The Journal of Organic Chemistry
ARTICLE
THF (40 mL) containing diisopropylethylamine (8.9 mL, 51.2 mmol)
and methoxymethyl ether (10.3 g, 128.1 mmol) was stirred at room
temperature for 15 h and concentrated in vauco to give a residue that was
portioned between CH2Cl2 and H2O. The organic layer was dried and
concentrated in vacuo to give a residue, which was subjected to column
Tetrameric model β-1 (top)ꢀβ-O-4 (bottom) (6EE): To a
solution of THF (60 mL) containing 25EE (1.2 g, 1.63 mmol) was
added 3 N HCl (20 mL) at room temperature and the solution was
stirred for 12 h at the room temperature. The solution was concentrated
following extraction with CH2Cl2 and 1 N HCl. The organic extracts
were dried and concentrated in vacuo to give a residue that was subjected
to column chromatography (EtOAc:hexane 2:1) to yield the diastere-
omeric mixture 6EE (230 mg, 22%). Diastereomeric mixture: 1H NMR
(CDCl3) 3.32ꢀ3.36 (m, 1H), 3.69 (s, 3H), 3.72 (s, 3H), 3.77 (s, 3H),
3.78 (s, 3H), 3.85 (s, 6H), 3.85ꢀ3.91 (m, 1H), 4.11ꢀ4.17 (m, 2H),
4.28ꢀ4.31 (m, 1H), 4.41ꢀ4.43 (m, 1H), 4.94ꢀ4.97 (m, 1H), 5.18 (d,
1H, J = 5 Hz), 6.61ꢀ7.05 (m, 13H); 13C NMR (CDCl3) 52.3, 55.6, 557,
55.8, 55.9, 60.6, 72.6, 77.5, 87.2, 109.5, 109.7, 110.4, 110.8, 112.1, 112.2, 114.1,
118.4, 119.1, 120.8, 121.6, 124.2, 131.7, 133.9, 135.1, 146.7, 147.8, 148.0,
148.1, 148.4, 148.4, 149.7, 151.5; HRMS (ES) m/z 673.2632 (M þ Na,
C36H42O11Na requires 673.2625).
1
chromatography (EtOAc:hexane 1:3) to yield 20E (2.0 g, 72%). H
NMR (CDCl3) 1.26 (t, 3H, J = 7 Hz), 3.34 (s, 3H), 3.72 (s, 3H), 3.73 (s,
3H), 3.75 (s, 3H), 3.76 (s, 3H), 3.84ꢀ3.86 (m, 1H), 4.11ꢀ4.16 (m, 1H),
4.21ꢀ4.26 (m, 1H), 4.51 (s, 2H), 5.03 (d, 1H, J = 10.5 Hz), 6.54ꢀ6.61
(m, 5H), 6.67 (s, 1H); 13C NMR (CDCl3) 14.1, 55.7, 55.7, 55.9, 58.8,
60.9, 79.9, 94.0, 110.0, 110.3, 110.6, 111.5, 120.5, 121.2, 127.2, 130.6,
148.2, 148.4, 148.5, 148.6, 172.6; HRMS (ES) m/z 457.1837 (M þ Na,
C23H30O8Na requires 457.1838).
erythro-2,3-(Dimethoxyphenyl)-3-methoxymethyloxy-1-
propanol (22E): To solution of THF (50 mL) containing 1.0 M
LiAlH4 (4.9 mL, 4.9 mmol) was added 20E (2.1 g, 4.8 mmol) at room
temperature. After 3 h of stirring, H2O (20 mL) and 1 N HCl (20 mL)
were added at 0 °C and the solution was extracted with CH2Cl2. The
organic extracts were dried and concentrated in vacuo to give a residue
that was subjected to column chromatography (EtOAc:hexane 1:1) to
yield 22E (1.05 g, 62%). 1H NMR (CDCl3) 3.04ꢀ3.07 (m, 1H), 3.43 (s,
3H), 3.71 (s, 3H), 3.74 (s, 3H), 3.78 (s, 3H), 3.79 (s, 3H), 3.91ꢀ3.96
(m, 1H), 4.15ꢀ4.19 (m, 1H), 4.49ꢀ4.53 (m, 2H), 4.78 (d, 1H, J = 10
Hz), 6.43 (s, 1H), 6.52ꢀ6.55 (m, 2H), 6.61ꢀ6.66 (m, 3H); 13C NMR
(CDCl3) 54.5, 55.7, 55.8, 56.0, 66.0, 82.0, 93.8, 110.0, 110.3, 110.9,
111.8, 120.3, 120.5, 131.5, 131.8, 147.7, 148.4, 148.5, 148.6; HRMS (ES)
m/z 415.1735 (M þ Na, C21H28O7Na requires 415.1733).
