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670 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 5.81 (ddd, J = 7.3, 10.1, by using EtOAc (5 × 5 mL). The combine EtOAc layers were dried
17.1 Hz, 1 H), 5.36 (d, J = 17.1 Hz, 1 H), 5.25 (d, J = 10.1 Hz, 1 H),
4.69–4.66 (m, 2 H), 3.97–3.94 (t, J = 8.2 Hz, 1 H), 3.86 (dt, J = 2.8,
with anhydrous Na2SO4 and concentrated. The residue was purified
by flash column chromatography (petroleum ether/EtOAc, 1.5:1) to
8.2 Hz, 1 H), 3.80–3.75 (m, 1 H), 3.57–3.57 (m, 1 H), 3.39 (s, 3 H), give 24 (157.5 mg, 84 %) as a colorless liquid; Rf = 0.26 (petroleum
1.71–1.66 (m, 1 H), 1.64–1.60 (m, 2 H), 1.58–1.54 (m, 1 H), 1.47–1.43 ether/EtOAc, 1.5:1). [α]D25 = –10.2 (c = 2.5, CHCl3). IR (CHCl3): νmax
=
˜
(m, 4 H), 1.42–1.4 (m, 8 H), 1.36–1.28 (m, 10 H), 0.90 (t, J = 6.9 Hz,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 135.1, 118.9, 108.6, 95.8,
83.0, 77.2, 74.7, 71.9, 55.6, 37.5, 37.4, 37.1, 35.1, 31.9, 29.8, 27.4, 26.9,
25.6, 25.3, 24.8, 22.6, 14.0 ppm. HRMS (ESI+): calcd. for C22H42O5Na
[M + Na]+ 409.29144; found 409.29245.
3455, 3013, 2937, 2863, 1721, 1629, 1456, 1408, 1375, 1208, 1143,
1098, 1040, 924, 758, 668 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.38
(dd, J = 1.2, 17.1 Hz, 1 H), 6.11 (dd, J = 10.3, 17.1 Hz, 1 H), 5.89 (ddd,
J = 6.1, 10.5, 17.1 Hz, 1 H), 5.80 (dd, J = 1.2, 10.3 Hz, 1 H), 5.33 (d,
J = 17.1 Hz, 1 H), 5.24 (d, J = 10.5 Hz, 1 H), 4.94 (quin, J = 6.2 Hz, 1
H), 4.66 (s, 2 H), 4.17–4.13 (m, 1 H), 3.94 (doublet-like, 1 H), 3.82–
3.77 (m, 1 H), 3.40 (s, 3 H), 3.32 (br. s, 1 H), 2.44 (br. s, 1 H), 1.70–
1.49 (m, 8 H), 1.31–1.27 (m, 12 H), 0.87 (t, J = 6.9 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 166.1, 136.4, 130.2, 128.9, 116.9, 96.3,
76.0, 75.7, 74.5, 70.4, 55.8, 35.3, 34.7, 34.1, 34.0, 31.7, 29.5, 25.3, 25.2,
24.9, 22.5, 14.0 ppm. HRMS (ESI+): calcd. for C22H40O6Na [M + Na]+
423.27185; found 423.27171.
(6R,12R)-13-[(4S,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]-12-
(methoxymethoxy)tridecan-6-yl Acrylate (22a): Acryloyl chloride
(0.095 mL, 1.16 mmol, 1.5 equiv.) was added dropwise under N2 to
a solution of compound 21a (300 mg, 0.776 mmol, 1 equiv.), Et3N
(0.33 mL, 2.33 mmol, 3 equiv.), and a catalytic amount of DMAP in
anhydrous CH2Cl2 (2 mL) at 0 °C, and the mixture was stirred at 0 °C
for 2 h. Upon completion of the reaction, the mixture was poured
into brine (2 mL), and the resulting mixture was extracted with
CH2Cl2 (3 × 4 mL). The combined organic phases were washed with
(6R,12R,14S,15S)-12,14,15-Trihydroxyheptadec-16-en-6-yl
Acrylate (23b): To acetonide 22b (50 mg, 0.113 mmol, 1 equiv.) in
brine (2 × 2 mL), dried with Na2SO4, and evaporated under reduced CH3CN/CH3OH (4:1, 0.2 mL) was added HCl (3
N solution, 19 μL) at
pressure. The crude product was purified by flash column chroma- 0 °C, and the resulting mixture was stirred at room temperature for
tography (petroleum ether/EtOAc, 19:1) to give 22a (253 g, 74 %)
as a pale yellow liquid; Rf = 0.42 (petroleum ether/EtOAc, 85:15).
