3286
L. Liu, R. Breslow / Bioorg. Med. Chem. 12 (2004) 3277–3287
residue was re-dissolved in 100 mL of methanol. Two
milliliters of H SO (concd) was added. The reaction was
refluxed for 2 h. The solvent was removed. The solution
was neutralized using NaHCO (aq) solution. The prod-
3
(CD OD, 300 MHz): 8.43, s, 1H; 5.75, s, 1H; 5.11, s, 2H;
2
4
3.99, s, 2H; 3.76, s, 3H; 3.62, s, 6H; 3.32, m, 4H; 2.95, m,
8H; 2.59, s, 3H; 2.48, m, 4H. This product (0.12 g) was
dissolved in 2 mL of methanol. Triethylamine (0.4 mL)
was added. Then 0.4 mL of acetic anhydride was added.
The reaction was stirred at room temperature for 0.5 h.
The product was purified using flash chromatography.
3
uct was extracted out using methylene chloride. Yield:
1
quantitative. CI MS: 339.9 (M+1). H NMR (CD OD,
3
3
2
00 MHz): 7.80, s, 1H; 4.92, s, 2H; 3.72, s, 6H; 3.69, s, 2H;
.82, t, 4H, J ¼ 6:8 Hz; 2.58, t, 4H; 2.49, s, 3H.
1
CI MS: 567.3 (M+1). FAB MS+: 569.41 (M+1). H
NMR (CD OD, 300 MHz): 8.47, s, 1H; 5.78, s, 1H; 5.13,
3
s, 2H; 3.99, s, 2H; 3.78, s, 3H; 3.62, s, 6H; 3.40, m, 8H;
2.85, m, 4H; 2.59, s, 3H; 2.48, m, 4H, 2.05, s, 6H.
4
methyl)-(2-methoxycarbonyl-ethyl)-amino]-propionic acid
.2.25.
3-[(4-Formyl-5-hydroxy-6-methyl-pyridin-3-yl-
methyl ester (14). Two grams of 13 was dissolved in
1
00 mL of methylene chloride. Ten grams of MnO
added. The reaction was stirred at room temperature for
h. The product was purified using flash chromatogra-
2
was
4.2.30. G2-Ac (protected). FAB MS+: 1109.9. (Exact
1
mass for C H N O : 1108.7.) H NMR (CD OD,
88 14 14
50
3
4
300 MHz): 8.38, s, 1H; 5.78, s, 1H; 5.12, s, 2H; 3.98, s,
2H; 3.70, s, 3H; 3.55, s, 6H; 3.28, m, 20H; 2.95–2.38, m,
31H; 2.02, s, 12H.
1
phy. Yield: 86%. CI MS: 337.9 (M+1). H NMR
CDCl , 300 MHz): 11.57, s, 1H; 10.47, s, 1H; 8.02, s,
H; 3.91, s, 2H; 3.70, s, 6H; 2.91, t, 4H, J ¼ 6:8 Hz; 2.61,
s, 3H; 2.54, t, 4H.
(
1
3
4
1
.2.31. G2-Me (protected). FAB MS+: 1053.3 (M+1).
075.2 (M+Na). (Exact mass for C50 10: 1052.7.)
O, 300 MHz): 8.29, s, 1H; 5.73, s, 1H; 5.05,
96 14
H N O
1
H NMR (D
2
4
.2.26. 3-[(4-Dimethoxymethyl-5-hydroxy-6-methyl-pyr-
s, 2H; 3.79, s, 2H; 3.54, s, 3H; 3.40, s, 6H; 3.20, m, 12H;
2
idin-3-ylmethyl)-(2-methoxy-carbonyl-ethyl)-amino]-prop-
ionic acid methyl ester (15). Compound 14 (1.8 g) was
dissolved in 20 mL of methanol. Twenty milliliters of
HC(OCH ) was added. One gram Me–C H –SO H was
3 3 6 4 3
added. The reaction was refluxed overnight. The prod-
uct was purified using flash chromatography. Yield:
.75–2.20, m, 39H; 2.11, s, 24H.
4
.2.32. G3-Ac (protected). MALDI MS: 2211.0 (M+23).
1
(Exact mass for C98
(D O, 300 MHz): 8.31, s, 1H; 5.81, s, 1H; 5.12, s, 2H;
H
176
N
30
O
26: 2189.3.) H NMR
2
1
4.28, s, 2H; 3.62, s, 3H; 3.55, s, 6H; 3.45–2.39, m, 115H;
.98, s, 24H.
