incorporated to the main organic layer. The latter was dried over
anhydrous Na2SO4 and the solvent was eliminated under reduced
pressure. Column chromatography was performed on a silica
gel column (60–200 mm) and elution with the indicated solvent
mixture.
1,20-Bis(tert-butyldiphenylsilyloxy)eicos-10E,Z-ene-5,16-dione
(25)
Obtained as described above as an E/Z mixture: colourless oil;
1H NMR (signals from the major E isomer) d 7.70 (8H, br d, J
~ 7.5 Hz), 7.45–7.25 (12H, br m), 5.40–5.35 (2H, m), 3.67 (4H, t,
J = 6.5 Hz), 2.37 (8H, br q, J ~ 7.5 Hz), 2.00 (4H, m), 1.65 (4H,
br quint, J ~ 7 Hz), 1.57 (8H, m), 1.35 (4H, br quint, J ~ 7 Hz),
1.06 (18H, s); 13C NMR (signals from the major E isomer) d 211.0
(¥ 2), 133.9 (¥ 4), 19.2 (¥ 2) (C), 135.5 (¥ 8), 130.2 (¥ 2), 129.5
(¥ 4), 127.6 (¥ 8) (CH), 63.5 (¥ 2), 42.5 (¥ 2), 42.4 (¥ 2), 37.3 (¥ 2),
32.0 (¥ 2), 29.2 (¥ 2), 23.3 (¥ 2), 20.3 (¥ 2) (CH2), 26.9 (¥ 6) (CH3).
(5R,6R,7R,7aR)-6,7-Bis(benzyloxy)-5-(13-tert-butyldiphenyl-
silyloxy-9-oxotridec-3E,Z-enyl)tetrahydropyrrolo[1,2-c]oxazol-
3(1H)-one (23)
Procedure A): Compounds 11 (197 mg, 0.5 mmol), 14 (422 mg,
1 mmol) and Grubbs’ catalyst 22 (42 mg, 0.05 mmol) were
dissolved in dry, deoxygenated CH2Cl2 (8 mL). The mixture was
heated at reflux under N2 for 24 h. Solvent removal under reduced
pressure gave a residue which was dissolved in Et2O (25 mL).
The organic layer was washed three times with water and then
dried on Na2SO4. After this, charcoal (1 g) was added and the
suspension stirred for 24 h at room temperature. Solvent removal
under reduced pressure and column chromatography on silica gel
(elution with hexanes-EtOAc, 8 : 2) yielded compound 23 (248 mg,
63% as a 4 : 1 E/Z mixture). In addition, homodimers 24 (57 mg,
30% based on 11) and 25 (269 mg, 66% based on 14) were isolated,
likewise as ~ 4 : 1 E/Z mixtures. Procedure B): Compounds 11
(197 mg, 0.5 mmol), 14 (422 mg, 1 mmol) and Grubbs’ catalyst 22
(42 mg, 0.05 mmol) were dissolved in dry, deoxygenated CH2Cl2
(8 mL). The reaction mixture was placed in a CEM Discover
microwave oven and heated for 1 h at 100 ◦C (100 W power).
Work-up as above gave 23 (240 mg, 62%) together with 24 and 25
in yields similar to those of procedure A). Homodimer 25 could be
recycled to 23 through reaction with 11 under the same metathesis
conditions. It gave compound 23 in 57% yield, together with excess
25 and homodimer 24. Title compound (E + Z mixture): colourless
13-[(2R,3R,4R,5R)-3,4-Bis(benzyloxy)-5-(hydroxymethyl)-
pyrrolidin-2-yl]-1-hydroxytridec-10E-en-5-one (26)
A solution of compound 23 (315 mg, 0.4 mmol) in EtOH–H2O
3 : 1 (10 mL) was treated with NaOH (400 mg, 10 mmol). The
reaction mixture was stirred at reflux for 8 h. After this, all volatiles
were removed under reduced pressure and the residue was taken
into brine, followed by extraction with EtOAc (3 ¥ 10 mL). The
organic layer was then dried on anhydrous Na2SO4 and evaporated
under reduced pressure. The residue was subjected to column
chromatography on silica gel (elution with CHCl3–MeOH, from
95 : 5 to 90 : 10) to furnish compound 26 (150 mg, 72%) as a
4 : 1 E/Z mixture. For the synthesis of broussonetine D, the E/Z
mixture was used as such in the hydrogenation step (see below).
Title compound (E + Z mixture): colourless oil; IR nmax 3390 (br,
-1
1
=
OH), 1709 (C O) cm ; H NMR (signals from the major E isomer)
d 7.40–7.30 (10H, br m), 5.40–5.30 (2H, m), 4.60–4.50 (4H, m),
3.85 (1H, m), 3.75–3.70 (1H, m), 3.65–3.55 (4H, br m), 3.45 (1H,
m), 3.25–3.20 (1H, m), 3.15 (3H, br s, NH, 2 OH), 2.43 (2H, t,
J = 7 Hz), 2.38 (2H, t, J = 7 Hz), 2.20–1.95 (4H, br m), 1.75–1.50
(8H, br m), 1.35 (2H, br quint, J ~ 7.5 Hz); 13C NMR (signals
from the major E isomer) d 211.2, 138.0, 137.9 (C), 131.0, 129.5,
129.0, 128.5 (¥ 2), 128.4 (¥ 2), 127.9 (¥ 2), 127.7 (¥ 3), 88.8, 85.5,
62.3, 61.6 (CH), 72.1 (¥ 2), 63.7, 61.5, 42.6, 42.3, 33.1, 32.2, 32.0,
29.5, 29.1, 23.3, 20.0 (CH2); HR FABMS m/z 524.3390 (M + H+),
calcd. for C32H46NO5, 524.3376.
