k) D. Ranganathan, S. Kurur, K. P. Madhusudanan,
R. Roy and I. L. Karle, J. Peptide Res., 1998, 51, 297–302;
(l ) D. Ranganathan, S. Kurur, R. Gilardi and I. L. Karle,
Biopolymers, 2000, 54, 289–295; (m) S. A. Vinogradov and D. F.
Wilson, Chem. Eur. J., 2000, 6, 2456–2461; (n) S. A. Vinogradov, L.
W. Lo and D. F. Wilson, Chem. Eur. J., 1999, 5, 1338–1347; (o) I. B.
Rietveld, E. Kim and S. A. Vinogradov, Tetrahedron, 2003, 59,
3821–3831.
4 (a) R. H. E. Hudson and M. J. Damha, J. Am. Chem. Soc., 1993,
115, 2119–2124; (b) R. H. E. Hudson, S. Robidoux and M. J.
Damha, Tetrahedron Lett., 1998, 39, 1299–1302; (c) M. S.
Shchepinov, I. A. Udalova, A. J. Bridgman and E. M. Southern,
Nucleic Acids Res., 1997, 25, 4447–4454.
5 (a) R. Balasubramanian, P. Rao and U. Maitra, Chem. Commun.,
1999, 2353–2354; (b) R. Balasubramanian and U. Maitra, J. Org.
Chem., 2001, 66, 3035–3040.
6 (a) H. F. Chow and C. C. Mak, J. Chem. Soc., Perkin Trans. 1, 1994,
2223–2228; (b) H. F. Chow and C. C. Mak, Tetrahedron Lett., 1996,
37, 5935–5938; (c) H. F. Chow and C. C. Mak, J. Chem. Soc., Perkin
Trans. 1, 1997, 91–95.
1
for convergently synthesised material: H NMR: δH (500 MHz;
CD3OD) 7.80–8.00 (8H, m, Ar–H), 7.40–7.60 (12H, m, Ar–H),
4.65 (1H, m, COCH(CH2)NH), 4.53 (1H, m, COCH(CH2)NH),
4.44 (1H, m, COCH(CH2)NH), 3.40 (4H, m, CH2NH), 3.20
(2H, m, CH2NH), 1.40–2.10 (18H, m, CH2); [α]D ϩ2.5 (c = 1,
MeOH).
Synthesis of ؉H3N-G2(COOMe) TFA؊
Boc-G2(COOMe) (0.69 g, 0.8 mmol) was dissolved in a mini-
mum of dichloromethane (5 ml), and trifluoroacetic acid (4.0 g,
2.75 ml, 35 mmol) was added. This was stirred under a nitrogen
atmosphere for 24 h and the solvent and excess trifluoracetic
acid were removed by rotary evaporation. Acetonitrile (3 ×
50 ml) and diethylether (3 × 50 ml) were added separately and
removed by rotary evaporation and the product was dried
under high vacuum to produce a hygroscopic white solid in
quantitative yield. 1H NMR: δH (270 MHz; D2O) 4.40 (1H, m,
COCH(CH2)NH), 4.02 (1H, t, 6.5, COCH(CH2)NH), 3.90 (1H,
t, 6.5, COCH(CH2)NH), 3.73 (3H, s, CH3O), 3.20 (2H, t, 6.5,
CH2NH), 2.97 (4H, m, CH2NH), 1.40–2.00 (18H, m, CH2); 13
C
NMR: δC (67.9 MHz; D2O) 174.5 (COOCH3), 170.3, 169.8
(CHCONH), 163.4 (q, 36, CF3COO–), 116.0 (q, 290, CF3),
53.6, 53.5, 53.4 (all COCH(CH2)NH), 53.3 (CH3O), 39.7, 39.5
(both CH2NH), 30.9, 30.4, 28.2, 26.9, 23.7, 23.0, 21.9, 21.5 (all
CH2); MS: EI m/z 439.3 ([M ϩ Na Ϫ 4CF3CO2H]ϩ, 100), 417.2
([M ϩ H Ϫ 4CF3CO2H]ϩ, 45), 289.1 (37); TLC (90 : 10 : 0.1,
DCM–MeOH–triethylamine): Rf = 0.
Synthesis of ؉H3N-G2(COOMe) Cl؊
Boc-G2COOMe (2.15 g, 2.6 mmol) was dissolved in a mini-
mum of dichloromethane (10 ml), and HCl in diethylether
(10 ml, 1 M, 10 mmol) was added. This was stirred under a
nitrogen atmosphere for 48 h and the solvent and excess
reagents were removed by rotary evaporation. The product
could be isolated using the following procedure: acetonitrile
(2 × 10 ml) and diethylether (2 × 10 ml) were added separately
and removed by rotary evaporation and the product was dried
under high vacuum to produce a white powder (0.66 g, 1.17
mmol, 45%). δH (270 MHz; D2O) 4.47 (1H, dd, 5.0, 9.0,
COCH(CH2)NH), 4.10 (1H, t, 6.5, COCH(CH2)NH), 3.96 (1H,
t, 6.5, COCH(CH2)NH), 3.76 (3H, s, CH3O), 3.28 (2H, m,
7 For a recent review see: (a) N. Rockendorf and T. K. Lindhorst,
Top. Curr. Chem., 2001, 217, 201–238 for selected examples see;
(b) S. Ghorai, A. Bhattacharjya, A. Basak, A. Mitra and R. T.
