[CH3(CH2)17]2NCOCH2OCH2CO-Gly-Gly-Gly-Pro-Gly-Gly-
Gly-OCH(CH3)2, ‘‘C18-isopropyl,’’ 10
[CH3(CH2)17]2NCOCH2OCH2CO-Gly-Gly-Gly-Pro-Gly-Gly-
Gly-O(CH2)6CH3, ‘‘C18-heptyl,’’ 11
.
HCl GGG-OCH(CH3)2. GGG (1.0 g, 5.3 mmol) was sus-
.
TsOH GGG-OC7H15. GGG (2.0 g, 10.6 mmol) and
pended in 2-PrOH (10 ml), cooled (5 1C), SOCl2 (0.8 ml, 11.0
mmol) was added dropwise, and the mixture was heated under
reflux (4 d). After evaporation of solvent, PhMe (20 ml) was
added and evaporated. The residue was dried at high vacuum
and crystallized from CH3OH : Et2O (20 ml : 40 ml) to give
white crystals which were crystallized a second time to afford
pure product (0.87 g, 61%), mp 185–186 1C. 1H NMR
(CD3OD): 1.25 (6H, d, J ¼ 6.3 Hz, OCH(CH3)2), 3.76 (2H,
s, Gly CH2), 3.92 (2H, s, Gly CH2), 4.00 (2H, s, Gly CH2), 5.04
(1H, m, OCH(CH3)2. 13C NMR (CD3OD): 22.1, 41.7, 42.4,
43.2, 70.4, 168.0, 170.9, 171.9. IR (nujol): cmꢀ1 3330, 3232,
2954, 2924, 2854, 1732, 1703, 1646, 1789, 1573, 1548, 1489,
1461, 1411, 1377, 1219, 1153, 1102, 1033, 961, 911, 820, 723.
p-TsOH ꢁ H2O (2.2 g, 11.6 mmol) were added to 1-heptanol
(12 g, 103.3 mmol) and PhMe (40 ml). The mixture was heated
to reflux and water was removed azeotropically (Dean–Stark
trap, h). The mixture was cooled (rt), evaporated, and crystal-
lized from CH3OH : Et2O (20 ml : 60 ml) to give 4.32 g (89%) of
a white solid, mp 149–150 1C. 1H NMR (CD3OD): 0.91 (3H, t,
J ¼ 7.2 Hz, CH3(CH2)4CH2CH2O), 1.32 (8H, m, CH3
(CH2)4CH2CH2O), 1.64 (2H, bs, CH3(CH2)4CH2CH2O), 2.37
(3H, s, Ar–CH3), 3.65–3.75 (2H, m, Gly CH2), 3.93 (2H, s, Gly
CH2), 3.98 (2H, s, Gly CH2), 4.11 (2H, t, J ¼ 6.6 Hz,
CH3(CH2)4CH2CH2O), 7.24 (2H, d, J ¼ 8.1 Hz, Ar–H), 7.71
(2H, d, J ¼ 8.1 Hz, Ar-H). 13C NMR (CD3OD): 14.5, 21.4,
23.8, 27.0, 29.8, 30.2, 33.0, 41.7, 42.1, 43.2, 66.6, 127.1, 130.0,
141.9, 143.6, 168.1, 171.4, 171.9. IR (nujol): cmꢀ1 3336, 3263,
3110, 2922, 2853, 2719, 1740, 1706, 1685, 1651, 1594, 1547,
1499, 1461, 1412, 1377, 1368, 1313, 1232, 1214, 1175, 1128,
1037, 1014, 912, 816, 738, 724, 684.