6 h. Upon completion of the reaction (as indicated by TLC analysis),
the reaction mixture was quenched with a saturated NaHCO3 solu-
[α]D25 = –3.1 (c = 3.8, CHCl3). IR (CHCl3): νmax = 3452, 3063, 2935, tion. The aqueous layer was extracted with EtOAc, and the organic
˜
2861, 1963, 1894, 1829, 1722, 1593, 1461, 1437, 1375, 1220, 1104,
layer was dried with Na2SO4 and concentrated. The crude residue
1
1042, 926, 870, 824, 758, 704 cm–1. H NMR (400 MHz, CDCl3): δ = was purified by flash column chromatography (petroleum ether/
6.39 (dd, J = 1.5, 17.4 Hz, 1 H), 6.12 (dd, J = 10.5, 17.4 Hz, 1 H),
5.84–5.76 (m, 2 H), 5.30 (d, J = 17.1 Hz, 1 H), 5.24 (d, J = 10.5 Hz, 1
H), 4.95 (quin, J = 6.4 Hz, 1 H), 4.68 (s, 2 H), 4.51 (t, J = 6.9 Hz, 1 H),
4.37 (ddd, J = 3.2, 6.9, 9.8 Hz, 1 H), 3.77–3.72 (m, 1 H), 3.39 (s, 3 H),
1.57–1.54 (m, 7 H), 1.48 (s, 3 H), 1.37 (s, 3 H), 1.35–1.25 (m, 13 H),
0.88 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.0,
134.5, 130.1, 129.0, 118.0, 108.1, 96.0, 79.7, 74.9, 74.7, 74.5, 55.6,
35.8, 35.2, 34.1, 31.7, 29.7, 28.2, 25.6, 25.2, 24.9, 24.8, 22.5, 13.9 ppm.
HRMS (ESI+): calcd. for C25H44O6Na [M + Na]+ 463.30240; found
463.30301.
EtOAc, 7:3) to afford 23b (25 mg, 62 %) as a colorless liquid; Rf =
0.26 (petroleum ether/EtOAc, 1.5:1). [α]D25 = –4.4 (c = 0.6, CHCl3). IR
(CHCl3): νmax = 3375, 3020, 2929, 1710, 1600, 1420, 1216, 1044, 928,
˜
763, 670 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.39 (dd, J = 1.0,
17.4 Hz, 1 H), 6.12 (dd, J = 10.5, 17.4 Hz, 1 H), 5.90–5.80 (m, 2 H),
5.37 (d, J = 17.4 Hz, 1 H), 5.26 (d, J = 10.5 Hz, 1 H), 4.95 (quin, J =
6.8 Hz, 1 H), 4.02 (t, J = 6.4 Hz, 1 H), 3.95–3.93 (m, 1 H), 3.81 (br. s,
1 H), 3.10 (br. s, 1 H), 2.52 (br. s, 1 H), 2.41 (br. s, 1 H), 1.74–1.69 (m,
1 H), 1.64–1.60 (m, 1 H), 1.60–1.55 (m, 4 H), 1.47–1.42 (m, 2 H), 1.30–
1.28 (m, 11 H), 0.88 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 166.2, 137.2, 130.3, 128.9, 117.8, 76.2, 74.5, 71.8, 69.2,
38.4, 37.3, 34.1, 34.0, 31.7, 29.2, 25.5, 25.2, 24.9, 22.5, 14.0 ppm.
HRMS (ESI+): calcd. for C20H36O5Na [M + Na]+ 379.24521; found
379.24550.
