C. Gennari et al.
FULL PAPER
7.7 Hz, 3 H), 0.99 (d, J = 7.5 Hz, 3 H), 1.04 (d, J = 6.8 Hz, 3 H), NMR (400 MHz, CDCl3): δ = 0.02 (s, 3 H), 0.04 (s, 6 H), 0.07 (s,
1.07 (d, J = 6.5 Hz, 3 H), 1.24–1.36 (m, 4 H), 1.52–1.71 (m, 7 H), 6 H), 0.08 (s, 6 H), 0.10 (s, 3 H), 0.83 (d, J = 6.8 Hz, 6 H), 0.82–
2.24 (m, 1 H), 2.82–2.89 (m, 2 H), 3.06 (m, 1 H), 3.30 (s, 3 H), 3.31 0.95 (m, 8 H), 0.84 (s, 9 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 0.92 (s, 9
(m, 1 H), 3.38 (s, 3 H), 3.75 (s, 1 H), 3.93 (m, 1 H), 4.34 (d, JAB
10.2 Hz, 1 H, upfield part of an AB system), 4.60 (d, JAB
10.2 Hz, 1 H, downfield part of an AB system), 4.83 (m, 1 H), 5.08
(d, J = 10.0 Hz, 1 H), 5.14–5.24 (m, 2 H), 5.49 (t, J = 10.2 Hz, 1
H), 5.60 (d, J = 11.3 Hz, 1 H), 5.67 (t, J = 9.3 Hz, 1 H), 6.02–6.13
=
=
H), 1.04 (d, J = 6.8 Hz, 3 H), 1.10 (d, J = 6.9 Hz, 3 H), 1.20–1.39
(m, 5 H), 1.47–1.55 (m, 2 H), 1.59–1.67 (m, 2 H), 2.53 (m, 1 H),
2.62 (m, 1 H), 2.97 (m, 1 H), 3.31–3.35 (m, 2 H), 3.61 (m, 1 H),
3.72 (s, 3 H), 3.80 (s, 3 H), 3.92 (m, 1 H), 4.49–4.57 (m, 1 H), 4.50
(d, JAB = 10.6 Hz, 1 H, upfield part of an AB system), 4.54 (d, JAB
(m, 2 H), 6.31 (t, J = 11.2 Hz, 1 H), 6.71 (dt, J = 10.6, 16.8 Hz, 1 = 10.6 Hz, 1 H, downfield part of an AB system), 5.09 (d, J =
H), 6.81 (d, J = 7.7 Hz, 2 H), 7.29 (d, J = 7.7 Hz, 2 H), 7.84 (m, 1
H) ppm. HRMS (ESI): calcd. for C41H64O8Na: 707.44934 [M +
Na]+; found 707.44853.
10.6 Hz, 1 H), 5.17 (d, J = 16.8 Hz, 1 H), 5.26 (dd, J = 9.3, 10.9 Hz,
1 H), 5.55–5.62 (m, 2 H), 5.59 (d, J = 11.1 Hz, 1 H), 5.97–6.02 (m,
2 H), 6.52–6.62 (m, 2 H), 6.86 (d, J = 8.6 Hz, 2 H), 7.27 (d, J =
8.8 Hz, 2 H), 7.36 (dd, J = 11.3, 15.5 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = –4.5 (CH3), –4.3 (CH3), –4.2 (CH3), –4.1
(CH3), –4.0 (CH3), –3.7 (CH3), –3.5 (CH3), –2.9 (CH3), 9.2 (CH3),
13.5 (CH3), 16.7 (CH3), 18.1 (C0), 18.2 (C0), 18.4 (C0), 18.9 (CH3),
20.9 (CH3), 20.6 (CH3), 25.8 (CH3), 25.9 (CH3), 26.0 (CH3), 26.2
(CH3), 29.7 (CH2), 30.1 (CH), 31.6 (CH2), 34.3 (CH), 35.1 (CH),
36.1 (CH), 40.5 (CH), 41.0 (CH2), 43.4 (CH2), 43.5 (CH), 51.0
(CH3), 55.3 (CH3), 66.7 (CH), 72.2 (CH), 72.7 (CH), 75.1 (CH2),
80.3 (CH), 84.4 (CH), 113.6 (CH), 115.4 (CH), 117.2 (CH2), 126.8
(CH), 128.9 (CH), 129.0 (CH), 131.3 (CH), 131.4 (C0), 132.3 (CH),
132.4 (CH), 134.5 (CH), 145.6 (CH), 147.3 (CH), 158.9 (C0), 166.9
(R,2Z,4E)-Methyl 6-((4S,6S)-6-{(1Z,3R,4S,5S,7S,10R,11S,12S,
13S,14Z)-4,10-Dihydroxy-12-[(4-methoxybenzyl)oxy]-3,5,7,11,13-
pentamethylheptadeca-1,14,16-trien-1-yl}-2,2-dimethyl-1,3-dioxan-
4-yl)hepta-2,4-dienoate (28b-acetonide): A small crystal of PPTS
was added to a solution of 28b-acetonide precursor (6.0 mg,
8.8 μmol) in 2,2-dimethoxypropane (0.45 mL) and DCM (0.1 mL).