Cbz-PGGG-OCH(CH3)2. General procedure 2. Quantities
used: Cbz-L-Proline (0.48 g, 1.9 mmol), and HCl ꢁ GGG-O-
CH(CH3)2 (0.5 g, 1.9 mmol). The crude material was chroma-
tographed (silica gel, CH3OH : CH2Cl2 98 : 2 - 85 : 5) to give
Cbz-PGGG-OC7H15. General procedure 2. Quantities used:
Cbz-L-Proline (1.08 g, 4.3 mmol) and TsOH ꢁ GGG-OC7H15
(2.0 g, 4.4 mmol). The crude product was chromatographed
(silica gel, CH3OH : CHCl3 98 : 2 - 95 : 5) to give colorless
crystals (2.01 g, 90%), mp 94–96 1C. 1H NMR: 0.87 (3H, t, J ¼
6.9 Hz, CH3(CH2)4CH2CH2O), 1.27 (8H, m, CH3(CH2)4CH2
CH2O), 1.60 (2H, bs, CH3(CH2)4CH2CH2O), 1.75–2.20 (4H,
m, Pro NCH2CH2CH2), 3.45-3.60 (2H, m, Pro NCH2
CH2CH2), 3.75–4.00 (6H, Gly CH2), 4.07 (2H, t, J ¼ 6.6 Hz,
CH3(CH2)4CH2CH2O), 4.24 (1H, t, J ¼ 6.3 Hz, Pro CH), 5.02–
5.17 (2H, m, PhCH2O), 7.00 (1H, bs, NH), 7.21 (1H, bs, NH),
7.33 (5H, m, Ar–H), 7.68 (1H, bs, NH). 13C NMR: 14.0, 22.5,
25.7, 28.5, 28.8, 29.5, 31.6, 41.2, 43.0, 43.4, 47.1, 61.0, 65.5,
67.6, 127.8, 128.2, 128.5, 136.2, 156.0, 169.4, 169.7, 171.7,
173.3. IR (CHCl3): cmꢀ1 3310, 3068, 2955, 2931, 2858, 1749,
1669, 1541, 1419, 1360, 1206, 1125, 1091, 1030, 986, 919, 770,
731, 698.
1
colorless crystals (0.74 g, 86%), mp 93–95 1C. H NMR: 1.21
(6H, d, J ¼ 6.3 Hz, OCH(CH3)2), 1.80–2.10 (4H, m, Pro
NCH2CH2CH2), 3.45-3.60 (2H, m, Pro NCH2CH2CH2),
3.80–4.10 (6H, Gly CH2), 4.24 (1H, t, J ¼ 6.3 Hz, Pro CH),
4.90–5.20 (3H, OCH(CH3)2, PhCH2O), 7.08 (1H, t, J ¼ 6.0 Hz,
NH), 7.33 (5H, Ar–H), 7.44 (1H, t, J ¼ 6.0 Hz, NH), 7.75 (1H,
t, J ¼ 6.0 Hz, NH). 13C NMR: 21.7, 24.7, 29.5, 41.4, 42.9, 43.3,
47.1, 61.0, 67.5, 69.0, 127.7, 128.1, 128.5, 136.2, 156.0, 169.1,
169.5, 169.9, 173.3. IR (CHCl3): cmꢀ1 3312, 3066, 2981, 2938,
2882, 1744, 1669, 1541, 1420, 1376, 1359, 1210, 1108, 1031,
984, 947, 920, 772, 734, 699, 669.
PGGG-OCH(CH3)2. General procedure 3. Quantities used:
Cbz-PGGG-OCH(CH3)2 (0.36 g, 0.8 mmol). Product: white
solid (0.25 g, 100%), mp 144–145 1C. 1H NMR (CD3OD):
1.251 (6H, d, J ¼ 6.3 Hz, OCH(CH3)2), 1.75–2.30 (4H, m, Pro
NCH2CH2CH2), 3.00–3.15 (2H, m, Pro NCH2CH2CH2), 3.85–
3.95 (7H, Gly CH2, and Pro CH), 5.02 (1H, m, OCH(CH3)2).
13C NMR (CD3OD): 22.1, 26.7, 31.7, 42.4, 43.4, 43.7, 48.0,
61.6, 70.4, 170.9, 172.2, 176.7. IR (nujol): cmꢀ1 3177, 2922,
2855, 2726, 1740, 1647, 1542, 1461, 1377, 1304, 1206, 1170,
1028, 967, 770, 722.
PGGG-OC7H15. General procedure 3. Quantities used: Cbz-
PGGG-OC7H15 (1.0 g, 1.9 mmol). Product: a white, waxy solid
1
(0.74 g, 100%). H NMR (CD3OD): 0.91 (3H, t, J ¼ 7.2 Hz,
CH3(CH2)4CH2CH2O), 1.32 (8H, m, CH3(CH2)4CH2CH2O),
1.65 (2H, bs, CH3(CH2)4CH2CH2O), 1.75–2.20 (4H, m, Pro
NCH2CH2CH2), 2.70–3.00 (2H, m, Pro NCH2CH2CH2), 3.70–
4.05 (7H, Gly CH2, Pro CH), 4.13 (2H, t, J ¼ 6.6 Hz,
CH3(CH2)4CH2CH2O). 13C NMR (CD3OD): 14.5, 22.3, 23.8,
26.1, 26.8, 27.0, 27.1, 27.4, 29.8, 30.2, 31.9, 33.0, 42.1, 43.5,
43.7, 43.8, 61.7, 64.3, 66.5, 171.0, 171.4, 172.0, 178.2. IR
(nujol): cmꢀ1 3284, 3177, 2921, 2855, 1740, 1653, 1461, 1377,
1155, 1077, 1029, 967, 892, 846, 770, 723.
