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A. Makarasen et al.
PAPER
1 H), 4.25 (t, J = 7.5 Hz, 1 H), 4.38–4.50 (m, 1 H), 4.57–4.68 (m, 1
H), 4.70–4.80 (m, 1 H), 4.99 (d, J = 3.2 Hz, 1 H), 5.03 (d, J = 2.8
Hz, 1 H), 5.08–5.14 (m, 3 H), 5.19 (dd, J = 10.9, 2.7 Hz, 1 H), 5.28
(dd, J = 9.5, 2.7 Hz, 1 H), 7.02 (d, J = 5.6 Hz, 1 H), 7.28–7.36 (m,
5 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.88 (d, J = 7.5 Hz, 1 H), 7.95 (d,
J = 8.0 Hz, 1 H), 8.21 (d, J = 5.9 Hz, 1 H), 8.28 (d, J = 6.1 Hz, 1 H).
HRMS (FAB+): m/z [M + H]+ calcd for C63H110N7O21: 1300.7755;
found: 1300.7709.
Anal. Calcd for C63H109N7O21: C, 58.18; H, 8.45; N, 7.54. Found: C,
58.02; H, 8.38; N, 7.67.
Cereulide LVK1-N-Boc (51)
13C NMR (CDCl3, 101 MHz): d = –5.3, –5.0, 16.2, 16.3, 16.5, 17.7,
18.0, 18.9, 19.0, 19.3, 20.8, 20.9, 21.2, 23.1, 23.2, 23.3, 24.3, 24.4,
25.7, 28.4, 29.1, 29.6, 29.7, 30.0, 30.2, 30.9, 32.7, 40.2, 40.5, 40.8,
40.9, 41.1, 47.8, 49.5, 49.7, 52.6, 59.0, 59.2, 66.7, 72.7, 72.9, 73.0,
77.5, 78.8, 128.0, 128.4, 135.8, 155.9, 169.9, 170.4, 170.5, 170.8,
170.9, 171.5, 172.0, 172.2, 172.5, 173.0, 174.9.
Cereulide LVK1-N-Boc (51) was prepared from compound 50 ac-
cording to the same procedure used for the synthesis of cereulide
(1). Compound 50 was obtained as yellow-white solid; yield: 13.8
mg (58%); mp 89–91 °C.
27
26
[a]D +4.84 (c 0.62, CHCl3) (H+ form); [a]D +5.00 (c 0.58,
CHCl3) (K+ form); [a]D27 +3.97 (c 0.63, CHCl3) (NH4+ form).
HRMS (ESI-MS+): m/z [M + H]+ calcd for C76H130N7O21Si:
1504.9089; found: 1504.9108.
IR (NaCl film): 3316, 1752, 1657, 1539, 1465 cm–1.
1H NMR (CDCl3, 400 MHz): d (H+ form) = 0.86–1.08 (m, 48 H),
1.44 (s, 9 H), 1.24–1.55 (m, 11 H), 1.60–1.79 (m, 11 H), 1.80–1.94
(m, 2 H), 2.21–2.41 (m, 5 H), 3.02–3.19 (m, 2 H), 4.01–4.12 (m, 2
H), 4.30–4.45 (m, 4 H), 4.75–4.90 (m, 1 H), 4.97 (d, J = 3.4 Hz, 1
H), 5.00 (d, J = 3.2 Hz, 1 H), 5.03 (d, J = 3.2 Hz, 1 H), 5.21–5.26
(m, 1 H), 5.27–5.33 (m, 2 H), 7.70 (dd, J = 6.1, 3.0 Hz, 2 H), 7.77
(d, J = 7.2 Hz, 2 H), 7.83 (dd, J = 6.6, 3.8 Hz, 2 H).
13C NMR (CDCl3, 101 MHz): d (H+ form) = 15.7, 15.8, 15.9, 16.8,
16.9, 18.5, 18.6, 19.2, 19.3, 19.4, 21.3, 21.6, 22.8, 23.1, 23.3, 23.4,
24.4, 24.6, 28.4, 28.5, 28.7, 29.2, 29.5, 30.4, 30.5, 30.6, 39.9, 40.5,
40.6, 48.7, 48.8, 52.8, 59.3, 59.6, 72.6, 72.8, 73.1, 78.5, 78.6, 78.8,
156.0, 170.4, 170.5, 170.7, 170.9, 171.2, 171.5, 171.7, 172.1.
