C. Jacopin et al. / Bioorg. Med. Chem. Lett. 12 (2002) 1447–1450
1449
le Cancer (ARC) the MENRT and the Region Ile-de-
France (SESAME).
H-4.16 octadecyl), 1.26 (m, 4H, H-13 pentadecyl and H-3
octadecyl), 1.28 (m, 2H, H-17 octadecyl), 1.43 (m, 2H, H-14
pentadecyl), 1.46 (m, 6H, H-2 octadecyl, H-2 and H-3 butyl),
1.51 (m, 2H, H-2 pentadecyl), 1.60 (m, 2H, H-2 propyl), 1.64
(m, 2H, H-2 propyl), 2.62 (m, 2H, H-3-propyl), 2.63 (m, 4H, H-
1 propyl and H-4 butyl), 2.64 (m, 2H, H-1 butyl), 2.72 (m, 2H,
H-3 propyl), 2.74 (m, 2H, H-1 propyl), 3.14 (m, 2H, H-15
pentadecyl), 3.32 (m, 2H, NHCH2CO), 3.35 (m, 2H, H-1 pen-
tadecyl and H-1 octadecyl), 3.53 (m, 1H, H-2 gal), 3.58 (m, 1H,
H-5 gal), 3.60 (m, 1H, H-4 gal), 3.72 (m, 2H, H-6 gal), 4.03 (m,
1H, H-3 gal), 4.17 (m, 2H, H-1 gal).
13C RMN (CDCl3) d 14.09 (C-18 octadecyl), 22.69 (C-17
octadecyl), 25.99 (C-3 pentadecyl), 27.57 (C-3 octadecyl), 27.75
(C-13 pentadecyl), 29.3--30.2 (C-2, C-4, 16 octadecyl, C-4, 12
pentadecyl, C-14 pentadecyl), 32.70 (C-16 octadecyl), 40.23 (C-
1 propyl), 46.24 (C-1 octadecyl), 47.02 (C-15 pentadecyl), 47.63
(C-3-propyl), 48.01 (C-3 propyl), 48.25 (C-1 propyl), 49.64 (C-4
butyl), 50.25 (C-1 butyl), 50.60 (COCH2NH), 61.30 (C-1 pen-
tadecyl), 68.85 (C-6 gal), 70.00 (C-3 gal), 71.51 (C-4 gal), 73.93
(C-5 gal), 74.71 (C-2 gal), 103.64 (C-1 gal), 170.54 (NHCO).
Anal. calcd. for C51H105N5O7, 2 H2O C 65.45, H 11.65, N
7.48. Found C 65.68, H 11.32, N 7.32.
References and Notes
1. For some recent examples in these fields: (a) liposomes;
Tagawa, K.; Sendai, N.; Ohno, K.; Kawaguchi, T.; Kitano,
H.; Matsunaga, T. Bioconjug. Chem. 1999, 10, 354. (b) cationic
lipids; Behr, J. P.; Demeneix, B.; Loeffler, J. P.; Perez-Mutul,
J. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 6982. Byk, G.;
Dubertret, C.; Escriou, V.; Frederic, M.; Jaslin, G.; Rangara,
R.; Pitard, B.; Crouzet, J.; Wils, P.; Schwartz, B.; Scherman,
D. J. Med. Chem. 1998, 41, 224. Verderone, G.; Van Craynest,
N.; Boussif, O.; Santaella, C.; Bischoff, R.; Kolbe, H. V.;
Vierling, P. J. Med. Chem. 2000, 43, 1367. (c) lipid chelating
agents; Dietrich, C.; Boscheinen, O.; Scharf, K. D.; Schmitt,
L.; Tampe, R. Biochemistry 1996, 35, 1100.
2. Fuhrop, J.-H.; Tank, H. Chem. Phys. Lipids 1987, 43, 193.
3. (a) Ren, T.; Liu, D. Tetrahedron Lett. 1999, 40, 7621. (b)
Banerjee, R.; Mahidhar, Y. V.; Chaudhuri, A.; Gopal, V.;
Rao, N. M. J. Med. Chem. 2001, 44, 4176. (c) Ren, T.; Zhang,
G.; Liu, D. Bioorg. Med. Chem. Lett. 2001, 11, 2969.
4. Jacopin, C.; Hofland, H.; Scherman, D.; Herscovici, J.
Bioorg. Med. Chem. Lett. 2001, 11, 419.
