Temperature-controlled regioselectivity in the reductive cleavage of p-methoxybenzylidene acetals

Article abstract of DOI:10.1021/jo048999m

The regioselective ring opening of pyranosidic 4,6-p-methoxybenzylidene acetals with BH₃/Bu₂BOTf in THF can be tuned by adjusting the reaction temperature and reagent concentrations. Reductive cleavage at 0 °C resulted in the exclusive formation of 4-O-p-methoxybenzyl (PMB) ethers, whereas reaction at -78 °C produced 6-O-PMB ethers in high yields. The latter condition was observed to be compatible with a variety of acid-sensitive functional groups, including allyl and enol ethers. The presence of water does not interfere with reductive ring opening and may contribute toward in situ generation of H⁺ as a catalyst for 6-O-PMB ether formation. Reductive cleavage under rigorously aprotic conditions is greatly decelerated, and yields only the 4-O-PMB ether. The temperature-dependent reductive cleavage of the 4,6-acetal can be described in terms of kinetic versus thermodynamic control: Lewis-acid coordination of the more accessible O-6 is favored at higher temperatures, whereas protonation of the more basic but sterically encumbered O-4 predominates at low temperatures.

Full text of DOI:10.1021/jo048999m

Tem p er a tu r e-Con tr olled Regioselectivity in th e Red u ctive
Clea va ge of p-Meth oxyben zylid en e Aceta ls
J esu´s M. Herna´ndez-Torres, J ihane Achkar, and Alexander Wei*
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084
alexwei@purdue.edu
Received J une 14, 2004
The regioselective ring opening of pyranosidic 4,6-p-methoxybenzylidene acetals with
BH3/Bu2BOTf in THF can be tuned by adjusting the reaction temperature and reagent concentra-
tions. Reductive cleavage at 0 °C resulted in the exclusive formation of 4-O-p-methoxybenzyl (PMB)
ethers, whereas reaction at -78 °C produced 6-O-PMB ethers in high yields. The latter condition
was observed to be compatible with a variety of acid-sensitive functional groups, including allyl
and enol ethers. The presence of water does not interfere with reductive ring opening and may
contribute toward in situ generation of H+ as a catalyst for 6-O-PMB ether formation. Reductive
cleavage under rigorously aprotic conditions is greatly decelerated, and yields only the 4-O-PMB
ether. The temperature-dependent reductive cleavage of the 4,6-acetal can be described in terms
of kinetic versus thermodynamic control: Lewis-acid coordination of the more accessible O-6 is
favored at higher temperatures, whereas protonation of the more basic but sterically encumbered
O-4 predominates at low temperatures.
In tr od u ction
this transformation is at times limited by unpredictable
yields or regioselectivities, as well as by the sensitivities
of acid-labile or easily reducible functional groups.
A mild condition for the reductive cleavage of 4,6-
benzylidene-protected pyranosides was recently reported
by J iang and Chan, using BH3 in THF at 0 °C as the
hydride source and Bu2BOTf as a Lewis acid.11 This
reaction afforded 4-O-benzyl ethers in good to excellent
yields and with complete regioselectivity in most cases.
We have recently used similar conditions to prepare 4-O-
PMB ethers of orthogonally protected glucosamines from
their corresponding 4,6-anisylidene acetals, without det-
riment to the remaining functional groups.12 However,
at 0 °C the BH3/Bu2BOTf conditions were found not to
be compatible with alkenes, such as allyl ethers.13
Here we report that the reductive cleavage of ani-
sylidene acetals by BH3/Bu2BOTf can selectively produce
either regioisomer, simply by adjusting the reaction
temperatures and reagent concentrations. Strictly anhy-
drous conditions are not required because any traces of
water are consumed by excess borane, obviating the need
for molecular sieves. Furthermore, reductive ring opening
at low temperatures was determined to be compatible
with sensitive functional groups such as allyl and enol
ethers and other ketals, considerably expanding the scope
of this transformation. In addition to demonstrating the
practical benefits of this method for protecting group
Benzylidene and p-methoxybenzylidene (anisylidene)
acetals are widely employed as protecting groups for
intermediates possessing 1,2- and 1,3-diols.1 An especially
appealing feature of these acetals is their readiness to
undergo reductive cleavage to regioselectively protected
alcohols. Reaction conditions have been developed to
favor the formation of either regioisomer: for example,
reduction of 4,6-anisylidene-protected glucopyranosides
with NaCNBH3 under protic conditions produces 6-O-p-
methoxybenzyl (PMB) ethers in high yield,2 whereas
reductive cleavage with iBu2AlH3 or NaCNBH3 and
TMSCl4 yields 4-O-PMB ethers. Regioselectivity is thought
to be determined in the first case by differences in Lewis
basicity of the acetal oxygens (O-4 > O-6) and in the
second case by accessibility to the bulky Lewis acid (O-6
> O-4). The choice of solvent has also been shown to play
a role in some instances.5 However, despite the variety
of methods available for reductive cleavage of acetals,5-10
(1) (a) Greene, T. W.; Wuts, P. G. M. Protecting Groups in Organic
Synthesis, 3rd ed.; J ohn Wiley and Sons: New York, 1999. (b)
Kocienski, P. J . Protecting Groups, 3rd ed.; Thieme: Stuttgart,
Germany, 2004.
(2) (a) Garegg, P. J .; Hultberg, H. Carbohydr. Res. 1981, 93, C10.
(b) Poszgay, V.; Brisson, J .-R.; J ennings, H. J .; Allen, S.; Paulson, J .
C. J . Org. Chem. 1991, 56, 3378. (c) Mukhopadhyay, B.; Roy, N.
Carbohydr. Res. 2003, 338, 589.
(3) Sutherlin, D. P.; Armstrong, R. W. Tetrahedron Lett. 1993, 34,
4897.
(4) J ohansson, R.; Samuelsson, B. J . Chem. Soc., Chem. Commun.
1984, 3, 201.
(5) Oikawa, M.; Liu, W.-C.; Nakai, Y.; Koshida, S.; Fukase, K.;
Kusumoto, S. Synlett 1996, 1179.
(6) Ek, M.; Garegg, P. J .; Hultberg, H.; Oscarson, S. J . Carbohydr.
