Amphidinolide X and Y
FULL PAPER
Compound 54: Prepared analogously from compound 53 (25 mg,
44 mmol) as a colorless oil (14 mg, 71%). [a]2D0 =ꢀ31.6 (c=1.1, CH2Cl2);
1H NMR (400 MHz, CD2Cl2): d=6.91 (dd, J=15.7, 7.7 Hz, 1H), 5.79 (dd,
J=15.7, 1.2 Hz, 1H), 5.28–5.22 (m, 1H), 5.14–5.10 (m, 1H), 4.01 (dt, J=
7.4, 5.1 Hz, 1H), 3.74 (dt, J=7.7, 4.9 Hz, 1H), 2.87–2.80 (m, 1H), 2.71
(dd, J=16.7, 7.5 Hz, 1H), 2.58 (dd, J=16.7, 5.4 Hz, 1H), 2.40–2.27 (m,
4H), 2.15–2.06 (m, 3H), 2.11 (s, 3H), 1.69 (dd, J=13.1, 5.0 Hz, 1H),
1.66–1.42 (m, 4H), 1.60 (s, 3H), 1.37–1.27 (m, 3H), 1.30 (s, 3H), 1.11 (d,
J=6.8 Hz, 3H), 0.91 ppm (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CD2Cl2): d=206.2, 171.8 (2C), 154.2, 139.1, 120.9, 119.4, 84.5, 83.6, 77.4,
71.0, 47.8, 46.4, 46.2, 41.6, 36.5, 34.3, 33.1, 32.9, 30.9, 27.3, 19.8, 18.6, 16.7,
15.2 ppm; IR (film): n˜ =3439, 2964, 2930, 1717, 1654, 1264 cmꢀ1; MS (EI):
m/z (%): 452 (0.7) [M+], 294 (16), 233 (6), 181 (8), 163 (10), 156 (89),
122 (30), 95 (53), 84 (56), 71 (52), 55 (30), 43 (100); HRMS (ESI): m/z:
calcd for C25H40O7Na [M++Na]: 475.2666, found: 475.2664.
13C NMR (100 MHz, C6D6): d=204.8, 177.4, 172.1, 137.4, 125.8, 84.0,
82.6, 77.2, 73.9, 46.4, 46.2, 45.8, 41.9, 36.6, 36.4, 32.9, 32.1, 31.8, 30.1, 30.1,
27.2, 19.7, 18.4, 17.8, 17.1, 15.1 ppm; IR (film): n˜ =3421, 2961, 2932, 1723,
1713, 1154 cmꢀ1; MS (EI): m/z (%): 308 (17), 247 (5), 211 (5), 177 (7),
156 (87), 137 (13), 107 (35), 101 (27), 84 (59), 71 (37), 55 (47), 43 (100);
HRMS (ESI): m/z: calcd for C26H44O7Na [M++Na]: 491.2979, found:
491.2981.
Yamaguchi lactonizations and elaboration of the analogues
Compound 4: Et3N (8.6 mL, 62 mmol) and 2,4,6-trichlorobenzoyl chloride
(4.8 mL, 31 mmol) were successively added to
a solution of acid 46
(9.0 mg, 21 mmol) in THF (600 mL). The mixture was stirred for 1 h at
ambient temperature before most of the THF was removed under a flow
of Ar. The residue was dissolved in toluene (8.0 mL) and added via sy-
ringe pump over 2 h to a solution of DMAP (50 mg, 0.41 mmol) in tolu-
ene (30 mL) at ambient temperature. Once the addition was complete,
the mixture was stirred for 2 h before the reaction was quenched with aq.
