C. D. Schmidt, C. Böttcher, A. Hirsch
FULL PAPER
C39H63N3O10 (733.93): calcd. C 63.82, H 8.65, N 5.73; found C
63.81, H 8.66, N 5.70.
7.1 Hz, 3 H, CH3), 1.39 (s, 81 H, CH3), 1.55 (m, 2 H, CH2), 1.90
(m, 26 H, CH2), 2.07 (t, 3JH,H = 6.8 Hz, 2 H, CH2), 2.15 (m, 24 H,
CH2), 3.22 (m, 2 H, CH2), 4.20 (m, 1 H, CH), 5.07 (m, 2 H, CH2),
L
-2G(tBu)-Lys-NH-Cbz (L-3d): Purification: column chromatog-
3
6.00 (d, JH,H = 7.6 Hz, 1 H, NH), 6.17 (s, 3 H, NH), 6.70 (m 1
1
raphy (SiO2, ethyl acetate); yield 4.193 g (2.326 mmol, 91.8%). H
NMR (400 MHz, CDCl3): δ = 1.40 (s, 81 H, CH3), 1.42 (s, 9 H,
CH3), 1.55 (m, 2 H, CH2), 1.77 (m, 4 H, CH2), 1.92 (m, 24 H,
CH2), 2.16 (m, 24 H, CH2), 3.16 (m, 2 H, CH2), 3.81 (m, 1 H, CH),
H, NH), 7.28 (m, 5 H, Ar-H), 7.53 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 18.65 (1 C, CH3), 24.90 (1 C, CH2), 25.99
(1 C, CH2), 28.05 (27 C, CH3), 28.87 (1 C, CH2), 29.75 (18 C,
CH2), 31.59 (3 C, CH2), 31.66 (3 C, CH2), 36.97 (1 C, CH2), 39.15
(1 C, CH2), 50.43 (1 C, CH), 57.38 (3 C, Cquat), 57.46 (1 C, Cquat),
66.77 (1 C, CH2), 80.58 (9 C, Cquat), 128.06, 128.46 (5 C, Ar-CH),
136.42 (1 C, Ar-Cquat), 156.22 (1 C, NHCOOR), 172.32 (1 C,
NHCO), 172.71 (9 C, COOR), 172.92 (3 C, NHCO), 173.26 (1 C,
3
5.05 (s, 2 H, CH2), 5.26 (br. s, 1 H, NH), 5.75 (d, JH,H = 4.4 Hz,
1 H, NH), 6.03 (s, 1 H, NH), 6.11 (s, 3 H, NH), 7.30 (m, 5 H, Ar-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.92 (1 C, CH2), 28.05
(27 C, CH3), 28.39 (3 C, CH3), 29.32 (1 C, CH2), 29.79 (9 C, CH2),
29.94 (9 C, CH2), 30.93 (1 C, CH2), 31.35 (6 C, CH2), 40.51 (1 C,
CH2), 56.22 (1 C, CH), 57.26 (3 C, Cquat.), 57.88 (1 C, Cquat.), 66.43
(1 C, CH2), 79.66 (1 C, Cquat.), 80.49 (9 C, Cquat.), 127.93, 128.09,
128.40 (5 C, Ar-CH), 136.77 (1 C, Ar-Cquat.), 156.28, 156.59 (2 C,
NHCOOR), 172.66 (1 C, NHCOOR), 172.77 (9 C, COOR), 172.91
(3 C, NHCO) ppm. MS (FAB, NBA): m/z = 1802 [M+]. IR (ATR):
NHCO) ppm. MS (FAB, NBA): m/z = 1757 [M+]. IR (ATR): ν =
˜
3312, 2976, 2937, 1725, 1652, 1536, 1455, 1420, 1390, 1366, 1312,
1251, 1216, 1146, 1104, 1069, 953, 849, 757, 699 cm–1.
C93H156N6O25 (1758.26): calcd. C 63.53, H 8.94, N 4.78; found C
63.73, H 8.97, N 4.62.
ν = 3352, 2981, 2943, 1730, 1661, 1537, 1460, 1367, 1313, 1251, General Description of Hydrogenation Reactions. Procedure b:
˜
1151, 1104, 1043, 958, 850, 757, 703 cm–1. C95H160N6O26 (1802.31): Compound from Procedure a (see above) was solved in ethanol and
calcd. C 63.31, H 8.95, N 4.66; found C 62.99, H 8.89, N 4.52.
Pd/C catalyst was added. Hydrogen was flushed through for 5–
15 h. Afterwards the Pd-catalyst was removed by filtering the solu-
tion over Celite 500. The solvent was evaporated and without fur-
ther purification a white solid was obtained as product.
