April 2006
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room temperature. After completion of the reaction, the mixture was ex- 169.60, 169.57, 169.3, 168.5, 168.4, 165.5, 164.9, 133.33, 133.28, 131.77,
tracted with chloroform, washed with water, dried (MgSO4), and concentrat- 129.8, 129.1, 128.4, 101.7, 101.1, 100.5, 93.3, 78.6, 75.6, 74.1, 73.3, 72.0,
ed. The product was purified on silica gel column chromatography (chloro- 71.9, 71.7, 71.0, 70.9, 70.3, 69.93, 69.89, 69.2, 68.7, 67.5, 67.3, 66.9, 66.8,
form : methanolꢀ40 : 1) to give 18 (80 mg, 89.3%). [a]2D3 ꢃ4.5° (cꢀ0.7,
66.5, 65.9, 60.0, 59.8, 52.8, 39.5, 29.7, 29.3, 29.2, 26.6, 25.6, 20.8, 20.7,
CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.99—7.38 (20H, m, Ar-H), 5.60 20.62, 20.56. MALDI-TOF-MS: Calcd for C166H212N5O79Na: m/z 3562.3
(2H, t, H-3ꢁꢄ2), 5.36—5.29 (6H, m, H-2ꢁꢄ2, H-4ꢄ2, H-4ꢁꢄ2), 5.18—5.09 [MꢃNa]ꢃ. Found: m/z 3562.4 [MꢃNa]ꢃ.
(4H, m, H-2ꢄ2, H-2ꢅꢄ2), 5.01—4.92 (4H, br d, H-3ꢄ2, H-3ꢅꢄ2), 4.77
Compound 22 Compound 22 was synthesized from 21 according to the
(2H, d, H-1ꢁ), 4.45—4.43 (4H, br d, br d, H-1ꢄ2, H-1ꢅꢄ2), 4.08 (2H, d, H- procedure described for the synthesis of 20. Yield: 65 mg (96.7%). [a]2D3
5ꢁꢄ2), 3.96—3.45 (28H, m, H-4ꢁꢄ2, H-5ꢄ2, H-5ꢅꢄ2, H-6aꢄ2, H-6bꢄ2, ꢃ2.6° (cꢀ0.8, CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.92—7.31 (40H, m,
H-6aꢅꢄ2, H-6bꢅꢄ2, COOCH3ꢄ2, NCH2CO, NCH2 of b-alanine, OCH2 of Ar-H), 5.53 (4H, t, H-3ꢁꢄ4), 5.29—5.22 (12H, d, m, H-2ꢁꢄ4, H-4ꢄ4, H-
sugar unitꢄ2), 3.40 (6H, s, OCH3ꢄ2), 3.23—3.19 (4H, m, NCH2 of sugar 4ꢅꢄ4), 5.11—5.02 (8H, m, H-2ꢄ4, H-2ꢅꢄ4), 4.94—4.85 (8H, br d, H-3ꢄ4,
unitꢄ2), 2.40 (2H, m, COCH2 of b-alanine), 2.10—1.95 (36H, m,
OAcꢄ6ꢄ2), 1.60—1.33 [25H, m, t-Bu, (CH2)ꢄ4ꢄ2]. 13C-NMR (125 MHz,
CDCl3) d 170.2, 170.0, 169.9, 169.5, 169.3, 168.4, 165.4, 164.9, 133.33,
H-3ꢅꢄ4), 4.71 (4H, d, H-1ꢁ), 4.37 (8H, dd, H-1ꢄ4, H-1ꢅꢄ4), 4.01 (4H, d,
H-5ꢁꢄ4), 3.89—3.33 (72H, m, H-4ꢁꢄ4, H-5ꢄ4, H-5ꢅꢄ4, H-6aꢄ4, H-
6bꢄ4, H-6aꢅꢄ4, H-6bꢅꢄ4, COOCH3ꢄ4, NCH2CO of b-alanineꢄ3, NCH2
133.26, 129.8, 129.1, 128.4, 101.2, 100.9, 100.6, 80.7, 78.6, 74.1, 72.0, of b-alanineꢄ3, OCH2 of sugar unitꢄ4, OCH3ꢄ4), 3.12 (8H, m, NCH2 of
71.9, 71.8, 71.0, 70.9, 70.0, 69.1, 68.7, 67.5, 67.3, 67.2, 66.8, 60.4, 52.7,
39.6, 39.4, 29.7, 29.3, 28.2, 26.7, 26.6, 25.6, 20.8, 20.7, 20.61, 20.56.
