K. Suenaga et al. / Tetrahedron 60 (2004) 8509–8527
8525
2.16 (s, 2.55H), 2.28 (m, 1H), 2.40 (m, 1H), 2.53 (m, 1H),
2.87 (br s, 0.15H), 2.92 (br s, 0.85H), 2.94 (s, 0.45H), 3.03
(s, 3H), 3.06 (s, 2.55H), 3.58 (d, JZ17.6 Hz, 0.15H), 3.71
(d, JZ9.8 Hz, 0.85H), 3.74 (d, JZ9.8 Hz, 0.15H), 3.79 (d,
JZ15.1 Hz, 0.85H), 4.16 (ddd, JZ4.9, 5.4, 6.3 Hz, 1H),
4.21 (d, JZ15.1 Hz, 0.85H), 4.47 (d, JZ17.6 Hz, 0.15H),
4.61 (d, JZ11.7 Hz, 1H), 4.59–4.73 (m, 3H), 4.75 (dd, JZ
7.8, 8.3 Hz, 0.15H), 4.82 (dd, JZ8.9, 8.8 Hz, 0.85H), 4.89
(d, JZ11.7 Hz, 0.85H), 4.92 (d, JZ11.7 Hz, 0.15H), 5.11
(d, JZ3.4 Hz, 0.15H), 5.24 (m, 0.15H), 5.27 (d, JZ2.8 Hz,
0.85H), 5.30 (br t, JZ6.8 Hz, 1H), 5.52 (dd, JZ6.4,
8.8 Hz, 0.85H), 6.46(d, JZ8.8 Hz, 0.15H), 6.62 (d, JZ9.3 Hz,
0.85H), 6.71 (d, JZ8.3 Hz, 0.85H), 6.97 (d, JZ8.3 Hz,
0.15H), 7.08 (br t, JZ6.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) (major rotamer) d 10.3 (q), 11.4 (q), 11.7 (q), 12.7
(q), 13.9 (q), 14.0 (q), 14.3 (q), 16.9 (q), 17.4 (q), 19.1 (q),
19.6 (q), 20.7 (t), 22.2 (q), 23.0 (q), 24.7 (d), 26.1 (t), 30.0
(t), 30.60 (d), 30.63 (q), 31.2 (d), 36.5 (q), 37.2 (d), 37.8 (t),
38.3 (d), 51,1 (d), 52.8 (t), 53.3 (d), 57.0 (d), 73.4 (t), 74.4
(t), 76.1 (d), 77.6 (d), 80.9 (d), 94.4 (s), 127.7 (s), 130.6 (d),
135.0 (s), 141.4 (d), 166.5 (s), 168.7 (s), 169.9 (s), 170.1 (s),
171.6 (s, 2C); MS (FAB) m/z 979 (MCNa)C; HRMS (FAB)
a pad of Celite, and the residue was washed with EtOAc.
The filtrate and the washings were combined, washed with
10% aqueous citric acid (2!30 mL), H2O (30 mL), and
brine (30 mL), successively, dried (Na2SO4), and concen-
trated. The residual oil was purified by column chromato-
graphy on silica gel (200 g, CHCl3–MeOH 20:1) to give 38
(2.07 g, 97%) as a colorless powder. [a]3D0ZK11.2 (c 1.12,
MeOH); IR (KBr) 3400 (br), 1740 (sh), 1710, 1690, 1530,
1640, 1450, 1400, 1210, 1100, 1050 cmK1 1H NMR
;
(400 MHz, CDCl3) (major rotamer) d 0.69–0.91 (m, 30H),
1.09–1.75 (m, 5H), 1.33 (d, JZ7.3 Hz, 3H), 1.57 (br s, 3H),
1.81 (br s, 3H), 1.81–2.01 (m, 4H), 2.01 (br s, 3H), 2.04–
2.30 (m, 4H), 2.82 (s, 3H), 2.94 (s, 3H), 2.97 (s, 3H), 3.83 (d,
JZ15.3 Hz, 1H), 4.01 (d, JZ15.3 Hz, 1H), 4.20–4.80 (m,
9H), 4.91 (br s, 1H), 5.05 (br s, 1H), 5.37 (br t, JZ6.8 Hz,
1H), 5.43 (dd, JZ5.9, 9.8 Hz, 1H), 6.78–6.93 (m, 3H),
7.18–7.33 (m, 4H), 7.40–7.53 (m, 2H), 7.63–7.69 (m, 2H).
