2964
T. SUGAHARA et al.
1-(4-benzyloxy-3-methoxyphenyl)-3-[(R)-(4-benzyloxy-3-
methoxyphenyl)(methoxymethoxy)methyl]-2-trityloxymeth-
yl-1,4-butanediol (8). To a solution of KHMDS (17.2
ml, 0.5 M in toluene, 8.60 mmol) in THF (50 ml) was
added a solution of lactone 3 (4.10 g, 7.18 mmol) in
THF (20 ml) at ꢀ70 ꢁC. After 15 min at ꢀ70 ꢁC, a
solution of 4-benzyloxy-3-methoxybenzaldehyde (1.74 g,
7.18 mmol) in THF (10 ml) was added. The reaction
solution was stirred at ꢀ70 ꢁC for 30 min, and then sat.
aq. NH4Cl solution was added. The organic solution was
separated, washed with brine, and dried (Na2SO4).
Concentration followed by silica gel column chroma-
tography (EtOAc/hexane = 1/2) gave an aldol product
as a mixture of erythro and threo isomer (4:1) 4 (4.73 g,
5.82 mmol, 81%) as a colorless oil. NMR ꢁH (CDCl3):
2.24–2.28 (1H, m, 2-H), 2.61 (0.2H, dd, J 9.6, 5.8 Hz,
CHHOTr), 2.72 (0.2H, dd, J 9.6, 7.9 Hz, CHHOTr), 2.81
(0.8H, d, J 5.0 Hz, OH), 2.87–2.89 (1.6H, m, CH2OTr),
2.90 (0.2H, m, 3-H), 3.03 (0.8H, m, 3-H), 3.44 (0.6H, s,
OCH3), 3.56 (2.4H, s, OCH3), 3.74 (0.6H, s, OCH3),
3.81 (2.4H, s, OCH3), 4.00 (0.2H, d, J 2.0 Hz, OH), 4.88
(0.2H, dd, J 7.8, 2.0 Hz, ArCHOH)), 5.04 (0.8H, s,
OCH2Ph), 5.10 (3.2H, s, OCH2Ph), 5.33 (0.8H, dd, J
5.0, 3.2 Hz, ArCHOH), 5.59 (0.2H, d, J 7.8 Hz, 4-H),
5.70 (0.8H, d, J 7.6 Hz, 4-H), 6.48–6.56 (2H, m, ArH),
6.66–6.75 (3.2H, m, ArH), 6.83 (0.8H, d, J ¼ 1:8 Hz,
ArH), 7.02–7.18 (15H, m, ArH), 7.28–7.43 (10H, m,
ArH). Anal. Found: C, 78.30; H, 5.59. Calcd. for
C53H48O8: C, 78.09; H, 5.81%. A reaction mixture of
aldol product 4 (2.00 g, 2.46 mmol), MOMCl (6.00 ml,
79.0 mmol), and iso-Pr2NEt (27.5 ml, 158 mmol) in
CH2Cl2 (10 ml) was stirred at room temperature for
16 h before addition of MeOH and CH2Cl2. The organic
solution was separated, washed with 1 M aq. HCl
solution, sat. aq. NaHCO3 solution, and brine, and then
dried (Na2SO4). Concentration followed by silica gel
column chromatography (EtOAc/hexane = 1/3) gave
MOM ether 5 (1.94 g, 2.26 g, 92%) as a colorless oil and
diastereomeric mixture. Anal. Found: C, 76.72; H, 6.27.
Calcd. for C55H52O9: C, 77.08; H, 6.12%. To an ice-
cooled suspension of LiAlH4 (0.10 g, 2.64 mmol) in
THF (10 ml) was added a solution of lactone 5 (2.60 g,
3.03 mmol) in THF (20 ml). After the reaction mixture
had been stirred at room temperature for 1 h, sat. aq.
MgSO4 solution and K2CO3 were added. After filtration,
the filtrate was concentrated. The resulting residue was
applied to silica gel column chromatography (EtOAc/
(1H, s, ArCH(OMOM)), 5.13 (2H, s, ArCH2O), 6.10
(2H, s, ArCH2O), 6.76–6.82 (4H, m, ArH), 6.85 (1H, s,
ArH), 6.91 (1H, s, ArH), 7.14–7.46 (25H, m, ArH).
