528
NH), 8.2–8.1 (br. s, 1H, NH), 7.0 (d, 2H, C3 & C5–H, J
= 7.8 Hz), 6.9 (d, 2H, C2 & C6–H, J = 7.8 Hz), 4.6–4.3
(m, 1H, α-CH), 4.2–4.0 (m, 4H, α-CH), 3.75 (s, 3H,
4.1.2.6.
Boc-Glycyl-Glycyl-Tyrosinyl-Prolyl-Leucyl-
Isoleucyl-Leucine methyl ester (6)
Yellow semisolid mass, % yield: 62.8, [α]D: –61.5°,
Anal C42H67N7O11 [% C found (calcd.): 59.62
(59.65), % H found (calcd.): 7.91(7.93), % N found
(calcd.): 11.62 (11.60)]. The IR spectrum showed the
following characteristic absorption bands (KBr, cm–1).
3 315 (br, s, –NH), 2 930 (s, –CH), 1 730 (s, C=O ester),
1 695 (s, C=O amide), 1 670 (br. s, C=O amide), 1 645 (s,
C=O amide), 1 325 (s, C–N). The NMR spectrum pro-
vided the following characteristic chemical shifts
(CDCl3): δ 8.8–8.6 (br. s, 2H, NH), 8.2–7.9 (br. s, 4H,
NH), 6.9 (d, 2H, C3 & C5–H, J = 8.5 Hz), 6.7 (d, 2H, C2
& C6–H, J = 8.5 Hz), 4.6–4.3 (m, 5H, α-CH), 4.2–4.0 (m,
4H, α-CH), 3.75 (s, 3H, OCH3), 3.65–3.3 (m, 2H,
N–CH2), 3.1–3.0 (m, 2H, â-CH2), 2.2–1.6 (m, 10H,
CH2–CH2, CH2, CH2 & CH2), 1.45 (s, 9H, tBoc), 1.3–1.1
(m, 3H, –CH), 0.95 (doublet overlapped with triplet, 18H,
6CH3).
t
OCH3), 3.3–3.2 (m, 2H, â-CH2), 1.4 (s, 9H, Boc).
4.1.2.3. Boc-Prolyl-Leucine methyl ester (3)
White crystals, m.p. 93 °C, % yield: 75.4, Anal
C17H30N2O5 [% C found (calcd.): 59.58 (59.60), % H
found (calcd.): 8.78 (8.78), % N found (calcd.): 8.15
(8.15)]. The IR spectrum showed the following charac-
teristic absorption bands (KBr, cm–1). 3 250 (br, s, –NH),
2 950 (s, –CH), 1 710 (s, C=O ester), 1 700 (br, s, C=O
amide), 1 620 (s, C=O amide), 1 420 (s, C–N). The NMR
spectrum provided the following characteristic chemical
shifts (CDCl3): δ 6.4 (br. s, 1H, NH), 4.6–4.4 (m, 1H,
α-CH), 4.3–4.1 (m, 1H, α-CH), 3.7 (s, 3H, OCH3),
3.5–3.2 (m, 2H, N–CH2), 2.0–1.6 (m, 6H, CH2–CH2 &
t
CH2), 1.45 (s, 9H, Boc), 1.3–1.1 (m, 1H, CH), 0.95 (d,
6H, -(CH3)2, J = 6.0 Hz).
4.1.2.7. Pseudostellarin D (7)
4.1.2.4. Boc-Isoleucyl-Leucine methyl ester (4)
p-Nitrophenyl ester method:
White crystals, m.p. 70 °C, % yield: 76.3, Anal.