The reaction mixture was stirred at room temperature for 2 h, then
quenched with satd. aq. NaHCO3 (5 mL). Phases were separated
and the aqueous layer was extracted with DCM (3ϫ5 mL). The
combined organic extracts were dried with Na2SO4 and concen-
trated in vacuo. The crude product was purified by flash
chromatography (8:2 hexane/EtOAc) to give 28b-acetonide (6.3 mg,
100% yield) as a colorless oil; Rf = 0.59 (1:1 hexane/EtOAc). 1H
NMR (400 MHz, CDCl3): δ = 0.87–0.91 (m, 7 H), 0.94 (d, J =
6.8 Hz, 3 H), 0.96 (d, J = 7.0 Hz, 3 H), 1.03 (d, J = 6.8 Hz, 3 H),
1.08 (d, J = 6.9 Hz, 3 H), 1.11–1.15 (m, 1 H), 1.24–1.29 (m, 2 H),
1.33 (s, 3 H), 1.38 (s, 3 H), 1.42–1.50 (m, 3 H), 1.64–1.77 (m, 4 H),
2.63 (dd, J = 7.4 Hz, 16.3, 1 H), 2.70 (br. s, 1 H), 3.04–3.10 (m, 2
H), 3.41 (m, 1 H), 3.65–3.76 (m, 2 H), 3.72 (s, 3 H), 3.79 (s, 3 H),
4.41 (d, JAB = 10.3 Hz, 1 H, upfield part of an AB system), 4.54
(dd, J = 6.5, 15.6, Hz, 1 H), 4.68 (d, JAB = 10.3 Hz, 1 H, downfield
part of an AB system), 5.13 (d, J = 10.2 Hz, 1 H), 5.22 (d, J =
16.8 Hz, 1 H), 5.35 (m, 1 H), 5.46 (m, 2 H), 5.61 (d, J = 11.3 Hz,
1 H), 6.08 (m, 2 H), 6.58 (t, J = 11.3 Hz, 1 H), 6.66 (m, 1 H), 6.84
(d, J = 8.6 Hz, 2 H), 7.24 (m, 2 H), 7.39 (m, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 6.7 (CH3), 14.1 (CH3), 15.6 (CH3), 17.3
(CH3), 18.2 (CH3), 21.2 (CH3), 24.4 (CH3), 25.2 (CH3), 30.2 (CH),
31.7 (CH2), 32.4 (CH2), 32.5 (CH), 35.5 (CH), 35.9 (CH), 36.6
(CH2), 37.6 (CH2), 39.0 (CH), 41.6 (CH), 51.1 (CH3), 55.3 (CH3),
63.0 (CH), 69.7 (CH), 74.1 (CH2), 75.2 (CH), 79.1 (CH), 87.6 (CH),
100.7 (C0), 113.8 (CH), 115.7 (CH), 117.8 (CH2), 120.3 (CH), 127.0
(CH), 129.5 (CH), 130.3 (CH), 130.9 (C0), 132.4 (CH), 135.3 (CH),
136.6 (CH), 145.5 (CH), 146.9 (CH), 159.3 (C0), 166.9 (C0) ppm.
HRMS (ESI): calcd. for C44H68O8Na: 747.48064 [M + Na]+; found
747.48058.
(C ) ppm. IR (neat): ν = 773, 802, 836, 1005, 1040, 1082, 1174,
˜
0
1251, 1462, 1514, 1602, 1638, 1721, 2855, 2927, 2955 cm–1. HRMS
(ESI): calcd. for C65H120O8Si4Na: 1163.79525 [M + Na]+; found
1163.79475.
Methyl (2Z,4E,6R,7S,9S,10Z,12R,13S,14S,16S,19R,20R,
21S,22S,23Z)-7,9,13,19-Tetrakis[(tert-butyldimethylsilyl)oxy]-21-hy-
droxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-penta-
enoate (30b): DDQ (5.7 mg, 25 μmol, 1.3 equiv.) was added to a
solution of the PMB ether 29b (22.2 mg, 19.5 μmol, 1 equiv.) in
DCM (0.6 mL) stirred at 0 °C in the presence of 7 μL of a KH2PO4/
K2HPO4 buffer solution (pH = 7). The reaction was stirred at 0 °C
for 1 h before being quenched by dropwise addition of satd. aq.