A signal due to one proton (COOH) was not observed;
MS (FAB) m/z 1156 (MCNa)C; HRMS (FAB) calcd for
C61H91N5NaO13S [(MCNa)C] 1156.6232, found
1156.6240.
calcd for C44H Cl3N4NaO10S [(MCNa)C] 979.4166,
35
4.1.36. Lactam 39a. To a stirred solution of carboxylic acid
38 (427 mg, 0.377 mmol) in MeCN (20 mL) was added
diethylamine (2 mL), and the mixture was stirred at room
temperature for 2.5 h and concentrated. The residual oil was
purified by column chromatography on silica gel (12 g,
CHCl3–MeOH 30:1/5:1) to give crude amino acid 18
(344 mg) as a colorless powder. To a stirred solution of
crude amino acid 18 (344 mg) in CH2Cl2 (350 mL) and
DMF (35 mL) cooled at 0 8C were added 1-hydroxy-7-
azabenzotriazole (546 mg, 3.93 mmol) and 1-ethyl-3-(30-
dimethylaminopropyl)carbodiimide hydrochloride (734 mg,
3.84 mmol), and the mixture was stirred at room tempera-
ture for 40.5 h. The mixture was diluted with EtOAc
(200 mL), washed with 10% aqueous citric acid (2!
30 mL), H2O (30 mL), saturated aqueous NaHCO3 (30 mL),
and brine (30 mL), successively, dried (Na2SO4), and
concentrated. The residual oil was purified by column
chromatography on silica gel (FL-60D, 40 g, benzene–
acetone 10:1/5:1) to give 39a (222 mg, 66%) and 39b
(80.8 mg, 24%) as a colorless powder, respectively.
75
found 979.4139.
4.1.34. N-Methylalanine ester 37. To a stirred solution of
alcohol 36 (1.14 g, 1.19 mmol) in CH2Cl2 (4 mL) cooled at
0 8C were added N-Fmoc-N-methyl-L-alanine (578 mg,
1.78 mmol), 4-(dimethylamino) pyridine (78.7 mg,
0.644 mmol), and 1-ethyl-3-(30-dimethylaminopropyl)carbo-
diimide hydrochloride (440 mg, 2.30 mmol), and the
mixture was stirred at 0 8C for 2 h. The mixture was diluted
with EtOAc (120 mL), washed with 10% aqueous citric acid
(40 mL), H2O (40 mL), saturated aqueous NaHCO3
(40 mL), and brine (40 mL), successively, dried (Na2SO4),
and concentrated. The residual oil was purified by column
chromatography on alumina (20 g, benzene–EtOAc 1:1)
and subsequently on silica gel (50 g, benzene–acetone
10:1/5:1) to give 37 (1.41 g, 94%) as a colorless powder.