Chem. 1983, 2, 305.
(7) Debenham, S. D.; Toone, E. J . Tetrahedron: Asymmetry 2000,
11, 385.
(9) DeNinno, M. P.; Etienne, J . B.; Duplainter, K. C. Tetrahedron
Lett. 1995, 36, 669.
(10) Gelas, J . Adv. Carbohydr. Chem. Biochem. 1981, 39, 71.
(11) J iang, L.; Chan, T.-K. Tetrahedron Lett. 1998, 39, 355.
(12) Herna´ndez-Torres, J . M.; Liew, S.-T.; Achkar, J .; Wei, A.
Synthesis 2002, 487.
(13) Achkar, J .; Sanchez-Larraza, I.; Wei, A. Carbohydr. Res. 2002,
337, 83.
(8) Sakagami, M.; Hamana, H. Tetrahedron Lett. 2000, 41, 5547.
10.1021/jo048999m CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/18/2004
7206
J . Org. Chem. 2004, 69, 7206-7211

Reductive Cleavage of p-Methoxybenzylidene Acetals
TABLE 1. Regioselective Rin g Op en in g of
4,6-An isylid en e Aceta lsa ,b
manipulations, our studies include some mechanistic
explanations for the regioselectivity of reductive cleavage.
Resu lts a n d Discu ssion
Several anisylidene-protected pyranosides were sub-
jected to reductive ring opening with the conditions
outlined below, to obtain 4-O- and 6-O-PMB ethers in
high yields and regioselectivities. Treatment of the
anisylidene acetals with excess borane at high concentra-
tions (10 equiv, 1 M in THF) followed by the addition of
commercially available Bu2BOTf (2 equiv) at 0 °C pro-
duced exclusively the corresponding 4-O-PMB ethers, in
accord with previous reports (see Table 1, condition A).11
On the other hand, treating the anisylidene acetals with
BH3 and Bu2BOTf under more dilute conditions (5 equiv
of BH3, 0.2 M in THF) and at low temperatures (-78 to
-50 °C) produced the 6-O-PMB ethers in excellent yields
(see Table 1, condition B). Hydrogen evolution was often
observed upon addition of BH3 prior to the addition of
Bu2BOTf at 0 °C, indicating consumption of adventitious
water. The reactions were quenched with Et3N followed
by the slow addition of MeOH at 0 °C, and could be
concentrated without aqueous workup. The regioselec-
tivities were confirmed by acetylation of the alcohols and
1
characterization by H NMR spectroscopy.
The temperature-dependent reductive ring openings
proceeded with complete regioselectivity in nearly every
situation save for acetal 1g, which produced a 3.5:1
mixture of 6-O- to 4-O- PMB ethers under the low-
temperature conditions. The reaction pathways are likely
to be influenced by local steric crowding (see below); in
the case of 1g, the phthalimide at C-2 may force the bulky
tert-butyldimethylsilyl (TBS) ether at C-3 toward O-4 and
hinder its activation.14 The azide group on disaccharide
1h also survived the reduction conditions yielding the
desired PMB ethers in good yields. It is worth mentioning
that no 4,6-diol was observed, a side product that is often
produced by other reductive cleavage conditions.1-3
In addition to the protecting groups above, reductive
cleavage with BH3/Bu2BOTf was determined to be com-
patible with several other functional groups at -78 °C.
In particular, the allyl ether of 1i, the allyloxycarbonyl
(AOC) ester of 1j, and the dimethyl ketal of 1k all
remained intact during the reductive cleavage of the
anisylidene acetals to their corresponding 6-O-PMB
ethers (see Table 2). Glycals (1,2-unsaturated pyrano-
sides) were also found to be compatible with the low-
temperature reaction conditions: reductive cleavage of
glucal 1l afforded 6-O-PMB ether 3l in 85% isolated yield.
Reactions at higher temperatures or reagent concentra-
tions were not well-suited with these more reactive
functional groups. For example, in the case of dimethyl
ketal 1k the temperature was kept strictly at -78 °C to
minimize reductive ring opening of the 2,3-acetonide.15
We suspected that more than one acid catalyst was
responsible for the observed regioselectivities. In par-
ticular, we considered that the low-temperature reductive
cleavage might be catalyzed by the in situ generation of
H+, formed by the hydrolysis of Bu2BOTf. Low-temper-
a
b
Isolated yields. Selected acronyms: Bz ) benzoyl; Cbz )
benzyloxycarbonyl; Phth ) phthaloyl; PMB ) p-methoxybenzyl;
PMP ) p-methoxyphenyl; SEM ) (2-trimethylsilyl)ethoxymethyl;
TBS ) tert-butyldimethylsilyl. c Reaction condition A: BH3 (1 M
d
in THF, 10 equiv), Bu2BOTf (2 equiv), 0 °C. Reaction condition
B: BH3 (0.2 M in THF, 5 equiv), Bu2BOTf (2.5 equiv), -78 °C.
e For entries 1c, 1e, and 1g, the reactions were run at -50 °C.
ature reductive cleavage of benzylidene acetals to the O-6
ether has been reported previously with use of TfOH.8
Our initial attempts at reductive cleavage under aprotic
conditions did not appear to affect the reaction outcome:
for example, reduction of anisylidene acetal 4 at -78 °C
in base-washed glassware with molecular sieves and
freshly prepared Bu2BOTf16 yielded 6-O-PMB ether 5a
as the sole product (see Scheme 1). However, when 2,6-
(14) It should be noted that the 3-O-TBS ether does not compromise
the regioselectivity in the reductive cleavage of compound 1b.
(15) The reductive cleavage of acetonides to isopropyl ethers by
BH3/Bu2BOTf at 0 °C has been previously described; see ref 11.
J . Org. Chem, Vol. 69, No. 21, 2004 7207

Herna´ndez-Torres et al.
TABLE 2. Red u ctive Rin g Op en in g of 4,6-An isylid en e
Aceta ls w ith Acid - or Bor a n e-Sen sitive Gr ou p sa ,b
SCHEME 2. Red u ctive Clea va ge of Ben zylid en e
Aceta l 6
activated complex, with a negative effect on the formation
of the 4-O-PMB ether. In comparison, protonation of the
acetal is expected to be diffusion controlled and thus
presumably dictated by thermodynamics, which would
favor activation of the more basic O-4 oxygen and
cleavage to the 6-O-PMB ether.
