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S. B. Wan et al. / Bioorg. Med. Chem. 13 (2005) 2177–2185
6.81 (m, 2H), 6.18 (s, 1H), 6.13 (s, 1H), 4.87 (s, 4H), 4.77
(s, 2H), 4.38 (d, J = 6.1 Hz, 1H), 3.94 (m, 1H), 2.87 (A of
AB, J = 14.2, 1H), 2.71 (B of ABt, J = 14.2, 8.8 Hz, 1H);
13C NMR (CDCl3, 400 MHz): d 158.9, 158.7, 157.7,
157.1, 141.9, 136.8, 136.7, 129.5, 128.5, 128.4, 127.9,
127.6, 127.5, 127.4, 126.7, 119.2, 114.5, 113.2, 106.1,
95.7, 93.3, 76.7, 69.9, 69.8, 26.5; HRMS (ESI) calcd
for C36H34O6Na (M+Na) 585.2253, found 585.2293.
118.6, 114.2, 112.9, 110.9, 94.6, 94.0, 78.4, 70.0, 69.9,
69.8, 66.3, 28.2; HRMS (ESI) calcd for C36H32O5Na
(M+Na) 567.2147, found 567.2128.
Using the same procedure, (ꢀ)-22d was used as starting
material to afford (ꢀ)-25d with opposite configuration
and identical NMR spectra as the (+)-isomer.
4.17. (+)-(2S,3S)-cis-5,7-Bis(benzyloxy)-2-phenylchro-
man-3-ol ((+)-25e)
Using the same procedure, AD-mix-b was used to afford
(ꢀ)-22d with opposite configuration and identical NMR
spectra as the (+)-isomer.
Following the procedure used for the preparation of (+)-
25d, but with (+)-22e as starting material, (+)-25e was
obtained (47% yield) as a white solid; mp 60–62 °C;
[a]D +0.9 (c = 1.0, ethyl acetate); 1H NMR (CDCl3,
400 MHz): d 7.49–7.30 (m, 15H), 6.29 (d, J = 2.2 Hz,
1H), 6.27 (d, J = 2.2 Hz, 1H), 5.02 (br s, 1H), 4.99 (s,
4H), 4.25 (br s, 1H), 3.03 (A of ABt, J = 17.2, 1.4 Hz,
1H), 2.96 (B of ABt, J = 17.2, 4.2 Hz, 1H); 13C NMR
(CDCl3, 400 MHz): d 158.7, 158.2, 155.2, 138.1, 136.9,
136.8, 128.5, 128.4, 128.0, 127.9, 127.8, 127.4, 127.1,
126.2, 100.9, 94.6, 94.0, 78.6, 70.0, 69.8, 66.2, 28.2;
HRMS (ESI) calcd for C29H26O4Na (M+Na)
461.1729, found 461.1741.
4.15. (+)-(1S,2S)-3-[2,4-Bis(benzyloxy)-6-hydroxyphen-
yl]-1-phenylpropane-1,2-diol ((+)-22e)
Following the procedure used for the preparation of
(ꢀ)-29 but with 19e as starting material and AD-mix-a
as dihydroxylation regent, (+)-22e was obtained (47%
yield) as a white solid; mp 121–123 °C; [a]D +4.7
(c = 0.6, CHCl3); 1H NMR (CDCl3, 400 MHz): d
7.38–7.19 (m, 13H), 7.10 (m, 2H), 6.23 (d, J = 2.3 Hz,
1H), 6.17 (d, J = 2.3 Hz, 1H), 4.94 (s, 2H), 4.82 (AB,
J = 11.7 Hz, 2H), 4.47 (d, J = 6.6 Hz, 1H), 3.97 (m,
1H), 2.88 (A of ABt, J = 14.6, 3.6 Hz, 1H), 2.72 (B of
ABt, J = 14.6, 8.6 Hz, 1H); 13C NMR (CDCl3,
400 MHz): d 158.8, 157.6, 157.0, 140.0, 136.6, 136.5,
128.3, 128.2, 128.1, 128.0, 127.7, 127.4, 127.3, 126.8,
126.5, 105.9, 95.6, 93.2, 76.6, 69.8, 69.7, 26.2; HRMS
(ESI) calcd for C29H28O5Na (M+Na) 479.1834, found
479.1841.