MALDI-TOF-MS: Calcd for C114H147N3O54Na: m/z 2444.9 [MꢃNa]ꢃ.
Found: m/z 2445.4 [MꢃNa]ꢃ.
sugar unitꢄ4), 2.77—2.16 (3H, m, COCH2 of b-alanineꢄ3ꢄ1/2), 2.03—
1.76 (75H, COOCH3ꢄ6ꢄ4, COCH2 of b-alanineꢄ3ꢄ1/2), 1.48—1.19
[41H, m, t-Bu, (CH2)ꢄ4ꢄ4]. 13C-NMR (125 MHz, CDCl3): d 170.1, 170.0,
169.9, 169.5, 169.3, 168.4, 165.4, 164.9, 133.33, 133.26, 130.9, 129.8,
Compound 19 To
a solution of 18 (71 mg, 29.3 mmol) in di- 129.1, 128.8, 128.4, 101.2, 100.9, 100.7, 78.6, 74.1, 72.0, 71.9, 71.83,
chloromethane (1 ml) was added trifluoroacetic acid (1 ml). The reaction 71.75, 71.0, 70.8, 69.9, 69.1, 68.7, 67.5, 67.3, 67.2, 66.8, 66.2, 60.4, 52.7,
mixture was stirred for 1 h at room temperature. After completion of the re-
action, the mixture was concentrated and purified on silica gel column chro-
39.5, 29.6, 29.3, 29.2, 28.22, 28.19, 26.7, 25.61, 25.6, 20.8, 20.7, 20.61,
20.56. MALDI-TOF-MS: Calcd for C228H291N7O108Na: m/z 4877.7
matography (chloroform : methanolꢀ20 : 1) to give 19 (60 mg, 88.1%). [a]2D3 [MꢃNa]ꢃ. Found: m/z 4877.4 [MꢃNa]ꢃ.
ꢃ2.7° (cꢀ1.0, CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.99—7.38 (20H, m,
Compound 23 Compound 23 was synthesized from 22 according to the
Ar-H), 6.22 (1H, s, NH), 5.60 (2H, t, H-3ꢁꢄ2), 5.36—5.28 (6H, m, H-2ꢁꢄ2, procedure described for the synthesis of 21. Yield: 42 mg (66.0%). [a]2D3
H-4ꢄ2, H-4ꢅꢄ2), 5.18—5.09 (4H, m, H-2ꢄ2, H-2ꢅꢄ2), 5.03—4.93 (4H, m ꢃ2.9° (cꢀ0.8, CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.91—7.31 (40H, m,
H-3ꢄ2, H-3ꢅꢄ2), 4.79 (2H, d, H-1ꢁ), 4.46 (4H, br d, br d, H-1ꢄ2, H-1ꢅꢄ2), Ar-H), 5.53 (4H, t, H-3ꢁꢄ4), 5.29—5.22 (12H, d, m, H-2ꢁꢄ4, H-4ꢄ4, H-
