7134
A. K. Bhattacharya, K. C. Rana / Bioorg. Med. Chem. 19 (2011) 7129–7135
4
128.3, 128.5, 128.8, 128.9, 129.0, 129.4, 129.6, 136.4, 136.8 (d, JPC
7.22–7.39 (5H, m); dC (50 MHz, CDCl3) 16.2, 16.3, 21.9, 22.9,
3
3
4.0), 136.3, 139.3 (d, JPC 13.5), 156.1 and 170.2; dP (161 MHz,
24.7, 28.2, 40.7, 53.2, 54.9 (d, JPC 22.3), 62.0, 62.1, 80.1, 117.1
CDCl3) 28.34; ESI-MS: m/z 573.7 (M+Na)+.
(d, JPC 187.0), 127.3, 128.1, 128.9, 138.6, 150.8 (d, JPC 5.9),
155.9 and 172.0; dP (161 MHz, CDCl3) 17.80; ESI-MS: m/z 505.4
(M+Na)+.
1
2
4.2. General procedure for peptide coupling reaction
Compound 6 (135 mg, 0.5 mmol), HOBt (77 mg, 0.5 mmol) and
protected amino acid (0.5 mmol) were dissolved in dry THF (2 mL)
and the resulting solution was stirred in an ice-cooled water bath.
DCC (123 mg, 0.6 mmol) was added to it. Stirring was continued
for 1 h at 0 °C and an additional 1 h at rt. The solid which
separated was removed by filtration and the solvent evaporated
in vacuum. The crude dipeptide derivative was purified by chro-
matography on a silica gel column with ethyl acetate/petroleum
ether (3:2 to 4:1) as eluant to furnish the corresponding peptide
15a–j.
4.2.5. Compound (15e)
Yield: 60%; colourless syrup; (Found: C, 63.72; H, 6.32; N,
5.10.Calcd for C30H35N2O6P: C, 63.60; H, 6.23; N, 4.94%); mmax
(CHCl3)/cmꢂ1 3422, 3287, 3018, 1712, 1672, 1515, 1454, and
1216 cmꢂ1; dH (200 MHz, CDCl3) 1.20 (6H, t, JPH 6.9), 1.26 (3H, t,
3
3JPH 6.9), 2.83–3.05 (2H, m), 3.91–4.12 (4H, m), 4.39–4.55 (1H,
m), 4.93 (2H, s), 5.59–5.88 (2H, m) and 6.60–7.49 (15H, m); dC
3
(50 MHz, CDCl3) 16.2, 16.3, 37.9, 55.2 (d, JPC 22.7), 56.5, 62.4,
1
67.1, 117.5 (d, JPC 187.4), 126.0, 126.7, 127.3, 127.9, 128.2,
128.5, 128.7, 128.9, 129.0, 130.3, 130.4, 134.1, 136.0, 138.2, 150.7
2
(d, JPC 5.1), 155.9 and 171.0; dP (161 MHz, CDCl3) 17.71; ESI-MS:
4.2.1. Compound (15a)
m/z 589.0 (M+Na)+.
Yield: 53%; colourless syrup; (Found: C, 65.55; H, 6.33; N, 5.23.