C18H34N2O5 [% C found (calcd.): 60.30 (60.38), % H
found (calcd.): 9.46 (9.49), % N found (calcd.): 7.78
(7.81)]. The IR spectrum showed the following charac-
teristic absorption bands (KBr, cm–1). 3 540 (br, s, –NH),
2 975 (s, –CH), 1 735 (s, C=O ester), 1 675 (s, C=O
amide), 1 660 (s, C=O amide), 1 340 (s, C–N). The NMR
spectrum provided the following characteristic chemical
shifts (CDCl3): δ 6.6 (br. s, 1H, NH), 5.3 (br. s, 1H, NH),
4.6–4.5 (m, 1H, α-CH), 4.3–4.1 (m, 1H, α-CH), 3.7 (s,
The ester group of the linear segment (2 mmol) was
removed with LiOH (3 mmol) and the p-nitrophenyl ester
group was introduced using the following procedure:
The Boc-peptide (1.5 mmol) was dissolved in CHCl3
(15 mL) at 0 °C. Then p-nitrophenol (0.27 g, 2 mmol),
DCC (0.214 g, 1.5 mmol) were added and stirred for 12 h
at room temperature. The reaction mixture was filtered
and the filtrate was washed with NaHCO3 solution (10%)
until excess of p-nitrophenol was removed and finally
washed with 5 % HCl (5 mL) to get Boc-peptide-PNP
ester.
t
3H, OCH3), 2.0–1.8 (m, 4H, –CH2), 1.5 (s, 9H, Boc),
1.3–1.1 (m, 2H, 2–CH), 1.0 (doublet overlapped with
triplet, 12H, 4CH3).
To the above Boc-peptide-PNP ester (1.2 mmol) in
CHCl3 (15 mL), CF3COOH (0.274 g, 2.4 mmol) was
added, stirred for 1 h at room temperature and washed
with 10% NaHCO3 solution. The organic layer was dried
over anhydrous Na2SO4. To the peptide-PNP ester in
CHCl3 (20 mL), pyridine (1.4 mL, 2 mmol) was added
and kept at 0 °C for 10 d. The reaction mixture was
washed with 10% NaHCO3 until the byproduct
p-nitrophenol was removed completely and finally
washed with 5% HCl (5 mL). The organic layer was dried
over anhydrous Na2SO4. Chloroform and pyridine were
distilled off to get the crude product of the cyclized
compound, which was then recrystallized from CHCl3/n-
hexane. Pale yellow solid, m.p. 176–178 °C (lit.
177–179 °C), % yield 76.4, [α]D: –65.5° (lit. –64.8°),
Anal C36H55N7O8 [% C found (calcd.): 60.61
(60.59), % H found (calcd.): 7.70 (7.71), % N found
(calcd.): 15.69 (15.71)]. The IR spectrum showed the
following characteristic absorption bands (KBr, cm–1).
4.1.2.5. Boc-Prolyl-Leucyl-Isoleucyl-Leucine methyl
ester (5)
Brown semisolid mass, % yield: 73.0, [α]D: + 12.5°,
Anal C29H52N4O7 [% C found (calcd.): 61.20
(61.20), % H found (calcd.): 9.12 (9.15), % N found
(calcd.): 9.86 (9.85)]. The IR spectrum showed the
following characteristic absorption bands (KBr, cm–1).
3 245 (br, s, –NH), 2 935 (s, –CH), 1 740 (s, C=O ester),
1 690 (s, C=O amide), 1 675 (br. s, C=O amide), 1 650
(br. s, C=O amide), 1 350 (s, C–N). The NMR spectrum
provided the following characteristic chemical shifts
(CDCl3): δ 6.9–6.8 (br. s, 1H, NH), 6.4–6.2 (br. s, 1H,
NH), 4.8–4.6 (m, 2H, α-CH), 4.4–4.3 (m, 1H, α-CH),
4.2–4.0 (m, 1H, α-CH), 3.75 (s, 3H, OCH3), 3.5–3.1 (m,
2H, N–CH2), 2.3–1.5 (m, 10H, CH2–CH2, CH2
&
CH2–CH2), 1.45 (s, 9H, tBoc), 1.3–1.1 (m, 3H, CH), 0.95
(doublet overlapped with triplet, 18H, 6CH3).