A. Yajima, I. Shirakawa, N. Shiotani et al.
Tetrahedron xxx (xxxx) xxx
(3.5 mg, 17
for 3 h at 55 ꢁC, additional K2CO3 (9.1 mg, 66
(6.6 mg, 25 mol) were added to the reaction mixture. After stirring
m
mol) and 18-crown-6 (0.7 mg, 2.5
m
mol). After stirring
1722, 1614, 1575; 1H NMR (400 MHz, CDCl3):
d
(ppm) ¼ ꢀ0.005 (s,
mmol) and 18-crown-6
9H), ꢀ0.001 (s, 9H), 0.81 (d, J ¼ 6.4 Hz, 6H), 0.82 (d, J ¼ 6.4 Hz, 6H),
0.98 (t, J ¼ 8.0 Hz, 4H), 1.08e1.27 (m, 8H), 1.48 (m, 2H), 1.58 (s, 3H),
1.59 (s, 3H), 1.81 (m, 2H), 1.95 (m, 2H), 3.53 (s, 1H), 3.71 (s, 1H), 3.78
(t, J ¼ 8.0 Hz, 4H), 5.31e5.38 (m, 4H), 5.32 (s, 2H), 7.06 (d, J ¼ 7.8 Hz,
1H), 7.23 (s, 1H), 7.33 (d, J ¼ 8.2 Hz, 1H), 7.43 (d, J ¼ 7.8 Hz, 1H), 7.70
(dd, J ¼ 1.4, 8.2 Hz, 1H), 7.81 (d, J ¼ 1.4 Hz, 1H); 13C NMR (100 MHz,
m
for 17 h at 90 ꢁC, the reaction mixture was quenched with saturated
aqueous NH4Cl, and the aqueous layer was extracted with EtOAc.
The combined organic layer was washed with saturated aqueous
NaHCO3 and brine and dried with Na2SO4. After concentration
under reduced pressure, the residue was chromatographed on sil-
ica gel (hexane/EtOAc ¼ 5:1) to give 39 (7.6 mg, 63%) as a colorless
oil.
CDCl3):
d
(ppm) ¼ ꢀ1.4 (x6), 17.99, 18.03, 22.1, 22.2, 22.6 (x4), 27.6
(x2), 27.8 (x2), 39.38, 39.44, 42.2, 42.5, 66.3, 66.8, 67.0, 75.0, 75.2,
92.94, 92.96 114.0, 115.1, 121.1, 123.0, 126.95, 127.03, 130.0, 135.3,
136.1, 140.7, 154.4, 154.8, 166.0; HRMS (ESI-TOF) m/z calcd. for
[
a
]
28 þ3.6 (c ¼ 0.5, CHCl3); IR (film): nmax (cmꢀ1) ¼ 3555, 2952,
D
1732, 1602, 1505; 1H NMR (400 MHz, CDCl3):
d
(ppm) ¼ 0.002 (s,
C
42H72O8NaSiþ2 [MþNa]þ 783.4658, found 783.4625.
9H), 0.003 (s, 9H), 0.82 (d, 6.9 Hz, 6H), 0.97 (m, 4H), 1.08e1.32 (m,
4H), 1.49 (m, 1H), 1.57 (s, 3H), 1.82 (m, 1H), 1.93 (m, 1H), 2.29 (s, 6H),
3.71e3.81 (m, 5H), 4.95 (s, 2H), 5.17 (s, 2H), 5.31 (d, J ¼ 6.9 Hz, 1H),
5.32 (d, J ¼ 6.9 Hz, 1H), 6.44 (s, 1H), 6.47 (s, 2H), 6.53 (s, 1H), 6.55 (s,
1H), 6.62 (s, 1H), 7.03 (d, J ¼ 7.8 Hz, 1H), 7.19 (s, 1H), 7.32 (d,
4.3.8. (7S,70S)-Peniciaculin B (5)
Under Ar atmosphere, to a stirred solution of 41 (32.6 mg,
42.8
428
m
m
mol) in THF (1.5 mL) was added TBAF in THF (1.0 M, 428
mL,
J ¼ 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
(ppm) ¼ ꢀ1.4 (x6),
mol). After stirring for 6 h at rt and 15 h at 80 ꢁC, the reaction
18.0, 21.6, 21.7, 22.2, 22.6 (x2), 27.6, 27.9, 29.7, 39.5, 42.5, 66.3, 66.8,
69.8, 75.1, 92.9 (x2) 103.0, 104.7, 110.6, 111.8, 112.3, 113.0, 113.6,
120.7, 127.0, 135.1, 136.8, 140.5 (x2), 154.9, 157.8, 158.1, 158.5, 159.9;
HRMS (ESI-TOF) m/z calcd. for C41H64O7NaSiþ2 [MþNa]þ 747.4083,
found 747.4083.
mixture was quenched with H2O, and the aqueous layer was
extracted with ether. The combined organic layer was washed with
brine and dried with Na2SO4. After concentration under reduced
pressure, the residue was chromatographed on silica gel (hexane/
EtOAc ¼ 2:1) to give 5 (18.6 mg, 87%) as amorphous solids.