Purification Supelco C-8 reverse phase cartrige (100% water
to 100% acetonitrile then acetonitrile-MeOH 90--10).
11. 2-{3-[4-(3-Amino-propylamino)-butylamino]-propyl-amino}-
N-octadecyl-N-[15-pentadecyl(ß-d-manno-pyranosyl)]-acet-
amide (22).
5. Chenault, K. H.; Castro, A.; Chaflin, L. F.; Yang, J. J.
Org. Chem. 1996, 61, 5024.
6. Kitov, P. I.; Pavel, I.; Railton, C.; Bundle, D. R. Carbo-
hydr. Res. 1998, 307, 361.
7. Timmers, C. M.; Wigchert, S. C. M.; Leeuwenburgh, M. A.;
van der Marel, G. A.; van Boom, J. H. Eur. J. Org. Chem.
1998, 1, 91.
[a]D=0 (c 0.1 MeOH); 1H NMR (pyridine-d6) d ppm 0.77
(m, 3H, H-18 octadecyl), 1.22 (m, 46H, H-3, 12 pentadecyl
and H-4, 17 octadecyl) 1.26 (m, 4H, H-13 pentadecyl and H-3
octadecyl), 1.42 (m, 2H, H-14 pentadecyl), 1.49 (m, 2H, H-2
pentadecyl), 1.52 (m, 2H, H-2 octadecyl), 1.83 (m, 6H, H-2
butyl, H-2 propyl and H-3 butyl), 1.87 (m, 2H, H-2 propyl),
2.71 (m, 4H, H-1 and H-4 butyl), 2.72 (m, 2H, H-3-propyl),
2.88 (m, 4H, H-1 and H-3 propyl), 3.03 (m, 2H, H-1 propyl),
3.18 (m, 2H, H-15 pentadecyl), 3.4 (m, 2H, H-1 pentadecyl),
3.43 (m, 2H, H-1 octadecyl), 3.56 (NHCH2CO), 3.84 (m, 2H,
H-1 pentadecyl), 4.33 (m, 2H, H-6 man), 4.44 (m, 2H, H-6
man), 4.19 (m, 2H, H-4 man), 4.48 (m, 2H, H-2 and H-5 man),
4.57 (m, 2H, H-3 man), 5.24 (m, 2H, H-1 man).
13C NMR (pyridine-d6) d ppm 14.14 (C-18 octadecyl), 22.79
(C-17 octadecyl), 26.45 (C-3 pentadecyl), 27.03 (C-3 octadecyl),
27.26 (C-13 pentadecyl), 29.20–30.2 (C-2, C-4, 15 octadecyl, C-
4, 12 pentadecyl, C-14 pentadecyl), 31.71 (C-2 pentadecyl),
31.99 (C-16 octadecyl), 40.40 (C-1 propyl), 46.97 (C-1 octade-
cyl), 47.61 (C-15 pentadecyl), 47.85 (C-3-propyl), 48.13 (C-3
propyl), 48.46 (C-1 propyl), 48.78 (C-4 butyl), 48.98 (C-1 butyl),
50.55 (COCH2NH), 62.94 (C-1 pentadecyl), 62.94 (C-1 penta-
decyl), 67.38 (C-6 man), 67.38 (C-6 man), 68.99 (C-3 man),
72.05 (C-4 man), 72.98 (C-5 man), 75.10 (C-2 man), 101.42 (C-1
man), 170.98 NHCO). Anal. calcd. for C51H105N5O7, 0.5 H2O
C; 67.40, H; 11.67, N; 7.70. Found C; 67.11, H; 11.32, N; 7.09.
Purification Supelco C-8 reverse phase cartrige (100% water
to 100% acetonitrile then acetonitrile-MeOH 90–10).