Synthesis of Tetrameric Model β-1 (top)ꢀβ-O-4 (bottom)
(7TE)
Tetrameric model β-1 acetonide (top)ꢀβ-O-4 MOM (bottom)
(26TE): To a solution of CH3CN (60 mL) containing 16T (1.34 g, 3.6
mmol) was added NaH (60% in mineral oil) (143 mg, 3.6 mmol) at room
temperature. After 1 h of stirring at 80 °C, 23E (1.6 g, 3.0 mmol) was
added and the solution was stirred for 24 h at the same temperature. The
solution was concentrated following extraction with CH2Cl2 and H2O.
The organic extracts were dried and concentrated in vacuo to give a
residue that was subjected to column chromatography (EtOAc:hexane
1:1) to yield the diastereomeric mixture 26TE (1.2 g, 55%). Diastereo-
meric mixture: 1H NMR (CDCl3) 1.62 (s, 3H), 1.64 (s, 3H), 3.30 (s, 3H),
3.49 and 3.51 (s, 3H), 3.65 and 3.66 (s, 3H), 3.75 (s, 6H), 3.77 and 3.78 (s,
3H), 3.83 (s, 3H), 3.75ꢀ3.78 (m, 1H), 4.08 (d, 1H, J = 7 Hz), 4.10ꢀ4.15
(m, 1H), 4.18ꢀ4.22 (m, 1H), 4.50ꢀ4.53 (m, 1H), 4.57ꢀ4.64 (m, 2H),
4.71ꢀ4.75 (m, 1H), 5.02 (d, 1H, J = 5 Hz), 5.28 (d, 1H, J = 3 Hz), 6.37 (d,
1H, J = 16.5 Hz), 6.50ꢀ6.61 (m, 4H), 6.76ꢀ6.78 (m, 3H), 6.86ꢀ6.98 (m,
4H), 7.10 (s, 1H); 13C NMR (CDCl3) 18.8, 29.9, 45.0, 55.6, 55.8, 65.4,
67.9, 73.6, 82.0, 94.4, 99.3, 110.0, 110.4, 110.9, 112.1, 112.8, 112.9, 113.2,
118.2, 118.2, 120.5, 120.6, 120.7, 122.0, 122.3, 130.2, 130.3, 132.5, 133.5,
147.2, 147.3, 147.9, 147.9, 148.5, 148.6, 149.0, 150.6; HRMS (ES) m/z
757.3190 (M þ Na, C41H50O12Na requires 757.3200).
erythro-2,3-(3,4-Dimethoxyphenyl)-3-methoxymethyloxy-
1-tosylpropane (24E): To solution of CH2Cl2 (60 mL) containing
22E (1.6 g, 4.1 mmol) was added triethylamine (1.7 mL, 12.2 mmol) at
0 °C. After 1 h of stirring, TsCl (1.2 g, 6.1 mmol) was added and the
solution was stirred for 10 h at room temperature. The solution was
extracted with CH2Cl2 and sat. NaHCO3. The organic extracts were
dried and concentrated in vacuo to give a residue that was subjected to
column chromatography (EtOAc:hexane 1:1) to yield 24E (1.5 g, 66%).
1H NMR (CDCl3) 2.34 (s, 3H), 3.17ꢀ3.21 (m, 1H), 3.29 (s, 3H), 3.64
(s, 3H), 3.70 (s, 3H), 3.78 (s, 6H), 4.41ꢀ4.51 (m, 2H), 4.46 (s, 2H),
4.68 (d, 1H, J = 8.5 Hz), 6.33 (s, 1H), 6.39 (d, 1H, J = 7.5 Hz), 6.51ꢀ6.62
(m, 4H), 7.21 (d, 2H, J = 8 Hz), 7.57 (d, 2H, J = 8 Hz); 13C NMR
(CDCl3) 21.6, 51.2, 55.6, 55.7, 56.0, 70.7, 78.1, 94.0, 110.1, 110.3, 110.5,
111.7, 120.3, 121.2, 127.8, 129.6, 129.8, 131.0, 132.8, 144.5, 147.8, 148.3,
148.4, 148.5; HRMS (ES) m/z 569.1808 (M þ Na, C28H34O9NaS
requires 569.1821).
