S. Sommerwerk et al. / Bioorg. Med. Chem. 23 (2015) 5595–5602
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(13)), 1.47–1.28 (m, 2H, CH2 (16)), 1.44–1.38 (m, 2H, CH2 (15)),
0.91 (t, J = 6.9 Hz, 3H, CH3 (17)) ppm; 13C NMR (125 MHz, CDCl3):
d = 170.6 (C@O, C-18), 145.5 (CH@CH, C-9), 139.7 (CH@CH, C-11),
139.5 (CH@CH, C-2), 129.9 (CH@CH, C-10), 112.3 (CH@CH, C-3),
107.6 (CH@CH, C-8), 82.0 (C„C, C-7), 79.7 (C„C, C-4), 75.8
(C„C, C-6), 75.6 (C„C, C-5), 71.1 (CHOH, C-14), 63.8 (CH2OAc, C-
1), 39.9 (CH2, C-15), 36.6 (CH2, C-13), 29.2 (CH2, C-12), 20.9 (CH3,
C-19), 18.9 (CH2, C-16), 14.2 (CH3, C-17) ppm; MS (ESI, MeOH):
m/z = 318.1 (20%, [M+NH4]+), 323.1 (100%, [M+Na]+), 623.0 (24%,
[2M+Na]+).
ether (30 mL) and the organic layer was washed with water
(3 Â 30 mL) and brine (30 mL), dried (MgSO4), filtered and evapo-
rated to dryness. The residue was subjected to column chromatog-
raphy (silica gel, hexane/EtOAc, 9:1) to yield 18 (65 mg, 92%) as a
colorless solid; mp = 45–46 °C; Rf = 0.55 (hexane/ethyl acetate,
9:1); UV–vis (MeOH): kmax (loge) = 252 (3.61), 267 (3.57), 280
(3.35), 296 (3.54), 315 (3.67), 337 nm (3.54); IR (KBr):
2927w, 2196vw, 2125vw, 1716vs, 1635m, 1452w, 1382w, 1277s,
1123m, 1071m, 1026m, 988m, 711m cmÀ1 1H NMR (500 MHz,
m = 2959w,
;
CDCl3): d = 8.06–8.03 (m, 2H, CHaromat.), 7.59–7.56 (m, 1H,
CHaromat.), 7.47–7.43 (m, 2H, CHaromat.), 6.65 (dd, J = 15.3, 11.0 Hz,
1H, H-9), 6.41 (dt, J = 15.9, 5.7 Hz, 1H, H-16), 6.12 (dddt, J = 15.1,
10.8, 1.4, 0.7 Hz, 1H, H-8), 5.94 (ddt, J = 15.9, 2.8, 1.7 Hz, 1H, H-
15), 5.84 (dt, J = 15.1, 7.0 Hz, 1H, H-7), 5.57 (d, J = 15.4 Hz, 1H, H-
10), 4.89 (dd, J = 5.7, 1.7 Hz, 2H, CH2 (17)), 2.51 (t, J = 7.1 Hz, 2H,
CH2 (5)), 2.42–2.36 (m, 4H, CH2 (3) + CH2 (6)), 1.64–1.56 (m, 2H,
CH2 (2)), 0.91 (t, J = 7.4 Hz, 3H, CH3 (1)) ppm; 13C NMR (126 MHz,
CDCl3): d = 209.9 (C@O, C-4), 166.1 (C@O, C-18), 145.2 (CH@CH,
Data for 16: colorless liquid; Rf = 0.45 (hexane/EtOAc 8:2); IR
(KBr):
m
= 2933m, 2199w, 2120w, 1737s, 1636m, 1438m, 1384m,
UV–vis (MeOH): kmax (loge) = 208
1242s, 1027s, 986m cmÀ1
;
(3.68), 250 (3.83), 267 (3.78), 280 (3.55), 297 (3.77), 314 (3.89),
336 (3.76) nm; 1H NMR (500 MHz, CDCl3): d = 6.67 (ddd, J = 15.6,
10.7, 0.5 Hz, 1H, H-9), 6.27 (dt, J = 15.9, 5.8 Hz, 1H, H-2), 6.10 (dddt,
J = 15.2, 10.9, 1.5. 0.7 Hz, 1H, H-10), 5.88–5.80 (m, 2H, H-3 + H-11),
5.55 (d, J = 15.6 Hz, 1H, H-8), 4.92–4.84 (m, 1H, H-14), 4.61 (dd,
J = 5.8, 1.7 Hz, 2H, CH2 (1)), 2.17–2.10 (m, 2H, CH2 (12)), 2.07 (s,
3H, CH3 (19)), 2.02 (s, 3H, CH3 (21)), 1.68–1.59 (m, 2H, CH2 (13)),
1.58–1.41 (m, 2H, CH2 (15)), 1.40–1.21 (m, 2H, CH2 (16)), 0.89 (t,
J = 7.3 Hz, 3H, CH3 (17)) ppm; 13C NMR (125 MHz, CDCl3):
d = 170.9 (C@O, C-20), 170.5 (C@O, C-18), 145.4 (CH@CH, C-9),
139.5 (CH@CH, C-2), 138.9 (CH@CH, C-11), 130.0 (CH@CH, C-10),
112.3 (CH@CH, C-3), 107.9 (CH@CH, C-8), 81.9 (C„C, C-7), 79.7
(C„C, C-4), 75.7 (C„C, C5, C-6) 73.6 (CHOAc, C-14), 63.8
(CH2OAc, C-1), 36.4 (CH2, C-15), 33.4 (CH2, C-13), 28.9 (CH2, C-
12), 21.3 (CH3, C-21), 20.9 (CH3, C-19), 18.6 (CH2, C-16), 14.1
(CH3, C-17) ppm; MS (ESI, MeOH): m/z = 365.1 (100%, [M+Na]+),
706.9 (13%, [2 M+Na]+).
