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doi.org/10.1002/ejoc.202001591
140.3 (C-6), 134.9 (C-10), 133.1 (C-8), 130.6 (C-11), 129.8 (C-9), 122.5
(s), 1682 (m), 1587 (s), 1436 (w), 1371 (m), 1313 (w), 1236 (s), 1058
(m), 746 (m), 642 (w) cmÀ 1. HRMS-ESI C24H36O6Na calcd.: 441.2247,
found: 441.2243.
1
2
3
4
5
6
7
8
9
(C-7), 121.0 (C-13), 78.8 (C-15), 75.1 (C-5), 51.7 (C-22), 35.4 (C-16),
34.7 (C-4), 33.8 (C-2), 31.8 (C-18), 27.5 (C-21), 26.0 (C-26, C-7, C-28),
24.8 (C-17), 22.6 (C-19), 21.1 (C-3), 18.4 (C-25), 14.1 (C-20), À 4.6,
À 4.9 (C-23, C-24). IR (neat): v˜=3469 (br), 2954 (s), 2931 (s), 2858
(m), 1740 (s), 1682 (w), 1580 (s), 1437 (w), 1317 (w), 1253 (m), 1162
(w), 1092 (m), 838 (s), 779 (s), 742 (m), 611 (w), 596 (w), 584 (w).
HRMS-ESI C28H46O5SiNa calcd.: 513.3007, found: 513.2998.
(5S, 14R/S, 15S) 5-(O-Acetyl)-6,11-methylene-LXB4 methyl ester
XIV: Zinc(II) triflate (0.070 g, 0.19 mmol, 4.0 eq). was dried under
high vacuum (2×10À 2 mbar) at 200 C for 20 minutes before being
°
suspended in dry ether (2 mL) under Ar. The hydroxyketone 34
(0.020 g, 0.048 mmol, 1.0 eq.) dissolved in dry ether (3 mL) was
°
(5S, 15S) 5-(O-Acetyl)-15-(O-tert-butyldimethylsilyl)-6,11-meth-
ylene-14-oxo-LXB4 methyl ester 33b: Under Ar, the alcohol 33a
(0.070 g, 0.14 mmol, 1.0 eq.) dissolved in dry CH2Cl2 (5 mL) was
treated with N, N-dimethylaminopyridine (7.0 mg, 0.057 mmol,
0.4 eq.) and dry triethylamine (0.022 g, 0.030 mL, 0.21 mmol,
1.5 eq.). Then acetic anhydride (0.022 g, 0.020 mL, 0.21 mmol,
1.5 eq.) was added slowly at room temperature. The reaction was
stirred for 18 hours before being quenched with water. The
aqueous layer was extracted with EtOAc (3×10 mL). The combined
organic layers were washed with 1 m hydrochloric acid, sat aq.
NaHCO3 and brine and dried (MgSO4). The solvent was removed in
vacuo affording the product 33b (0.073 g, 0.14 mmol, 96%) as a
added. After 15 minutes the reaction was cooled to 0 C and
sodium borohydride (0.018 g, 0.48 mmol, 10.0 eq.) was added. The
°
reaction was stirred at 0 C for one hour and then warmed up to
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
room temperature and stirred for one hour until complete
discoloration. The reaction was quenched with aq. sat. NH4Cl and
extracted with ether (3×15 mL). The combined organic layers were
washed (brine) and dried (Na2SO4). The solvent was removed in
°
vacuo at a temperature below 30 C. The rotary evaporator was
ventilated with argon. The mixture of C14 epimers of alcohol XIV
(0.020 g, 0.048 mmol, quant.) was afforded as a colorless oil and
used directly for the next reaction. Rf (EtOAc/petroleum ether 1:2):
0.16. For spectroscopic data see supporting information.
°
yellow oil. Rf (EtOAc/petroleum ether 1:5): 0.42, [α]D =À 59.1 (c=
Under Ar, the diol XIV (0.025 g, 0.059 mmol, 1.0 eq.) was dissolved
in dry CH2Cl2 (3 mL) and treated with N, N-dimethylaminopyridine
3
1.0, 22 C, CH2Cl2), 1H-NMR (400 MHz, CDCl3): δ=7.39 (d, JHH
=
°
3
15.8 Hz, 1H, H-12), 6.96 (d, JHH =15.7 Hz, 1H, H-13), 6.63–6.56 (m,
2H, H-8, H-9), 6.55–6.48 (m, 1H, H-10), 6.23–6.16 (m, 1H, H-7), 5.27
(ddd, 3JHH =7.3 Hz, 3JHH =5.5 Hz, 4JHH =1.8 Hz, 1H, H-5), 4.22–4.09 (m,
°
(7.3 mg, 0.059 mmol, 1.0 eq.). The solution was cooled to 0 C and
1,1’-carbonyldiimidazole (0.015 g, 0.089 mmol, 1.5 eq.) was added.
