A. Fürstner et al.
dried over Na2SO4, and the solvent was carefully evaporated while keep-
ing the temperature at 08C. The residue was dissolved in THF (3 mL)
and added to the suspension of the sodium salt of acid 13 described
above. [15]Crown-5 ether was then introduced until a homogeneous solu-
tion had formed which was stirred overnight at ambient temperature.
Ether was added and the solution was successively washed with aq.
NaOH (10%, 08C), sat. aq. NaHCO3, and brine before it was dried
(Na2SO4) and evaporated. Purification of the crude product by flash
chromatography (CHCl3/ethyl acetate 25:1) afforded diyne 34 as a color-
less oil (45 mg, 58% over both steps). [a]2D0 =+43.08 (c 0.5, CH2Cl2);
1H NMR(400 MHz, CD 2Cl2): d=1.18 (d, J=6.9 Hz, 3H), 1.41–1.61 (m,
3H), 1.72–1.95 (m, 11H), 1.93 (d, J=1.4 Hz, 2H), 2.07 (td, J=2.0,
15.0 Hz, 1H), 2.28–2.34 (m, 2H), 2.39–2.48 (m, 1H), 2.69–2.87 (m, 2H),
3.09 (s, 3H), 3.23–3.27 (m, 2H), 3.78–3.83 (m, 1H), 3.79 (s, 3H), 3.90–
3.96 (m, 1H), 4.31 (d, J=14.4 Hz, 1H), 5.04 (d, J=14.4 Hz, 1H), 5.15–
5.20 (m, 1H), 5.67 (d, J=1.4 Hz, 1H), 6.88 (d, J=8.6 Hz, 2H), 7.26 (d,
J=8.6 Hz, 2H); 13C NMR(100 MHz, CD 2Cl2): d=3.2, 3.3, 17.8, 21.7,
25.3, 25.4, 26.3, 30.1, 32.8, 33.4, 34.2, 34.8, 47.3, 47.4, 55.3, 59.4, 65.8, 66.2,
76.0, 76.1, 78.4, 83.3, 101.6, 114.0, 117.6, 129.0, 129.8, 158.1, 159.2, 165.6,
172.7; IR(film): n˜ = 2919, 1702, 1672, 1512, 1443, 1247, 1173, 1092,
1032 cmꢁ1; MS (EI): m/z (%): 359 (19), 208 (14), 207 (95), 175 (37), 147
(43), 135 (100), 133 (33), 121 (97), 107 (21), 91 (16); HRMS (ESI+):
m/z: calcd for C29H37NO6S+Na: 550.22393; found: 550.22450 [M ++Na].
121 (91). HRMS (ESI+): m/z: calcd for C29H37NO6S+Na: 550.22393,
found: 550.22450 [M ++Na].
Cycloalkyne 45: Prepared analogously from diyne 44; colorless syrup
(22 mg, 82%). [a]2D0 =+66.3 (c 1.17, CDCl3); 1H NMR(300 MHz,
CDCl3): d=7.14 (d, J=8.7 Hz, 2H), 6.85 (d, J=8.7 Hz, 2H), 5.65 (d, J=
1.1 Hz, 1H), 5.28–5.21 (m, 1H), 5.15 (d, J=15.1 Hz, 1H), 4.92–4.79 (m,
1H), 4.24 (d, J=15.1 Hz, 1H), 3.90 (dd, J=9.0, 3.8 Hz, 1H), 3.79 (s, 3H),
3.40–3.26 (m, 3H), 3.13 (s, 3H), 2.48–2.21 (m, 4H), 2.20–2.07 (m, 2H),
2.00 (dd, J=15.4, 4.1 Hz, 1H), 1.88 (d, J=1.5 Hz, 3H), 1.75–1.61 (m,
3H), 1.50–1.36 (m, 2H), 1.12 (d, J=7.2 Hz, 3H); 13C NMR(75 MHz,
CDCl3): d=172.9, 165.9, 159.0, 156.2, 128.9, 128.7, 119.1, 114.1, 101.0,
86.2, 80.9, 66.8, 65.0, 57.7, 55.3, 47.9, 47.0, 33.9, 33.8, 33.3, 31.2, 21.1, 26.4,
26.3, 25.1, 22.0, 19.0; IR(film): n˜
= 2938, 1697, 1673, 1512, 1276,
1248 cmꢁ1; HRMS (ESI+): m/z: calcd for C29H37NO6S+Na: 550.2239;
found: 550.2239 [M ++Na].