[a]3D1ZC11.7 (c 1.07, CHCl3); IR (CHCl3) 3430, 3360 (br),
1750, 1690, 1640, 1510, 1450, 1400, 1310, 1235, 1150,
1
1050 cmK1; H NMR (400 MHz, CDCl3) d 0.77–1.02 (m,
30H), 1.15–1.75 (m, 5H), 1.42 (d, JZ7.3 Hz, 3H), 1.54 (s,
0.6H), 1.56 (s, 2.4H), 1.90–2.13 (m, 4H), 1.90 (s, 3H), 2.07
(s, 0.6H), 2.10 (s, 2.4H), 2.23–2.41 (m, 4H), 2.92 (s, 3H),
2.95 (s, 0.6H), 3.02 (s, 0.6H), 3.03 (s, 2.4H), 3.06 (s, 2.4H),
3.58 (d, JZ17.6 Hz, 0.2H), 3.80 (d, JZ15.1 Hz, 0.8H), 3.85
(m, 1H), 4.21 (d, JZ15.1 Hz, 0.8H), 4.22–4.94 (m, 7.4H),
4.62 (d, JZ11.7 Hz, 1H), 4.80 (dd, JZ5.4, 8.8 Hz, 0.8H),
4.89 (d, JZ11.7 Hz, 1H), 5.02 (d, JZ9.3 Hz, 1H), 5.20 (br
d, JZ2.4 Hz, 1H), 5.25 (br t, JZ7.3 Hz, 0.2H), 5.45–5.50
(m, 1H), 5.55 (dd, JZ6.8, 8.9 Hz, 0.8H), 6.45 (d, JZ8.3 Hz,
0.2H), 6.59 (d, JZ8.8 Hz, 0.8H), 6.61 (d, JZ8.3 Hz, 0.2H),
6.71 (d, JZ8.8 Hz, 0.8H), 6.88–7.02 (m, 1H), 7.26–7.78 (m,
8H); MS (FAB) m/z 1286 (MCNa)C; HRMS (FAB) calcd
Compound 39a. [a]2D8ZC14.7 (c 0.48, CHCl3); IR (CHCl3)
3420, 3360, 1735, 1700 (sh), 1685, 1645, 1510, 1460, 1410,
1280, 1250, 1095 cmK1 1H NMR (400 MHz, CDCl3)
;
(major rotamer) d 0.80 (d, JZ6.8 Hz, 3H), 0.87 (d, JZ
6.8 Hz, 3H), 0.88 (d, JZ6.8 Hz, 3H), 0.88–0.97 (m, 15H),
0.99 (d, JZ6.8 Hz, 3H), 1.03 (d, JZ6.8 Hz, 3H), 1.24–1.74
(m, 5H), 1.41 (d, JZ7.8 Hz, 3H), 1.59 (br s, 3H), 1.88–2.23
(m, 6H), 1.98 (br s, 3H), 2.09 (s, 3H), 2.32–2.45 (m, 2H),
2.96 (s, 3H), 2.98 (s, 3H), 3.09 (s, 3H), 3.47 (d, JZ16.6 Hz,
1H), 4.08 (m, 1H), 4.11 (d, JZ16.6 Hz, 1H), 4.54 (d, JZ
11.2 Hz, 1H), 4.58 (d, JZ11.2 Hz, 1H), 4.65 (q, JZ7.8 Hz,
1H), 4.84 (dd, JZ8.9, 8.8 Hz, 1H), 4.93 (d, JZ11.2 Hz,
1H), 4.94 (dd, JZ3.7, 9.3 Hz, 1H), 4.99 (d, JZ3.4 Hz, 1H),
5.27 (t, JZ7.3 Hz, 1H), 5.51 (br t, JZ6.8 Hz, 1H), 6.63 (d,
JZ8.8 Hz, 1H), 7.21 (dd, JZ5.4, 8.8 Hz, 1H), 7.32 (d, JZ
9.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) (major rotamer)
d 9.9 (q), 10.8 (q), 11.8 (q), 12.6 (q), 13.7 (q), 14.12 (q),
14.16 (q), 14.21 (q), 16.3 (q), 17.3 (q), 19.6 (q), 20.0 (q),
20.9 (t), 22.4 (q), 23.2 (q), 24.6 (d), 26.2 (t), 28.6 (t), 30.4
(q), 30.5 (d), 31.2 (d), 31.7 (q), 35.7 (q), 36.6 (d), 37.7 (d),
for C63H Cl3N5NaO13S [(MCNa)C] 1286.5376, found
35
92
1286.5390.
4.1.35. Carboxylic acid 38. To
a stirred solution of
N-methylalanine ester 37 (2.39 g, 1.89 mmol) in THF
(75 mL) and 1 M NH4OAc (15 mL) was added activated
Zn powder (8.6 g, 132 mmol), and the mixture was stirred at
room temperature for 2 h. The mixture was filtered through