sat. NH4Cl. The organic layer was washed with brine, dried over Na2SO4,
filtered and evaporated, and the residue was purified by flash chromatog-
raphy (hexanes/ethyl acetate 7:1) to afford compound 4 as a colorless oil
(4.8 mg, 56%). [a]2D0 =ꢀ32.4 (c=0.5, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7.12 (dd, J=15.8, 7.2 Hz, 1H), 5.78 (d, J=15.8 Hz, 1H),
5.26–5.19 (m, 2H), 4.96 (d, J=10.3 Hz, 1H), 3.97 (dt, J=11.0, 3.7 Hz,
1H), 2.81–2.66 (m, 2H), 2.69 (dd, J=16.1, 6.0 Hz, 1H), 2.61–2.55 (m,
2H), 2.41 (dd, J=13.3, 6.4 Hz, 1H), 2.20–2.08 (m, 3H), 2.14 (s, 3H),
2.00–1.92 (m, 1H), 1.85 (dd, J=13.8, 1.4 Hz, 1H), 1.55 (s, 3H), 1.60–1.52
(m, 1H), 1.34 (s, 3H), 1.32 (s, 3H), 1.15 (d, J=6.9 Hz, 3H), 0.92 ppm (d,
J=6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=205.3, 170.6, 165.7,
153.1, 135.4, 126.1, 120.2, 81.0, 80.4, 78.7, 74.3, 47.2, 45.5, 41.5, 35.6, 35.3,
33.1, 30.6, 30.3, 28.8, 26.4, 18.1, 17.5, 15.4 ppm; IR (film): n˜ =2966, 2928,
1735, 1365 cmꢀ1; MS (EI): m/z (%): 420 (29) [M+], 255 (31), 141 (14),
110 (51), 95 (32), 59 (38), 43 (100); HRMS (ESI): m/z: calcd for
C24H36O6Na [M++Na]: 443.2404, found: 443.2407.
Compound 56: Prepared analogously from ester 55 (35 mg, 55 mmol) as a
colorless oil (25 mg, 52% over two steps). [a]2D0 =ꢀ28.3 (c=0.95,
CH2Cl2); 1H NMR (400 MHz, CD2Cl2): d=7.25 (d, J=8.6 Hz, 2H), 7.02
(dt, J=15.7, 6.4 Hz, 1H), 6.87 (d, J=8.6 Hz, 2H), 5.83 (dt, J=15.7,
1.5 Hz, 1H), 5.22–5.18 (m, 1H), 5.01 (dd, J=9.4, 0.8 Hz, 1H), 4.44 (d, J=
11.2 Hz, 1H), 4.36 (d, J=11.2 Hz, 1H), 3.93–3.83 (m, 1H), 3.79 (s, 3H),
3.77–3.72 (m, 1H), 3.69 (s, 3H), 2.70–2.41 (m, 6H), 2.12–1.96 (m, 2H),
2.08 (s, 3H), 1.78 (dd, J=13.0, 4.0 Hz, 1H), 1.61 (d, J=1.2 Hz, 3H),
1.66–1.44 (m, 4H), 1.38–1.26 (m, 2H), 1.27 (s, 3H), 0.93 (d, J=6.8 Hz,
3H), 0.92 ppm (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CD2Cl2): d=
206.3, 172.1, 170.2, 159.9, 149.9, 137.9, 131.2, 129.8, 125.4, 122.0, 114.3,
84.5, 83.4, 82.5, 74.0, 71.8, 55.8, 45.9, 45.8, 43.0, 36.5, 36.3, 33.7, 33.2, 30.7,
28.1, 26.5, 18.5, 17.2, 16.7, 15.0 ppm; IR (film): n˜ =2959, 2933, 1720, 1654,
1514, 1248, 1267, 1172 cmꢀ1; MS (EI): m/z (%): 428 (3), 140 (24), 121
(100); HRMS (ESI): m/z: calcd for C33H48O8Na [M++Na]: 595.3241,
found: 595.3238.
Compound 57: Prepared analogously from compound 56 (22 mg,
38 mmol) as a colorless oil (14 mg, 81%). [a]2D0 =ꢀ28.2 (c=0.9, CH2Cl2);
1H NMR (400 MHz, CD2Cl2): d=7.02 (dt, J=15.7, 6.4 Hz, 1H), 5.84 (dt,
J=15.7, 1.3 Hz, 1H), 5.22–5.18 (m, 1H), 5.02 (dd, J=9.7, 1.0 Hz, 1H),
4.04–3.96 (m, 1H), 3.72–3.68 (m, 1H), 2.69–2.42 (m, 7H), 2.17–2.01 (m,
3H), 2.10 (s, 3H), 1.69–1.55 (m, 4H), 1.62 (d, J=1.1 Hz, 3H), 1.48–1.27
(m, 5H), 1.28 (s, 3H), 0.93 (d, J=6.7 Hz, 3H), 0.91 ppm (t, J=7.2 Hz,
3H); 13C NMR (100 MHz, CD2Cl2): d=206.4, 172.2, 169.9, 149.8, 137.7,
125.6, 122.2, 84.2, 82.9, 77.2, 74.2, 46.2, 46.2, 45.9, 36.5, 36.4, 33.3, 32.9,
30.7, 28.0, 27.1, 18.4, 17.4, 16.7, 15.0 ppm; IR (film): n˜ =2961, 2932, 1715,
1656, 1256, 1154 cmꢀ1; MS (EI): m/z (%): 452 (<0.9) [M+], 308 (20), 247
(6), 211 (7), 177 (9), 156 (100); HRMS (ESI): m/z: calcd for C25H40O7Na
[M++Na]: 475.2666, found: 475.2672.