(6R,12R)-13-[(4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]-12-
(methoxymethoxy)tridecan-6-yl Acrylate (22b): Compound 21b
(70 mg, 0.181 mmol, 1 equiv.) was treated with acryloyl chloride
(22 μL, 0.272 mmol, 1.5 equiv.), Et3N (76 μL, 0.543 mmol, 3 equiv.),
and a catalytic amount of DMAP in CH2Cl2 (1 mL) under the same
conditions as described for the synthesis of 22a to give compound
(6R,12R,14S,15R)-12,14,15-Trihydroxyheptadec-16-en-6-yl
Acrylate (23a): Compound 22a (40 mg, 0.090 mmol) was treated
22b (59 mg, 74 %) as a pale yellow liquid; [α]D25 = –4.4 (c = 1.2, with with HCl (3
CHCl3). IR (CHCl3): νmax = 3395, 3021, 2935, 1711, 1601, 1526, 1416,
N
solution, 15 μL) in CH3CN/CH3OH (4:1, 0.15 mL)
under the same conditions as described for the synthesis of 23b to
1216, 1041, 927, 766, 671 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.39 give compound 23a (20.1 mg, 62 %) as a colorless liquid; [α]D25
˜
=
(dd, J = 1.2, 17.4 Hz, 1 H), 6.12 (dd, J = 10.4, 17.4 Hz, 1 H), 5.84–5.77
(m, 2 H), 5.36 (d, J = 17.1 Hz, 1 H), 5.25 (d, J = 10.4 Hz, 1 H), 4.95
(quin, J = 5.8 Hz, 1 H), 4.67 (s, 2 H), 3.95 (t, J = 8.2 Hz, 1 H), 3.86 (dt,
J = 2.4, 8.5 Hz, 1 H), 3.78–3.74 (m, 1 H), 3.38 (s, 3 H), 1.71–1.66 (m,
1 H), 1.63–1.50 (m, 8 H), 1.42 (s, 3 H), 1.40 (s, 3 H), 1.34–1.27 (m, 11
–1.8 (c = 0.9, CHCl3). IR (CHCl3): νmax = 3416, 3018, 2934, 2865, 1711,
˜
1626, 1521, 1412, 1289, 1215, 1110, 1048, 989, 767, 670 cm–1
.
1H
NMR (500 MHz, CDCl3): δ = 6.39 (dd, J = 1.2, 17.4 Hz, 1 H), 6.12 (dd,
J = 10.4, 17.4 Hz, 1 H), 5.91 (ddd, J = 6.4, 10.4, 17.1 Hz, 1 H), 5.81
(dd, J = 1.5, 10.4 Hz, 1 H), 5.35 (dt, J = 1.3, 17.1 Hz, 1 H), 5.27 (dt,
H), 0.88 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = J = 1.3, 10.4 Hz, 1 H), 4.98–4.93 (m, 1 H), 4.15–4.13 (m, 1 H), 4.00–
166.1, 135.1, 130.1, 129.0, 118.9, 108.6, 95.8, 83.0, 77.2, 74.8, 74.5,
55.6, 37.1, 35.1, 34.1, 31.7, 29.7, 27.4, 26.9, 25.3, 24.9, 24.8, 22.5,
14.0 ppm. HRMS (ESI+): calcd. for C25H44O6Na [M + Na]+ 463.30145;
found 463.30301.
3.91 (m, 2 H), 2.94 (br. s, 1 H), 2.47–2.40 (br. s, 2 H), 1.71–1.67 (m, 1
H), 1.58–1.50 (m, 6 H), 1.49–1.46 (m, 2 H), 1.33–1.28 (m, 11 H), 0.88
(t, J = 6.7 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.2, 136.4,
130.3, 128.9, 117.5, 76.1, 74.5, 71.2, 69.2, 37.5, 37.2, 34.1, 34.0, 31.7,
29.2, 25.6, 25.1, 24.9, 22.5, 14.0 ppm. HRMS (ESI+): calcd. for
C20H36O5Na [M + Na]+ 379.24530; found 379.24550.
(6R,12R,14S,15R)-14,15-Dihydroxy-12-(methoxymethoxy)-
heptadec-16-en-6-yl Acrylate (24): A mixture of isopropylidene
ketal 22a (200 mg, 0.4545 mmol, 1 equiv.) and a catalytic amount
(5S,6S,8R,14R,E)-5,6,8-Trihydroxy-14-pentyloxacyclotetradec-3-
of PPTS (12 mg, 0.0455, 0.1 equiv.) in CH3OH (2 mL) was stirred at en-2-one (2): To a solution of 23b (20 mg, 0.0561 mmol, 1 equiv.) in
room temperature for 24 h. Upon completion of the reaction (as
indicated by TLC analysis), the CH3OH was evaporated, and the oily
residue was diluted with water. The crude product was extracted
freshly distilled and degassed anhydrous CH2Cl2 (60 mL) was added
Grubbs second generation catalyst (5 mg, 0.00561 mmol, 0.1 equiv.),
and the resulting mixture was heated at reflux for 8 h under argon
Eur. J. Org. Chem. 2016, 1215–1226
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