Further support for this notion can be drawn from in-
vestigations on the effect of reagent concentration in the
regioselectivity of acetal cleavage. Reduction of acetals
1c and 4 at -78 °C with higher reagent concentrations
(cf. reaction condition A) also produced 6-O-PMB ethers
(3c and 5a , respectively) in high yield (>95%), whereas
reductions conducted at 0 °C with lower reagent concen-
trations (cf. reaction condition B) produced a mixture of
regioisomers, again favoring the 6-O-PMB ether (3c:2c
) 2.5:1; 5a :5b ) 11:1). These results suggest that
protonation is faster than the rate of acetal-Bu2BOTf
complex formation at low temperatures or under the
more dilute conditions, and provide additional testimony
to the high catalytic activity of the Bronsted acid.
Finally, it is worth mentioning that while 4,6-ani-
sylidene acetals could be reductively cleaved at low
temperatures to produce 6-O-PMB ethers, the less reac-
tive 4,6-benzylidene acetals were inert under these
conditions. Benzylidene acetal 6 was initially subjected
to BH3/Bu2BOTf at -78 °C (reaction condition B), then
slowly warmed over a period of hours until reductive
cleavage was observed at -30 °C, yielding exclusively
4-O-benzyl ether 7 in 82% yield (see Scheme 2). As it is
already known that excess TfOH can activate the cleav-
age of benzylidene acetals at -78 °C to yield 6-O-benzyl
ethers,8 our result indicates that catalytic quantities of
acid are not sufficient to activate the reductive cleavage
of benzylidene acetals at low temperatures.
a
b
Isolated yields. Selected acronyms: All ) allyl; AOC )
allyloxycarbonyl; Phth ) phthaloyl; PMB ) p-methoxybenzyl; PMP
) p-methoxyphenyl. c Reaction condition B: BH3 (0.2 M in THF,
d
5 equiv), Bu2BOTf (2.5 equiv), -78 °C. A small amount (<5%)
of side product with cleaved acetonide was also observed.
SCHEME 1. Red u ctive Clea va ge w ith F r esh ly
P r ep a r ed Bu 2BOTfa ,b
a
Isolated yields. b All reactions were performed in base-washed
glassware. Reaction condition C: BH3 (0.2 M in THF, 5 equiv),
Bu2BOTf (2.5 equiv), 4A mol sieves, -78 °C, 1.5 h. Reaction
condition D: BH3 (0.2 M in THF, 5 equiv), Bu2BOTf (2.5 equiv),
4A mol sieves, DTBMP (2.5 equiv), -78 to -45 °C, 36 h. See ref
16 for the preparation of Bu2BOTf.
Exp er im en ta l Section
Gen er a l P r oced u r es for Red u ctive Rin g Op en in g of
p-Meth oxyben zylid en e Aceta ls. The borane-THF complex
(1 M in THF), Bu2BOTf (1 M in CH2Cl2), and reagents for the
preparation of neat Bu2BOTf were obtained from Aldrich and
used as received. Note: Neat Bu2BOTf is highly pyrophoric
and must be distilled and stored under an inert atmosphere
(it can be kept as a solid at -20 °C). In addition, methane is
generated during the preparation of Bu2BOTf, resulting in a
highly combustible mixture that must be vented with caution.
Rea ction con d ition A: An oven-dried, 10-mL round-
bottomed reaction flask containing acetal 1a (50 mg, 0.09
mmol) was cooled to -10 °C under Ar and treated with
borane-THF complex (0.9 mL of a 1 M solution in THF). The
mixture was stirred at -10 °C for 15 min, then treated with
Bu2BOTf (176 µL of a 1 M solution in CH2Cl2) and warmed to
0 °C over a period of 10 min. The mixture was stirred at 0 °C
di-tert-butyl-4-methylpyridine (DTBMP) was added as an
acid scavenger the rate of reduction was greatly deceler-
ated, with no discernible ring opening after several hours
at -78 °C. Slowly warming the reaction mixture to -45
°C resulted in the exclusive formation of 4-O-PMB ether
5b. The formation of the 6-O-PMB ether is thus due to
the remarkably high catalytic activity of the trace Bron-
sted acid.
The regioselectivity of the reductions presented here
can be readily described in terms of kinetic versus
thermodynamic control.17 The O-6 acetal oxygen is steri-
cally more accessible for coordinating with Bu2BOTf or
H+, leading to rapid acetal cleavage at 0 °C. Lowering
the temperature reduces both the rate of Lewis-acid
complexation and the rate of hydride delivery to the
(16) Mukaiyama, T.; Inoue, T. Chem. Lett. 1976, 559. See note in
the Experimental Section.
(17) For a closely related discussion in an earlier work, see: Garegg,
P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982, 108, 97.
7208 J . Org. Chem., Vol. 69, No. 21, 2004

Reductive Cleavage of p-Methoxybenzylidene Acetals
for an additional 2 h, cooled to -10 °C, and treated with Et3N
(0.1 mL), then quenched by the dropwise addition of MeOH
(3.0 mL) until effervescence ceased. The mixture was warmed
to room temperature and stirred for 30 min, then concentrated
by rotary evaporation. Volatile components in the reaction
mixture were removed by azeotropic distillation with MeOH
(2 × 5 mL) and toluene (5 mL). The product was purified by
silica gel flash chromatography, using a 20-50% EtOAc-
hexanes gradient to yield the desired 4-O-PMB ether.
Rea ction con d ition B: An oven-dried, 10-mL round-
bottomed reaction flask containing acetal 1a (50 mg, 0.09
mmol) was dissolved in freshly distilled THF (1.8 mL) and
cooled to -78 °C under argon, then treated with borane-THF
complex (0.4 mL of a 1 M solution in THF). After 15 min, the
mixture was treated with Bu2BOTf (225 µL of a 1 M solution
in CH2Cl2) and stirred at -78 °C for up to 8 h or at -50 °C for
up to 6 h. The reaction was then quenched with Et3N (0.1 mL),
followed by the dropwise addition of MeOH (3.0 mL) until
effervescence ceased. The mixture was warmed to room
temperature and stirred for 30 min, then concentrated by
rotary evaporation and purified as described previously to yield
the desired 6-O-PMB ether.