[
a]
24 þ4.0 (c ¼ 0.34, MeOH); IR (KBr): nmax (cmꢀ1) ¼ 3459, 2953,
D
4.3.6. (S)-Peniciaculin A (4)
2868, 1698, 1577, 1507; 1H NMR (400 MHz, DMSO‑d6):
Under Ar atmosphere, to a stirred solution of 39 (9.8 mg,
d
(ppm) ¼ 0.76 (d, J ¼ 6.5 Hz, 3H), 0.770 (d, J ¼ 6.5 Hz, 3H), 0.772 (d,
14
fluoride (TBAF) in THF (1.0 M, 41
an additional TBAF in THF (1.0 M, 95
m
mol) in THF (1.5 mL) was added tetra-n-butylammonium
L, 41 mol). After stirring for 1 h,
L, 95 mol) was added to the
J ¼ 6.5 Hz, 3H), 0.78 (d, J ¼ 6.5 Hz, 3H), 0.94 (m, 1H), 1.05 (m, 5H),
1.26 (m, 2H), 1.42 (m, 2H), 1.49 (s, 3H), 1.50 (s, 3H), 1.65 (m, 2H), 1.88
(m, 1H), 1.97 (dd, J ¼ 4.1, 12.8, 12.8 Hz, 1H), 5.20 (s, 2H), 5.47 (s, 1H),
5.66 (s, 1H), 6.78 (s, 1H), 6.81 (d, J ¼ 7.8 Hz, 1H), 7.23 (d, J ¼ 7.8 Hz,
1H), 7.35 (d, J ¼ 1.3 Hz, 1H), 7.39 (dd, J ¼ 1.3, 7.8 Hz, 1H), 7.46 (d,
J ¼ 7.8 Hz, 1H), 9.89 (s, 1H), 10.01 (d, 1H); 13C NMR (100 MHz,
m
m
m
m
reaction mixture. After stirring for 15 h at 80 ꢁC, the reaction
mixture was quenched with H2O, and the aqueous layer was
extracted with ether. The combined organic layer was washed with
saturated aqueous NH4Cl and brine and dried with Na2SO4. After
concentration under reduced pressure, the residue was chroma-
tographed on silica gel (hexane/EtOAc ¼ 2:1) to give 4 (5.0 mg, 79%)
DMSO‑d6):
d
(ppm) ¼ 21.3 (x2), 22.3, 22.4, 22.5 (x2), 27.22, 27.24,
28.2, 28.6, 38.8 (x2), 41.1, 41.8, 65.6, 74.5, 75.1, 115.4, 116.3, 118.0,
119.6, 126.8, 127.3, 128.8, 132.1, 135.6, 138.7, 154.6, 155.0, 165.5;
HRMS (ESI-TOF) m/z calcd. for C30H44O6Naþ [MþNa]þ 523.3030,
found 523.3013.
as amorphous solids.
26
[
a
]
D
þ9.6 (c ¼ 0.049, MeOH); IR (KBr): nmax (cmꢀ1) ¼ 3404,
2924, 2851, 1585; 1H NMR (400 MHz, DMSO‑d6):
d
(ppm) ¼ 0.785
(d, J ¼ 6.4 Hz, 3H), 0.783 (d, J ¼ 6.4 Hz, 3H), 1.05 (m, 2H), 1.23 (m,
2H), 1.44 (m, 1H), 1.48 (s, 3H), 1.64 (m, 1H), 1.88 (m, 1H), 2.18 (s, 3H),
2.23 (s, 3H), 4.94 (s, 2H), 5.65 (s, 1H), 6.17 (s,1H), 6.24 (s,1H), 6.35 (s,
1H), 6.37 (s, 1H), 6.42 (s, 1H), 6.60 (s, 1H), 6.76 (s, 1H), 6.78 (d,
4.4. (S)-Hydroxysydonic acid (6)
To a stirred solution of 44 (197 mg, 665 mmol) in THF/H2O (v/
J ¼ 8.0 Hz, 1H), 7.20 (d, J ¼ 8.0 Hz, 1H), 9.41 (s, 1H), 9.86 (s, 1H); 13
C
v ¼ 1:1, 2 mL) was added LiOH$H2O (159 mg, 6.65 mmol) at 0 ꢁC.
