Artificial Macrosphelides
FULL PAPER
Synthesis of 18MS-2: In accordance with procedure 5-b, MEM ether 11
(59 mg, 0.13 mmol) gave 18MS-2 (35.4 mg, 60%) as a colorless solid:
M.p. 162–1648C (colorless powder from diethyl ether/hexane); 1H NMR
(CDCl3): d=7.05–6.98 (1H, m), 6.84 (1H, dd, J=15, 5.5 Hz), 6.29 (1H,
d, J=15 Hz), 6.06 (1H, dd, J=16, 1.3 Hz), 5.43–5.31 (1H, m), 5.25 (1H,
q, J=6.8 Hz), 4.98–4.92 (1H, m), 4.20 (1H, dd, J=5.1, 11 Hz), 2.72 (1H,
dd, J=9.6, 16 Hz), 2.66 (1H, dd, J=2.8, 16 Hz), 2.61–2.45 (4H, m), 2.28
(1H, br), 1.38 (3H, d, J=6.8 Hz), 1.37 (3H, d, J=6.4 Hz), 1.31 ppm (3H,
d, J=6.4 Hz); 13C NMR (CDCl3): d=196.4, 171.6, 169.9, 164.7, 147.7,
144.7, 124.9, 123.5, 77.3, 77.0, 76.7, 74.1, 73.9, 73.6, 68.0, 40.7, 32.8, 27.5,
20.0, 17.2, 16.3 ppm; IR (KBr): n˜ =3465, 1727, 1620 cmÀ1; MS (EI): m/z
368 [M+]; HRMS (EI): calcd for C18H24O8: 368.1471 [M+]; found:
368.1451; [a]2D4 =À42.5 (c=0.135 in CHCl3).
Synthesis of compound 12: In accordance with procedure 1-b, alcohol 7
(100 mg, 0.19 mmol) gave ester 12 (114 mg, 92%) as a colorless oil:
1H NMR (CDCl3): d=7.26–7.16 (1H, m), 7.21 (2H, d, J=8.6 Hz), 6.84
(2H, d, J=8.6 Hz), 6.84–6.77 (1H, m), 6.16–6.04 (1H, m), 6.01 (1H, dd,
J=16, 1.5 Hz), 5.75–5.65 (2H, m), 5.33–5.22 (3H, m), 5.09–5.05 (1H, m),
4.99–4.95 (1H, m), 4.73 (1H, d, J=6.9 Hz), 4.67 (1H, d, J=6.9 Hz), 4.52
(1H, d, J=12 Hz), 4.37–4.32 (1H, m), 4.30 (1H, d, J=12 Hz), 3.77 (3H,
s), 3.77–3.66 (2H, m), 3.64–3.56 (1H, m), 3.50–3.47 (2H, m), 3.34 (3H, s),
2.64 (1H, dd, J=15, 7.1 Hz), 2.48 (1H, dd, J=15, 6.1 Hz), 1.82 (3H, d,
J=5.0 Hz), 1.29 (3H, d, J=6.3 Hz), 1.18 (3H, d, J=6.6 Hz), 1.11 ppm
(3H, d, J=6.6 Hz); 13C NMR (CDCl3): d=169.2, 166.4, 164.8, 159.1,
145.5, 143.6, 139.8, 134.8, 130.2, 129.7, 129.3, 124.1, 119.8, 118.7, 113.7,
93.9, 81.5, 76.7, 72.2, 71.7, 71.1, 70.1, 67.7, 67.3, 59.1, 55.4, 41.3, 20.0, 18.9,
15.8, 15.2 ppm; IR (neat): n˜ =1719, 1645, 1615 cmÀ1; MS (EI): m/z 618
[M+]; HRMS (EI): calcd for C33H46O11: 618.3040 [M+]; found: 618.2993;
[a]2D4 =À36.1 (c=0.89 in CHCl3).
([D6]DMSO): d=169.1, 164.7, 164.4, 148.9, 145.0, 144.6, 125.9, 122.8,
119.9, 73.6, 72.6, 71.6, 71.4, 67.3, 19.6, 18.2, 17.4 ppm; IR (KBr): n˜ =3450,
1729, 1656 cmÀ1
;
MS (EI): m/z 368 [M+]; HRMS (EI): calcd for
C18H24O8: 368.1471 [M+]; found: 368.1450; [a]2D5 =+204.9 (c=0.10 in
MeOH).