R ea ct ion con d it ion C: A base-washed and oven-dried,
10-mL round-bottomed reaction flask containing acetal 4 (40
mg, 0.08 mmol) and 4A molecular sieves (200 mg) was charged
with freshly distilled THF (1.6 mL) and stirred for 30 min at
room temperature under argon. The reaction mixture was
cooled to -78 °C and treated with borane-THF complex (0.41
mL of a 1 M solution in THF). After 15 min, the mixture was
treated with freshly prepared Bu2BOTf 16 (200 µL of a 1 M
solution in CH2Cl2) and stirred at -78 °C for an additional 3
h. The reaction was then quenched with Et3N (0.1 mL),
followed by the dropwise addition of MeOH (3 mL) until
effervescence ceased. The mixture was warmed to room
temperature and stirred for 30 min, then filtered through
Celite, concentrated by rotary evaporation, and purified as
described in procedure A to yield the desired 6-O-PMB ether.
R ea ct ion con d it ion D: As in reaction condition C, but
with the addition of 2,6-di-tert-butyl-4-methylpyridine (2.5
equiv) prior to treatment with BH3-THF. Following addition
of the freshly prepared Bu2BOTf, the mixture was stirred at
-78 °C for 3 h, at -60 °C for 17 h, and finally at -45 °C for
16 h. The reaction mixture was quenched and purified as
described in reaction condition A to yield the desired 4-O-PMB
ether.
MHz, CDCl3) δ 7.56-7.59 (m, 2 H), 7.23-7.41 (m, 15 H), 6.59
(d, 2 H, J ) 8.1 Hz), 5.01 (t, 1 H, J ) 8.7 Hz), 4.87 (d, 1 H, J
) 9.9 Hz), 4.80 (d, 1 H, J ) 11.7 Hz), 4.70 (d, 1 H, J ) 9.9 Hz),
4.68 (d, 1 H, J ) 9.9 Hz), 4.63 (d, 1 H, J ) 11.7 Hz), 4.45 (s,
2 H), 3.82 (s, 3 H), 3.67 (t, 1 H, J ) 8.7 Hz), 3.52-3.60 (m, 4
H), 1.90 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 169.7, 159.2,
138.1, 137.8, 133.5, 131.9, 130.1, 129.4, 128.9, 128.4, 128.3,
127.9, 127.7, 127.6, 127.5, 113.7, 87.5, 84.0, 80.6, 77.6, 75.5,
75.4, 73.2, 70.8, 69.5, 55.2, 20.8; IR (thin film) 1746, 1613, 1584,
1513, 1455, 1362, 1231, 1175, 1050, 821, 744, 689 cm-1; [R]20
D
-15.5 (c 1.02, CHCl3); ESI-MS m/z 637 [M + Na]+.
Th iotolyl
6-O-Acetyl-2-O-ben zoyl-3-O-(ter t-bu tyld i-
m et h ylsilyl)-4-O-(p -m et h oxyb en zyl)-â-D-glu cop yr a n o-
sid e (6-O-a cetyl 2b). 1H NMR (300 MHz, CDCl3) δ 8.05 (d, 2
H, J ) 7.5 Hz), 7.60 (m, 1 H), 7.46 (m, 2 H), 7.30 (d, 2 H, J )
8.1 Hz), 7.22 (d, 2 H, J ) 8.1 Hz), 7.04 (d, 2 H, J ) 7.8 Hz),
6.86 (d, 2 H, J ) 8.1 Hz), 5.16 (t, 1 H, J ) 9.4 Hz), 4.77 (d, 1
H, J ) 10.5 Hz), 4.64 (d, 1 H, J ) 9.9 Hz), 4.45 (d, 1 H, J )
11.1 Hz), 4.40 (dd, 1 H, J ) 1.8 Hz, 12.9 Hz), 4.06 (dd, 1 H, J
) 4.8 Hz, 11.7 Hz), 3.92 (t, 1 H, J ) 8.5 Hz), 3.80 (s, 3 H), 3.58
(m, 1 H), 3.47 (t, 1 H, J ) 9.1 Hz), 2.31 (s, 3H), 2.06 (s, 3 H),
0.80 (s, 9 H), 0.37 (s, 3 H), -0.17 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 170.6, 165.3, 159.3, 138.0, 133.0, 130.2, 129.9, 129.6,
129.4, 129.2, 128.3, 113.8, 99.5, 68.8, 78.0, 77.1, 76.8, 74.9, 72.3,
63.1, 55.2, 29.6, 25.6, 21.1, 20.8, 1.0; [R]20 +22.8 (c 0.64,
D
CHCl3); ESI-MS m/z 689 [M + Na]+.
Th iotolyl
4-O-Acetyl-2-O-ben zoyl-3-O-(ter t-bu tyld i-
m et h ylsilyl)-6-O-(p -m et h oxyb en zyl)-â-D-glu cop yr a n o-
sid e (4-O-a cetyl 3b). 1H NMR (300 MHz, CDCl3) δ 8.04 (d, 2
H, J ) 8.4 Hz), 7.59 (m, 1 H), 7.46 (m, 2 H), 7.32 (d, 2 H, J )
7.2 Hz), 7.24 (d, 2 H, J ) 7.2 Hz), 6.99 (d, 2 H, J ) 7.8 Hz),
6.86 (d, 2 H, J ) 7.2 Hz), 5.18 (t, 1 H, J ) 9.3 Hz), 4.96 (t, 1
H, J ) 9.3 Hz), 4.70 (d, 1 H, J ) 10.2 Hz), 4.44 (d, 2 H, J )
11.7 Hz), 4.40 (d, 2 H, J ) 12.3 Hz), 3.98 (t, 1 H, J ) 8.7 Hz),
3.81 (s, 3 H), 3.53-3.63 (m, 3 H), 2.29 (s, 3 H), 1.97 (s, 3 H),
0.71 (s, 9 H), -0.03 (s, 3 H), -0.20 (s, 3 H); 13C NMR (125
MHz, CDCl3) δ 169.7 165.1, 159.2, 137.9, 133.1, 132.8, 130.2,
130.0, 129.9, 129.6, 129.5, 129.2, 128.4, 113.7, 96.5, 86.8, 77.7,
74.6, 73.3, 73.2, 72.4, 70.0, 55.3, 29.7, 21.2, 21.1, 17.7, -4.1,
-4.6; IR (thin film) 1734, 1613, 1514, 1493, 1373, 1250, 1228,
1176, 1146, 1092, 1057, 841, 810, 779, 710 cm-1; [R]20 +17.0
D
(c 1.00, CHCl3); ESI-MS m/z 689 [M + Na]+.