Calcd for C30H35N2O6P: C, 65.44; H, 6.41; N, 5.09%); mmax (CHCl3)/
cmꢂ1 3424, 3019, 1713, 1676, 1497, 1395 and 1215 cmꢂ1; dH
(200 MHz, CDCl3) 1.17–1.33 (6H, m), 3.04 (2H, dd, J 6.4, 5.4),
3.90–4.09 (4H m), 4.52–4.54 (1H, m), 4.94–5.00 (2H, m),
5.53–5.95 (2H, m), 5.71–5.72 (1H, br s), 6.65–7.00 (1H m) and
7.07–7.42 (15H, m); dC (50 MHz, CDCl3) 16.3, 16.4, 38.9, 55.0 (d,
4.2.6. Compound (15f)
Yield: 60%; colourless syrup; (Found: C, 65.24; H, 6.21; N,
7.22.Calcd for C32H36N3O6P: C, 65.18; H, 6.15; N, 7.13%); mmax
(CHCl3)/cmꢂ1 3419, 3297, 3019, 2933, 1712, 1675, 1500, 1216
and 1051 cmꢂ1; dH (200 MHz, CDCl3) 1.21–1.36 (6H, m), 3.04–
3.39 (2H, m), 3.91–4.14 (4H, m), 4.52–4.69 (1H, m), 5.06 (2H, s),
5.23–5.70 (2H, m), 6.27–6.89 (1H, m) and 6.84–7.72 (15H, m); dC
2
2
3JPC 21.6), 56.2, 61.9 (d, JPC 5.8), 62.1 (d, JPC 5.8), 66.9, 117.6
1
3
3
(d, JPC 187.4), 126.9, 127.1, 127.3, 127.4, 128.0, 128.1, 128.2,
(50 MHz, CDCl3) 16.3 (d, JPC 6.4), 16.4 (d, JPC 6.4), 28.2, 54.9 (d,
2
2
128.5, 128.7, 128.9, 129.4, 136.2, 136.3, 138.7, 150.4 (d, JPC
3JPC 23.6), 55.6, 62.1, 62.2 (d, JPC 5.5), 66.9, 109.9, 111.9, 117.6
1
4.7), 155.9 and 170.4; dP (161 MHz, CDCl3) 17.40; ESI-MS: m/z
(d, JPC 187.1), 118.8, 119.8, 122.1, 122.2, 124.1, 124.3, 127.1,
573.4 (M+Na)+.
127.3, 128.1, 128.2, 128.2, 128.6, 128.9, 129.0, 136.2, 136.6,
2
137.8, 138.1, 150.1 (d, JPC 4.5), 155.8 and 170.7; dP (161 MHz,
4.2.2. Compound (15b)
CDCl3) 17.90; ESI-MS: m/z 612.3 (M+Na)+.
Yield: 76%; colourless syrup; (Found: C, 62.68; H, 7.32; N, 5.35.
Calcd for C27H35N2O6P: C, 62.78; H, 7.22; N, 5.42%); mmax (CHCl3)/
cmꢂ1 3423, 3264, 3017, 2960, 2933, 1718, 1685, 1499, 1509,
1449, 1217 and 1028 cmꢂ1; dH (200 MHz, CDCl3) 0.85–0.88 (6H,
m), 1.15–1.34 (6H, m),1.52–1.64 (3H, m), 3.88–4.12 (4H, m),
4.33–4.37 (1H, m), 4.98–5.06 (2H, m), 5.73–5.79 (1H, m), 5.85–
6.05 (1H, m), 6.72–6.98 (1H, m) and 7.24–7.30 (10H, m); dC
4.2.7. Compound (15g)
Yield: 85%; colourless syrup; (Found: C, 67.64; H, 6.91; N, 4.70.
Calcd for C34H41N2O6P: C, 67.53; H, 6.83; N, 4.63%); mmax (CHCl3)/
cmꢂ1 3274, 3065, 2958, 1716, 1670, 1541, 1450 and 1239 cmꢂ1
;
dH (200 MHz, CDCl3) 0.89–0.92 (6H m,), 1.17–1.29 (6H, m),
1.60–1.69 (3H, m), 3.90–4.20 (5H, m), 4.32–4.39 (3H, m),
5.48–6.28 (2H, m), 6.74–6.98 (1H, m) and 7.22–7.84 (13H, m);
3
3
(50 MHz, CDCl3): 16.2 (d, JPC 6.6), 16.3 (d, JPC 6.6), 22.9, 23.0,
3
2
2
3
3
24.7, 41.8, 53.7, 54.9 (d, JPC 22.7), 62.1 (d, JPC 9.9), 62.0 (d, JPC
dC (50 MHz, CDCl3) 16.2 (d, JPC 6.2 Hz), 16.3 (d, JPC 6.2 Hz),
21.8, 23.1, 24.8, 41.3, 47.1, 53.9, 54.9, 62.3, 62.4, 67.1, 117.7 (d,
1JPC 186.9 Hz), 119.9, 125.0, 125.1, 125.8, 126.8, 127.1, 127.3,
127.7, 128.2, 129.0, 129.0, 138.3, 141.3, 141.4, 143.7, 143.9,
151.0, 156.5 and 171.8; dP (161 MHz, CDCl3): 17.95; ESI-MS: m/
1
9.9), 66.9, 117.2 (d, JPC 187.4), 127.3, 127.9, 128.1, 128.5, 128.7,
2
128.9, 136.2, 138.8, 150.8 (d, JPC 5.5), 156.2 and 172.0; dP
(161 MHz, CDCl3) 17.64; ESI-MS: m/z 517.4 (M+H)+.