4.09 (2H, d, H-5ꢁꢄ2), 3.97—3.40 (30H, m, H-4ꢁꢄ2, H-5ꢄ2, H-5ꢅꢄ2, H-
4ꢅꢄ4), 5.09—5.02 (8H, m, H-2ꢄ4, H-2ꢅꢄ4), 4.98—4.86 (8H, br d, H-3ꢄ4,
6aꢄ2, H-6bꢄ2, H-6aꢅꢄ2, H-6bꢅꢄ2, COOCH3ꢄ2, OCH3ꢄ2, OCH2 of H-3ꢅꢄ4), 4.71 (4H, d, H-1ꢁ), 4.38 (8H, dd, H-1ꢄ4, H-1ꢅꢄ4), 4.02 (4H,
sugar unitꢄ2), 3.26—3.21 (4H, m, NCH2 of sugar unitꢄ2), 3.01 (2H, t, d, H-5ꢁꢄ4), 3.92—3.33 (60H, m, H-4ꢁꢄ4, H-5ꢄ4, H-5ꢅꢄ4, H-6aꢄ4,
NCH2CO of b-alanine), 2.52 (2H, m, NCH2 of b-alanine), 2.10—1.95 (38H,
H-6bꢄ4, H-6aꢅꢄ4, H-6bꢅꢄ4, COOCH3ꢄ4, OCH2 of sugar unitꢄ4,
m, OAcꢄ6ꢄ2, COCH2 of b-alanine), 1.56—1.33 [16H, (CH2)ꢄ4ꢄ2]. 13C- OCH3ꢄ4), 3.10 (8H, m, NCH2 of sugar unitꢄ4), 2.10—1.89 (78H,
NMR (125 MHz, CDCl3): d 170.0, 169.6, 169.3, 168.4, 165.4, 164.9, OAcꢄ6ꢄ4, COCH2 of b-alanineꢄ3), 1.48—1.18 [32H, m, (CH2)ꢄ4ꢄ4].
133.33, 133.26, 129.8, 129.13, 129.10, 128.4, 101.2, 100.92, 100.87, 100.7, 13C-NMR (125 MHz, CDCl3): d 170.2, 170.05, 169.98, 169.6, 169.3, 168.4,
100.6, 78.6, 74.12, 74.09, 72.0, 71.93, 71.88, 71.8, 71.01, 70.98, 70.9, 70.0,
165.5, 164.9, 133.35, 133.28, 129.9, 129.7, 129.1, 128.4, 101.2, 100.9,
69.9, 69.14, 69.09, 68.7, 67.5, 67.4, 67.3, 66.9, 66.8, 60.4, 52.8, 45.4, 39.4, 100.6, 78.6, 74.12, 74.09, 72.0, 71.9, 71.7, 71.0, 70.9, 69.9, 69.1, 68.7,
39.2, 29.32, 29.28, 29.23,29.19, 26.6, 25.6, 25.5, 20.8, 20.7, 20.62, 20.56. 67.5, 67.3, 66.8, 60.4, 52.8, 39.5, 29.6, 29.3, 26.7, 25.5, 22.6, 20.8, 20.7,
MALDI-TOF-MS: Calcd for C109H140N3O52Na: m/z 2345.8 [MꢃNa]ꢃ. 20.62, 20.56. MALDI-TOF-MS: Calcd for C223H284N7O106Na: m/z 4778.7
Found: m/z 2345.5. [MꢃNa]ꢃ.
[MꢃNa]ꢃ. Found: m/z 4778.3 [MꢃNa]ꢃ.