Th iop h en yl 3,6-O-Dia cet yl-2-d eoxy-4-O-(p -m et h oxy-
ben zyl)-2-p h th a lim id o-â-D-glu cop yr a n osid e (6-O-a cetyl
1
2c). H NMR (300 MHz, CDCl3) δ 7.84-7.88 (m, 2 H), 7.73-
7.75 (m, 2 H), 7.38-7.40 (m, 2 H), 7.25-7.27 (m, 3 H), 7.15 (d,
2 H, J ) 8.4 Hz), 6.83 (d, 2 H, J ) 8.1 Hz), 5.80 (t, 1 H, J )
9.5 Hz), 5.70 (d, 1 H, J ) 10.5 Hz), 4.54 (d, 1 H, J ) 10.8 Hz),
4.47 (d, 1 H, J ) 11.1 Hz), 4.41 (dd, 1 H, J ) 2.1, 12.3 Hz),
4.24 (t, 1 H, J ) 10.3 Hz), 4.21 (dd, 1 H, J ) 5.1, 12.3 Hz),
3.79 (m, 1 H), 3.78 (s, 3 H), 3.67 (t, 1 H, J ) 9.4 Hz), 2.07 (s,
3 H), 1.82 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 170.5, 169.9,
159.5, 134.4, 134.1, 133.1, 131.3, 129.5, 129.4, 128.8, 128.2,
123.7, 123.4, 113.9, 99.9, 82.7, 75.7, 74.2, 62.9, 55.2, 54.0,
20.8, 20.6; IR (thin film) 1777, 1745, 718, 1612, 1514, 1385,
The regioselectivity of the reductive ring opening was
confirmed by acetylation of the free hydroxyl and characteriza-
tion by 1H NMR spectroscopy. Reduction products were dis-
solved in pyridine (0.5 mL) and treated with acetic anhydride
(250 µL) at 0 °C, stirred overnight at room temperature, then
quenched at 0 °C with EtOH and concentrated to dryness
followed by azeotropic distillation with toluene (3 × 2 mL).
Purification by silica gel flash chromatography with an
EtOAc-hexanes gradient afforded the acetate in nearly quan-
titative yield.
1225, 1088, 1034, 751, 720 cm-1; [R]20 +34.0 (c 1.00, CHCl3);
D
Th iop h en yl 6-O-Acetyl-2,3-O-d iben zyl-4-O-(p-m eth oxy-
ben zyl)-â-D-glu cop yr a n osid e (6-O-a cetyl 2a ). 1H NMR (300
MHz, CDCl3) δ 7.47-7.52 (m, 2 H), 7.19-7.34 (m, 13 H), 7.09
(d, 2 H, J ) 8.1 Hz), 6.76 (d, 2 H, J ) 8.1 Hz), 4.84 (d, 1 H, J
) 10.5 Hz), 4.83 (d, 1 H, J ) 10.2 Hz), 4.77 (d, 1 H, J ) 11.1
Hz), 4.69 (d, 1 H, J ) 11.7 Hz), 4.65 (d, 1 H, J ) 10.5 Hz), 4.56
(d, 1 H, J ) 9.9 Hz), 4.42 (d, 1 H, J ) 10.5 Hz), 4.26 (d, 1 H,
J ) 11.7 Hz), 4.14 (dd, 1 H, J ) 4.2 Hz, 11.7 Hz,), 3.72 (s, 3
H), 3.64 (m, 1 H), 3.39-3.47 (m, 3 H), 2.00 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 170.6, 159.5, 138.2, 137.9, 133.6, 132.0,
129.8, 129.7, 128.8, 128.5, 128.4, 128.2, 127.9, 127.8, 127.7,
127.6, 113.9, 87.5, 86.7, 80.9, 77.1, 76.9, 75.8, 75.5, 74.7, 63.2,
55.2, 20.8; IR (thin film) 1742, 1613, 1514, 1455, 1362, 1249,
ESI-MS m/z 628 [M + Na]+.
Th iop h en yl 3,4-O-Dia cet yl-2-d eoxy-6-O-(p -m et h oxy-
ben zyl)-2-p h th a lim id o-â-D-glu cop yr a n osid e (4-O-a cetyl
1
3c). H NMR (300 MHz, CDCl3) δ 7.87-7.90 (m, 2 H), 7.75-
7.78 (m, 2 H), 7.42-7.45 (m, 2 H), 7.24-7.29 (m, 5 H), 6.89 (d,
2 H, J ) 8.7 Hz), 5.82 (t, 1 H, J ) 9.6 Hz), 5.74 (d, 1 H, J )
10.5 Hz), 5.16 (t, 1 H, J ) 9.6 Hz), 4.52 (d, 1 H, J ) 11.4 Hz),
4.45 (d, 1 H, J ) 11.7 Hz), 4.38 (t, 1 H, J ) 10.5 Hz), 3.89 (m,
1 H), 3.84 (s, 3 H), 3.63 (d, 2 H, J ) 4.2 Hz), 1.92 (s, 3 H), 1.83
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 170.2, 169.6, 159.2, 134.3,
132.8, 131.4, 129.9, 129.4, 128.9, 128.1, 123.6, 113.7, 83.1, 77.5,
73.2, 71.8, 69.6, 68.8, 55.3, 53.7, 20.6, 20.4; IR (thin film) 1777,
1751, 1718, 1612, 1514, 1384, 1235, 1070, 1038, 752, 720 cm-1
;
1066, 1030, 822, 741, 698 cm-1; [R]20 +5.0 (c 1.02, CHCl3);
D
[R]20 +43.1 (c 1.00, CHCl3); ESI-MS m/z 628 [M + Na]+.
