T. Tashiro et al. / Bioorg. Med. Chem. 21 (2013) 3066–3079
3077
(1H, t, J = 6.0 Hz), 4.40–4.33 (3H, m), 4.33–4.27 (2H, m), 4.04 (1H,
dd, J = 10, 6.0 Hz), 3.96 (1H, dd, J = 10, 6.5 Hz), 3.54–3.47 (2H, m),
2.43 (1H, dt, J = 14, 7.0 Hz), 2.40 (1H, dt, J = 14, 7.0 Hz), 2.30–2.23
(1H, m), 1.95–1.84 (2H, m), 1.80 (2H, quint., J = 7.0 Hz), 1.71–1.62
(1H, m), 1.48–1.14 (66H, m), 1.14 (3H, dt, J = 1.0, 7.0 Hz), 0.84
(6H, t, J = 7.0 Hz) ppm; dC (126 MHz, pyridine-d5): 173.1, 101.5,
76.6, 72.4, 71.4, 70.84, 70.79, 70.7, 70.1, 68.8, 66.7, 51.3, 36.8,
34.2, 32.2, 32.11, 30.3, 30.1, 30.03, 30.02, 30.00, 29.98, 29.97,
29.93, 29.91, 29.87, 29.81, 29.75, 29.62, 29.60, 26.5, 26.4, 22.9,
15.5, 14.3 ppm; HRMS (FAB+) m/z calcd for C52H104NO9 [M+H]+
886.7711, found 886.7714.
br t, J = 7.5 Hz), 2.31–2.23 (1H, m), 1.94–1.84 (2H, m), 1.80 (2H,
quint., J = 7.5 Hz), 1.72–1.62 (1H, m), 1.48 (3H, d, J = 6.0 Hz),
1.46–1.15 (66H, m), 0.84 (6H, t, J = 7.0 Hz) ppm; dC (126 MHz, pyr-
idine-d5): 173.1, 101.4, 76.7, 73.2, 72.6, 71.6, 69.9, 68.5, 67.5, 51.3,
36.8, 32.11, 32.10, 30.4, 30.1, 30.02, 30.01, 29.98, 29.97, 29.96,
29.91, 29.90, 29.86, 29.8, 29.7, 29.60, 29.59, 26.5, 26.4, 22.9, 17.2,
14.3 ppm; HRMS (FAB+) m/z calcd for
842.7449, found 842.7448.
C
50H100NO8 [M+H]+
4.1.11.6. (2S,3S,4R)-1-O-(6-Deoxy-6-fluoro-
syl)-2-(hexacosanamido)octadecane-1,3,4-triol
83). In the same manner as described above, 11f (81 mg,
a
-D
-galactopyrano-
16 (RCAI-
4.1.11.3. (2S,3S,4R)-2-(Hexacosanamido)-1-O-(6-O-propyl-
galactopyranosyl)octadecane-1,3,4-triol 13 (RCAI-86).
a
-
In
D
-
0.072 mmol) was converted to 16 (RCAI-83, 49 mg, 79%) as color-
less powder. Mp 123.5–127.0 °C; ½a D22
ꢂ
+50.7 (c 0.24, pyridine); mmax
the same manner as described above, 11c (169 mg, 0.144 mmol)
was converted to 13 (RCAI-86, 80 mg, 61%) as colorless powder.
(KBr): 3440 (br s, OH), 3310 (br s, NH), 1635 (br s, CO), 1545 (br m),
1150 (br m), 1075 (br s, C–O), 1030 (br s, C–O) 795 (m), 720 (m)
cmꢁ1; dH (500 MHz, pyridine-d5): 8.45 (1H, d, J = 9.0 Hz), 7.15
(1H, br s), 6.91 (1H, br s), 6.65 (1H, br s), 6.47 (1H, br s), 6.11
(1H, br s), 5.55 (1H, d, J = 4.0 Hz), 5.31–5.26 (1H, m), 5.00 (1H,
ddd, J = 49, 9.5, 7.5 Hz), 4.95 (1H, ddd, J = 47, 9.5, 4.5 Hz), 4.67
(1H, dd, J = 11, 5.5 Hz), 4.60 (1H, dd, J = 10, 4.0 Hz), 4.50 (1H, br
dt, J = 14, 6.5 Hz), 4.39 (1H, dd, J = 10, 3.5 Hz), 4.36–4.29 (4H, m),
2.43 (1H, dt, J = 15, 7.5 Hz), 2.41 (1H, dt, J = 15, 7.5 Hz), 2.32–2.25
(1H, m), 1.96–1.84 (2H, m), 1.80 (2H, quint., J = 7.5 Hz), 1.72–1.62
(1H, m), 1.47–1.16 (66H, m), 0.85 (6H, t, J = 7.0 Hz) ppm; dC
(126 MHz, pyridine-d5): 173.1, 101.4, 84.2 (d, J = 167 Hz), 76.7,
72.5, 71.0, 70.7 (d, J = 21 Hz), 70.3 (d, J = 6.9 Hz), 69.9, 68.6, 51.1,
36.8, 34.4, 32.1, 30.4, 30.1, 30.03, 30.02, 29.99, 29.98, 29.97,
29.92, 29.91, 29.85, 29.8, 29.7, 29.61, 29.60, 26.5, 26.4, 22.9,
Mp 104.0–106.5 °C; ½a D23
ꢂ
+43.0 (c 0.30, pyridine); mmax (KBr):