Compound 5: Prepared analogously from seco-acid 57 (10 mg, 23 mmol)
as a colorless oil (5.8 mg, 58%). [a]2D0 =ꢀ29.4 (c=0.6, CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.12–7.05 (m, 1H), 5.85 (d, J=15.6 Hz, 1H),
5.23–5.19 (m, 1H), 5.16–5.13 (m, 1H), 4.97 (d, J=10.3 Hz, 1H), 3.94 (dt,
J=11.0, 3.7 Hz, 1H), 2.76 (dd, J=16.4, 6.0 Hz, 1H), 2.74–2.66 (m, 1H),
2.58 (dd, J=16.4, 7.2 Hz, 1H), 2.54–2.38 (m, 3H), 2.22–2.08 (m, 3H),
2.14 (s, 3H), 1.95 (tt, J=13.1, 3.3 Hz, 1H), 1.74 (dd, J=13.9, 2.5 Hz, 1H),
1.57–1.30 (m, 6H), 1.55 (s, 3H), 1.28 (s, 3H), 0.94 (d, J=6.9 Hz, 3H),
0.93 ppm (t, J=7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=205.6,
172.2, 165.6, 148.1, 135.7, 126.1, 123.0, 83.0, 80.7, 78.5, 74.7, 47.0, 44.4,
43.7, 35.7, 35.5, 34.5, 30.6, 30.5, 28.5, 24.7, 18.2, 17.9, 15.4, 14.7 ppm; IR
(film): n˜ =2960, 2931, 1719, 1659 cmꢀ1; MS (EI): m/z (%): 434 (83) [M+],
308 (14), 290 (13), 269 (36), 247 (13), 193 (16), 153 (25), 138 (66), 125
(30), 107 (29), 95 (66), 82 (16), 67 (19), 55 (35), 43 (100); HRMS (ESI):
m/z: calcd for C25H38O6Na [M++Na]: 457.2561, found: 457.2557.
Compound 59: Prepared analogously from ester 58 (37 mg, 57 mmol) as a
colorless oil (23 mg, 68% over 2 steps). [a]2D0 =ꢀ29.5 (c=1.1, CH2Cl2);
1H NMR (400 MHz, C6D6): d=7.24 (d, J=8.7 Hz, 2H), 6.83 (d, J=
8.7 Hz, 2H), 5.46–5.42 (m, 1H), 5.21 (dd, J=9.6, 1.1 Hz, 1H), 4.36 (d, J=
11.5 Hz, 1H), 4.26 (d, J=11.5 Hz, 1H), 4.17–4.13 (m, 1H), 3.70–3.65 (m,
1H), 3.34 (s, 3H), 2.76 (ddd, J=9.6, 6.9, 4.3 Hz, 1H), 2.49 (dd, J=16.3,
7.7 Hz, 1H), 2.31 (dd, J=16.3, 5.4 Hz, 1H), 2.26–1.87 (m, 7H), 1.82–1.48
(m, 7H), 1.74 (s, 3H), 1.60 (d, J=1.2 Hz, 3H), 1.40–1.31 (m, 4H), 1.37 (s,
3H), 0.96 (d, J=6.9 Hz, 3H), 0.90 (t, J=7.2 Hz, 3H), 0.80 ppm (d, J=
6.4 Hz, 3H); 13C NMR (100 MHz, C6D6): d=204.3, 177.7, 171.7, 159.9,
137.3, 131.0, 129.5, 125.8, 114.2, 84.2, 83.0, 82.2, 73.5, 71.5, 54.9, 45.7, 45.5,
43.0, 41.6, 36.3, 36.1, 33.5, 31.7, 31.6, 30.0, 29.8, 26.3, 19.4, 18.2, 17.2, 16.7,
14.9 ppm; IR (film): n˜ =3114, 2961, 2932, 1731, 1711, 1514, 1456, 1248,
1172 cmꢀ1; MS (EI): m/z (%): 428 (3), 331 (2), 190 (3), 140 (23), 121
(100); HRMS (ESI): m/z: calcd for C34H52O8Na [M++Na]: 611.3554,
found: 611.3560.