8. Banoub, J.; Bundle, D. R. Can. J. Chem. 1979, 57, 2085.
9. Typical experimental for the glycosidation of peracetylated
carbohydrates by alkylamino-1alkan-1-ol: To a solution of 6
(1.5 g, 4.52 mmol) in dry acetonitrile (50 mL) was added
tin(IV) chloride (0.63 mL 5.41 mmol) at 0 ꢀC. The solution was
stirred for 30 min then (15-hydroxy-pentadecyl)-octadecyl car-
bamic acid benzyl ester 5 (3.13 g, 4.97 mmol) was added. After
5 h all 6 has disappeared and the reacting mixture was diluted
with diethyl ether and quenched with sodium hydrogen phos-
phate. The aqueous phase was extracted with diethyl ether and
the combined organic extracts were washed with sodium
hydrogen carbonate and brine, dried (MgSO4). After removal
of the solvent the resulting oil was purified (flash chromato-
graphy, heptane–ethyl acetate 6:4) to give 7 in 69% yield. 7
[a]D=À12 (c 0.66 CH2Cl2); MS (CI), m/e 918 (M+NH4+);
1H NMR (CDCl3) d ppm 0.87 (t, 3H, J=6.96 Hz, H-33), 1.2
(d, 3H, J=6.51 Hz, H-6), 1.25 (m, 54H, (CH2)27), 1.52 (m,
6H, OCH2CH2, H-14 and H-17), 1.95, 2.05 and 2.15 (s, 3H,
OCOCH3), 3.14–3.25 (m, 4H, H-15 and H-16), 3.44 (m, 1H,
OCHaCH2), 3.63 (m, 1H, OCHbCH2), 3.79 (m, 1H, H-5), 4.41
(d, 1H, J=7.98 Hz, H-1), 4.99 (dd, 1H, J=3.52 and 10.46 Hz,
H-3), 5.09 (s, 2H, OCH2Phe), 5.16 (dd, 1H, J=7.98 and
10.46 Hz, H-2), 5.23 (dd, J=3.52 and 3.31 Hz, H-4), 7.32 (m,
5H, Phe).
12. 2-{3-[4-(3-Amino-propylamino)-butylamino]-propyl-amino}-
N-octadecyl-N-[15-pentadecyl-(a-l-6-deoxy-galactopyranosyl)]-
acetamide(23).
13C RMN (CDCl3) d (ppm) 14.7 (C-33), 17.3 (C-2), 20.7
(CH3COO), 27.3 (C-6), 29.72 ((CH2)27), 25.9–32 (OCH2CH2,
C-14, C-17), 47.2–48 (C-15 and C-16), 66.9 (CH2Phe), 69.6
(OCH2CH2), 69.4 (C-2), 70.6 (C-5), 70.8 (C-4), 71.4 (C-3), 96.2
(C-1), 128.4 (Phe), 156.2 and 171.3 (CO). Anal. calcd. for
C53H91NO10 : C, 70.55; H, 10.17; N, 1.55. Found: C, 70.67; H,
10.23; N, 1.71.
10. 2-{3-[4-(3-Amino-propyl-amino)-butylamino]-propylamino}-
N-octadecyl-N-[15-pentadecyl-(ß-d-galactopyranosyl)]-acet-
amide (11).
[a]d=0 (c 0.1 MeOH); 1H NMR (CDCl3) d ppm 0.88 (t, 3H,
m, 1H, H-18 octadecyl), 1.21 (m, 48H, H-3, 13 pentadecyl and
[a]D=0 (c 0.1 MeOH); 1H NMR (CDCl3) d ppm 0.81 (m,
3H, H-18 octadecyl), 1.18 (m, 6H, H-3 octadecyl, H-17 octa-
decyl and H-13 pentadecyl), 1.2 (m, 48H, H-3, 13 pentadecyl
and H-4, 16 octadecyl), 1.22 (m, 2H, H-3 pentadecyl), 1.32 (m,
3H, H-6 fuc), 1.5 (m, 2H, H-2 pentadecyl), 2.51 (m, 2H, H-4
butyl), 2.51 (m, 2H, H-1 butyl), 2.58 (m, 2H, H-3-propyl), 2.59
(m, 2H, H-1 propyl), 2.73 (m, 2H, H-1 propyl), 3.08 (m, 2H,
H-3 propyl), 3.09 (m, 2H, H-1 octadecyl), 3.14 (m, 2H, H-15
pentadecyl), 3.26 (m, 2H, NHCH2CO ), 3.41 (m, 2H, H-1
pentadecyl), 3.48 (m, 2H, H-3 fuc), 3.48 (m, 2H, H-4 fuc), 3.62
(m, 2H, H-5 fuc), 3.76 (m, 2H, H-1 pentadecyl), 3.94 (m, 2H,
H-2 fuc), 4.22 (m, 2H, H-1 fuc).