8
3
6
6%. CI MS: 383.9 (M+1). H NMR (CDCl
3
,
00 MHz): 8.95, s, 1H; 7.98, s, 1H; 6.30, s, 1H; 3.95, s,
1
H; 3.82, s, 2H; 3.70, s, 6H; 2.91, t, 4H, J ¼ 6:8 Hz; 2.61,
s, 3H; 2.54, t, 4H.
4.2.33. G3-Me (protected). MALDI MS: 2076.4. (Exact
1
mass for C H N O : 2077.5). H NMR (D O,
192 30 18
98
2
3
00 MHz): 8.29, s, 1H; 5.72, s, 1H; 5.03, s, 2H; 3.78, s,
4
methyl-pyridin-3-ylmethyl)-(2-methoxycarbonyl-ethyl)-
.2.27.
3-[(4-Dimethoxymethyl-5-methoxymethoxy-6-
2H; 3.64, s, 3H; 3.45, s, 6H; 3.35–2.18, m, 28H; 2.80–
2.30, m, 84H; 2.25, s, 48H.
amino]-propionic acid methyl ester (16). Compound 15
(1.2 g) was dissolved in 40 mL of DMF. NaH (0.14 g)
was added. After 30 min, 0.25 mL of MeOCH Cl was
4.2.34. G4-Ac (protected). MALDI MS: 4360.24 (M+1),
2
added. The reaction was stirred at room temperature
overnight. The product was purified using flash chro-
352 62 50
4383.69 (M+23). (Exact mass for C194H N O :
4350.7.) H NMR (D O, 300 MHz): 3.50, sb, 92H; 3.00–
2
2.50, m, 151H; 1.98, s, 48H.
1
1
matography. Yield: 86%. CI MS: 428.8 (M+1).
NMR (CD
s, 2H; 3.99, s, 2H; 3.71, s, 6H; 3.68, s, 3H; 3.52, s, 6H;
H
3
OD, 300 MHz): 8.48, s, 1H; 5.79, s, 1H; 5.13,
2
.89, t, 4H, J ¼ 6:8 Hz; 2.60, m, 7H.
4.2.35. G4-Me (protected). MALDI MS: 4150.0 (M+23).
1
(
(
Exact mass for C194
H
384
N
62
O
D O, 300 MHz): 8.28, s, 1H; 5.69, s, 1H; 5.05, s, 2H;
34: 4127.0.) H NMR
2
4
.2.28. G1-Me (protected). Compound 15 (0.08 g) was
3.79, s, 2H; 3.60, s, 3H; 3.48, s, 6H; 3.28, m, 60H; 2.95–
2.25, m, 183H; 2.22, s, 96H.
dissolved in 2 mL of MeOH. One milliliter of N,N-di-
methylethylenediamine was added. The reaction was
stirred at 60 ꢁC for 3 days. The product was purified
1
using flash chromatography. CI MS: 541.3 (M+1). H
4.2.36. G5-Ac (protected). MILDI MS: 7600–9300.
1
NMR (D
2
O, 300 MHz): 8.31, s, 1H; 5.70, s, 1H; 5.08, s,
H; 3.80, s, 2H; 3.61, s, 3H; 3.41, s, 6H; 3.30, m, 4H;
.85–2.25, m, 27H.
(Exact mass for C386
(D
1.98, s, 96H.
H
704
N
126
O
98: 8673.4.) H NMR
2
2
2
O, 300 MHz): 3.50, sb, 188H; 3.00–2.50, m, 311H;
4
.2.29. G1-Ac (protected). One gram of 15 was dissolved
4.2.37. G5-Me (protected). MILDI MS: 6000–8000.
1
in 20 mL of methanol. Forty milliliters of ethylenedi-
amine was added. The reaction was stirred at room
temperature for 48 h. The product was purified using
768 126
(Exact mass for C386H N O66: 8226.1.) H NMR
(D O, 300 MHz): 8.24, s, 1H; 5.61, s, 1H; 5.01, s, 2H;
2
3.56, s, 3H; 3.38, s, 6H; 3.25, m, 124H; 2.95–2.25, m,
375H; 2.22, s, 192H.
1
flash chromatography. CI MS: 483.6 (M+1). H NMR