Anal. Calcd for C76H129N7O21Si: C, 60.65; H, 8.64; N, 6.51. Found:
C, 60.66; H, 8.65; N, 6.37.
L-O-Valine-L-valine-D-O-leucine-D-alanine-L-O-valine-L-va-
line-D-O-leucine-D-alanine-L-O-valine-L-lysine(Boc)-D-O-leu-
cine-D-alanine Benzyl Ester (49)
Compound 49 was prepared from compound 48 according to the
same procedure used for the synthesis of compound 16. Compound
49 was obtained as a white solid; yield: 0.04 g (84%); mp 75–77 °C.
[a]D26 –3.86 (c 1.74, CHCl3).
IR (NaCl film): 3313, 1750, 1650, 1542, 1457 cm–1.
1H NMR (CDCl3, 400 MHz): d = 0.81–1.09 (m, 48 H), 1.19–1.87
(m, 13 H), 1.38–1.52 (m, 9 H), 1.42 (s, 9 H), 1.88–1.99 (m, 2 H),
2.02–2.17 (m, 2 H), 2.22–2.45 (m, 3 H), 3.08 (d, J = 5.5 Hz, 2 H),
3.82–4.00 (m, 2 H), 4.04 (dd, J = 8.7, 6.3 Hz, 1 H), 4.08–4.19 (m, 2
H), 4.31–4.39 (m, 2 H), 4.47–4.67 (m, 1 H), 4.73–4.85 (m, 1 H),
4.97 (d, J = 3.3 Hz, 1 H), 5.04 (d, J = 2.9 Hz, 1 H), 5.13 (s, 2 H),
5.14–5.22 (m, 2 H), 5.28 (dd, J = 9.0, 4.2 Hz, 1 H), 7.28–7.43 (m, 6
H), 7.67–7.80 (m, 2 H), 7.87 (d, J = 7.5 Hz, 1 H), 8.02 (d, J = 6.1
Hz, 1 H), 8.16 (d, J = 5.6 Hz, 1 H).
13C NMR (CDCl3, 101 MHz): d = 15.9, 16.1, 16.2, 16.3, 16.8, 17.4,
18.6, 18.7, 18.9, 19.0, 19.1, 19.2, 19.5, 21.0, 21.2, 22.6, 23.1, 23.2,
23.3, 23.4, 24.3, 24.4, 24.5, 28.4, 28.9, 29.1, 29.3, 29.9, 30.0, 30.2,
30.6, 31.8, 40.2, 40.6, 40.7, 48.1, 48.9, 49.5, 53.0, 59.3, 59.8, 66.7,
72.6, 73.0, 73.1, 76.2, 78.7, 78.8, 127.9, 128.0, 128.4, 135.8, 156.0,
169.9, 170.5, 170.6, 171.1, 171.6, 171.8, 172.2, 172.9, 175.4.
1H NMR (CDCl3, 400 MHz): d (K+ form) = 0.84–1.17 (m, 48 H),
1.22–1.70 (m, 33 H), 2.18–2.41 (m, 5 H), 3.02–3.22 (m, 2 H), 3.84
(dd, J = 10.9, 5.0 Hz, 2 H), 4.13–4.23 (m, 1 H), 4.24–4.34 (m, 3 H),
4.64 (t, J = 3.3 Hz, 3 H), 4.72–4.86 (m, 4 H), 8.13 (d, J = 4.4 Hz, 1
H), 8.21–8.32 (m, 4 H), 8.37 (d, J = 4.3 Hz, 1 H).
13C NMR (CDCl3, 101 MHz): d (K+ form) = 15.1, 15.2, 16.6, 16.8,
18.6, 19.2, 20.2, 21.0, 21.5, 22.8, 23.1, 23.2, 23.3, 24.3, 24.5, 28.4,
28.5, 29.1, 29.7, 30.1, 39.9, 40.5, 40.7, 40.8, 50.1, 50.2, 50.3, 54.9,
61.7, 73.6, 73.8, 74.0, 79.5, 79.6, 79.7, 156.0, 171.3, 171.4, 172.2,
172.3, 172.4, 175.6, 175.7, 176.1, 176.2.