Compound 36: A catalytic amount of Lindlar catalyst was added to a so-
lution of cycloalkyne 35 (15 mg, 0.028 mmol) in CH2Cl2 (3 mL). The flask
was evacuated three times and filled with hydrogen and the reaction mix-
ture was vigorously stirred overnight. The catalyst was filtered off
through a pad of silica gel and the filtrate was evaporated to give cycloal-
kene 36 in analytically pure form as a white foam (15 mg, quant.). [a]D20
=
+1178 (c 0.75, CHCl3); 1H NMR(400 MHz, CD 2Cl2): d=0.98 (d, J=
6.6 Hz, 3H), 1.24–1.95 (m, 8H), 1.90 (d, J=1.3 Hz, 3H), 2.04–2.41 (m,
3H), 2.70–2.85 (m, 2H), 3.14 (s, 3H), 3.18–3.29 (m, 2H), 3.78–3.83 (m,
1H), 3.79 (s, 3H), 4.22–4.30 (m, 1H), 4.33 (d, J=14.4 Hz, 1H), 5.01 (d,
J=14.4 Hz, 1H), 5.06–5.13 (m, 1H), 5.28 (dd, J=3.0, 11.4 Hz, 1H), 5.60
(d, J=1.3 Hz, 1H), 6.87 (d, J=8.6 Hz, 2H), 7.23 (d, J=8.6 Hz, 2H);
13C NMR(100 MHz, CD 2Cl2): d=21.9, 24.3, 25.4, 26.7, 29.4, 30.0, 31.5,
32.4, 35.1, 35.6, 47.5, 47.6, 55.3, 59.3, 63.4, 67.6, 102.3, 114.0, 118.6, 128.1,
129.1, 129.9, 135.0, 155.0, 159.2, 165.9, 172.7; IR(film): n˜ = 2925, 2854,
Diyne 44: Prepared as described above from acid 13 and alcohol 41.
[a]2D0 =+59.0 (c 1.04, CHCl3); 1H NMR(300 MHz, CDCl 3): d=7.15 (d,
J=8.3 Hz, 2H), 6.86 (d, J=8.7 Hz, 2H), 5.72 (d, J=1.1 Hz, 1H), 5.24–
5.11 (m, 2H), 4.26 (d, J=15.5 Hz, 1H), 3.90 (dd, J=9.4, 3.8 Hz, 2H),
3.80 (s, 3H), 3.41–3.18 (m, 2H), 3.09 (s, 3H), 2.89–2.72 (m, 2H), 2.40–
2.29 (m, 3H), 2.03 (d, J=3.4 Hz, 2H), 1.96 (d, J=1.1 Hz, 3H), 1.86–1.78
(m, 1H), 1.77–1.74 (m, 6H), 1.73–1.34 (m, 5H), 1.11 (d, J=6.8 Hz, 3H);
13C NMR(75 MHz, CDCl 3): d=173.0 (C), 165.7 (C), 159.0 (C), 158.0
(C), 128.8 (C), 128.6 (CH), 117.8 (CH), 114.1 (CH), 100.6 (C), 83.3 (C),
78.5 (C), 77.2 (C), 76.2 (C), 76.0 (C), 65.5 (CH), 65.4 (CH), 57.6 (CH),
55.3 (CH3), 47.8 (CH3), 46.9 (CH2), 34.3 (CH2), 33.4 (CH2), 32.8 (CH2),
32.7 (CH2), 31.4 (CH2), 26.3 (CH2), 26.0 (CH), 25.6 (CH3), 21.4 (CH3),
1700, 1670, 1512, 1453, 1274, 1247, 1089, 1028, 734 cmꢁ1
.
