B. Poojary – S. L. Belagali · Cyclonitroproctolin
1311
δ = 6.1 (br.s, 1H, -NH), 5.15 (s, 1H, -OH), 4.9 – 4.4 (m, 2H, General procedure for the synthesis of cyclonitroproctolin
β-CH & α-CH), 4.3 – 4.1 (m,1H, α-CH), 3.7(s, 3H, -OCH3), (6)
3.6 – 3.2 (m, 2H, N-CH2), 2.3 – 1.6 (m, 4H, -CH2- CH2), 1.4
(s, 9H, Boc), 1.1 (d, 3H, J = 6.5 Hz, CH3). -C15H26N2O6
(330): calcd. C 54.54, H 7.87, N 8.48; found C 54.50, H 7.85,
N 8.44.
To the solution of Boc-nitroargininyl-tyrosinyl-leucyl-
prolyl-threonine-p -nitrophenyl ester (1.2 mmol) in chloro-
form (15 ml), trifluoroacetic acid (0.274 g, 2.4 mmol) was
added, stirred for 1 h at r. t. and washed with 10% sodium
bicarbonate solution. The organic layer was dried over an-
hydrous sodium sulphate. To the resulting Boc-deprotected
peptide-p-nitrophenyl ester in tetrahydrofuran (15◦ml), pyri-
dine (1.4 ml, 2 mmol) was added and kept at 4 C for ten
days. The reaction mixture was washed with 10% sodium
bicarbonate solution until the byproduct p-nitrophenol was
removed completely and finally washed with 5% HCl (5 ml).
The organic layer was dried over anhydrous sodium sul-
phate. Tetrahydrofuran and pyridine were distilled under re-
duced pressure to get cyclonitroproctolin. The crude product
was purified by silica gel column chromatography using the
dichloromethane-methanol system and finally recrystallized
from EtOAc-n-hexane.
t
Boc-tyrosinyl-leucyl-prolyl-threonine methyl ester (4)
IR(CHCl3): ν = 3600 (br.s, O-H str.), 3200 (br.s, N-H
str.), 3080 (m, =C-H str.), 2920 (m, C-H str.), 2880 (m, C-H
str.), 1740 (s, C=O str. ester), 1690 (s, C=O str. amide),
1670 (s, C=O str. amide), 1450 (s, C-H def.), 1430 (m, C-N
str.), 1390 (s, N-H def.), 1300 (s, C-O str.), 1250 (m, C-O
1
str.), 950 – 850 (m, C-H def.) cm−1. – H NMR (300 MHz,
CDCl3): δ = 8.2 (br.s, 2H, -NH), 7.6 (br.s, 1H, -NH), 7.2 (d,
2H, J = 6.5 Hz, Ar-C8H & -C5H), 6.95 (d, 2H, J = 6.5 Hz,
Ar-C2H & -C6H), 6.5 (br.s, 1H, -NH), 5.2 (s, 1H, -OH), 4.9 –
4.8 (m, 1H, β-CH), 4.65 – 4.4 (m, 3H, α-CH), 4.3 – 4.0 (m,
2H, α-CH), 3.75 (s, 3H, -OCH3), 3.6 – 3.2 (m, 4H, N-CH2 &
β-CH2), 2.2 – 1.6 (m, 4H, -CH2- CH2), 1.6 – 1.5 (m, 1H,
◦
Pale white solid; m.p. 153 – 155 C. – IR(CHCl3): ν =
t
β-CH2), 1.4 (s, 9H, Boc), 1.3 (d, 3H, J = 6.5 Hz, -CH3),
3600 (br.s, O-H str.), 3325 (br.s, N-H str.), 3020 (m, =C-H
str.), 2920 (s, C-H str.), 2850 (s, C-H str.), 1690 (s, C=O
str. amide), 1680 (s, C=O str. amide), 1660 (s, C=O str.
amide), 1610 (s, C=N str.), 1540 (s, NO2), 1450 (s, C-H def.),
1410 (m, C-N str.), 1400 (s, N-H def.), 1380 (s, NO2), 1110
(m, C-O str.), 970 – 915 (m, C-H def.) cm−1. – 1H NMR
(300 MHz, DMSO-d6): δ = 8.2 (br.s, 2H, -NH / OH), 7.6
(br.s, 3H, -NH), 7.0 (d, 2H, J = 6.5 Hz, Ar-C8H & -C5H), 6.9
(d, 2H, J = 6.5 Hz, Ar-C2H & -C6H), 6.4 (br.s, 3H, -NH), 5.2
(s, 1H, -OH), 4.7 – 4.5 (m, 4H, α-CH & β-CH), 4.4 – 4.2 (m,
3H, α-CH), 3.5 – 3.1 (m, 4H, N-CH2 & β-CH2), 2.2 – 1.7 (m,
8H, -CH2-CH2 & -CH2), 1.6 – 1.4 (m, 4H, β-CH2 & -CH2),
1.2 – 1.1 (m, 4H, γ-CH & -CH3), 0.95 (d, 6H, J = 6.5 Hz,
C(CH3)2). – FAB mass: m/z 676 [M++ H]. -C30H45N9O9
(675): calcd. C 53.30, H 6.60, N 18.65; found C 53.38,
H 6.66, N 18.74.
1.2 – 1.1 (m, 1H, -CH-), 0.98 (d, 6H, J = 6.5 Hz, -CH3).
-C30H46N4O9 (606): calcd. C 59.40, H 7.59, N 9.24; found
C 59.40, H 7.59, N 9.24.
Boc-nitroargininyl-tyrosinyl-leucyl-prolyl-threonine methyl
ester (5)
IR(CHCl3): ν = 3600 (br.s, O-H str.), 3320 (br.s, N-H
str.), 3030 (m, =C-H str.), 2930 (m, C-H str.), 2880 (m, C-H
str.), 1750 (s, C=O str. ester), 1690 (br.s, C=O str. amide),
1670 (s, C=O str. amide), 1530 (s, NO2), 1450 (s, C-H def.),
1420 (m, C-N str.), 1400 (s, N-H def.), 1380 (s, NO2), 1250
(s, C-O str.), 1110 (m, C-O str.), 970-870 (m, C-H def.)
cm−1. – 1H NMR (300 MHz, CDCl3): δ = 8.3 (br.s, 2H,
-NH), 7.6 (br.s, 2H, -NH), 7.1 (d, 2H, J = 6.5 Hz, Ar-C8H & -
C5H), 6.8 (d, 2H, J = 6.5 Hz, Ar-C2H & -C6H), 6.4 (br.s, 3H,
-NH), 5.2 (s, 1H, -OH), 4.9 – 4.7 (m, 4H, α-CH & β-CH),
4.6 – 4.4 (m, 3H, α-CH), 3.37 (s, 3H, O-CH3), 3.5 – 3.2 (m,
6H, N-CH2 & β-CH2), 2.2 – 1.8 (m, 4H, -CH2- CH2), 1.65 –
Acknowledgements
t
1.5 (m, 6H, N-CH2 & β-CH2), 1.45 (s, 9H, Boc), 1.3 (d,
The authors are grateful to Ms. Beena Mascarenhas, KMC
3H, J = 6.5 Hz, -CH3), 1.2 – 1.1 (m, 1H, -CH), 0.98 (m, Hospital, Manipal for biological screening of the cyclic pep-
9H, 3 -CH3). – C36H57N9O12 (807): calcd. C 53.50, H 7.00, tides. This work was supported by Mangalore University
N 15.58; found C 53.56, H 7.10, N 15.63.
from UGC minor research grant.
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