1H NMR (CDCl3, 400 MHz): d (NH4+ form) = 0.79–1.19 (m, 48 H),
1.22–2.00 (m, 33 H), 2.18–2.40 (m, 5 H), 3.00–3.25 (m, 2 H), 3.82
(dd, J = 10.6, 4.5 Hz, 2 H), 4.10–4.21 (m, 1 H), 4.22–4.33 (m, 3 H),
4.69 (dd, J = 5.1, 2.9 Hz, 3 H), 4.74–4.89 (m, 4 H), 5.73–6.16 (m, 4
H), 7.91–7.98 (m, 1 H), 8.00–8.13 (m, 4 H), 8.16 (d, J = 4.3 Hz, 1
H).
HRMS (FAB+): m/z [M + H]+ calcd for C70H116N7O21: 1390.8224;
found: 1390.8206.
+
13C NMR (CDCl3, 101 MHz): d (NH4 form) = 15.2, 15.3, 16.5,
Anal. Calcd for C70H115N7O21: C, 60.46; H, 8.33; N, 7.05. Found: C,
60.42; H, 8.26; N, 6.97.
16.7, 18.6, 19.1, 20.1, 21.0, 21.1, 21.5, 22.7, 23.0, 23.1, 23.3, 24.3,
24.5, 28.4, 28.6, 29.2, 29.7, 30.2, 39.9, 40.6, 40.8, 40.9, 50.0, 50.1,
54.7, 61.5, 73.8, 74.0, 74.3, 79.5, 79.6, 156.0, 171.1, 171.3, 172.1,
172.2, 172.3, 175.5, 175.6, 175.8, 176.0.
HRMS (FAB+): m/z [M]+ calcd for C63H108N7O20 (H+ form):
1282.7649; found: 1282.7639.
L-O-Valine-L-valine-D-O-leucine-D-alanine-L-O-valine-L-va-
line-D-O-leucine-D-alanine-L-O-valine-L-lysine(Boc)-D-O-leu-
cine-D-alanine-OH (50)
Compound 50 was prepared from compound 49 according to the
same procedure used for the synthesis of compound 14. Compound
50 was obtained as a white solid; yield: 22.5 mg (99%); mp 103–
105 °C.
[a]D25 +5.61 (c 1.27, CHCl3).
IR (NaCl film): 3312, 1749, 1654, 1540, 1458 cm–1.
1H NMR (CDCl3, 400 MHz): d = 0.78–1.13 (m, 48 H), 1.30–2.48
(m, 37 H), 2.98–3.21 (m, 2 H), 3.82–4.64 (m, 7 H), 4.75–5.32 (m, 7
H), 7.39–8.19 (m, 6 H).
Anal. Calcd for C63H108N7O20 (H+ form): C, 58.95; H, 8.48; N, 7.64.
Found: C, 58.82; H, 8.23; N, 7.59.
Cereulide LVK1 (4)
Cereulide LVK1 (4) was prepared from compound 51 according to
the same procedure used for the synthesis of cereulide DAK1 (2).
Compound 4 was obtained as yellow-white solid; yield: 10.2 mg
(quant.); mp 125–128 °C.
IR (NaCl film): 3302, 1749, 1656, 1540, 1467 cm–1.
13C NMR (CDCl3, 101 MHz): d = 16.0, 16.3, 16.4, 16.8, 18.6, 18.9,
19.1, 19.3, 19.5, 21.1, 21.3, 23.1, 23.2, 23.3, 24.3, 24.5, 28.4, 29.2,
29.3, 30.1, 30.5, 30.9, 31.8, 40.1, 40.6, 40.7, 49.1, 49.3, 52.7, 52.8,
59.4, 72.9, 73.4, 78.6, 79.0, 156.1, 170.3, 171.1, 171.2, 171.8,
172.0.
1H NMR (CDCl3, 400 MHz): d (K+ form) = 0.80–1.17 (m, 48 H),
1.22–1.41 (m, 1 H), 1.42–1.54 (m, 10 H), 1.58–2.06 (m, 13 H),
2.19–2.40 (m, 5 H), 2.96–3.18 (m, 2 H), 3.77–3.88 (m, 2 H), 4.18–
4.39 (m, 4 H), 4.58–4.65 (m, 3 H), 4.75–4.88 (m, 3 H), 8.05–7.66
(m, 3 H), 8.13 (d, J = 4.6 Hz, 1 H), 8.15 (d, J = 4.8 Hz, 1 H), 8.23
Synthesis 2009, No. 13, 2184–2204 © Thieme Stuttgart · New York