Compound 46: Prepared analogously by Lindlar reduction of cycloalkyne
45; colorless oil (16 mg, 86%). [a]2D0 =+115.8 (c 0.91, CH2Cl2); 1H NMR
(400 MHz, CDCl3): d=7.14 (d, J=8.3 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H),
5.69 (d, J=1.3 Hz, 1H), 5.26 (td, J=11.2, 2.8 Hz, 1H), 5.18 (d, J=
15.7 Hz, 1H), 5.18–5.13 (m, 1H), 5.06 (td, J=10.9, 1.5 Hz, 1H), 4.26 (d,
J=15.7 Hz, 1H), 4.20–4.08 (m, 1H), 3.90 (dd, J=9.1, 4.0 Hz, 1H), 3.79
(s, 3H), 3.38–3.26 (m, 2H), 3.13 (s, 3H), 2.79–2.63 (m, 2H), 2.39–2.29 (m,
1H), 2.24 (dt, J=15.4, 2.0 Hz, 1H), 2.20–2.07 (m, 2H), 1.97 (d, J=15.4,
4.0 Hz, 1H), 1.91 (dd, J=15.4, 4.0 Hz, 1H), 1.76–1.11 (m, 6H), 0.92 (d,
J=6.6 Hz, 3H); 13C NMR(75 MHz, CDCl 3): d=172.9, 166.2, 159.0,
153.9, 135.2, 128.9, 128.4, 127.7, 118.9, 114.1, 101.3, 67.2, 63.0, 57.9, 55.3,
47.8, 46.8, 35.6, 34.9, 32.3, 31.5, 29.6, 26.5, 26.2, 24.4, 22.6, 22.0; IR(film):
n˜ = 2954, 1700, 1673, 1512, 1275, 1248, 1022 cmꢁ1; HRMS (ESI+): m/z:
calcd for C29H39NO6S+Na: 552.2389; found: 552.2396 [M ++Na].
17.9 (CH2), 3.5 (CH3); IR(film): n˜ = 2973, 1704, 1676, 1513, 1082 cmꢁ1
;
HRMS (ESI+): m/z: calcd for C33H43NO6S+Na: 604.2705; found:
604.2709 [M ++Na].
Cycloalkyne 35: CH2Cl2 (30 mL) was added to a solution of [Mo{N-
ACHTREUNG
(tBu)(Ar)}3] (37) (1.3 mg, 5 mol%, Ar=3,5-dimethylphenyl)[27] in toluene
(0.5 mL).
This catalyst solution was transferred into a flask containing a solution of
diyne 34 (25 mg, 0.043 mmol) in toluene (2 mL). The resulting mixture
was stirred at 808C for 20 h before it was fil-
tered through a pad of silica gel. Evaporation
Latrunculin B (2): Cerium ammonium nitrate (CAN, 31 mg, 0.057 mmol)
was added to a vigorously stirred suspension of cycloalkene 36 (12 mg,
0.023 mmol) in MeCN/water 2:1 (0.5 mL). After 20 min, the mixture
became homogeneous and stirring was continued for additional 3 h. For
work-up, the solution was extracted three times with CH2Cl2, the com-
bined organic layers were dried (Na2SO4) and the
of the filtrate followed by flash chromato-
graphic purification of the residue (ethyl ace-
tate/hexanes 1:4) gave cycloalkyne 35 as white
crystals (16 mg, 70%). [a]2D0 =+61.38 (c 0.75,