NaHCO3 (8 mL). After diluting with DCM (18 mL), layers were
separated and the aqueous phase was extracted with DCM
(3 ϫ 10 mL). The combined organic extracts were washed with
brine (2ϫ10 mL), dried with Na2SO4 and concentrated under re-
duced pressure. The crude product was purified by flash
chromatography (6:4 hexane/DCM) to give the desired product 30b
(17.0 mg, 85% yield) as a colorless oil; Rf = 0.38 (95:5 hexane/
1
EtOAc). H NMR (400 MHz, CDCl3): δ = 0.02 (s, 3 H), 0.05 (s, 9
H), 0.07 (s, 3 H), 0.09 (s, 6 H), 0.11 (s, 3 H), 0.87–0.94 (m, 11 H),
0.89 (s, 9 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 0.92 (s, 9 H), 0.95 (d, J =
6.7 Hz, 6 H), 1.04 (d, J = 6.8 Hz, 3 H), 1.25–1.34 (m, 3 H), 1.38–
1.44 (m, 2 H), 1.50–1.71 (m, 4 H), 2.35 (br. s, 1 H), 2.53 (m, 1 H),
Methyl (2Z,4E,6R,7S,9S,10Z,12R,13S,14S,16S,19R,20R, 2.63 (m, 1 H), 2.80 (m, 1 H), 3.35 (m, 1 H), 3.48 (dd, J = 2.2,
21S,22S,23Z)-7,9,13,19-Tetrakis[(tert-butyldimethylsilyl)oxy]-21-
7.6 Hz, 1 H), 3.73 (s, 3 H), 3.74–3.78 (m, 1 H), 3.93 (m, 1 H), 4.54
[(4-methoxybenzyl)oxy]-6,12,14,16,20,22-hexamethylhexacosa-
(t, J = 8.8 Hz, 1 H), 5.12 (d, J = 10.3 Hz, 1 H), 5.21 (d, J = 16.9 Hz,
2,4,10,23,25-pentaenoate (29b): 2,6-Lutidine (9 μL, 78 μmol, 1 H), 5.22–5.28 (m, 1 H), 5.42 (t, J = 10.5 Hz, 1 H), 5.56–5.63 (m,
4 equiv.) and TBSOTf (9 μL, 39 μmol, 2 equiv.) were added drop-
wise to a stirred solution of 28b (20.0 mg, 19.5 μmol, 1 equiv.) in
DCM (0.2 mL) cooled to –78 °C. After stirring at –78 °C for 2 h,
the reaction was quenched by adding satd. aq. NaHCO3 (1.5 mL)
dropwise, then it was warmed to room temperature. The mixture
was diluted with DCM (5 mL), layers were separated and the aque-
ous phase was extracted with DCM (3ϫ5 mL). The combined or-
ganic extracts were washed with brine (2 ϫ 5 mL), dried with
Na2SO4 and evaporated under reduced pressure. The crude product
was purified by flash chromatography (95:5 hexane/EtOAc) to give
1 H), 5.59 (d, J = 11.0 Hz, 1 H), 5.99 (dd, J = 7.1, 15.5 Hz, 1 H),
6.09 (t, J = 11.1 Hz, 1 H), 6.55 (t, J = 11.4 Hz, 1 H), 6.63 (td, J =
10.8, 17.1 Hz, 1 H), 7.36 (dd, J = 11.3, 15.4 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = –4.4 (CH3), –4.3 (CH3), –4.2 (CH3),
–4.1 (CH3), –4.0 (CH3), –3.8 (CH3), –3.7 (CH3), –2.9 (CH3), 6.7
(CH3), 14.1 (CH3), 15.6 (CH3), 17.7 (CH3), 18.0 (C0), 18.1 (C0),
18.4 (C0), 20.7 (CH3), 21.0 (CH3), 25.8 (CH3), 25.9 (CH3), 26.0
(CH3), 26.1 (CH3), 30.9 (CH), 31.0 (CH2), 31.6 (CH2), 34.2 (CH),
36.0 (CH), 36.2 (CH), 37.5 (CH), 41.1 (CH2), 43.4 (CH2), 43.5
(CH), 51.1 (CH3), 66.7 (CH), 72.2 (CH), 77.3 (CH), 77.9 (CH),
the desired product 29b (22.2 mg, 100% yield) as a pale yellow oil; 80.2 (CH), 115.4 (CH), 117.7 (CH2), 126.8 (CH), 129.8 (CH), 131.2
1
Rf = 0.80 (8:2 hexane/EtOAc). [α]2D9 = –14.7 (c = 0.4, CHCl3). H
(CH), 132.3 (CH), 132.5 (CH), 135.4 (CH), 145.6 (CH), 147.3
2658
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2643–2661