F. Yokokawa et al. / Tetrahedron 56 (2000) 1759–1775
1773
C7-H), 5.85–5.95 (2H, m, CH2vCHCH2×2), 6.57 (1H, br,
Gly-NH), 7.24 (3H, m, ArH), 7.47 (2H, m, ArH); 13C NMR
(CDCl3) d 10.2, 13.0, 17.8, 18.3, 18.4, 19.6, 25.5, 29.2, 30.5,
30.9, 32.6, 36.6, 36.7, 36.8, 41.0, 47.2, 62.6, 65.2, 65.6,
83.3, 117.6, 118.4, 127.2, 129.1, 129.8, 130.0, 130.3,
132.0, 132.7, 136.0, 141.1, 155.4, 168.7, 170.0, 172.1,
173.9. Anal. Calcd for C41H61N3O8Se: C, 61.33; H, 7.66;
N, 5.23. Found: C, 61.44; H, 7.70; N, 4.95.
(2S,3S,4E,6E)-3-Trimethylsiloxy-2,4,6,8,8-pentamethyl-
4,6-nonadioenol (45). The aldol adduct 44 (4.03 g, 5.3
mmol) was treated as described for the synthesis of 28 to
afford the alcohol 45 as a pale yellow oil (1.81 g, quant.): IR
1H NMR and 13C NMR spectra were identical with 28.
[a]2D5ϩ8.8 (c 1.0, MeOH). Anal. Calcd. for
C20H40NO2Si: C, 70.52; H, 11.84. Found: C, 70.26; H,
11.75.
Protected linear peptide (43). The ester 42 (21 mg,
0.026 mmol) was treated as described for the synthesis of
Methyl (4S,5S,2Z,6E,8E)-5-Triethylsiloxy-4,6,8,10,10-pen-
tamethyl-6,8-undecadienoate (46). The alcohol 45 (788
mg, 2.30 mmol) was treated as described for the synthesis
of 31 to afford the ester 46 as a colorless oil (724 mg, 80%):
25 to afford the protected linear peptide 43 as a colorless oil
neat
(16 mg, quant.): [a]D25Ϫ82.0 (c 0.54, CHCl3); IR n
max
cmϪ1 3324, 1738, 1732, 1684, 1636, 1507, 1456, 1375,
1364, 1326, 1273, 1244, 1192, 1150, 1090, 1063, 936,
932, 777, H NMR (CDCl3) d 0.84 (3H, d, J6.6 Hz,
IR, H NMR and 13C NMR spectra were identical with
1
31. [a]2D1ϩ34.0 (c 1.0, CHCl3); Anal. Calcd for
C23H42O2Si·0.5H2O: C, 68.43; H, 10.74. Found: C, 68.69;
H, 10.47.
1
Val-CH3), 0.98 (3H, d, J6.6 Hz, Val-CH3), 1.04 (3H, d,
J6.9 Hz, C13-CH3), 1.12 (9H, s, t-Bu), 1.33 (3H, d,
J6.9 Hz, Ala-CH3), 1.68 (3H, s, C14-CH3), 1.75 (3H, s,
C15-CH3), 2.32 (1H, m, C4-H), 2.65 (1H, m, Val-
(CH3)2CH), 3.00 (3H, s, N-CH3), 3.05 (2H, s, C2-CH2)
3.97 (1H, dd, J18.2, 5.0 Hz, Gly-CH2), 4.07 (1H, dd,
J178, 5.9 Hz, Gly-CH2), 4.56 (4H, m, CH2CHCH2×2),
4.61 (2H, m, Ala-a-H, Val-a-H), 5.02 (2H, s, C12-H), 5.16–
5.34 (6H, m, CH2vCHCH2×2, C5-H, C9-H), 5.62 (1H, br,
Ala-NH), 5.77 (1H, s, C7-H), 5.83–5.98 (2H, m,
CH2vCHCH2×2), 6.45 (1H, br, Gly-NH); 13C NMR
(CDCl3) d 14.1, 14.8, 17.8, 18.3, 18.4, 19.6, 25.4, 30.5,
30.9, 32.6, 40.5, 40.9, 41.4, 47.2, 62.8, 65.4, 65.6, 81.7,
115.8, 117.7, 118.4, 130.1, 130.4, 132.0, 132.7, 134.3, 140.7,
143.0, 155.3, 168.6, 169.9, 171.0, 173.9. MS m/z: 645 (Mϩ).
(4S,5S)-5-((1E,3E)-1,3,6,6-Tetramethyl-1,3-hexadienyl)-
4-methyl-2-pentene-5-olide (47). The ester 46 (600 mg,
1.5 mmol) was treated as described for the synthesis of 32
to afford the lactone 47 as a colorless oil (200 mg, 54%): IR,
1H NMR and 13C NMR spectra were identical with 32.
[a]2D3ϩ96.1 (c 0.4, CHCl3). HRMS (EI) m/z Calcd for
C16H24O2: 248.1776. Found: 248.1783.