-1
1
=
oil; IR nmax 1760, 1712 (C O) cm ; H NMR (signals from the
major E isomer) d 7.70 (4H, br d, J ~ 7.5 Hz), 7.45–7.25 (16H, br
m), 5.50–5.45 (2H, m), 4.61 (2H, br d, J = 11.6 Hz), 4.50–4.40 (3H,
m), 4.10 (1H, dd, J = 9, 4 Hz), 4.05 (1H, m), 4.00–3.90 (2H, m),
3.87 (1H, m), 3.68 (2H, t, J = 6 Hz), 2.40–2.35 (4H, m), 2.20–2.10
(2H, m), 2.05–2.00 (2H, m), 1.70–1.60 (4H, m), 1.60–1.55 (4H, m),
1.38 (2H, br quint, J ~ 7.5 Hz), 1.07 (9H, s); 13C NMR (signals
from the major E isomer) d 211.1, 161.2, 137.3, 137.2, 134.0 (¥ 2),
19.2 (C), 135.5 (¥ 4), 131.1, 129.5 (¥ 2), 129.0, 128.6 (¥ 2), 128.5
(¥ 2), 128.2, 127.9, 127.7 (¥ 4), 127.6 (¥4), 88.8, 87.8, 62.8, 62.3
(CH), 72.7, 71.6, 67.2, 63.5, 42.5, 42.4, 32.3, 32.1, 32.0, 29.2, 29.1,
23.3, 20.3 (CH2), 26.9 (¥ 3) (CH3); HR FABMS m/z 788.4377
(M + H+), calcd. for C49H62NO6Si, 788.4346.
(5R,6R,7R,7aR)-6,7-Bis(benzyloxy)-5-[(10S)-10,13-
bis(benzyloxy)tridec-3E,Z-enyl]tetrahydropyrrolo[1,2-c]oxazol-
3(1H)-one (27)
The metathesis reaction was carried out with compounds 11
(197 mg, 0.5 mmol), 21 (366 mg, 1 mmol) and Grubbs’ catalyst
22 (42 mg, 0.05 mmol) in dry, deoxygenated CH2Cl2 (8 mL) under
the same conditions as in the previous case. Work-up as above
afforded 27 (220 mg, 60%, as a 4 : 1 E/Z mixture), together with the
expected homodimers. Title compound (E + Z mixture): colourless
(5R,5¢R,6R,6¢R,7R,7aR,7¢R,7a¢R)-5,5¢-(Hex-3E,Z-ene-1,6-diyl)-
bis(6,7-bis(benzyloxy)tetrahydropyrrolo[1,2-c]oxazol-3(1H)-one)
(24)
-1
1
=
oil; IR nmax 1760 (C O) cm ; H NMR (signals from the major
E isomer) d 7.45–7.30 (20H, br m), 5.55–5.45 (2H, m), 4.65–4.60
(2H, m), 4.55–4.40 (7H, br m), 4.12 (1H, dd, J = 9, 4 Hz), 4.08
(1H, m), 3.94 (2H, m), 3.88 (1H, dd, J = 5, 2.6 Hz), 3.52 (2H,
br t, J ~ 6.5 Hz), 3.45 (1H, br quint, J ~ 5.5 Hz), 2.20–2.10 (2H,
m), 2.10–2.00 (2H, m), 1.80–1.50 (8H, br m), 1.50–1.30 (6H, br
m); 13C NMR (signals from the major E isomer) d 161.2, 139.0,
138.6, 137.3, 137.2 (C), 131.5, 128.5 (¥ 2), 128.4 (¥ 2), 128.3 (¥ 2),
128.2 (¥ 2), 128.1, 127.9, 127.8 (¥ 2), 127.7 (¥ 3), 127.6 (¥ 2),
127.5 (¥ 2), 127.4, 127.3, 88.8, 87.7, 78.7, 62.7, 62.2 (CH), 72.7,
Obtained as described above as an E/Z mixture: colourless oil; 1H
NMR (signals from the major E isomer) d 7.45–7.20 (20H, br m),
5.50–5.40 (2H, m), 4.60 (4H, br d, J = 11.8 Hz), 4.50–4.40 (6H,
br m), 4.10–4.00 (4H, m), 3.95–3.80 (6H, br m), 2.20–2.00 (4H,
br m), 1.70–1.50 (4H, br m); 13C NMR (signals from the major E
isomer) d 161.2 (¥ 2), 137.5 (¥ 2), 137.3 (¥ 2) (C), 130.0 (¥ 2), 128.7
(¥ 5), 128.5 (¥ 5), 128.2 (¥ 2), 127.9 (¥ 2), 127.8 (¥ 6), 88.8 (¥ 2),
87.9 (¥ 2), 62.8 (¥ 2), 62.3 (¥ 2) (CH), 72.7 (¥ 2), 71.6 (¥ 2), 67.2
(¥ 2), 32.0 (¥ 2), 29.3 (¥ 2) (CH2).
1358 | Org. Biomol. Chem., 2009, 7, 1355–1360
This journal is
The Royal Society of Chemistry 2009
©