C-9), 139.6 (CH@CH, C-16), 138.1 (CH@CH, C-7), 133.4 (CHaromat.
,
C22), 130.4 (CH@CH, C-8), 129.9 (Caromat.), 129.8 (CHaromat), 128.6
(CHaromat., C21), 112.4 (CH@CH, C-15), 108.2 (CH = CH, C-10), 81.9
(C„C, C-11), 79.8 (C„C, C-14), 75.8 (C„C, C-12), 75.8 (C„C, C-
13), 64.2 (CH2, C-17), 45.0 (CH2, C-6), 41.8 (CH2, C-5), 27.0 (CH2,
C-3), 17.4 (CH2, C-2), 13.9 (CH3, C-1) ppm; MS (ESI, MeOH):
m/z = 377.8 (54%, [M+NH4]+), 383.1 (78%, [M+Na]+), 563.1 72%,
([3M+2Na]2+), 742.9 (100%, [2M+Na]+); Anal. Calcd for C24H24O3
(360.45): C 79.97, H 6.71; found: C 79.63, H 6.95.
4.3.16. (2E,8E,10E) 14-Oxo-2,8,10-heptadecatriene-4,6-diyn-1-
yl-chloroacetate (19)
To a solution of 13 (50 mg, 0.20 mmol) and triethylamine
(25 mg, 0.25 mmol) in dry DCM (5 mL) chloroacetyl chloride
(28 mg, 0.25 mmol) was added. Reaction and workup as described
above followed by column chromatography (silica gel,
hexane/EtOAc, 9:1) gave 19 (55 mg, 85%) as a colorless solid;
mp = 64–65 °C; Rf = 0.39 (silica gel, hexane/ethyl acetate, 8:2);
UV–vis (MeOH): kmax (loge) = 211 (3.82), 252 (4.01), 267 (3.97),
280 (3.74), 296 (3.95), 315 (4.07), 338 nm (3.94); IR (KBr):
4.3.14. (2E,8E,10E) 14-Oxo-2,8,10-heptadecatriene-4,6-diyn-1-
yl-acetate (17)
To a solution of 13 (50 mg, 0.20 mmol) and triethylamine
(25 mg, 0.25 mmol) in dry DCM (5 mL) acetyl chloride (20 mg,
0.25 mmol) was added. The mixture was stirred for 1 h, diluted
with ether (30 mL), and the organic layer was washed with water
(3 Â 30 mL) and brine (30 mL), dried (MgSO4), filtered and evapo-
rated to dryness. The residue was subjected to column chromatog-
raphy (silica gel, hexane/EtOAc, 9:1) to yield 17 (54 mg, 93%) as a
colorless oil, Rf = 0.39 (hexane/ethyl acetate, 8:2); UV–vis
(MeOH): kmax (loge) = 252 (3.81), 266 (3.77), 296 (3.75), 314
m
= 2966m, 2936w, 2195vw, 2125vw, 1742vs, 1700s, 1631w,
1414m, 1381w, 1318m, 1196vs, 1128w, 1078w, 977s cmÀ1 1H
;
NMR (500 MHz, CDCl3): d = 6.67 (dd, J = 15.5, 10.9 Hz, 1H, H-9),
6.28 (dt, J = 15.9, 6.0 Hz, 1H, H-16), 6.12 (dddt, J = 15.1, 10.8, 1.4,
0.7 Hz, 1H, H-8), 5.90–5.81 (m, 2H, H-15 + H-7), 5.56 (d,
J = 15.5 Hz, 1H, H-10), 4.74 (dd, J = 6.0, 1.6 Hz, 2H, CH2 (17)), 4.08
(s, 2H, CH2 (19)), 2.51 (t, J = 7.1 Hz, 2H, CH2 (5)), 2.42–2.35 (m,
4H, CH2 (3) + CH2 (6)), 1.64–1.56 (m, 2H, CH2 (2)), 0.91 (t,
J = 7.4 Hz, 3H, CH3 (1)) ppm; 13C NMR (125 MHz, CDCl3):
d = 209.9 (C@O, C-4), 166.9 (C@O, C-18), 145.4 (CH@CH, C-9),
138.2 (CH@CH, C-16), 138.1 (CH@CH, C-7), 130.4 (CH@CH, C-8),
113.5 (CH@CH, C-15), 108.1 (CH@CH, C-10), 82.2 (C„C, C-11),
79.4 (C„C, C-14), 76.3 (C„C, C-12), 75.7 (C„C, C-13), 65.3 (CH2,
C-17), 45.0 (CH2, C-6), 41.7 (CH2, C-5), 40.8 (CH2, C-19), 27.0
(CH2, C-3), 17.4 (CH2, C-2), 13.9 (CH3, C-1) ppm; MS (ESI, MeOH):
m/z = 333.0 (18%, [M+H]+), 350.1 (56%, [M+NH4]+), 355.0 (82%,
[M+Na]+), 521.9 (66%, [3M+2Na]2+), 686.7 (30%, [2M+Na]+); Anal.