3420 (br s, OH), 3280 (br m, NH), 1645 (br s, CO), 1545 (br m),
1080 (br s, C–O), 720 (m) cmꢁ1; dH (500 MHz, pyridine-d5): 8.44
(1H, d, J = 8.5 Hz), 7.04 (1H, br s), 6.70 (1H, br s), 6.42 (1H, d,
J = 6.0 Hz), 6.35 (1H, br s), 6.07 (1H, br s), 5.52 (1H, d, J = 4.0 Hz),
5.27–5.22 (1H, m), 4.65 (1H, dd, J = 11, 5.5 Hz), 4.61 (1H, br d,
J = 9.5 Hz), 4.46 (1H, t, J = 6.5 Hz), 4.41–4.34 (2H, m), 4.36 (1H,
dd, J = 11, 5.0 Hz), 4.34–4.28 (2H, m), 4.06 (1H, dd, J = 9.5, 6.0 Hz),
3.97 (1H, dd, J = 9.5, 6.5 Hz), 3.47–3.39 (2H, m), 2.44 (2H, dt,
J = 15, 7.0 Hz), 2.41 (1H, dt, J = 15, 7.0 Hz), 2.31–2.24 (1H, m),
1.95–1.85 (2H, m), 1.81 (2H, quint., J = 7.5 Hz), 1.72–1.63 (1H, m),
1.56 (2H, sext., J = 7.0 Hz), 1.47–1.17 (66H, m), 0.87 (3H, br t,
J = 7.0 Hz), 0.85 (6H, t, J = 7.0 Hz) ppm; dC (126 MHz, pyridine-d5):
173.0, 101.5, 76.6, 73.0, 72.4, 71.4, 70.9, 70.8, 70.7, 70.1, 68.7,
51.2, 36.7, 34.3, 32.1, 30.3, 30.1, 30.02, 30.01, 29.99, 29.97, 29.92,
29.90, 29.86, 29.8, 29.7, 29.61, 29.59, 26.5, 26.4, 23.4, 22.9, 14.3,
14.3 ppm; HRMS (FAB+) m/z calcd for
C
50H99NO8F [M+H]+
860.7355, found 860.7357.
10.8 ppm; HRMS (FAB+) m/z calcd for
C
53H106NO9 [M+H]+
4.1.11.7. (2S,3S,4R)-1-O-(b-
ido)octadecane-1,3,4-triol 18 (RCAI-87).
L
-rabinopyranosyl)-2-(hexacosanam-
In the same man-
900.7868, found 900.7866.
ner as described above, 11g (205 mg, 0.187 mmol) was converted
to 18 (RCAI-87, 49 mg, 32%) as colorless powder. Mp 151.0–
4.1.11.4. (2S,3S,4R)-1-O-(6-Deoxy-6-methyl-
syl)-2-(hexacosanamido)octadecane-1,3,4-triol
64). In the same manner as described above, 11d (247 mg,
a
-
D
-galactopyrano-
14 (RCAI-
153.0 °C; ½a 2D4
ꢂ
+75.1 (c 0.20, pyridine); mmax (KBr): 3480 (w, OH),
3240 (br s, OH), 3100 (w, NH), 1615 (s, CO), 1570 (br m), 1140
(br s, C–O), 1100 (m, C–O), 1080 (br s, C–O) 1020 (s, C–O), 1000
(s, C–O), 720 (m) cmꢁ1; dH (500 MHz, pyridine-d5, 45 °C): 8.14
(1H, d, J = 8.5 Hz, NH), 6.61 (1H, br s, OH), 6.30 (1H, br s, OH),
6.14 (1H, br d, J = 5.0 Hz, OH), 5.92 (1H, br s, OH), 5.82 (1H, br s,
OH), 5.46 (1H, d, J = 3.5 Hz, 10-H), 5.20–5.15 (1H, m, 2-H), 4.59
(1H, dd, J = 11, 5.5 Hz, 1-Ha), 4.53 (1H, dd, J = 9.5, 3.5 Hz, 20-H),
4.36 (1H, dd, J = 9.5, 3.0 Hz, 30-H), 4.29–4.22 (3H, m, 3-, 4-, 40-H),
4.25 (1H, dd, J = 11, 4.5 Hz, 1-Hb), 4.15 (1H, br d, J = 12 Hz, 50-Ha),
3.99 (1H, dd, J = 12, 2.5 Hz, 50-Hb), 2.41 (1H, dt, J = 15, 7.5 Hz, 200-
Ha), 2.38 (1H, dt, J = 15, 7.5 Hz, 200-Hb), 2.28–2.21 (1H, m, 5-Ha),
1.93–1.84 (2H, m, 5-Hb, 6-Ha), 1.80 (2H, quint., J = 7.5 Hz, 300-H2),
1.72–1.63 (1H, m, 6-Hb), 1.48–1.20 (66H, m), 0.87 (6H, t,
J = 7.0 Hz, 18-, 2600-H3) ppm; dC (126 MHz, pyridine-d5): 173.0,
101.7, 76.7, 72.5, 70.8, 70.3, 70.2, 68.4, 64.4, 51.1, 36.8, 34.4,
32.1, 30.3, 30.1, 30.02, 30.01, 29.98, 29.97, 29.91, 29.90, 29.85,
29.8, 29.7, 29.61, 29.59, 26.5, 26.4, 22.9, 14.3 ppm. This spectrum
indicates the conformation of 18 as 4C1; HRMS (FAB+) m/z calcd
for C49H98NO8 [M+H]+ 828.7292, found 828.7294.