CH2Cl2); 1H NMR(600 MHz, CD 2Cl2): d=
5.74 (quint., J=1.2 Hz, 1H, H2), 2.90 (ddd,
solvent was evaporated. Purification of the resi-
J=8.0, 9.0, 12.7 Hz, 1H, H4a), 2.59 (dddd, J=
due by flash chromatography (ethyl acetate/hex-
1.0, 5.1, 7.3, 12.6 Hz, 1H), 2.37 (m, 1H, H5a),
anes 1:2) afforded latrunculin B (2) as a colorless
2.34 (m, 1H, H5b), 2.45 (m, 1H, H8), 1.63 (m,
1H, H9a), 1.44 (m, 1H, H9b), 1.67 (m, 1H,
oil (7 mg, 78%). [a]2D0 =+1228 (c 0.55, CHCl3);
1H NMR(400 MHz, CDCl 3): d=0.95 (d, J=
H10a), 1.58 (m, 1H, H10b), 4.71 (dtd, J=1.8, 6.8, 11.6 Hz, 1H, H11),
2.30 (ddt, J=1.8, 3.1, 14.2 Hz, 1H, H12a), 1.37 (ddd, J=2.6, 11.7,
14.3 Hz, 1H, H12b), 5.35 (quint., J=2.9 Hz, 1H, H13), 2.10 (ddd, J=2.0,
2.8, 14.7 Hz, 1H, H14a), 1.95 (dd, J=3.5, 14.7 Hz, 1H, H14b), 3.80 (ddd,
J=1.1, 6.1, 9.0 Hz, 1H, H16), 3.48 (dd, J=8.9, 11.7 Hz, 1H, H17a), 3.40
(dd, J=6.0, 11.7 Hz, 1H, H17b), 1.86 (d, J=1.4 Hz, 3H, H19), 1.14 (d,
J=7.0 Hz, 3H, H20), 3.79 (brs, 1H, OH), 5.68 (s, 1H, NH); 13C NMR
(150 MHz, CD2Cl2): d=165.3 (C1), 118.2 (C2), 156.1 (C3), 32.7 (C4), 18.3
(C5), 79.6 (C6), 86.3 (C7), 25.6 (C8), 31.3 (C9), 34.1 (C10), 63.9 (C11),
33.4 (C12), 68.8 (C13), 31.0 (C14), 97.7 (C15), 61.6 (C16), 28.8 (C17),
174.7 (C18), 24.2 (C19), 22.7 (C20); IR(film): n˜ = 2935, 1695, 1672,
1512, 1444, 1276, 1248, 1214, 1093, 1031 cmꢁ1; MS (EI): m/z (%): 305
(100), 287 (20), 273 (13), 255 (26), 227 (15), 213 (23), 203 (15), 149 (11),
6.3 Hz, 3H), 1.07–2.39 (m, 11H), 1.90 (d, J=
1.3 Hz, 3H), 2.60–2.80 (m, 2H), 3.39 (dd, J=6.3,
11.6 Hz, 1H), 3.47 (dd, J=8.8, 11.6 Hz, 1H),
3.81–3.85 (m, 1H), 3.87 (s, 1H, OH), 4.24 (brt,
J=10.6 Hz, 1H), 5.05 (dt, J=1.5, 11.2 Hz, 1H),
5.25 (dt, J=3.0, 11.2 Hz, 1H), 5.43–5.46 (m, 1H),
5.68 (d, J=1.3 Hz, 1H), 5.77 (s, 1H, NH); 13C NMR(100 MHz, CDCl 3):
see Table 1; IR(film): n˜ = 3328, 2952, 1678, 1278, 1092, 1057 cmꢁ1
.
16-epi-Latrunculin
B (3): Prepared analogously from compound 46
(5.6 mg, 54%). [a]2D4 =+85 (c 0.24, CHCl3) [lit.: [a]2D4 =+76 (c 0.2,
CHCl3)];[11] 1H NMR(400 MHz, CDCl ): d=5.67 (d, J=1.3 Hz, 1H), 5.51
3
(br s, 1H), 5.31–5.21 (m, 1H), 5.24 (dd, J=11.4, 2.8 Hz, 1H), 5.08–5.00
128
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 115 – 134