H. Moriyama et al. / Bioorg. Med. Chem. 9 (2001) 1479–1491
1489
chloride in the presence of triethylamine to afford 34e
(70 mg, 11.8%) as a colorless solid: 1H NMR (250 MHz,
CDCl3) d 0.80–0.95 (m, 3H), 1.15–1.45 (m, 28H), 1.65–
1.80 (m, 2H), 2.37 (t, 2H, J=7.0 Hz), 3.93 (s, 3H), 3.95
(s, 3H), 6.85 (d, 1H, J=8.5 Hz), 7.20 (s, 2H), 7.63 (d,
2H, J=8.7 Hz), 7.75–7.85 (m, 3H), 7.97 (dd, 1H, J=2.6,
1.7 Hz), 8.33 (s, 1H), 8.67 (d, 1H, J=2.0 Hz), 9.08 (s,
1H), 9.23 (d, 1H, J=2.1 Hz);TOF–MS 710 (M ++Na),
726 (M++K).
3-[3-(4-Octadecanoylaminophenyl)propionylamino]-30,4-
oxydibenzoicꢁacid (5). Yield 99.1% as a colorless solid;
1
mp 209–213 C (dec.); H NMR (250 MHz, DMSO-d6)
d 0.75–0.90 (m, 3H), 1.10–1.70 (m, 30H), 2.25 (t, 2H,
J=7.4 Hz), 2.60–2.70 (m, 2H), 2.70–2.80 (m, 2H), 6.95
(d, 1H, J=8.6 Hz), 7.11 (d, 2H, J=8.3 Hz), 7.25–7.35
(m, 1H), 7.46 (d, 1H, J=8.3 Hz), 7.50–7.60 (m, 1H),
7.60–7.70 (m, 1H), 7.70–7.80 (m, 1H), 8.61 (bs, 1H),
9.60 (s, 1H), 9.73 (s, 1H);TOF–MS 709 (M ++Na).
Methyl 3-(4-octadecanoylaminobenzoylamino)-4-phenoxy-
benzoate (34f). yield 80.7% as a solid;mp 103–107 ꢁC;
1H NMR (250 MHz, CDCl3) d 0.88 (t, 3H, J=7.1 Hz),
1.10–1.45 (m, 28H), 1.60–1.85 (m, 2H), 2.39 (t, 2H,
J=7.1 Hz), 3.92 (s, 3H), 6.84 (d, 1H, J=8.6 Hz), 7.11
(d, 2H, J=7.5 Hz), 7.20–7.50 (m, 4H), 7.65 (d, 2H,
J=8.5 Hz), 7.75 (dd, 1H, J=8.5, 2.0 Hz), 7.84 (d, 2H,
J=8.7 Hz), 8.53 (bs, 1H), 9.25 (d, 1H, J=2.0 Hz). Anal.
(C39H52N2O5) calcd for C, 74.49;H, 8.33;N, 4.45;
found C, 74.39;H, 8.22;N, 4.55.
3-(3-Octadecanoylaminobenzoylamino)-30,4-oxydibenzoic
acidꢁ (6). Yield 42.0% as a colorless solid;mp 168–
1
169 C; H NMR (250 MHz, DMSO-d6) d 0.83 (t, 3H,
J=7.0 Hz), 1.10–1.70 (m, 30H), 2.28 (t, 2H, J=7.0 Hz),
6.98 (d, 1H, J=9.0 Hz), 7.30–7.40 (m, 2H), 7.45–7.60
(m, 3H), 7.70–7.90 (m, 3H), 8.00–8.05 (m, 1H), 8.32 (d,
1H, J=2.0 Hz), 9.98 (bs, 1H), 10.03 (bs, 1H);TOF–MS
681(M++Na).
3-(2-Octadecanoylaminobenzoylamino)-30,4-oxydibenzo-
ate (7). Yield 23.0% as a colorless powder;mp 180–
183 ꢁC; 1H NMR (250 MHz, DMSO-d6) d 0.70–0.95 (m,
3H), 1.00–1.38 (m, 28H), 1.40–1.63 (m, 2H), 2.21 (t, 2H,
J=7.4 Hz), 7.01 (d, 1H, J=8.5 Hz), 7.15 (t, 1H,
J=7.6 Hz), 7.35 (dd, 1H, J=8.1, 2.2 Hz), 7.40–7.59 (m,
3H), 7.64 (d, 1H, J=7.8 Hz), 7.75 (d, 1H, J=7.6 Hz),
7.80 (dd, 1H, J=8.5, 2.1 Hz), 8.10 (d, 1H, J=8.3 Hz),
8.38 (d, 1H, J=2.0 Hz), 10.14 (s, 1H), 10.53 (s, 1H);
TOF–MS 681(M++Na).
Ethyl 4-[4-methoxycarbonyl-2-(4-octadecanoylaminoben-
zoylamino)-phenoxy]butanoate (40). Yield 87.1% as a
solid; 1H NMR (250 MHz, CDCl3) d 0.88 (t, 3H,
J=7.1 Hz), 1.20 (t, 3H, J=7.1 Hz), 1.20–1.80 (m, 30H),
2.15–2.30 (m, 2H), 2.38 (t, 2H, J=7.6 Hz), 2.52 (t, 2H,
J=6.8 Hz), 3.90 (s, 3H), 4.09 (q, 2H, J=7.1 Hz), 4.20 (t,
2H, J=6.2 Hz), 6.93 (d, 1H, J=8.6 Hz), 7.21 (s, 1H),
7.67 (d, 2H, J=8.7 Hz), 7.81 (dd, 1H, J=8.6, 2.1 Hz),
7.91 (d, 2H, J=8.7 Hz), 8.48 (s, 1H), 9.15 (d, 1H,
J=2.1 Hz);TOF–MS 689 (M ++Na), 705 (M++K).