The reaction was stirred at room temperature overnight. The
reaction was quenched with water and acidified with 1 m
hydrochloric acid. The aqueous layer was extracted with EtOAc (3×
10 mL). The combined organic layers were washed (brine) and dried
(Na2SO4). The solvent was removed in vacuo at a temperature
2
1H, H-15), 3.63 (s, 3H, H-22), 2.78 (d, JHH =13.4 Hz, 1H, H-21’), 2.52
2
3
(d, JHH =13.4 Hz, 1H, H-21’’), 2.24 (t, JHH =7.5 Hz, 2H, H-2), 2.03 (s,
3H, H-30), 1.79–1.58 (m, 4H, H-4, H-16), 1.58–1.44 (m, 2H, H-3), 1.44–
1.32 (m, 2H, H-17), 1.32–1.20 (m, 4H, H-18, H-19), 0.95 (s, 9H, H-26,
3
H-27, H-28), 0.87 (t, JHH =6.8 Hz, 3H, H-20), 0.08 (s, 3H), 0.06 (s, 3H)
°
below 30 C. The residue was purified via column chromatography
(H-23, H-24). 13C-NMR (100 MHz, CDCl3): δ=202.3 (C-14), 173.6 (C-1),
170.1 (C-29), 144.8 (C-12), 135.1 (C-10), 134.8 (C-6), 132.8 (C-8), 131.1
(C-11), 130.4 (C-9), 124.9 (C-7), 121.1 (C-13), 78.7 (C-15), 76.8 (C-5),
51.7 (C-22), 35.5 (C-16), 33.5 (C-2), 32.2 (C-4), 31.8 (C-18), 27.0 (C-21),
26.0 (C-26, C-27, C-28), 24.8 (C-17), 22.6 (C-19), 21.2 (C-30), 21.0 (C-
3), 18.3 (C-25), 14.1 (C-20), À 4.6, À 4.9 (C-23, C-24). IR (neat): v˜=
3018 (w), 2952 (m), 2929 (m), 2857 (m), 1740 (s), 1682 (w), 1581 (m),
1468 (w), 1436 (w), 1369 (w), 1313 (w), 1234 (s), 1163 (w), 1092 (w),
1024 (w), 958 (w), 838 (m), 778 (m), 745 (m), 669 (w), 618 (w), 593
(w), 582 (w) cmÀ 1. HRMS-ESI C30H48O6SiNa calcd.: 555.3112, found:
555.3119.
(EtOAc/petroleum ether 1:3 to 2:1) affording the trans- 36 and cis-
35 carbonates as well as a dicarbamate XV. Yields: Cis-carbonate
35: Yield: 0.010 g (0.022 mmol, 38%) as a colorless oil. Trans-
carbonate 36 (14-epi): Yield: 5.0 mg (0.011 mmol, 19%) as a
colorless oil. Dicarbamate XV: Yield: 0.010 g (0.016 mmol, 28%) as a
pale-yellow oil. Rf (EtOAc/petroleum ether 2:1): 0.31. For spectro-
scopic data see supporting information.
(S)-5-Acetoxy-5-(6-((E)-2-((4R,5S)-2-oxo-5-pentyl-1,3-dioxolan-4-yl)
vinyl)cyclohepta-1,3,5-trien-1-yl)pentanoic acid methyl ester (cis-
°
carbonate) 35: Rf (EtOAc/petroleum ether 1:2): 0.50, [α]D = +6.9
(c=1.0, 22 C, CH2Cl2), 1H-NMR (600 MHz, C6D6): δ=6.37–6.31 (m,
°
(5S 15S) 5-(O-Acetyl)-6,11-methylene-14-oxo-LXB4 methyl ester
34: Under Ar, the silyl ether 33b (0.020 g, 0.038 mmol, 1.0 eq.) was
2H, H-8, H-9), 6.13–6.08 (m, 2H, H-7, H-12), 5.93–5.90 (m, 1H, H-10),
3
3
5.76 (dd, JHH =15.7 Hz, JHH =7.7 Hz, 1H, H-13), 5.41–5.38 (m, 1H, H-
°
dissolved in dry THF (2 mL) and cooled to 0 C. Then a 1:1 mixture
3
5), 4.39 (td, 3JHH =7.6 Hz, 3JHH =1.1 Hz, 1H, 14), 3.84 (ddd, JHH
=
of tetrabutylammonium fluoride 1.0 m in THF (0.19 mL, 0.19 mmol,
5.0 eq.) and acetic acid (0.011 g, 0.011 mL, 0.19 mmol, 5.0 eq.) in dry
THF (3 mL) was added dropwise. The reaction was warmed to room