ESI-MS m/z 637 [M + Na]+.
D
Th iop h en yl 4-O-Acetyl-2,3-O-d iben zyl-6-O-(p-m eth oxy-
Th ioph en yl 6-O-Acetyl-2-deoxy-4-O-(p-m eth oxyben zyl)-
3-O-(2-(tr im eth ylsilyl)eth oxym eth yl)-2-p h th a lim id o-â-D-
ben zyl)-â-D-glu cop yr a n osid e (4-O-a cetyl 3a ). 1H NMR (300
J . Org. Chem, Vol. 69, No. 21, 2004 7209

Herna´ndez-Torres et al.
glu cop yr a n osid e (6-O-a cetyl 2e). 1H NMR (300 MHz,
CDCl3) δ 7.82-7.94 (m, 2 H), 7.73-7.77 (m, 2 H), 7.38-7.42
(m, 2 H), 7.20-7.24 (m, 5 H), 6.85 (d, 2 H, J ) 8.7 Hz), 5.52
(d, 1 H, J ) 10.5 Hz), 4.68-4.71 (m, 3 H), 4.38-4.53 (m, 3 H),
4.26 (t, 1 H, J ) 10.2 Hz), 4.20 (dd, 1 H, J ) 5.1, 12.0
Hz), 3.80 (s, 3 H), 3.70 (m, 1 H), 3.55 (t, 1 H, J ) 9.3 Hz),
3.06-3.13 (m, 2 H), 2.06 (s, 3 H), 0.31-0.42 (m, 1 H), -0.05
(m, 1 H), -0.22 (s, 9 H); 13C NMR (125 MHz, CDCl3) δ 132.6,
132.1, 132.0, 129.7, 128.7, 127.8, 123.4, 113.9, 97.2, 83.4, 81.0,
78.2, 74.7, 65.9, 63.0, 55.3, 54.8, 29.7, 20.9, 17.2, -1.5; IR (thin
film) 1777, 1742, 1716, 1613, 1514, 1388, 1249, 1088, 1037,
859, 834, 749, 720, 691 cm-1; [R]20D +32.5 (c 0.80, CHCl3); ESI-
MS m/z 716 [M + Na]+.
1109, 1089, 1034, 839, 720, 691 cm-1; [R]20 +40.2 (c 1.02,
D
CHCl3); ESI-MS m/z 700 [M + Na]+.
Th iop h en yl 4-O-Acet yl-3-O-(ter t-b u t yld im et h ylsilyl)-
2-d eoxy-6-O-(p -m et h oxyb en zyl)-2-p h t h a lim id o-â-D-glu -
1
cop yr a n osid e (4-O-a cetyl 3g). H NMR (300 MHz, CDCl3)
δ 7.74-7.92 (m, 4 H), 7.36-7.38 (m, 2 H), 7.18-7.23 (m, 5 H),
6.86 (d, 2 H, J ) 8.1 Hz), 5.55 (d, 1 H, J ) 10.5 Hz), 4.96 (t, 1
H, J ) 9.3 Hz), 4.60 (t, 1 H, J ) 9.1 Hz), 4.44 (d, 1 H, J ) 12.3
Hz), 4.40 (d, 1 H, J ) 11.7 Hz), 4.31 (t, 1 H, J ) 10.2 Hz), 3.81
(s, 3 H), 3.75 (m, 1 H), 3.52-3.63 (m, 2 H), 1.97 (s, 3 H), 0.66
(s, 9 H), -0.06 (s, 3 H), -0.42 (s, 3 H); 13C NMR (125 MHz,
CDCl3) δ 169.8, 159.2, 134.3, 132.4, 132.1, 130.1, 129.5, 128.8,
127.7, 113.7, 83.6, 77.6, 73.5, 73.2, 71.3, 70.0, 56.5, 55.3, 25.3,
21.3, 17.6, -4.5, -4.7; IR (thin film) 1777, 1746, 1716, 1613,
1514, 1470, 1387, 1249, 1227, 1109, 1086, 1060, 1037, 840, 757,
Th ioph en yl 4-O-Acetyl-2-deoxy-6-O-(p-m eth oxyben zyl)-
3-O-(2-(tr im eth ylsilyl)eth oxym eth yl)-2-p h th a lim id o-â-D-
glu cop yr a n osid e (4-O-a cetyl 3e). 1H NMR (300 MHz,
CDCl3) δ 7.82-7.92 (m, 2 H), 7.73-7.77 (m, 2 H), 7.39-7.42
(m, 2 H), 7.18-7.23 (m, 5 H), 6.86 (d, 2 H, J ) 8.1 Hz), 5.55
(d, 1 H, J ) 10.2 Hz), 5.01 (t, 1 H, J ) 9.3 Hz), 4.56 (d, 1 H, J
) 6.9 Hz), 4.55 (d, 1 H, J ) 6.6 Hz), 4.53 (t, 1 H, J ) 9.3 Hz),
4.46 (s, 2 H), 4.34 (t, 1 H, J ) 10.2 Hz), 3.81 (s, 3 H), 3.78 (m,
1 H), 3.59 (d, 2 H, J ) 4.2 Hz), 3.08-3.15 (m, 2 H), 1.98 (s, 3
H), 0.41 (m, 1 H), 0.11 (m, 1 H), -0.21 (s, 9 H); 13C NMR (125
MHz, CDCl3) δ 169.6, 159.3, 132.1, 131.9, 129.5, 128.9, 127.8,
123.7, 123.5, 113.8, 99.0, 96.6, 83.7, 78.6, 77.8, 73.3, 72.2, 69.6,
55.4, 54.8, 29.8, 20.9, 17.3, -1.5; IR (thin film) 1777, 1748,
1716, 1613, 1513, 1388, 1225, 1227, 1173, 1108, 1037, 860, 835,
721 cm-1; [R]20 +54.0 (c 1.00, CHCl3); ESI-MS m/z 700 [M +
D
Na]+.