182-[DGA]-GGGPGGG-OCH(CH3)2. General procedure 2.
Quantities used: 182-[DGA]-GGG-OH (0.27 g, 0.3 mmol) and
PGGG-OCH(CH3)2 (0.11 g, 0.3 mmol). Crude product was
crystallized (CH3OH) to give a white solid (0.26 g, 70%), mp
182-[DGA]-GGGPGGG-OC7H15. General procedure 2.
Quantities used: 182-[DGA]-GGG-OH (0.16 g, 0.2 mmol)
and PGGG-OC7H15 (0.08 g, 0.2 mmol). Crude product was
chromatographed (silica gel, CH3OH : CHCl3 9 : 1 - 85 : 15)
1
129–131 1C. H NMR: 0.87 (6H, t, J ¼ 6.9 Hz, CH3(CH2)15
CH2CH2N), 1.20–1.30 (66H, CH3(CH2)15CH2CH2N, OCH
(CH3)2), 1.51 (2H, m, CH3(CH2)15CH2CH2N), 1.95–2.25 (4H,
m, Pro NCH2CH2CH2), 3.08 (2H, t, J ¼ 7.5 Hz, CH3(CH2)15
CH2CH2N), 3.27 (2H, t, J ¼ 7.5 Hz, CH3(CH2)15CH2CH2N),
3.75–4.40 (19H, Pro NCH2CH2CH2, Gly CH2, Pro CH and
COCH2O), 5.01 (1H, m, OCH(CH3)2), 7.33 (1H, bs, NH), 7.50
(1H, bs, NH), 7.87 (3H, bs, NH), 8.34 (1H, bs, NH). 13C NMR:
14.1, 21.8, 22.7, 25.2, 26.9, 27.1, 27.6, 28.9, 29.0, 29.3, 29.4,
29.5, 29.6, 29.7, 31.9, 41.5, 42.0, 43.0, 43.5, 46.3, 47.0, 61.3,
69.2, 69.6, 71.6, 168.4, 168.8, 169.5, 170.0, 170.1, 170.3, 170.6,
171.2, 173.2. IR (CHCl3): cmꢀ1 3308, 2920, 2851, 1744, 1652,
1540, 1467, 1376, 1338, 1209, 1129, 1109, 1031, 722. Anal.
Calcd. for 60H110N8O11 ꢁ H2O: C 63.35, C H 9.92, N 9.85.
Found: C 63.40, H 9.92, N 9.52%.
1
to give a white solid (0.14 g, 61%), mp 99–101 1C. H NMR:
0.85–0.90 (9H, CH3(CH2)15CH2CH2N, CH3(CH2)4CH2
CH2O), 1.24 (68H, m, CH3(CH2)15CH2CH2N, CH3(CH2)4CH2
CH2O), 1.49 (4H, bs, CH3(CH2)15CH2CH2N), 1.60 (2H, bs,
CH3(CH2)4CH2CH2O), 1.80–2.20 (4H, m, Pro NCH2
CH2CH2), 3.05 (2H, t, J ¼ 7.5 Hz, CH3(CH2)15CH2CH2N),
3.24 (2H, t, J ¼ 7.5 Hz, CH3(CH2)15CH2CH2N), 3.45–3.75
(2H, m, Pro NCH2CH2CH2), 3.85–4.10(16H, Gly CH2,
CH3(CH2)4CH2CH2O, COCH2O), 4.27 (2H, s, COCH2O),
4.36 (1H, t, J ¼ 6.6 Hz, Pro CH), 7.65 (2H, bs, NH), 7.89
(1H, bs, NH), 8.03 (1H, bs, NH), 8.26 (1H, bs, NH), 8.42 (1H,
bs, NH). 13C NMR: 14.0, 14.1, 22.6, 22.7, 25.1, 25.8, 26.9, 27.1,
N e w J . C h e m . , 2 0 0 5 , 2 9 , 2 9 1 – 3 0 5
301