D
-2G(tBu)-Lys-NH-(2Cl)Cbz D-3d): Purification: column
(
chromatography (SiO2, ethyl acetate); yield 0.870 g (0.474 mmol,
45.5%). 1H NMR (400 MHz, CDCl3): δ = 1.40 (s, 81 H, CH3), 1.43
(s, 9 H, CH3), 1.53 (m, 2 H, CH2), 1.84 (m, 4 H, CH2), 1.94 (m,
L- and D-1G(tBu)-Lys-NH2 (4a): Yield 655 mg (1.018 mmol,
24 H, CH2), 2.17 (m, 24 H, CH2), 3.18 (m, 2 H, CH2), 3.81 (m, 1 92.96%), 887 mg (1.38 mmol, 98.7%). 1H NMR (400 MHz,
H, CH), 5.17 (s, 2 H, CH2), 5.36 (br. s, 1 H, NH), 5.77 (br. s, 1 H, CDCl3): δ = 1.21 (m, 1 H, CH2), 1.38 (s, 9 H, CH3), 1.39 (s, 27 H,
NH), 6.13 (s, 4 H, NH), 7.17 (m, 1 H, Ar-H), 7.21 (m, 1 H, Ar- CH3), 1.50 (m, 4 H, CH2), 1.73 (m, 1 H, CH2), 1.90 (m, 6 H, CH2),
3
H), 7.34 (m, 1 H, Ar-H), 7.41 (m, 1 H, Ar-H) ppm. 13C NMR
2.14 (m, 6 H, CH2), 2.72 (t, JH,H = 6.8 Hz, 2 H, CH2), 3.15 (br. s,
3
(75 MHz, CDCl3): δ = 22.89 (1 C, CH2), 28.02 (27 C, CH3), 28.35 2 H, NH2), 3.89 (1 H, CH), 5.14 (d, JH,H = 7.8 Hz, 1 H, NH),
(3 C, CH3), 29.30 (1 C, CH2), 29.72 (9 C, CH2), 29.83 (9 C, CH2), 6.47 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.71
30.80 (1 C, CH2), 31.28 (3 C, CH2), 31.86 (3 C, CH2), 40.53 (1 C, (1 C, CH2), 28.04 (9 C, CH3), 28.30 (3 C, CH3), 29.63 (3 C, CH2),
CH2), 56.18 (1 C, CH), 57.18 (3 C, Cquat.), 57.85 (1 C, Cquat.), 63.60 29.68 (1 C, CH2), 29.79 (3 C, CH2), 31.82 (1 C, CH2), 41.19 (1 C,
(1 C, CH2), 79.61 (1 C, Cquat.), 80.48 (9 C, Cquat.), 126.76, 129.13,
CH2), 54.92 (1 C, CH), 57.50 (1 C, Cquat), 80.01 (1 C, Cquat), 80.59
129.34, 129.64, 133.34, 134.47 (6 C, Ar-C), 156.26 (1 C, (3 C, Cquat), 155.85 (1 C, NHCOOR), 171.38 (1 C, NHCO), 172.72
NHCOOR), 158.31 (1 C, NHCOOR), 172.75 (9 C, COOR), 172.82
(3 C, COOR) ppm. MS (FAB, NBA): m/z = 644 [M+]. IR (ATR):
(1 C, NHCO), 172.89 (3 C, NHCO) ppm. MS (MALDI, sin): m/z
ν = 3280, 2981, 2940, 1721, 1509, 1458, 1392, 1367, 1317, 1253,
˜
= 1858 [M + Na+]. IR (ATR): ν = 3328, 2978, 2937, 1726, 1673,
1155, 1101, 1055, 951, 849, 762, 652, 634, 614 cm–1.
˜
1529, 1457, 1392, 1367, 1315, 1257, 1152, 1101, 1035, 958, 920,
C33H61N3O9·1CH3CH2OH (643.86 + 46.07): calcd. C 60.93, H
849, 800, 758, 732 cm–1. C95H159ClN6O26·1CHCl3 (1836.78 + 9.79, N 6.09; found C 60.67, H 9.34, N 6.24.
119.38): calcd. C 58.94, H 8.24, N 4.30; found C 59.25, H 7.93, N
4.27.