3-(4-Hexadecanoylaminobenzoylamino) -30,4- oxydiben-
zoic acid (8). Yield 8.7% as a colorless powder;mp
239–240 ꢁC (dec.); 1H NMR (250 MHz, DMSO-d6) d
0.75–0.95 (m, 3H), 1.10–1.45 (m, 24H), 1.50–1.70 (m,
2H), 2.32 (t, 2H, J=6.8 Hz), 7.02 (d, 1H, J=8.5 Hz),
7.35 (dd, 1H, J=8.1, 2.6 Hz), 7.45–7.60 (m, 2H), 7.60–
7.90 (m, 6H), 8.38 (d, 1H, J=2.6 Hz), 9.78 (s, 1H), 10.06
(s, 1H);TOF–MS 653 (M ++Na).
General procedure for the preparation of 3–18: 3-(4-
Octadecanoylamino-benzoylamino)-30,4-oxydibenzoic acid
(3). 25a (300 mg, 0.44 mM) was dissolved in 1,4-diox-
ane–MeOH (9–3 mL), and 1 N NaOH (4.1 mL) was
added to the solution, and then the mixture was stirred
for 5.5 h at rt. Cold water (30 mL) was added to the
mixture, the resulting mixtute was adjusted to pH 1
using c HCl, and then extracted with AcOEt. The
organic layer was washed with water and brine succes-
sively, dried over MgSO4, and concentrated. The
resulting precipitate was washed with n-hexane
(30 mL), and then purified by HPLC eluting with 9:1
CH3CN/0.1% TFA aq to afford 3 (63 mg, 21.9%) as a
colorless powder: mp 240 ꢁC (dec.); 1H NMR
(250 MHz, DMSO-d6) d 0.80–0.85 (m, 3H), 1.10–1.34
(m, 28H), 1.46–1.65 (m, 2H), 2.30 (t, 2H, J=7.4 Hz),
7.00 (d, 1H, J=8.6 Hz), 7.30–7.40 (m, 1H), 7.45–7.60
(m, 2H), 7.60–7.85 (m, 6H), 8.37 (d, 1H, J=2.2 Hz),
9.79 (s, 1H), 10.07 (s, 1H);TOF–MS 681(M ++Na).
Anal. (C39H50N2O7*H2O) calcd for C, 69.21;H, 7.74 ;
N, 3.95;found C, 68.95;H, 7.57;N, 4.23.
3-(4-Tetradecanoylaminobenzoylamino)-30,4-oxydibenzoic
acid (9). Yield 22.8% as a pale red solid;mp >216 ꢁC;
1H NMR (250 MHz, DMSO-d6) d 0.80–0.95 (m, 3H),
1.15–1.40 (m, 22H), 2.25–2.40 (m,2H), 7.01 (d, 1H,
J=8.5 Hz), 7.30–7.40 (m, 1H), 7.45–7.60 (m, 2H), 7.60–
7.85 (m, 5H), 8.37 (d, 1H, J=2.3 Hz), 9.77 (s, 1H), 10.05
(s, 1H);TOF–MS 625 (M ++Na).
3-[4-(2-Heptylnonanoylamino)benzoylamino]-30,4-oxydi-
benzoic acid (10). Yield 70.6% as a colorless solid;mp
235–237 ꢁC; 1H NMR (250 MHz, DMSO-d6) d 0.70–
0.95 (m, 6H), 1.00–1.45 (m, 22H), 1.45–1.70 (m, 2H),
2.25–2.45 (m, 1H), 7.02 (d, 1H, J=8.6 Hz), 7.25–7.40
(m, 1H), 7.40–7.60 (m, 2H), 7.60–7.90 (m, 6H), 8.37 (d,
1H, J=1.6 Hz), 9.79 (bs, 1H), 10.04 (bs, 1H);TOF–MS
653 (M++Na).
3-[(4-Octadecanoylaminophenyl)acetylamino]-30,4-oxydi-
benzoic acid (4). Yield 29.7% as a colorless solid;mp
225–231 ꢁC (dec.); 1H NMR (250 MHz, DMSO-d6) d
0.84 (t, 3H, J=7.3 Hz), 1.00–1.50 (m, 28H), 1.40–1.70
(m, 2H), 2.27 (t, 2H, J=7.4 Hz), 3.65 (s, 2H), 6.97 (d,
1H, J=8.5 Hz), 7.16 (d, 2H, J=8.5 Hz), 7.20–7.40 (m,
1H), 7.40–7.60 (m, 4H), 7.67 (dd, 1H, J=8.6, 2.1 Hz),
7.77 (d, 1H, J=7.7 Hz), 8.50–8.70 (m, 1H), 9.79 (s, 1H),
9.81 (s, 1H);TOF–MS 695 (M ++Na).
3-[4-[(9Z,12Z)-9,12-Octadecadienoylamino]benzoylamino]-
30,4-oxydibenzoic acid (11). yield 32.2% as a colorless
ꢁ
1
solid;mp 224–226 C; H NMR (250 MHz, DMSO-d6)
d 0.83 (t, 3H, J=7.0 Hz), 1.20–1.40 (m, 14H), 1.55–1.65
(m, 2H), 1.95–2.05 (m, 4H), 2.31 (t, 2H, J=7.0 Hz), 2.72
(t, 2H, J=5.0 Hz), 5.20–5.40 (m, 4H), 7.01 (d, 1H,
J=9.0 Hz), 7.30–7.40 (m, 1H), 7.52 (d, 1H, J=8.0 Hz),