temperature and stirring was continued for three days. The solvent
was evaporated and the residue was purified via column chroma-
tography (EtOAc/petroleum ether 1:3) affording the hydroxyketone
34 (0.013 g, 0.031 mmol, 83%) as a yellow oil. Rf (EtOAc/petroleum
3
3
10.3 Hz, JHH =7.6 Hz, JHH =3.5 Hz, 1H, H-15), 3.34 (s, 3H, H-22), 2.77
(d, JHH =13.3 Hz, 1H, H-21’), 2.31 (d, JHH =13.3 Hz, 1H, H-21’’), 2.11
(td, JHH =7.3 Hz, JHH =2.0 Hz, 2H, H-2), 1.67 (s, 3H, H-24), 1.61–1.51
2
2
3
4
(m, 2H, H-4), 1.50–1.41 (m, 2H, H-3), 1.41–1.25 (m, 2H, H-16), 1.21–
3
1.12 (m, 2H, H-19), 1.09–1.02 (m, 4H, H-17, H-18), 0.84 (t, JHH
=
7.3 Hz, 3H, H-20). 13C-NMR (150 MHz, C6D6): δ=173.0 (C-1), 169.6 (C-
23), 154.1 (C-25), 136.9 (C-12), 133.9 (C-6), 131.1 (C-8), 130.3 (C-9),
130.2 (C-11), 129.2 (C-10), 124.5 (C-7), 121.6 (C-13), 79.9 (C-14), 79.7
(C-15), 76.4 (C-5), 51.1 (C-22), 33.4 (C-2), 32.1 (C-4), 31.5 (C-18), 30.1
(C-16), 28.0 (C-21), 25.7 (C-17), 22.8 (C-19), 21.4 (C-3), 20.7 (C-24),
14.2 (C-20). IR (neat): v˜=3018 (w), 2956 (m), 2931 (m), 2862 (w),
1803 (s), 1737 (s), 1638 (w), 1437 (m), 1370 (m), 1238 (s), 1175 (m),
1041 (m), 975 (m), 851 (w), 745 (m), 668 (w), 643 (w), 634 (m), 623
(m), 608 (m), 596 (m) cmÀ 1. HRMS-ESI C25H34O7Na calcd.: 469.2197,
found: 469.2188.
ether 1:3): 0.42, [α]D =À 72.4 (c=1.0, 23 C, CH2Cl2), 1H-NMR
(400 MHz, CDCl3): δ=7.40 (dd, 3JHH =15.7 Hz, 4JHH =0.7 Hz, 1H, H-
12), 6.72–6.58 (m, 3H, H-8, H-9, H-13), 6.58–6.54 (m, 1H, H-10), 6.22
°
°
3
3
(d, JHH =5.4 Hz, 1H, H-7), 5.29 (t, JHH =6.7 Hz, 1H, H-5), 4.44 (s, 1H,
2
H-15), 3.64 (s, 3H, H-22), 2.76 (d, JHH =13.4 Hz, 1H, H-21’), 2.49 (d,
3
2JHH =13.4 Hz, 1H, H-21’’), 2.27 (t, JHH =7.1 Hz, 2H, H-2), 2.04 (s, 3H,
H-24), 1.93–1.79 (m, 1H, H-16’), 1.79–1.66 (m, 2H, H-4), 1.65–1.37 (m,
3
5H, H-3, H-16’’, H-17), 1.36–1.26 (m, 4H, H-18, H-19), 0.88 (t, JHH
=
6.5, 3H, H-20). 13C-NMR (100 MHz, CDCl3): δ=201.1 (C-14), 173.7 (C-
1), 170.2 (C-23), 145.3 (C-12), 135.7 (C-10), 135.1 (C-6), 133.4 (C-8),
130.3 (C-9), 129.9 (C-11), 124.6 (C-7), 121.0 (C-13), 76.6 (C-5), 75.9 (C-
15), 51.8 (C-22), 34.6 (C-16), 33.4 (C-2), 32.3 (C-4), 31.8 (C-18), 27.3
(C-21), 24.7 (C-17), 22.7 (C-19), 21.2 (C-24), 21.0 (C-3), 14.2 (C-20). IR
(neat): v˜=3460 (br), 3018 (w), 2949 (m), 2929 (m), 2863 (w), 1738
(S)-5-Acetoxy-5-(6-((E)-2-((4S,5S)-2-oxo-5-pentyl-1,3-dioxolan-4-yl)
vinyl)cyclohepta-1,3,5-trien-1-yl)pentanoic acid methyl ester
(trans-carbonate) 36 (14-epi): Rf (EtOAc/petroleum ether 1:2): 0.62,
[α]D =À 59.8 (c=1.0, 22 C, CH2Cl2), 1H-NMR (600 MHz, C6D6): δ=
°
°
3
4
6.38–6.31 (m, 2H, H-8, 9H-), 6.07 (dd, JHH =4.8 Hz, JHH =1.6 Hz, 1H,
Eur. J. Org. Chem. 2021, 1156–1167
1164
© 2020 The Authors. European Journal of Organic Chemistry published
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