Tetrameric model β-1 (top)ꢀβ-O-4 (bottom) (7TE): To a
solution of THF (60 mL) containing 26TE (0.24 g, 0.33 mmol) was
added 3 N HCl (10 mL) at room temperature and the solution was stirred
for 12 h at the room temperature. The solution was concentrated
following extraction with CH2Cl2 and 1 N HCl. The organic extracts
were dried and concentrated in vacuo to give a residue that was subjected
to column chromatography (EtOAc:hexane 2:1) to yield the diastereo-
Synthesis of Tetrameric Model β-O-4 (top)ꢀβ-1 (bottom)
(6EE)
1
meric mixture 7TE (43 mg, 21%). Diastereomeric mixture: H NMR
Tetrameric model β-O-4 actonide (top)ꢀβ-1 MOM
(bottom) (25EE): To a solution of CH3CN (60 mL) containing 12E
(3.9 g, 10.8 mmol) was added NaH (60% in mineral oil) (450 mg, 11.3
mmol) at room temperature. After 1 h of stirring at 80 °C, 24E (3.94 g, 7.2
mmol) was added and the solution was stirred for 24 h at the same
temperature. The solution was concentrated following extraction with
CH2Cl2 and H2O. The organic extracts were dried and concentrated in
vacuo to give a residue that was subjected to column chromatography
(EtOAc:hexane 1:1) to yield the diastereomeric mixture 25EE (2.54 g,
48%). Diastereomeric mixture: 1H NMR (CDCl3) 1.49 (s, 3H), 1.62 (s,
3H), 3.22 (s, 3H), 3.32ꢀ3.36 (m, 1H), 3.66 (s, 3H), 3.72 (s, 6H), 3.74 (s,
3H), 3.76 (s, 3H), 3.78 (s, 3H), 3.98ꢀ4.01 (m, 1H), 4.08ꢀ4.17 (m, 2H),
4.23ꢀ4.25 (m, 1H), 4.46ꢀ4.50 (m, 1H), 4.50 (s, 2H), 4.88 (d, 1H, J = 8.5
Hz), 4.98ꢀ5.01 (m, 1H), 6.45 (d, 1H, J = 8 Hz), 6.51 (d, 1H, J = 8 Hz),
6.55 (s, 1H), 6.59ꢀ6.66 (m, 4H), 6.75ꢀ6.85 (m, 4H), 7.00 (s, 2H); 13C
NMR (CDCl3) 19.6, 28.5, 51.5, 55.6, 55.9, 62.8, 69.3, 74.5, 77.1, 78.1, 94.1,
99.4, 110.2, 110.4, 111.4, 112.0, 112.6, 113.1, 117.3, 117.4, 119.8, 119.9,
120.3, 121.4, 122.6, 131.7, 132.0, 147.0, 147.5, 148.1, 148.3, 149.4, 150.3;
HRMS (ES) m/z 757.3195 (M þ Na, C41H50O12Na requires 757.3200).
(CDCl3) 3.00ꢀ3.05 (m, 1H), 3.70 (s, 3H), 3.78, (s, 3H), 3.81 (s, 3H),
3.84 (s, 6H), 3.88 (s, 3H), 3.92ꢀ3.94 (m, 1H), 3.98ꢀ4.00 (m, 1H),
4.12ꢀ4.21 (m, 2H), 4.53ꢀ4.57 (m, 1H), 4.87ꢀ4.90 (m, 1H), 4.97ꢀ5.01
(m, 1H), 6.45ꢀ6.56 (m, 2H), 6.64ꢀ6.82 (m, 5H), 6.87ꢀ6.91 (m, 3H),
6.97ꢀ7.05 (m, 2H), 7.15ꢀ7.18 (m, 1H); 13C NMR (CDCl3) 54.5, 55.4,
55.7, 55.8, 64.2, 66.3, 68.2, 68.3, 72.9, 75.6, 79.3, 84.8, 109.5, 110.0, 110.8,
111.0, 111.3, 112.1, 112.2, 118.7, 118.9, 120.4, 120.9, 121.1, 121.4, 123.9,
130.8, 132.1, 147.3, 147.6, 148.3, 148.6, 148.8, 149.0, 149.2, 149.5, 151.4;
HRMS (ES) m/z 673.2628 (M þ Na, C36H42O11Na requires 673.2625).
Synthesis of Potential Degradation Products of Tetra-
meric Model Compounds 27E, 28E, 31E, and 32
Compound 30E: To a solution of CH3CN (60 mL) containing 12E
(2.5 g, 6.94 mmol) was added NaH (60% in mineral oil) (280 mg, 6.94
mmol) at room temperature. After 1 h of stirring at 80 °C, 29 (2.7 g, 10.4
mmol) was added and the solution was stirred for 24 h at the same
temperature. The solution was concentrated following extraction with
CH2Cl2 and H2O. The organic extracts were dried and concentrated in
vacuo to give a residue that was subjected to column chromatography
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dx.doi.org/10.1021/jo200253v |J. Org. Chem. 2011, 76, 2840–2852