Th ioph en yl 3-O-Acetyl-4-O-(6-O-acetyl-2-azido-2-deoxy-
3-O-ben zyl-4-O-(p-m eth oxyben zyl)-r-D-glu cop yr a n osyl)-
2-d eoxy-6-O-(p -m et h oxyb en zyl)-2-p h t h a lim id o-â-D-glu -
1
cop yr a n osid e (6-O-a cetyl 2h ). H NMR (300 MHz, CDCl3)
δ 7.83-7.90 (m, 2 H), 7.73-7.75 (m, 2 H), 7.41-7.44 (m, 2 H),
7.17-7.35 (m, 12 H), 6.85-6.89 (m, 4 H), 5.81 (t, 1 H, J ) 9.6
Hz), 5.74 (d, 1 H, J ) 11.1 Hz), 5.10 (d, 1 H, J ) 3.6 Hz), 4.84
(d, 1 H, J ) 11.1 Hz), 4.79 (d, 1 H, J ) 11.1 Hz), 4.73 (d, 1 H,
J ) 10.5 Hz), 4.53 (s, 2 H), 4.45 (d, 1 H, J ) 11.4 Hz), 4.24 (t,
1 H, J ) 10.6 Hz), 4.18 (dd, 1 H, J ) 4.2, 11.7 Hz), 4.08 (d, 1
H, J ) 10.5 Hz), 3.94 (t, 1 H, J ) 8.7 Hz), 3.81 (s, 3 H), 3.78
(s, 3 H), 3.75-3.87 (m, 5 H), 3.48 (t, 1 H, J ) 9.3 Hz), 3.34
(dd, 1 H, J ) 3.6, 10.5 Hz), 2.00 (s, 3 H), 1.88 (s, 3 H); 13C
NMR (75 MHz, CDCl3) δ 170.5, 170.0, 167.9, 167.3, 159.5,
159.2, 137.6, 134.4, 134.1, 133.1, 131.8, 131.3, 131.2, 130.1,
129.7, 129.5, 129.2, 128.9, 128.5, 128.2, 128.0, 127.9, 123.6,
123.5, 113.8, 99.3, 82.6, 80.1, 78.7, 77.3, 76.1, 75.5, 74.7, 74.1,
73.1, 70.2, 68.7, 63.7, 62.5, 55.3, 55.2, 54.0, 29.7, 20.7, 20.5;
IR (thin film) 2109, 1777, 1744, 1718, 1612, 1513, 1385, 1245,
749, 720, 691 cm-1; [R]20 +67.3 (c 1.01, CHCl3); ESI-MS m/z
D
716, [M + Na]+.
Th ioph en yl 6-O-Acetyl-3-O-ben zyloxycar bon yl-2-deoxy-
4-O-(p-m eth oxyben zyl)-2-p h th a la m id o-â-D-glu cop yr a n o-
sid e (6-O-a cetyl 2f). 1H NMR (300 MHz, CDCl3) δ 7.70-7.88
(m, 4 H), 7.37-7.40 (m, 2 H), 7.09-7.24 (m, 10 H), 6.79 (d, 2
H, J ) 8.7 Hz), 5.68 (t, 1 H, J ) 9.3 Hz), 5.64 (d, 1 H, J ) 10.5
Hz), 4.90 (s, 2 H), 4.54 (d, 1 H, J ) 10.8 Hz), 4.42 (d, 1 H, J )
10.5 Hz), 4.39 (d, 1 H, J ) 9.9 Hz), 4.33 (t, 1 H, J ) 10.3 Hz),
4.22 (dd, 1 H, J ) 4.8, J ) 11.7 Hz), 3.77-3.82 (m, 1 H), 3.77
(s, 3 H), 3.71 (t, 1 H, J ) 9.6 Hz), 2.05 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 170.5, 159.4, 154.5, 134.8, 134.2, 134.1, 133.1,
131.3, 129.7, 129.2, 128.8, 128.4, 128.3, 128.2, 127.9, 123.6,
113.8, 82.8, 78.3, 76.84, 75.4, 74.4, 69.8, 62.8, 55.2, 53.8, 20.8;
IR (thin film) 1777, 1750, 1718, 1613, 1513, 1385, 1248, 1089,
10.73, 1031, 822, 753, 720 cm-1; [R]20 +41.8 (c 1.03, CHCl3);
D
ESI-MS m/z 1025 [M + Na]+.
Th ioph en yl 3-O-Acetyl-4-O-(4-O-acetyl-2-azido-2-deoxy-
3-O-ben zyl-6-O-(p-m eth oxyben zyl)-r-D-glu cop yr a n osyl)-
2-d eoxy-6-O-(p -m et h oxyb en zyl)-2-p h t h a lim id o-â-D-glu -
1
cop yr a n osid e (4-O-a cetyl 3h ). H NMR (300 MHz, CDCl3)
1034, 750, 720, 693 cm-1; [R]20 +19.5 (c 0.77, CHCl3); ESI-
D
δ 7.84-7.90 (m, 2 H), 7.73-7.76 (m, 2 H), 7.41 (m, 2 H), 7.20-
7.32 (m, 12 H), 6.86 (m, 4 H), 5.82 (t, 1 H, J ) 9.5 Hz), 5.78 (d,
1 H, J ) 10.5 Hz), 5.12 (s, 1 H), 5.05 (t, 1 H, J ) 9.3 Hz), 4.72
(d, 1 H, J ) 11.1 Hz), 4.53 (d, 1 H, J ) 11.1 Hz), 4.47 (s, 2 H),
4.39 (d, 1 H, J ) 10.5 Hz), 4.30 (d, 1 H, J ) 10.5 Hz), 4.26 (t,
1 H, J ) 10.5 Hz), 4.95 (t, 1 H, J ) 9.2 Hz), 3.81 (s, 3 H), 3.78
(s, 3 H), 3.78-3.89 (m, 5 H), 3.42 (d, 1 H, J ) 9.9 Hz), 3.52 (s,
2 H), 1.89 (s, 3 H), 1.83 (s, 3 H); 13C NMR (125 MHz, CDCl3)
δ 170.1, 169.5, 167.9, 167.2, 159.2, 158.6, 137.5, 134.3, 134.1,
133.1, 131.7, 131.3, 131.0, 130.4, 129.7, 129.5, 129.1, 128.8,
128.4, 128.1, 127.9, 127.8, 123.6, 123.5, 113.8, 99.5, 99.0, 82.6,
78.9, 77.8, 74.9, 73.9, 73.2, 73.9, 70.6, 70.1, 68.9, 68.3, 63.3,
55.2, 53.9, 29.7, 20.7, 20.6; IR (thin film) 2110, 1777, 1745,
MS m/z 720 [M + Na]+.