Synthesis of compound 15: In accordance with procedure 4-a, alcohol 14
(60 mg, 0.13 mmol) gave the corresponding ketone 15 (40 mg, 66%) as a
colorless oil: 1H NMR (CDCl3): d=7.33–7.24 (1H, m), 7.08 (1H, dd, J=
15, 12 Hz), 6.78 (1H, dd, J=16, 8.8 Hz), 6.55 (1H, d, J=15 Hz), 6.18
(1H, d, J=16 Hz), 6.09 (1H, d, J=15 Hz), 5.44–5.35 (1H, m), 4.90 (1H,
q, J=5.5 Hz), 4.80–4.68 (3H, m), 4.25–4.19 (1H, t, J=8.5 Hz), 3.82–3.75
(1H, m), 3.68–3.58 (1H, m), 3.56–3.52 (2H, m), 3.39 (3H, s), 2.89 (1H,
dd, J=16, 9.9 Hz), 2.56 (1H, dd, J=16, 1.9 Hz), 1.45 (3H, d, J=6.9 Hz),
1.44 (3H, d, J=6.0 Hz), 1.30 ppm (3H, d, J=6.3 Hz); 13C NMR (CDCl3):
d=197.1, 170.8, 164.4, 164.0, 146.3, 142.5, 139.7, 129.1, 128.6, 126.1, 93.6,
78.9, 77.4, 71.7, 71.3, 69.4, 67.5, 59.3, 40.8, 20.4, 18.2, 16.9 ppm; IR (neat):
n˜ =1735, 1710, 1644, 1618 cmÀ1; MS (EI): m/z 454 [M+]; HRMS (EI):
calcd for C22H30O10: 454.1839 [M+]; found: 454.1814; [a]2D6 =À31.0 (c=
0.44 in CHCl3).
Synthesis of 18MS-4: In accordance with procedure 5-a, MEM ether 15
(49 mg, 0.11 mmol) gave 18MS-4 (32 mg, 80%) as a colorless solid: M.p.
150–1528C (colorless powder from diethyl ether/hexane); 1H NMR
(CDCl3): d=7.32–7.27 (1H, m), 7.10 (1H, dd, J=15, 12 Hz), 6.88 (1H,
dd, J=15, 6.1 Hz), 6.57 (1H, d, J=15 Hz), 6.17 (1H, d, J=15 Hz), 6.12
(1H, d, J=15 Hz), 5.43–5.37 (1H, m), 4.92 (1H, q, J=7.3 Hz), 4.76–4.71
(1H, m), 4.26 (1H, t, J=8.3 Hz), 2.85 (1H, dd, J=10, 16 Hz), 2.58 (1H,
dd, J=11, 16 Hz), 1.48 (3H, d, J=6.0 Hz), 1.45 (3H, d, J=7.2 Hz),
1.39 ppm (3H, d, J=6.4 Hz); 13C NMR (CDCl3): d=197.0, 170.7, 164.6,
164.2, 147.4, 142.6, 139.7, 129.0, 128.7, 124.6, 75.6, 72.7, 69.4, 53.7, 40.8,
20.3, 17.8, 16.8 ppm; IR (KBr): n˜ =3468, 1708, 1618 cmÀ1; MS (EI): m/z
366 [M+]; HRMS (EI): calcd for C18H22O8: 366.1315 [M+]; found:
366.1303; [a]2D5 =+63.0 (c=0.26 in MeOH).