0.288 mmol) was converted to 14 (RCAI-64, 151 mg, 61%) as color-
less powder. Mp 130.0–133.5 °C; ½a D26
ꢂ
+55.7 (c 0.36, pyridine); mmax
(KBr): 3440 (br m, OH), 3270 (br m, NH), 1645 (br s, CO), 1540 (m),
1090 (br m, C–O), 1035 (br m, C–O) cmꢁ1; dH (400 MHz, pyridine-
d5): 8.49 (1H, d, J = 8.8 Hz), 6.98 (1H, br s), 6.59 (1H, br s), 6.44 (1H,
br d, J = 7.2 Hz), 6.13 (2H, br s), 5.48 (1H, d, J = 3.6 Hz), 5.33–5.26
(1H, m), 4.64 (1H, dd, J = 10, 5.6 Hz), 4.60–4.54 (1H, m), 4.38–
4.27 (3H, m), 4.27 (1H, dd, J = 10, 4.8 Hz), 4.17 (1H, br s), 3.99
(1H, t, J = 6.8 Hz), 2.44 (2H, t, J = 6.8 Hz), 2.35–2.25 (1H, m), 2.15–
2.03 (1H, m), 1.98–1.77 (5H, m), 1.74–1.61 (1H, m), 1.47–1.16
(66H, m), 1.05 (3H, t, J = 7.2 Hz), 0.84 (6H, t, J = 7.2 Hz) ppm; dC
(100 MHz, pyridine-d5): 173.0, 101.2, 76.8, 72.9, 72.5, 71.7, 70.2,
68.1, 51.1, 36.8, 34.5, 32.1, 30.4, 30.1, 30.02, 29.99, 29.93, 29.86,
29.8, 29.7, 29.6, 26.5, 26.4, 24.4, 22.9, 14.3, 10.8 ppm; HRMS
(FAB+) m/z calcd for
C
51H102NO9 [M+H]+ 856.7605, found
856.7606.
4.1.11.5. (2S,3S,4R)-1-O-(
do)octadecane-1,3,4-triol 15 (RCAI-58).
a
-
D
-Fucopyranosyl)-2-(hexacosanami-
In the same manner
as described above, 11e (52 mg, 0.47 mmol) was converted to 15
4.1.11.8. (2S,3S,4R)-1-O-[6-O-(methoxylmethyl)-
anosyl]-2-(hexacosanamido)octadecane-1,3,4-triol 23 (RCAI-
113). In the same manner as described above, 22a (175 mg,
a-D-galactopyr-
(RCAI-58, 34 mg, 85%) as colorless powder. Mp 127.0–129.0 °C;
½
a 2D7
+47.4 (c 0.31, pyridine); mmax (KBr): 3360 (br s, OH), 3300
ꢂ
(m, NH), 1645 (br s, CO), 1545 (m), 1085 (br m, C–O), 1050 (br
m, C–O), 720 (m) cmꢁ1; dH (500 MHz, pyridine-d5): 8.41 (1H, d,
J = 8.5 Hz), 6.38 (1H, br s), 5.44 (1H, d, J = 3.5 Hz), 5.27–5.22 (1H,
m), 4.97 (4H, br s), 4.61 (1H, dd, J = 10, 5.0 Hz), 4.53 (1H, dd,
J = 10, 4.0 Hz), 4.36 (1H, dd, J = 10, 3.5 Hz), 4.32–4.26 (3H, m),
4.28 (1H, dd, J = 10, 5.0 Hz), 4.06 (1H, br d, J = 2.0 Hz), 2.42 (2H,
0.129 mmol) was converted to 23 (RCAI-113, 84 mg, 72%) as color-
less powder. Mp 109.5–111.0 °C; ½a D21
ꢂ
+43.1 (c 0.30, pyridine); mmax
(KBr): 3440 (br s, OH), 3280 (s, NH), 1640 (br s, CO), 1545 (br m),
1140 (br s, C–O), 1075 (br s, C–O), 1050 (br s, C–O), 720 (br s)
cmꢁ1; dH (500 MHz, pyridine-d5): 8.40 (1H, d, J = 8.5 Hz), 6.40
(1H, br s), 5.52 (1H, d, J = 4.0 Hz), 5.27–5.22 (1H, m), 5.20 (4H, br