Compound 20 To a solution of 19 (34 mg, 14.6 mmol) and 17 (59 mg,
Compound 24 Compound 24 was synthesized from 23 according to the
44.2 mmol) in DMF (2 ml) were added triethylamine (7.3 ml, 52.4 mmol) procedure described for the synthesis of 14. Yield: 28.4 mg (86.4%). [a]2D3
and DEPC (6.2 ml, 40.9 mmol). The reaction mixture was stirred for 16 h at
room temperature. After completion of the reaction, the mixture was ex- (6H, m, C10H6 of dansyl glycine), 7.91—7.31 (40H, m, Ar-H), 5.53 (4H, t,
tracted with chloroform, washed with water, dried (Na2SO4), and concentrat- H-3ꢁꢄ4), 5.29—5.21 (12H, d, m, H-2ꢁꢄ4, H-4ꢄ4, H-4ꢅꢄ4), 5.10—5.02
ed. The product was purified on silica gel column chromatography (chloro- (8H, m, H-2ꢄ4, H-2ꢅꢄ4), 5.00—4.85 (8H, br d, H-3ꢄ4, H-3ꢅꢄ4), 4.71
(4H, d, H-1ꢁ), 4.36 (8H, dd, H-1ꢄ4, H-1ꢅꢄ4), 4.02 (4H, d, H-5ꢁꢄ4), 3.90—
ꢃ1.2° (cꢀ1.0, CHCl3). 1H-NMR (500 MHz, CDCl3): d 8.47—8.16, 7.11
form : methanolꢀ30 : 1) to give 20 (66 mg, 71.4%). [a]2D3 ꢃ0.4° (cꢀ0.9,
CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.99—7.38 (30H, m, Ar-H), 5.60 3.32 (72H, m, H-4ꢁꢄ4, H-5ꢄ4, H-5ꢅꢄ4, H-6aꢄ4, H-6bꢄ4, H-6aꢅꢄ4, H-
(3H, t, H-3ꢁꢄ3), 5.36—5.29 (9H, m, H-2ꢁꢄ3, H-4ꢄ3, H-4ꢅꢄ3), 5.18—5.09 6bꢅꢄ4, COOCH3ꢄ4, NCH2CO of b-alanineꢄ3, NCH2 of b-alanineꢄ3,
(6H, m, H-2ꢄ3, H-2ꢅꢄ3), 5.01—4.92 (6H, br d, H-3ꢄ3, H-3ꢅꢄ3), 4.77 OCH2 of sugar unitꢄ4, OCH3ꢄ4), 3.11 (8H, m, NCH2 of sugar unitꢄ4),
(3H, d, H-1ꢁ), 4.45—4.43 (6H, br d, br d, H-1ꢄ3, H-1ꢅꢄ3), 4.08 (3H, d, H- 2.81 (6H, s, NC2H6 of dansyl glycine), 2.64—2.24 (3H, m, COCH2 of b-
5ꢁꢄ3), 3.97—3.40 (53H, m, H-4ꢁꢄ3, H-5ꢄ3, H-5ꢅꢄ3, H-6aꢄ3, H-6bꢄ3, alanineꢄ3ꢄ1/2), 2.10—1.89 (75H, m, OAcꢄ6ꢄ4, COCH2 of b-
H-6aꢅꢄ3, H-6bꢅꢄ3, COOCH3ꢄ3, NCH2COꢄ2, NCH2ꢄ2 of b-alanine, alanineꢄ3ꢄ1/2), 1.48—1.18 [32H, m, (CH2)ꢄ4ꢄ4]. 13C-NMR (125 MHz,
OCH2 of sugar unitꢄ3, OCH3ꢄ3), 3.22 (6H, m, NCH2 of sugar unitꢄ3), CDCl3): d 170.1, 170.05, 169.97, 169.6, 169.5, 169.3, 168.4, 165.5, 164.9,
2.70—2.40 (4H, m, COCH2ꢄ2 of b-alanine), 2.10—1.96 (54H, m,
OAcꢄ6ꢄ3), 1.55—1.26 [33H, m, t-Bu, (CH2)ꢄ4ꢄ3]. 13C-NMR (125 MHz,
CDCl3): d 170.1, 170.0, 169.9, 169.52, 169.47, 169.3, 168.4, 165.4, 164.9,
133.33, 133.26, 129.8, 129.1, 128.4, 101.2, 100.89, 100.85, 100.6, 78.6,
74.1, 72.0, 71.9, 71.8, 71.0, 70.8, 69.9, 69.1, 68.7, 67.5, 67.3, 67.2, 66.8,
60.4, 52.7, 29.32, 29.29, 26.7, 25.6, 25.5, 20.8, 20.7, 20.61, 20.56. MALDI-
133.35, 133.28, 129.8, 129.6, 129.2, 128.4, 101.2, 100.9, 100.7, 78.6, 74.13,
74.11, 72.0, 71.9, 71.8, 71.0, 70.9, 69.9, 69.1, 68.7, 67.5, 67.3, 66.8, 60.4,
52.8, 45.4, 39.64, 39.56, 29.7, 29.3, 26.7, 26.6, 25.59, 25.56, 20.8, 20.7,
20.62, 20.57. MALDI-TOF-MS: Calcd for C237H297N9O109SNa: m/z 5067.8
[MꢃNa]ꢃ. Found: m/z 5069.5 [MꢃNa]ꢃ.