Synthesis of compound 13: In accordance with procedure 2, the PMB
ether 12 (95 mg, 0.15 mmol) gave the alcohol 13 (72 mg, 95%) as a color-
less oil: 1H NMR (CDCl3): d=7.25–7.16 (1H, m), 6.82 (1H, dd, J=6.0,
16 Hz), 6.21–6.11 (2H, m), 6.02 (1H, dd, J=1.5, 16 Hz), 5.84–5.69 (2H,
m), 5.38–5.27 (2H, m), 5.20 (1H, d, J=10 Hz), 5.09–5.02 (1H, m), 4.96–
4.87 (1H, m), 4.73 (1H, d, J=6.9 Hz), 4.67 (1H, d, J=6.9 Hz), 4.39–4.34
(1H, m), 4.20–4.15 (1H, m), 3.78–3.71 (1H, m), 3.64–3.55 (1H, m), 3.50–
3.46 (2H, m), 3.35 (3H, s), 2.67 (1H, dd, J=16, 7.4 Hz), 2.53 (1H, dd,
J=16, 5.2 Hz), 2.45–2.30 (1H, br), 1.83 (3H, d, J=5.2 Hz), 1.33 (3H, d,
J=6.3 Hz), 1.20 (3H, d, J=6.6 Hz), 1.15 ppm (3H, d, J=6.6 Hz);
13C NMR (CDCl3): d=169.8, 166.4, 165.0, 145.5, 143.9, 139.8, 135.8,
129.7, 123.9, 118.7, 117.4, 93.9, 74.6, 73.8, 71.7, 71.1, 67.8, 67.3, 59.1, 41.4,
20.2, 18.9, 15.2, 14.4 ppm; IR (neat): n˜ =3486, 1716, 1644, 1619 cmÀ1; MS
(EI): m/z 498 [M+]; HRMS (EI): Calcd for C25H38O10: 498.2465 [M+];
found: 498.2424; [a]2D5 =À20.9 (c=1.04 in CHCl3).
Synthesis of compound 16: In accordance with procedure 1-b, carboxylic
acid 5 (117 mg, 0.34 mmol) and alcohol 4 (50 mg, 0.23 mmol) gave ester
16 (105 mg, 85%) as a colorless oil: 1H NMR (CDCl3): d=7.24 (2H, d,
J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 6.81 (1H, dd, J=6.3, 16 Hz), 5.99
(1H, d, J=16 Hz), 5.82–5.70 (1H, m), 5.31 (1H, d, J=10 Hz), 5.27 (1H,
d, J=17 Hz), 5.07–5.02 (1H, m), 4.74 (1H, d, J=7.1 Hz), 4.71 (1H, d, J=
7.1 Hz), 4.56 (1H, d, J=12 Hz), 4.36 (1H, d, J=12 Hz), 4.07–4.03 (1H,
m), 3.80 (3H, m), 3.84–3.73 (3H, m), 3.67–3.60 (1H, m), 3.54–3.50 (1H,
m), 3.37 (3H, m), 1.24 (3H, d, J=6.3 Hz), 1.17 (3H, d, J=6.3 Hz), 0.86
(9H, s), 0.04 (3H, s), 0.02 ppm (3H, s); 13C NMR (CDCl3): d=165.2,
159.0, 145.6, 134.9, 130.3, 129.2, 123.9, 119.4, 113.7, 94.0, 81.7, 80.0, 72.1,
71,8, 70.7, 70.6, 70.2, 67.3, 59.1, 55.3, 26.0, 20.1, 18.2, 15.7, À4.4,
À4.5 ppm; IR (neat): n˜ =1719, 1646, 1610 cmÀ1; MS (EI): m/z 552 [M+];
HRMS (EI): calcd for C29H48O8Si: 552.3118 [M+]; found: 552.3120;
[a]2D4 =À31.4 (c=4.42 in CHCl3).
Synthesis of compound 14: In accordance with procedure 3, compound
13 (87 mg, 0.17 mmol) gave 14 (29.1 mg, 37%) as a colorless solid.: M.p.
1
170–1728C (colorless plates from CH2Cl2/hexane); H NMR (CDCl3): d=
7.04 (1H, dd, J=11, 15 Hz), 6.74 (1H, dd, J=16, 8.8 Hz), 6.44 (1H, dd,
J=16, 1.1 Hz), 6.14 (1H, dd, J=16, 1.5 Hz), 6.05 (1H, d, J=16 Hz), 5.75
(1H, d, J=15 Hz), 5.48–5.41 (1H, m), 4.86–4.74 (2H, m), 4.75 (1H, d,
J=7.1 Hz), 4.70 (1H, d, J=7.1 Hz), 4.19–4.08 (2H, m), 3.81–3.75 (1H,
m), 3.67–3.61 (1H, m), 3.56–3.52 (2H, m), 3.38 (3H, s), 2.64 (1H, dd, J=
17, 10 Hz), 2.49 (1H, dd, J=17, 2.2 Hz), 1.42 (3H, d, J=6.0 Hz), 1.34
(3H, d, J=6.3 Hz), 1.30 ppm (3H, d, J=6.3 Hz); 13C NMR (CDCl3): d=
169.4, 165.2, 164.4, 146.0, 144.6, 142.4, 127.0, 126.0, 121.1, 93.7, 79.0, 73.7,
73.3, 71.7, 70.5, 67.9, 67.4, 59.2, 40.8, 20.3, 18.5, 18.1 ppm; IR (KBr): n˜ =
3478, 1744, 1708, 1641 cmÀ1; MS (EI): m/z 456 [M+]; HRMS (EI): calcd
for C22H32O10: 456.1996 [M+]; found: 456.2030; [a]2D8 =+39.3 (c=0.10 in
CHCl3).