After stirring for 16 h at rt, the reaction mixture was quenched with
saturated aqueous NH4Cl. The aqueous layer was acidified with 1 N
HCl and extracted with EtOAc. The combined organic layer was
washed with brine and dried with Na2SO4. After concentration
under reduced pressure, the residue was chromatographed on sil-
ica gel (hexane/EtOAc ¼ 1:2) to give 6 (182 mg, 97%) as colorless
NMR (100 MHz, DMSO‑d6):
d
(ppm) ¼ 21.1 21.2, 21.3, 22.4, 22.5, 27.3,
28.6, 38.8, 41.9, 69.0, 75.2, 102.8, 102.9, 109.9, 110.5, 111.2, 111.6,
115.2, 117.8, 126.6, 131.8, 136.3, 140.1, 140.2, 155.0, 157.46, 157.53,
158.4, 159.5; HRMS (ESI-TOF) m/z calcd. for C29H36O5Naþ [MþNa]þ
487.2455, found 487.2442.
4.3.7. 4-((S)-2-Hydroxy-6-methylheptan-2-yl)-3-((2-
(trimethylsilyl)ethoxy)methoxy)benzyl 4-((S)-2-hydroxy-6-
methylheptan-2-yl)-3-((2-(trimethylsilyl)ethoxy)methoxy)benzoate
(41)
solids.
19
M.p. 131e132 ꢁC; [
a
]
þ1.0 (c ¼ 1.0, MeOH); IR (film): nmax
D
(cmꢀ1) ¼ 3212, 2970, 2926, 1686, 1574, 1369, 1294, 1217; 1H NMR
(400 MHz, DMSO‑d6):
d
(ppm) ¼ 0.97 (s, 3H), 0.98 (s, 3H), 1.05 (m,
To a stirred solution of 37 (21.4 mg, 53.9
67.1 mol) in CH2Cl2 (1.5 mL) were added 1-(3-
dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI)
(21.9 mg, 112 mol) and DMAP (2.8 mg, 22
mol) at 0 ꢁC. After
mmol) and 40 (20.6 mg,
1H), 1.18e1.34 (m, 3H), 1.50 (s, 3H), 1.65 (dd, J ¼ 3.6, 12.4, 12.4 Hz,
1H), 1.93 (dd, J ¼ 4.0, 10.0, 12.7 Hz, 1H), 4.00 (s, 1H), 5.50 (s, 1H), 7.29
(d, J ¼ 1.4 Hz,1H), 7.33 (dd, J ¼ 1.4, 7.8 Hz,1H), 7.41 (d, J ¼ 7.8 Hz,1H),
m
m
m
9.98 (s, 1H); 1H NMR (400 MHz, CD3OD):
d
(ppm) ¼ 1.10 (s, 3H), 1.11
stirring for 19 h at rt, the reaction mixture was quenched with
saturated aqueous NH4Cl, and the aqueous layer was extracted with
EtOAc. The combined organic layer was washed with saturated
aqueous NaHCO3 and brine and dried with Na2SO4. After concen-
tration under reduced pressure, the residue was chromatographed
on silica gel (hexane/EtOAc ¼ 4:1) to give 41 (34.7 mg, 88%) as a
colorless oil.
(s, 3H),1.28 (m, 1H),1.35e1.47 (m, 3H), 1.61 (s, 3H),1.80 (m,1H),1.98
(m, 1H), 7.29 (d, J ¼ 8.2 Hz, 1H), 7.37 (d, J ¼ 1.6 Hz, 1H), 7.44 (dd,
J ¼ 1.6, 8.2 Hz, 1H); 13C NMR (100 MHz, acetone-d6):
d (ppm) 19.5,
29.7 (x2), 44.3, 44.9, 70.1, 78.6, 118.7, 121.0, 127.6, 131.3, 136.7, 157.3,
167.4; 13C NMR (100 MHz, CD3OD):
d (ppm) 20.0, 28.8, 29.1, 29.2,
43.9, 45.0, 71.4, 77.8,118.6,121.5,127.8,131.6,138.0,156.9,169.8 (See
Tables S4 and S5); HRMS (ESI-TOF) m/z calcd. for C15H21Oꢀ5 [M ꢀ H]e
281.1394, found 281.1395.
[
a
]
D
26 þ4.5 (c ¼ 1.0, CHCl3); IR (film): nmax (cmꢀ1) ¼ 3521, 2953,
8