Ester (49). The lactone 47 (50 mg, 0.20 mmol) was treated
as described for the synthesis of 34 to afford the ester 49 as a
colorless oil (30 mg, 18%): [a]2D3Ϫ43.6 (c 0.33, CHCl3);
neat
max
IR n
cmϪ1 3325, 3090, 1732, 1684, 1651, 1522, 1478,
1456, 1418, 1377, 1275, 1244, 1190, 1148, 1065, 1022, 995,
1
930, 779, 739; H NMR (CDCl3) d 0.66 (3H, d, J6.9 Hz,
(4R,5S)-Antillatoxin (1c). The protected linear peptide 43
(23 mg, 0.0356 mmol) was treated as described for the
C13-CH3), 0.82 (3H, d, J6.6 Hz, Val-CH3), 0.96 (3H, d,
J6.3 Hz, Val-CH3), 1.12 (9H, s, t-Bu), 1.30 (3H, d,
J6.1 Hz, Ala-CH3), 1.66 (3H, s, C14-CH3), 1.75 (3H, s,
C15-CH3, 2.16 (1H, m, C4-H), 2.28–2.46 (3H, m, C3-H,
Val-(CH3)CH, C2-CH2), 2.75–2.84 (2H, m, C2-H,
PhSeCH2), 2.98 (3H, s, N-CH3), 3.02 (1H, m, PhSeCH2),
3.50 (2H, dd, J14.0, 4.1 Hz, Gly-CH2), 4.01 (1H, dd,
J18.1, 6.9 Hz, Val-a-H), 4.53 (4H, m, CH2vCHCH2×2),
4.62 (1H, m, Ala-a-H), 4.88 (1H, d, J10.2 Hz, C5-H),
5.19–5.34 (5H, m, CH2vCHCH2×2, C9-H), 5.63 (1H, d,
J7.9 Hz, Ala-NH), 5.81 (1H, s, C7-H), 5.83–5.96 (2H,
m, CH2vCHCH2×2), 6.42 (1H, t, J5.3 Hz, Gly-NH),
7.27 (3H, m, ArH), 7.51 (2H, m, ArH); 13C NMR (CDCl3)
d 10.3, 12.9, 17.8, 18.4, 19.6, 25.3, 30.3, 30.9, 31.5, 32.6,
34.3, 34.5, 35.8, 40.7, 47.2, 62.5, 65.4, 65.6, 82.7, 117.6,
118.4, 127.1, 129.7, 129.9, 130.3, 132.1, 132.7, 133.0,
136.4, 141.1, 155.4, 168.7, 169.8, 172.5, 173.8. Anal.
Calcd for C41H61N3O8Se·0.5EtOAc: C, 60.98; H, 7.74; N,
4.96. Found: C, 61.26; H, 7.80; N, 4.16.
synthesis of 1a to afford the desired product 1c as a colorless
neat
oil (6 mg, 37%): [a]2D4Ϫ64.8 (c 0.13, MeOH); IR n
max
cmϪ1 3291, 1744, 1686, 1626, 1534, 1464, 1262; H NMR
1
(DMSO-d6) d 0.76 (3H, d, J6.9 Hz, Val-CH3), 0.90 (3H, d,
J7.3 Hz, C13-CH3), 1.00 (3H, d, J6.3 Hz, Val-CH3), 1.11
(9H, s, t-Bu), 1.18 (3H, d, J6.3 Hz, Ala-CH3), 1.63 (3H, s,
C14-CH3), 1.73 (3H, d, J1.0 Hz, C15-CH3), 2.18–2.24 (2H,
m, C4-H, Val-(CH3)2CH), 2.64 (3H, s, N-CH3), 2.94 (1H, s,
C2-H), 3.04 (1H, s, C2-H), 3.67 (1H, dd, J16.8, 5.0 Hz,
Gly-CH2), 3.93 (1H, d, J9.6 Hz, Val-a-H), 4.18 (1H, dd,
J16.8, 6.9 Hz, Gly-CH2), 4.64 (1H, m, Ala-a-H), 4.78
(1H, s, C5-H), 4.94, (1H, s, C12-H), 5.00 (1H, s, C12-H),
5.20 (1H, s, C9-H), 5.61 (1H, s, C7-H), 8.00 (1H, br,
Gly-NH), 8.35 (1H, d, J8.3 Hz, Ala-NH); 13C NMR
(DMSO-d6) d 14.0, 15.6, 17.7, 17.9, 18.7, 27.1, 29.0,
30.8, 32.2, 40.9, 41.7, 42.2, 44.9, 64.9, 81.2, 124.9,
130.4, 130.6, 139.6, 144.7, 167.9, 169.1, 169.4, 171.4.
HRMS (EI) m/z Calcd for C28H45N3O5:503.3359. Found:
503.3362.
Protected linear peptide (50). The ester 49 (20 mg,
0.025 mmol) was treated as described for the synthesis of
[1R, 2S)]-2-(N-Benzyl-n-mesitylenesulfonyl)amino-1-phenyl-
1-propyl(2R, 3R, 4E, 6E)-3-triethylsiloxy-2,4,6,8,8-penta-
methyl-4,6-nonadienoate (44). The alcohol 10 (13.5 g,
8.0 mmol) was treated as described for the synthesis of
27 to afford the aldol adduct 44 as a colorless oil (5.59 g,
35 to afford the protected linear peptide 50 as a colorless oil
(12 mg, 80%): [a]D23Ϫ52.4 (c 1.26 CHCl3); IR n
cmϪ1
neat
max
3325, 3090, 1735, 1686, 1640, 1526, 1466, 1414, 1380,
1367, 1333, 1282, 1242, 1192, 1152, 1063, 994, 930; H
1
NMR (CDCl3) d 0.82 (3H, d, J6.6 Hz, Val-CH3), 0.95
(6H, m, C13-CH3, Val-CH3), 1.13 (9H, s, t-Bu), 1.32 (3H,
d, J6.9 Hz, Ala-CH3), 1.68 (3H, d, J0.99 Hz, C14-CH3),
1.78 (3H, d, J0.99 Hz, C15-CH3), 2.30 (1H, m, C4-H), 2.59
(1H, m, Val-(CH3)CH), 3.00 (3H, s, N-CH3), 3.05 (2H, m,
1
92%): IR H NMR and 13C NMR spectra were identical
with 27. [a]2D1ϩ54.1 (c 1.0, CHCl3); Anal. Calcd for
C45H65NO5SSi: C, 71.10; H, 8.62; N 1.84. Found: C,
70.98; H, 8.65; N 1.59.