Synthesis of compound 17: In accordance with procedure 6-a, TBS ether
16 (1.60 g, 2.9 mmol) gave alcohol 17 (1.20 g, 95%) as a colorless oil:
1H NMR (CDCl3): d=7.23 (2H, d, J=8.8 Hz), 6.85 (2H, d, J=8.8 Hz),
6.81 (1H, dd, J=6.0, 16 Hz), 6.03 (1H, dd, J=1.5, 16 Hz), 5.81–5.69 (1H,
m), 5.32 (1H, d, J=10 Hz), 5.28 (1H, d, J=17 Hz), 5.08–4.99 (1H, m),
4.78 (1H, d, J=7.1 Hz), 4.71 (1H, d, J=7.1 Hz), 4.56 (1H, d, J=11 Hz),
4.35 (1H, d, J=11 Hz), 4.24–4.20 (1H, m), 3.79 (3H, m), 3.96–3.73 (3H,
m), 3.71–3.63 (1H, m), 3.58–3.52 (1H, m), 3.38 (3H, m), 1.22 (3H, d, J=
6.3 Hz), 1.15 ppm (3H, d, J=6.3 Hz); 13C NMR (CDCl3): d=165.2, 159.1,
143.8, 134.9, 130.4, 129.3, 124.9, 119.6, 113.8, 94.6, 81.6, 81.0, 72.3, 71.8,
70.3, 69.2, 67.7, 59.2, 55.5, 17.9, 15.7 ppm; IR (neat): n˜ =3456, 1710, 1646,
1611 cmÀ1; MS (EI): m/z 438 [M+]; HRMS (EI): calcd for C23H34O8:
438.2254 [M+]; found: 438.2281; [a]D25 =À52.7 (c=1.73 in CHCl3).
Synthesis of compound 18: In accordance with procedure 1-a, carboxylic
acid 6 (1.07 g, 5.0 mmol) and alcohol 17 (1.1 g, 2.5 mmol) gave ester 18
(1.43 g, 90%) as a colorless oil: 1H NMR (CDCl3): d=7.24 (2H, d, J=
8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 6.79 (1H, dd, J=6.3, 16 Hz), 6.06 (1H,
dd, J=16, 1.4 Hz), 5.82–5.70 (1H, m), 5.31 (1H, d, J=10 Hz), 5.29 (1H,
d, J=16 Hz), 5.07–4.99 (2H, m), 4.76 (1H, d, J=7.1 Hz), 4.70 (1H, d, J=
7.1 Hz), 4.57 (1H, d, J=12 Hz), 4.36 (1H, d, J=12 Hz), 4.34–4.21 (2H,
m), 3.83–3.76 (1H, m), 3.80 (3H, s), 3.68–3.60 (1H, m), 3.55–3.51 (2H,
Synthesis of 18MS-3: In accordance with procedure 5-a, MEM ether 14
(21.5 mg, 0.05 mmol) gave 18MS-3 (16.2 mg, 95%) as a colorless solid:
M.p. 194–1968C (colorless plates from CHCl3); 1H NMR ([D6]DMSO):
d=7.02 (1H, dd, J=15, 11 Hz), 6.62 (1H, dd, J=16, 8.5 Hz), 6.42 (1H,
dd, J=15, 12 Hz), 6.15–6.02 (2H, m), 5.79 (1H, d, J=15 Hz), 5.64 (1H,
d, J=6.0 Hz), 5.59 (1H, d, J=5.8 Hz), 5.31–5.20 (1H, m), 4.70–4.60 (1H,
m), 4.50–4.40 (1H, m), 4.07–3.99 (1H, m), 3.98–3.89 (1H, m), 2.74 (1H,
dd, J=17, 1.8 Hz), 2.56 (1H, dd, J=17, 10 Hz), 1.31 (3H, d, J=6.0 Hz),
1.26 (3H, d, J=6.3 Hz), 1.19 ppm (3H, d, J=6.3 Hz); 13C NMR
Chem. Eur. J. 2009, 15, 5799 – 5813
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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