4.18. (+)-(2S,3S)-5,7-Bis(benzyloxy)-2-(3-benzyloxyphen-
yl)chroman-3-yl 3,4,5-tris(benzyloxy)benzoate ((+)-35)
Following the procedure used for the preparation of (+)-
33 but with (+)-25d as starting material, (+)-35 was ob-
tained (80% yield) as a white solid: mp 107–109 °C, [a]D
1
+65.1 (c = 1.3, CHCl3); H NMR (CDCl3, 400 MHz): d
4.16. (+)-(2S,3S)-cis-5,7-Bis(benzyloxy)-2-(3-benzyloxy-
phenyl)chroman-3-ol ((+)-25d)
7.41–7.17 (m, 31H), 7.12 (s, 1H), 6.99 (d, J = 7.4 Hz,
1H), 6.86 (d, J = 6.8 Hz, 1H), 6.39 (s, 1H), 6.31 (s,
1H), 5.62 (br s, 1H), 5.14 (br s, 1H), 5.02 (s, 4H), 5.01
(s, 4H), 4.99 (s, 2H), 4.84 (AB, J = 11.4 Hz, 2H), 3.11
(br s, 2H); 13C NMR (CDCl3, 400 MHz): d 164.8,
158.5, 157.7, 155.2, 152.0, 139.1, 137.2, 136.6, 136.5,
136.2, 129.2, 128.4, 128.3, 128.2, 128.1, 127.9, 127.7,
127.6, 127.4, 127.2, 126.9, 124.7, 118.8, 114.1, 113.0,
108.7, 100.6, 94.4, 93.6, 77.3, 74.8, 70.7, 69.9, 69.7,
69.6, 68.4, 25.7; HRMS (ESI) calcd for C64H54O9Na
(M+Na) 989.3666, found 989.3633.
To a suspension of (1S,2S)-3-[2,4-bis(benzyloxy)-6-
hydroxyphenyl]-1-phenylpropane-1,2-diol (360 mg, 0.79
mmol) in 1,2-dichloroethane (10 mL) was added triethyl
orthoformate (170 mg, 1.6 mmol), followed by PPTS
(118 mg, 0.47 mmol). The mixture was stirred at rt for
20 min and the solid dissolved, and then evaporated
the solvent under vacuum. The residue was dissolved
in dry CH2Cl2 (10 mL), the solution was cooled to ꢀ5
to 0 °C, and AcBr (145 mg, 112 mmol) was added drop-
wise. The mixture was stirred at ꢀ5 to 0 °C for 45 min,
distilled the solvent under vacuum. Acetone (15 mL)
and K2CO3 (160 mg) were added successively. After
the mixture was stirred at rt for 6 h, methanol (15 mL)
and another batch of K2CO3 (160 mg) were added. Then
the mixture was stirred at rt overnight. After evaporating
the solvent, water (30 mL) was added, extracted with
CH2Cl2, the combined organic phases was dried
(MgSO4) and solvent was distilled under vacuum. The
residue was purified by chromatograph on silica gel (n-
hexane/EtOAc = 3/1 v/v), then recrystallized to give a
white solid 170 mg (49%); mp 85–87 °C; [a]D +37.4
Using the same procedure, (ꢀ)-25 was used as starting
material to afford (ꢀ)-35 with opposite configuration
and identical NMR spectra as the (+)-isomer.
4.19. (+)-(2S,3S)-5,7-Bis(benzyloxy)-2-(3-benzyloxyphen-
yl)chroman-3-yl 3,4,5-tris(benzyloxy)benzoate ((+)-36)
Following the procedure used for the preparation of
(+)-33 but with (+)-25e as starting material, (+)-36 was
obtained (82% yield) as a white solid: mp 130–132 °C,
[a]D +2.9 (c = 1.5, CHCl3); 1H NMR (CDCl3,
400 MHz): d 7.39–7.24 (m, 30H), 7.19 (s, 2H), 6.39 (d,
J = 2.2 Hz, 1H), 6.31 (d, J = 2.2 Hz, 1H), 5.60 (br s,
1H), 5.16 (br s, 1H), 5.07 (s, 2H), 5.03 (s, 2H), 5.02 (s,
2H), 5.01 (s, 2H), 4.99 (s, 2H), 3.10 (br s, 2H); 13C
NMR (CDCl3, 400 MHz): d 164.9, 158.5, 157.7, 155.3,
152.0, 142.0, 137.5, 137.1, 136.6, 136.5, 136.3, 128.4,
128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.2,
126.9, 126.2, 124.7, 108.7, 100.6, 94.3, 93.6, 77.4, 74.8,
1
(c = 1.1, ethyl acetate); H NMR (CDCl3, 400 MHz): d
7.45–7.31 (m, 16H), 7.18 (br s, 1H), 7.08 (d,
J = 7.3 Hz, 1H), 6.96 (d, J = 7.5 Hz, 1H), 6.30 (d,
J = 6.7 Hz, 2H), 5.08 (s, 2H), 5.00 (s, 4H), 4.79 (br s,
1H), 4.26 (br s, 1H), 3.05 (AB, J = 17.2 Hz, 2H); 13C
NMR (CDCl3, 400 MHz): d 159.0, 158.7, 158.2, 155.1,
139.8, 136.8, 129.6, 128.5, 127.9, 127.8, 127.5, 127.1,