L
- and D-1G(tBu)-Ala-NH2 (4b): Yield 221 mg (0.454 mmol,
85.15%), 651 mg (1.338 mmol, 97.7%). 1H NMR (CDCl3,
3
L-
and
D-2G(tBu)-Ala-NH-Cbz (3e): Purification: column 300 MHz): δ = 1.31 (d, JH,H = 6.8 Hz, 3 H, CH3), 1.39 (s, 27 H,
chromatography (SiO2, ethyl acetate/hexanes, 1:1); yield 1.128 g
CH3), 1.93 (m, 6 H, CH2), 2.16 (m, 6 H, CH2), 2.46 (br. s, 2 H,
NH2), 3.47 (m, 1 H, CH), 7.20 (s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 21.37 (1 C, CH3), 28.04 (9 C, CH3), 29.69
(0.686 mmol, 60.6%), 0.715 g (0.434 mmol, 51.7%). 1H NMR
3
(400 MHz, CDCl3): δ = 1.31 (d, JH,H = 7.1 Hz, 3 H, CH3), 1.39
(s, 81 H, CH3), 1.91 (m, 24 H, CH2), 2.15 (m, 24 H, CH2), 3.96 (t, (3 C, CH2), 29.72 (3 C, CH2), 51.05 (1 C, CH), 56.68 (1 C, Cquat),
3JH,H = 6.6 Hz, 1 H, CH), 5.12 (m, 2 H, CH2), 6.03 (br. s, 3 H,
80.54 (3 C, Cquat), 172.66 (3 C, COOR), 172.86 (1 C, NHCO) ppm.
MS (FAB, NBA): m/z = 488 [M+]. IR (ATR): ν = 2981, 2927, 1722,
3
3
NH), 6.09 (d, JH,H = 5.6 Hz, 1 H, NH), 7.29 (t, JH,H = 7.5 Hz, 2
H, Ar-H), 7.38 (m, 3 H, Ar-H), 8.00 (s, 1 H, NH) ppm. 13C NMR 1668, 1529, 1460, 1367, 1321, 1220, 1151, 1043, 950, 919, 749, 664
(100 MHz, CDCl3): δ = 18.28 (1 C, CH3), 28.02 (27 C, CH3), 29.73,
cm–1. C25H46N2O7 (486.64): calcd. C 61.70, H 9.53, N 5.76; found
˜
29.86 (18 C, CH2), 30.89, 31.31 (6 C, CH2), 52.15 (1 C, CH), 57.23 C 61.35, H 9.19, N 5.66.
(3 C, Cquat), 57.66 (1 C, Cquat), 66.65 (1 C, CH2), 80.50 (9 C, Cquat),
L
- and D-1G(tBu)-C6-Ala-NH2 (4c): Yield 342 mg (0.570 mmol,
127.60, 127.73, 128.31 (5 C, ArC-H), 136.83 (1 C, ArCquat), 156.38
(1 C, NHCOOR), 172.74 (9 C, COOR), 172.92 (4 C, NHCO) ppm.
97.9%), 261 mg (0.435 mmol, 98.9%). 1H NMR (300 MHz,
CDCl3): δ = 1.32 (m, 5 H, CH3 + CH2), 1.40 (s, 27 H, CH3), 1.49
(m, 2 H, CH2), 1.59 (m, 2 H, CH2), 1.92 (t, JH,H = 7.8 Hz, 6 H,
CH2), 2.09 (t, JH,H = 7.4 Hz, 2 H, CH2), 2.18 (t, JH,H = 7.8 Hz,
6 H,CH2), 2.33 (br. s, 2 H, NH2), 3.21 (m, 2 H, CH2), 3.51 (m, 1
H, CH), 5.96 (br. s, 1 H, NH), 7.38 (s, 1 H, NH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.43 (1 C, CH3), 25.21 (1 C, CH2), 26.41
(1 C, CH2), 28.04 (9 C, CH3), 29.14 (1 C, CH2), 29.81 (3 C, CH2),
29.90 (3 C, CH2), 37.19 (1 C, CH2), 38.74 (1 C, CH2), 50.62 (1 C,
CH), 57.29 (1 C, Cquat), 80.69 (3 C, Cquat), 172.40 (1 C, NHCO),
MS (FAB, NBA): m/z = 1645 [M+]. IR (ATR): ν = 3334, 2981,
˜
3
2939, 1727, 1672, 1540, 1456, 1367, 1317, 1251, 1230, 1217, 1152,
1104, 956, 849, 759 cm–1. C87H135N5O24 (1645.10): calcd. C 63.52,
H 8.88, N 4.26; found C 63.02, H 9.05, N 4.25.
3
3
L- and D-2G(tBu)-C6-Ala-NH-Cbz (3f): Purification: column
chromatography (SiO2, ethyl acetate 100%); yield
1.506 g
(0.856 mmol, 62.1%), 0.819 g (0.466 mmol, 72.3%). 1H NMR
3
(400 MHz, CDCl3): δ = 1.28 (m, 2 H, CH2), 1.35 (d, JH,H
=
5346
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Eur. J. Org. Chem. 2009, 5337–5349