Compound 6: Prepared analogously from acid 54 (15 mg, 34 mmol) as a
colorless oil (4.8 mg, 32%). Because of the sensitivity of the product, the
flash chromatography should be carried out as fast as possible. [a]D20
=
ꢀ35.4 (c=0.8, C6H6); 1H NMR (400 MHz, C6D6): d=7.00 (dd, J=15.8,
7.3 Hz, 1H), 5.92 (dd, J=15.8, 1.1 Hz, 1H), 5.47–5.41 (m, 1H), 5.27–5.19
(m, 2H), 4.14 (ddd, J=10.4, 5.3, 3.1 Hz, 1H), 2.50–2.37 (m, 1H), 2.44
(dd, J=16.1, 6.9 Hz, 1H), 2.22–2.19 (m, 2H), 2.14–1.99 (m, 7H), 1.69 (s,
3H), 1.65 (dd, J = 13.6, 3.9 Hz, 1H), 1.53–1.25 (m, 5H), 1.38 (s, 3H),
1.23 (s, 3H), 0.85 (t, J=7.1 Hz, 3H), 0.70 ppm (d, J=7.0 Hz, 3H);
13C NMR (100 MHz, C6D6): d=203.6, 170.7, 165.2, 151.8, 136.3, 121.3,
121.0, 82.2, 80.3, 78.8, 70.3, 47.5, 44.8, 44.4, 41.0, 35.5, 33.9, 32.5, 31.2,
29.7, 25.4, 19.1, 18.0, 15.5, 14.8 ppm; IR: n˜ =2961, 2932, 1717, 1654,
1268 cmꢀ1; MS (EI): m/z (%): 434 (62) [M+], 309 (7), 294 (36), 283 (17),
233 (9), 181 (8), 151 (16), 138 (100), 123 (25), 113 (25), 95 (82), 81 (24),
55 (25), 43 (93); HRMS (ESI): m/z: calcd for C25H38O6Na [M++Na]:
457.2561, found: 457.2560.
Compound 60: Prepared analogously from compound 59 (22 mg,
37 mmol) as
a
colorless oil (12.5 mg, 71%). [a]2D0 =ꢀ28.2 (c=1.1,
CH2Cl2); 1H NMR (400 MHz, C6D6): d=5.43 (dt, J=7.2, 5.2 Hz, 1H),
5.29 (brs, 2H), 5.23 (dd, J=9.6, 1.0 Hz, 1H), 3.91–3.85 (m, 2H), 2.75–
2.64 (m, 1H), 2.49 (dd, J=16.3, 7.5 Hz, 1H), 2.31 (dd, J=16.3, 5.4 Hz,
1H), 2.25–2.08 (m, 5H), 2.02–1.88 (m, 3H), 1.81–1.57 (m, 4H), 1.75 (s,
3H), 1.59 (d, J=1.0 Hz, 3H), 1.49–1.25 (m, 5H), 1.35 (s, 3H), 0.95 (d, J=
6.8 Hz, 3H), 0.87 (t, J=7.1 Hz, 3H), 0.80 ppm (d, J=6.2 Hz, 3H);
Compound 7: Prepared analogously from seco-acid 49 (6.0 mg, 15 mmol)
as a colorless oil (0.9 mg, 16%). Because of the sensitivity of the product,
the flash chromatography should be carried out as fast as possible. [a]D20
=
ꢀ24 (c=0.3, C6H6); 1H NMR (400 MHz, C6D6): d=6.96 (dt, J=15.8,
6.5 Hz, 1H), 5.86 (d, J=15.8 Hz, 1H), 5.37 (dq, J=6.4, 4.2 Hz, 1H), 5.27
Chem. Eur. J. 2009, 15, 4030 – 4043
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4041