NMR ꢁC (CDCl3): 47.2, 48.4, 55.75, 55.80, 56.4, 56.5,
60.3, 62.0, 70.9, 71.0, 77.7, 87.3, 94.7, 109.7, 110.2,
113.3, 113.5, 117.8, 120.1, 125.2, 126.8, 127.1, 127.6,
128.1, 128.3, 128.4, 128.9, 133.1, 136.9, 137.0, 137.3,
137.7, 143.5, 146.7, 147.8, 149.2, 149.6. FABMS m=z
(%): 861 (ðM þ HÞþ, 0.2), 243 (100). HRFABMS
ðM þ HÞþ: Calcd. for C55H57O9, 861.4002. Found,
861.4001. 3-[(R)] isomer 8: NMR ꢁH (CDCl3): 1.83
(1H, m, CH), 2.33 (1H, s, OH), 2.58 (1H, m, CH), 3.12
(1H, dd, J 10.0, 3.4 Hz, CHHOTr), 3.25 (1H, dd, J 10.0,
9.4 Hz, CHHOTr), 3.32 (3H, s, OCH3), 3.61 (3H, s,
OCH3), 3.71 (1H, m, CHHOH), 3.78 (3H, s, OCH3),
4.12 (1H, m, CHHOH), 4.49 (2H, s, OCH2OCH3), 4.65
(1H, br. s, OH), 4.79 (1H, d, J 10.0 Hz, 1-H), 4.83 (1H,
s, ArCHOMOM), 5.07 (2H, s, ArCH2O), 5.14 (2H, s,
ArCH2O), 6.31–6.33 (2H, m, ArH), 6.59 (1H, d, J
8.2 Hz, ArH), 6.83 (1H, d, J 8.2 Hz, ArH), 6.88 (1H, d, J
8.1 Hz, ArH), 6.95 (1H, s, ArH), 7.11–7.46 (25H, m,
ArH). NMR ꢁC (CDCl3): 44.4, 45.6, 55.6, 55.78, 55.80,
57.9, 59.4, 69.8, 70.9, 77.9, 86.7, 94.7, 108.8, 110.4,
113.1, 113.3, 116.9, 120.9, 125.2, 126.7, 127.1, 127.2,
127.5, 127.7, 127.9, 128.1, 128.3, 128.4, 128.5, 128.9,
132.6, 136.4, 136.8, 137.3, 137.7, 143.8, 146.4, 148.2,
149.0, 150.2. FABMS m=z (%): 861 (ðM þ HÞþ, 2), 243
(100). HRFABMS ðM þ HÞþ: Calcd. for C55H57O9,
861.4002. Found, 861.3996.
(1S,2S,3R)-1-(4-Benzyloxy-3-methoxyphenyl)-3-[(R)-
(4-benzyloxy-3-methoxyphenyl)(methoxymethoxy)methyl]-
2-hydroxymethyl-1,4-butanediol (9). To a solution of 3-
[(R)]-trityl ether 8 (0.78 g, 0.91 mmol) in ether (40 ml)
was added formic acid (40 ml) at ꢀ10 ꢁC. After stirring
at ꢀ10 ꢁC for 10 min, CHCl3 and H2O were added. The
organic solution was separated, washed with sat. aq.
NaHCO3 solution, and dried (Na2SO4). Concentration
followed by silica gel column chromatography (EtOAc/
hexane = 1/1 and EtOAc/hexane = 4/1) gave 3-[(R)]-
triol 9 (0.30 g, 0.48 mmol, 53%) as a colorless oil,
20
½ꢀꢂ
¼ þ65 (c 1.2, CHCl3). The trityl ether (0.10 g,
D
0.16 mmol, 18%) was recovered. NMR ꢁH (CDCl3): 1.80
(1H, m, CH), 2.36 (1H, m, CH), 2.61 (1H, br. s, OH),
3.35 (3H, s, OCH3), 3.56 (1H, m, CHHOH), 3.67 (1H,
m, CHHOH), 3.74 (3H, s, OCH3), 3.85 (3H, s, OCH3),
4.03 (1H, m, CHHOH), 4.18 (1H, m, CHHOH), 4.51
(2H, s, OCH2OCH3), 4.56 (1H, br. s, OH), 4.92 (1H, d, J
7.9 Hz, 1-H), 5.04 (1H, s, ArCH(OMOM)), 5.09 (2H, s,
ArCH2O), 5.13 (2H, s, ArCH2O), 6.62–6.65 (2H, m,
ArH), 6.76 (1H, d, J 8.3 Hz, ArH), 6.83–6.89 (3H, m,
ArH), 7.25–7.44 (10H, m, ArH). NMR ꢁC (CDCl3):
45.7, 45.8, 55.8, 56.0, 59.4, 61.2, 71.0, 72.2, 78.2, 94.7,
109.1, 110.7, 113.5, 113.7, 117.3, 120.2, 127.2, 127.8,
127.9, 128.5, 128.6, 132.7, 136.7, 136.9, 137.1, 146.9,
148.1, 149.4, 150.0. FABMS m=z (%): 619 (ðM þ HÞþ,
1), 154 (100). HRFABMS ðM þ HÞþ: Calcd. for
C36H43O9, 619.2907. Found, 619.2909.
toluene = 1/4) to give 3-[(3S)] isomer 6 (Rf 0.16,
20
2.08 g, 2.42 mmol, 80%) as a colorless oil, ½ꢀꢂ
¼
D
ꢀ45 (c 2.2, CHCl3) and 3-[(3R)] isomer 8 (Rf 0.10,
20
0.49 g, 0.57 mmol, 19%) as a colorless oil, ½ꢀꢂ
¼
D
þ30 (c 1.2, CHCl3). 3-[(S)] isomer 6: NMR ꢁH (CDCl3):
2.26 (1H, m, CH), 2.32 (1H, s, OH), 2.65 (1H, m, CH),
3.18 (3H, s, OCH3), 3.22 (1H, dd, J 9.0, 9.0 Hz,
CHHOTr), 3.45–3.56 (3H, m, CHHOTr, CH2OH), 3.77
(3H, s, OCH3), 3.81 (3H, s, OCH3), 4.33 (1H, d, J 6.0
Hz, OCHHOCH3), 4.37 (1H, d, J 6.0 Hz, OCHHOCH3),
4.54 (1H, br. s, OH), 4.60 (1H, d, J 9.3 Hz, 1-H), 5.05