4.2.3. Compound (15c)
z 627.8 (M+Na)+
.
Yield: 77%; colourless syrup; (Found: C, 62.88; H, 7.36; N, 5.35.
Calcd for C27H37N2O6P: C, 62.78; H, 7.22; N, 5.42%); mmax (CHCl3)/
cmꢂ1 3427, 3018, 1680, 1495, 1393, 1368, 1216, 1165, 1052 and
1029 cmꢂ1; dH (200 MHz, CDCl3): 1.22–1.34 (6H, m), 1.35 (9H, s),
3.04–3.08 (2H, m), 3.96–4.11 (4H, m), 4.40–4.44 (1H, m),
5.22–5.42 (1H, m), 5.62–5.92 (1H, m), 6.67–6.93 (1H, m) and
7.10–7.29 (10H, m); dC (50 MHz, CDCl3) 16.3, 16.4, 28.2, 38.3,
4.2.8. Compound (15h)
Yield: 54%; colourless syrup; (Calcd for C33H48N3O7P: C, 62.94;
H, 7.68; N, 6.67%); mmax (CHCl3)/cmꢂ1 3633, 3424, 3019, 1698,
1497, 1392, 1369, 1216 and 1028 cmꢂ1; dH (200 MHz, CDCl3)
0.83–0.90 (6H, m), 1.22–1.37 (15H, m), 1.49–1.69 (3H, m), 2.97–
3.06 (2H, m), 4.01–4.11 (4H, m), 4.25–4.35 (1H, m), 4.44–4.55
(1H, m), 5.03–5.07 (1H, m), 5.74–5.98 (2H, m), 6.70–7.00 (1H, m)
and 7.13–7.34 (10H, m); dC (50 MHz, CDCl3) 16.3, 16.4, 21.8, 22.9,
3
1
54.9 (d, JPC 22.7), 56.2, 62.0, 62.1, 80.1, 116.9 (d, JPC 187.7),
125.2, 126.8, 126.9, 127.3, 128.1, 128.6, 128.7, 128.9, 128.9,
2
3
129.3, 136.4, 138.5, 150.6 (d, JPC 5.9), 155.5 and 170.8; dP
24.7, 28.1, 37.8, 40.7, 52.0, 52.1, 55.2 (d, JPC 27.8), 61.9, 62.1,
(161 MHz, CDCl3) 17.70; ESI-MS: m/z 539.4 (M+Na)+.
80.6, 117.4 (d, JPC 186.6), 127.0, 127.1, 127.4, 127.6, 128.1,
2
1
128.7, 128.8, 128.9, 129.2, 129,2, 136.2, 138.6, 150.6 (d, JPC 5.8),
4.2.4. Compound (15d)
155.7, 170.9 and 171.6; dP (161 MHz, CDCl3) 17.72; ESI-MS: m/z
Yield: 62%; colourless syrup; (Found: C, 59.81; H, 8.02; N,
5.93.Calcd for C24H39N2O6P: C, 59.74; H, 8.15; N, 5.81%) ; mmax
(CHCl3)/cmꢂ1 3432, 3019, 1688, 1496, 1392, 1369, 1216 and
1028 cmꢂ1; dH (200 MHz, CDCl3) 0.88–0.94 (6H, m), 1.23–1.34
(6H, m), 1.38 (9H, s), 1.48–1.69 (3H, m),3.97–4.15 (4H, m),
5.06–5.31 (1H, m), 5.72–5.92 (2H, m), 6.74–6.99 (1H, m) and
652.8 (M+Na)+.
4.2.9. Compound (15i)
Yield: 50%; colourless syrup; (Found: C, 65.27; H, 6.86; N, 6.42.
Calcd for C36H46N3O7P: C, 65.14; H, 6.99; N, 6.33%); mmax (CHCl3)/
cmꢂ1 3421, 3286, 3019, 2932, 1685, 1497, 1369, 1216 and