Williamson, J. Org. Chem., 2003, 68, 617–620; (c) B. Colonna,
V. D. Harding, S. A. Nepogodiev, F. M. Raymo, N. Spencer and
J. F. Stoddart, Chem. Eur. J., 1998, 4, 1244–1254; (d ) L. V.
Backinowsky, P. I. Abronina, A. S. Shashkov, A. A. Grachev, N. K.
Kochetkov, S. A. Nepogodiev and J. F. Stoddart, Chem. Eur. J.,
2002, 8, 4412–4423; W. B. Turnbull, S. A. Kalovidouris and
J. F. Stoddart, Chem. Eur. J., 2002, 8, 2988–3000.
8 For representative examples see: (a) J. G. Weintraub, S. Broxer,
N. M. Paul and J. R. Parquette, Tetrahedron, 2001, 57, 9393–9402;
(b) M. R. Rauckhorst, P. J. Wilson, S. A. Hatcher, C. M. Hadad and
J. R. Parquette, Tetrahedron, 2003, 59, 3917–3923; (c) D. M. Junge,
M. J. Wu, J. R. McElhanon and D. V. McGrath, J. Org. Chem., 2000,
65, 5306–5314; (d ) J. R. McElhanon and D. V. McGrath, J. Org.
Chem., 2000, 65, 3525–3529; (e) S. Cicchi, A. Goti, C. Rosini and
A. B. Brandi, Eur. J. Org. Chem., 1998, 2591–2597; ( f ) J. R.
McElhanon and D. V. McGrath, J. Am. Chem. Soc., 1998, 120,
1647–1656; (g) D. V. McGrath, M. J. Wu and U. Chaudhry,
Tetrahedron Lett., 1996, 37, 6077–6080; (h) P. Murer and
D. Seebach, Helv. Chim. Acta, 1998, 81, 603–631; (i) H. T. Chang,
C. T. Chen, T. Kondo, G. Siuzdak and K. B. Sharpless,
Angew. Chem., Int. Ed. Engl., 1996, 35, 182–186; (j) A. Cherestes,
T. October and R. Engel, Heteroat. Chem., 1998, 9, 485–494;
(k) J. M. LaPierre, K. Skobridis and D. Seebach, Helv. Chim. Acta,
1993, 76, 2419–2432; (l ) V. Lellek and I. Stibor, J. Mater. Chem.,
2000, 10, 1061–1073.
CH2NH), 3.00 (4H, m, CH2NH), 1.40–2.00 (18H, m, CH2); 13
C
NMR: δC (67.9 MHz; D2O) 173.9 (COOCH3), 170.3, 170.1
(CHCONH), 54.3, 54.1, 53.9 (all COCH(CH2)NH), 53.0
(CH3O), 40.5, 40.3, 40.2 (all CH2NH), 34.9, 34.7, 32.3, 32.1,
28.1, 23.1, 22.6, 15.5, 14.2 (all CH2); MS: EI m/z 417 ([M ϩ H Ϫ
4HCl]ϩ, 100%), 209 (23). HR FAB MS C19H14N6O4Na requires
417.3189, measured 417.3188; TLC (90 : 10 : 0.1, DCM–
MeOH–triethylamine): Rf = 0; IR: νmax (KBr disc)/cmϪ1 3444s,
3242m, 3068w, 2931s, 1734m, 1674s, 1628m, 1571m, 1502w,
1271w, 1227w, 1178w, 1140w, 800w, 735w, 667w, 552w, 484w;
[α]D ϩ14.8 (c = 1, MeOH).
9 (a) R. G. Denkewalter, J. Kolc and W. J. Lukasavage, USP, 4 289 872/
1981, assigned to Allied Corp, Chem. Abstr., 1985, 102, 79324q;
(b) J. P. Tam, Proc. Natl. Acad. Sci., U. S. A., 1988, 85, 5409–5413.
10 A. V. Davis, M. Driffield and D. K. Smith, Org. Lett., 2001, 3, 3075–
3078.
11 For chromatographic stationary phases based on dendritic -lysine
see: (a) M. Driffield, D. M. Goodall, A. S. Klute, D. K. Smith and
K. Wilson, Langmuir, 2002, 18, 8660–8665; (b) M. Driffield, D. M.
Goodall, A. S. Klute and D. K. Smith, unpublished results; for
stationary phases based on different dendritic peptides see; (c) B. T.
Mathews, A. E. Beezer, M. J. Snowden, M. J. Hardy and J. C.
Mitchell, New J. Chem., 2001, 25, 807–818; (d ) B. T. Mathews, A. E.
Beezer, M. J. Snowden, M. J. Hardy and J. C. Mitchell,
Chromatographia, 2001, 53, 147–155.
Acknowledgements
We would like to thank EPSRC and Pfizer Global Research and
Development for financial support (CASE award) to MD. Dr
Peter O’Brien is acknowledged for numerous useful conversa-
tions and much helpful advice.
References and notes
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 6 1 2 – 2 6 2 0
2619