Synthesis of (-)-(5S,8R,13S,16R)-pyrenophorol
(
3S,6S)-6-(tert-Butyldimethylsilyloxy)hept-1-en-3-ol
J = 6.0 Hz, –CH ), 0.81 (s, 9H, 3 –CH ), 0.03 (s, 6H, 2 –
3 3
1
3
(
11, C H O Si)
2
CH ) ppm; C NMR (75 MHz, CDCl ): d = 149.3, 131.1,
1
3
28
3
3
To a stirred solution of 3.8 g alcohol 9 (11.87 mmol,
1
128.2, 128.8, 127.6, 121.0, 72.7, 57.8, 55.3, 35.8, 30.2,
3
.0 eq) in 50 cm dry THF, 1.21 g imidazole (17.80 mmol,
24.9, 23.8, 22.4, -4.3 ppm; IR (neat): v = 2,932, 2,863,
-
1,739, 1,456, 1,268, 1,108 cm ; ESI–MS: m/z = 387
1
1
.5 eq), 3.73 g Ph P (14.22 mmol, 1.2 eq), and 3.0 g
3
?
([M ? Na] ).
iodine (11.87 mmol, 1.0 eq) were added at 0 °C. After
3
h the reaction mixture was neutralized by 10 cm aq.
1
(
(
4R,7R,E)-Methyl 7-(tert-butyldimethylsilyloxy)-4-
NaHCO3 solution and extracted with 10 % EtOAc in
3
hexane (2 9 50 cm ). The combined organic layers were
4-methoxybenzyloxy)oct-2- enoate (13, C H O Si)
23 38 5
3
To a solution of 1.95 g 12 (5.35 mmol, 1.0 eq) in 30 cm
CH Cl , 0.22 g Grubbs catalyst II (0.26 mmol, 0.05 eq)
3
washed with 50 cm water, 25 cm brine, dried (Na SO ),
3
2
4
2
2
and evaporated under reduced pressure. The residue was
filtered through a pad of silica (silica gel, 60–120 mesh,
was added under N atmosphere. After heating the solution
2
to reflux, 2.4 g ethyl acrylate (21.41 mmol) dissolved in
3
cm dry deoxygenated CH Cl was added. The mixture
1
0 % EtOAc in pet. ether) to afford 10 (3.3 g, 66 %) as a
yellow colored liquid.
8
2
2
was then stirred at reflux for 2 h. After cooling to 25 °C, it
was quenched through addition of 0.64 cm DMSO
3
Iodo derivative 10 (3.3 g, 7.83 mmol, 1.0 eq) in 30 cm
3
dry ether was immediately treated with 0.72 g sodium metal
pieces (31.32 mmol, 4.0 eq) and stirred at 25 °C for 12 h.
The reaction mixture was quenched with few drops of
(9.0 mmol) followed by stirring overnight. Volatiles were
evaporated under reduced pressure and the residue was
purified by column chromatography (silica gel, 60–120
mesh, 5 % EtOAc in pet. ether) to furnish 13 (1.55 g,
3
MeOH, evaporated and extracted with EtOAc (2 9 50 cm ).
3
3
It was washed with 20 cm water, 20 cm brine, dried
Na SO ), and evaporated. Purification of the residue by
2
D
5
6
9 %) as a yellow liquid. [a] = ?46.6° (c = 1.7,
(
2
4
1
CHCl ); H NMR (CDCl , 300 MHz): d = 7.20 (d, 2H,
3
3
column chromatography (silica gel, 60–120 mesh, 8 %
J = 8.1 Hz, ArH-PMB), 6.89 (d, 2H, J = 8.1 Hz, ArH-
EtOAc in pet. ether) afforded 11 (1.5 g, 77 %) as a colorless
5
PMB), 6.64 (dd, 1H, J = 6.3, 15.6 Hz, olefinic), 5.78 (d,
2
D
1
oil. [a] = ?75.9° (c = 0.18, CHCl3);
H
NMR
1
H, J = 15.6 Hz, olefinic), 4.41 (d, 1H, J = 11.7 Hz,
benzylic), 4.36 (d, 1H, J = 11.7 Hz, benzylic), 3.81 (m,
H, –OCH), 3.68 (s, 3H, OCH ), 3.59 (s, 3H, OCH ), 3.49
(
300 MHz, CDCl ): d = 5.89 (m, 1H, olefinic), 5.09 (m,
3
2
1
0
H, olefinic), 4.02 (m, 1H, –OCH), 3.83 (m, 1H, –OCH),
1
3
3
.60–1.34 (m, 4H, 2 –CH ), 1.09 (d, 3H, J = 5.4 Hz, –CH ),
2
3
(m, 1H, –OCH), 1.68–1.39 (br m, 4H, 2 –CH ), 1.17 (d,
2
1
.88 (s, 9H, 3 –CH ), 0.01 (s, 6H, 2 –CH ) ppm; C NMR
3
3
3
6
2
1
5
H, J = 6.1 Hz, –CH ), 0.81 (s, 9H, 3 –CH ), 0.04 (s, 6H,
3 3
13
(
75 MHz, CDCl ): d = 141.5, 114.3, 73.3, 68.7, 35.4, 32.7,
3
–CH ) ppm; C NMR (CDCl , 75 MHz): d = 167.2,
3
3
2
6.0, 23.7, 18.0, -4.9, -4.8 ppm; IR (neat): v = 3,386,
1
58.6, 145.6, 128.1, 123.2, 116.8, 113.3, 79.8, 72.2, 66.6,
-
2
,956, 2,857, 1,498, 1,373, 1,253, 1,134, 1,048, 833 cm
;
3.1, 51.8, 35.8, 30.3, 25.6, 23.3, 18.4, -4.7 ppm; IR
?