Calcd for C19H21ClO3 (332.82): C 68.57, H 6.36; found: C 68.45, H
6.54.
(3.85), 337 nm (3.72); IR (film):
2125vw, 1743vs, 1714m, 1636m, 1585w, 1383w, 1364w, 1237s,
1076m, 1027m, 987m cmÀ1 1H NMR (500 MHz, CDCl3): d = 6.66
m = 2962w, 2928w, 2201vw,
;
(dd, J = 15.4, 11.0 Hz, 1H, H-9), 6.28 (dt, J = 15.9, 5.8 Hz, 1H, H-
16), 6.12 (dddt, J = 15.0, 10.7, 1.4, 0.7 Hz, 1H, H-8), 5.88–5.81 (m,
2H, H-15 + H-7), 5.56 (d, J = 15.6 Hz, 1H, H-10), 4.62 (dd, J = 5.8,
1.7 Hz, 2H, CH2 (17)), 2.51 (t, J = 7.1 Hz, 2H, CH2 (5)), 2.42–2.36
(m, 4H, CH2 (3) + CH2 (6)), 2.08 (s, 3H, CH3 (19)), 1.64–1.56 (m,
2H, CH2 (2)), 0.91 (t, J = 7.4 Hz, 3H, CH3 (1)) ppm; 13C NMR
(125 MHz, CDCl3): d = 209.9 (C@O, C-4), 170.5 (C@O, C-18), 145.2
(CH@CH, C-9), 139.6 (CH@CH, C-16), 138.1 (CH@CH, C-7), 130.4
(CH@CH, C-8), 112.3 (CH@CH, C-15), 108.2 (CH@CH, C-10), 81.8
(C„C, C-11), 79.8 (C„C, C-14), 75.8 (C„C, C-12), 75.7 (C„C, C-
13), 63.8 (CH2, C-17), 45.0 (CH2, C-6), 41.8 (CH2, C-5), 27.0 (CH2,
C-3), 20.9 (CH3, C-19), 17.4 (CH2, C-2), 13.9 (CH3, C-1) ppm; MS
(ESI, MeOH): m/z = 316.0 (100%, [M+NH4]+), 321.1 (46%, [M+Na]+),
337.0 (10%, [M+K]+), 618.9 (12%, [2M+Na]+); Anal. Calcd for
C19H22O3 (298.38): C 76.48, H 7.43; found: C 76.31, H 7.55.
4.3.17. (2E,8E,10E) 14-Oxo-2,8,10-heptadecatriene-4,6-diynal
(20)
To a solution of 13 (50 mg, 0.20 mmol) in acetone (4 mL) at 0 °C
Jones reagent [freshly prepared from CrO3 (20 mg, 0.20 mmol), H2O
(65 mg) and H2SO4 (20 mg)] was added. The mixture was stirred
for 30 min at 0 °C; MeOH (0.5 mL) was added. After stirring for
additional 10 min, the reaction was diluted with ether (30 mL),
and the organic layer was washed with water (3 Â 30 mL) and
4.3.15. (2E,8E,10E) 14-Oxo-2,8,10-heptadecatriene-4,6-diyn-1-
yl-benzoate (18)
To a solution of (13 (50 mg, 0.20 mmol) and triethylamine
(25 mg, 0.25 mmol) in dry DCM (5 mL) benzoyl chloride (35 mg,
0.25 mmol) was added. After 1 h the reaction was diluted with