Compound 2 Compound 2 was synthesized from 24 according to the
TOF-MS: Calcd for C171H219N5O81Na: m/z 3661.3 C114H147N3O54Na. Found: procedure described for the synthesis of 1. Yield: 6.8 mg (94.0%): [a]2D3
m/z 3661.4 [MꢃNa]ꢃ.
ꢂ17.1° (cꢀ0.2, H2O). 13C-NMR (125 MHz, 1 : 1 CD3OD–D2O): d 104.5,
104.1, 103.8, 83.3, 77.5, 76.5, 74.8, 74.3, 73.94, 73.89, 71.9, 71.4, 69.9,
69.7, 60.9, 49.8, 46.0, 40.4, 31.1, 30.0, 29.6, 27.1, 26.0.
Compound 21 Compound 21 was synthesized from 20 according to the
procedure described for the synthesis of 19. Yield: 49 mg (76.3%). [a]2D3
ꢃ5.0° (cꢀ0.6, CHCl3). 1H-NMR (500 MHz, CDCl3): d 7.99—7.38 (30H, m,
Ar-H), 5.60 (3H, t, H-3ꢁꢄ3), 5.36—5.29 (9H, m, H-2ꢁꢄ3, H-4ꢄ3, H-
4ꢅꢄ3), 5.17—5.09 (6H, m, H-2ꢄ3, H-2ꢅꢄ3), 5.03—4.93 (6H, br d, H-3ꢄ3, 0.22 mmol) and DEPC (24 ml, 0.16 mmol). The reaction mixture was stirred
H-3ꢅꢄ3), 4.78 (3H, d, H-1ꢁ), 4.47—4.45 (6H, m, H-1ꢄ3, H-1ꢅꢄ3), 4.10— for 16 h at room temperature. After completion of the reaction, the mixture
Compound 18 To a solution of 13 (160 mg, 0.14 mmol) and 25
(14.3 mg, 57.9 mmol) in DMF (2 ml) were added triethylamine (30 ml,
4.08 (3H, m, H-5ꢁꢄ3), 3.97—3.40 (49H, m, H-4ꢁꢄ3, H-5ꢄ3, H-5ꢅꢄ3, H-
was extracted with chloroform, washed with water, dried (MgSO4), and con-
6aꢄ3, H-6bꢄ3, H-6aꢅꢄ3, H-6bꢅꢄ3, COOCH3ꢄ3, NCH2CO, NCH2 of b- centrated. The product was purified on silica gel column chromatography
alanine, OCH2 of sugar unitꢄ3, OCH3ꢄ3), 3.22 (6H, m, NCH2 of sugar (chloroform : methanolꢀ40 : 1) to give 18 (132 mg, 94.1%).
unitꢄ3), 2.70—2.40 (4H, m, COCH2ꢄ2 of b-alanine), 2.10—1.96 (58H,
m, OAcꢄ6ꢄ3, NCH2CO, NCH2 of b-alanine), 1.55—1.26 [24H, m,
Compound 26 To a solution of 19 (45 mg, 19.4 mmol) and 25 (1.9 mg,
7.7 mmol) in DMF (1 ml) were added triethylamine (4 ml, 29 mmol)
(CH2)ꢄ4ꢄ3]. 13C-NMR (125 MHz, CDCl3): d 170.2, 170.05, 169.97, and DEPC (3.2 ml, 21.3 mmol). The reaction mixture was stirred for 16 h at