ESI–MS: m/z = 267 ([M ? Na] ).
(
neat): v = 2,938, 1,729, 1,608, 1,512, 1,451, 1,379, 1,164,
-
,038 cm ; ESI–MS: m/z = 459 ([M ? Na] ).
1
?
1
tert-Butyl[(2R,5R)-5-(4-methoxybenzyloxy)hept-6-en-2-
yloxy]dimethylsilane (12, C H O Si)
2
(4R,7R,E)-7-(tert-Butyldimethylsilyloxy)-4-
1 36 3
To a cooled (0 °C) solution of 1.4 g 11 (5.73 mmol,
(4-methoxybenzyloxy)oct-2-enoic acid (14, C H O Si)
2
2 36 5
3
.0 eq) in 20 cm dry THF, 0.41 g NaH (17.21 mmol,
3
1
To a solution of 1.4 g 13 (3.31 mmol, 1.0 eq) in 10 cm
3
.0 eq) was added, stirred for 30 min, and treated with a
THF:MeOH:water (3:1:1), 0.24 g LiOH (9.95 mmol) was
added and stirred at 25 °C for 4 h. The pH of reaction
mixture was adjusted to acidic with 1 N HCl solution and
3
solution of 1.25 g PMBBr (6.30 mmol) in 15 cm dry
THF. After 7.5 h stirring at room temperature, the reaction
3
mixture was quenched with 10 cm sat. NH Cl solution
3
and extracted with ethyl acetate (2 9 50 cm ). The organic
3
4
extracted with 20 cm ethyl acetate. Organic layers were
3
3
washed with 10 cm water, 10 cm brine, dried (Na SO ),
2 4
3
3
layers were washed with water (2 9 10 cm ), 10 cm
brine, and dried (Na SO ). Solvent was evaporated under
evaporated under reduced pressure, and purified the residue
by column chromatography (silica gel, 60–120 mesh, 35 %
EtOAc in pet. ether) to give 14 (1.06 g, 79 %) as a
2
4
reduced pressure and the residue was purified by column
chromatography (silica gel, 60–120 mesh, 5 % EtOAc in
pet. ether) to furnish 12 (1.75 g, 85 %) as a yellow liquid.
2
5
1
colorless oil. [a]D = ?12.6° (c = 0.9, CHCl ); H NMR
3
(CDCl , 300 MHz): d = 7.20 (d, 2H, J = 8.0 Hz, ArH-
3
2
D
5
1
[
a] = ?28.6° (c = 1.2, CHCl ); H NMR (300 MHz,
PMB), 6.86 (dd, 1H, J = 6.2, 15.7 Hz, olefinic), 6.83 (d,
2H, J = 8.0 Hz, ArH-PMB), 5.71 (d, 1H, J = 15.7 Hz,
olefinic), 4.41 (d, 1H, J = 11.5 Hz, benzylic), 4.27 (d, 1H,
J = 11.5 Hz, benzylic), 3.83 (m, 1H, –OCH), 3.67 (s, 3H,
OCH ), 3.47 (m, 1H, –OCH), 1.67–1.52 (m, 2H, –CH ),
3
CDCl ): d = 7.19 (d, 2H, J = 8.6 Hz, ArH-PMB), 6.83 (d,
3
2
H, J = 8.6 Hz, ArH-PMB), 5.84 (m, 1H, olefinic), 5.19
m, 2H, olefinic), 4.50, 4.28 (2d, 2H, J = 11.4 Hz, –OCH2
Ar), 3.78 (m, 1H, –OCH), 3.66 (s, 3H, –OCH ), 3.62 (m,
(
3
3
2
1
H, –OCH), 1.61–1.28 (m, 4H, 2 –CH ), 1.14 (d, 3H,
2
1.49 (m, 2H, –CH ), 1.07 (d, 6H, J = 6.1 Hz, –CH ), 0.81
2
3
123