Th ioph en yl 4-O-Acetyl-3-O-ben zyloxycar bon yl-2-deoxy-
6-O-(p-m eth oxyben zyl)-2-p h th a la m id o-â-D-glu cop yr a n o-
sid e (4-O-a cetyl 3f). 1H NMR (300 MHz, CDCl3) δ 7.82-7.90
(m, 2 H), 7.75-7.80 (m, 2 H), 7.42 (dd, 2 H, J ) 1.5, 8.1 Hz),
7.17-7.29 (m, 10 H), 6.89 (d, 2 H, J ) 8.7 Hz), 5.71 (t, 1 H, J
) 9.7 Hz), 5.69 (d, 1 H, J ) 10.5 Hz), 5.17 (t, 1 H, J ) 9.7 Hz),
4.95 (d, 1 H, J ) 12.3 Hz), 4.89 (d, 1 H, J ) 12.3 Hz), 4.50 (d,
1 H, J ) 11.4 Hz), 4.46 (t, 1 H, J ) 10.5 Hz), 4.45 (d, 1 H, J )
11.4 Hz), 3.89 (m, 1 H), 3.84 (s, 3 H), 3.63 (d, 2 H, J ) 4.2 Hz),
1.80 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 169.4, 159.2, 154.4,
134.8, 134.2, 132.7, 131.4, 129.9, 129.4, 128.9, 128.4, 128.3,
128.1, 127.9, 123.7, 123.6, 113.7, 83.2, 77.5, 75.4, 73.2, 69.7,
69.6, 68.9, 55.3, 53.5, 20.4; IR (thin film) 1755, 1718, 1613,
1718, 1613, 1513, 1385, 1227, 1034, 820, 751, 720, 699 cm-1
;
[R]20 +33.8 (c 1.01, CHCl3); ESI-MS m/z 1025 [M + Na]+.
D
1513, 1385, 1251, 1221, 1067, 1036, 751, 720, 695 cm-1; [R]20
D
Allyl 2-Deoxy-3,4-O-d ia cetyl-6-O-(p-m eth oxyben zyl)-2-
ph th alim ido-â-D-glu copyr an oside (4-O-acetyl 3i). 1H NMR
(300 MHz, CDCl3) δ 7.83-7.86 (m, 2 H), 7.71-7.74 (m, 2 H),
7.25 (d, 2 H, J ) 8.4 Hz), 6.89 (d, 2 H, J ) 8.4 Hz), 5.78 (t, 1
H, J ) 9.9 Hz), 5.67 (m, 1 H), 5.38 (d, 1 H, J ) 8.7 Hz), 5.15
(t, 1 H, J ) 9.9 Hz), 5.09 (d, 1 H, J ) 16.8 Hz), 5.03 (d, 1 H, J
) 10.5 Hz), 4.52 (d, 1 H, J ) 11.4 Hz), 4.44 (d, 1 H, J ) 11.7
Hz), 4.33 (t, 1 H, J ) 9.6 Hz), 4.28 (dd, 1 H, J ) 4.8, 12.9 Hz),
4.04 (dd, 1 H, J ) 6.3, 12.9 Hz), 3.79 (m, 1 H), 3.81 (s, 3 H),
3.59 (d, 2 H, J ) 3.9 Hz), 1.92 (s, 3 H), 1.83 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 170.2, 169.6, 159.2, 134.2, 133.4, 131.4,
129.8, 129.5, 123.5, 117.6, 113.7, 97.0, 73.3, 73.2, 70.9, 70.0,
69.9, 68.6, 55.3, 54.7, 20.7, 20.5; IR (thin film) 1777, 1752, 1718,
+38.0 (c 1.00, CHCl3); ESI-MS m/z 720 [M + Na]+.
Th iop h en yl 6-O-Acet yl-3-O-(ter t-b u t yld im et h ylsilyl)-
2-d eoxy-4-O-(p -m et h oxyb en zyl)-2-p h t h a lim id o-â-D-glu -
1
cop yr a n osid e (6-O-a cetyl 2g). H NMR (300 MHz, CDCl3)
δ 7.79-7.98 (m, 4 H), 7.39-7.42 (m, 2 H), 7.27-7.31 (m, 5 H),
6.90 (d, 2 H, J ) 8.4 Hz), 5.60 (d, 1 H, J ) 10.5 Hz), 4.80 (d,
1 H, J ) 11.1 Hz), 4.53 (t, 1 H, J ) 9.7 Hz), 4.49 (d, 1 H, J )
11.1 Hz), 4.46 (d, 1 H, J ) 11.4 Hz), 4.30 (t, 1 H, J ) 10.2 Hz),
4.16 (dd, 1 H, J ) 5.4, 11.7 Hz), 3.84 (s, 3 H), 3.76 (m, 1 H),
3.51 (t, 1 H, J ) 9.0 Hz), 2.11 (s, 3 H), 0.79 (s, 9 H), 0.04 (s, 3
H), -0.38 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 170.6, 159.2,
134.3, 132.4, 132.3, 129.7, 129.0, 128.7, 127.8, 113.8, 83.3, 79.7,
77.2, 74.7, 73.6, 63.2, 56.5, 55.2, 25.7, 20.9, 17.6, -4.1, -4.6;
IR (thin film) 1777, 1743, 1716, 1613, 1514, 1471, 1387, 1249,
1612, 1513, 1387, 1236, 1173, 1042, 722 cm-1; [R]20 +55.0 (c
D
0.74, CHCl3); ESI-MS m/z 576 [M + Na]+.
7210 J . Org. Chem., Vol. 69, No. 21, 2004

Reductive Cleavage of p-Methoxybenzylidene Acetals
Th iotolyl 3-O-Allyloxyca r bon yl-4-O-a cetyl-2-a zid o-2-
d eoxy-6-O-(p-m eth oxyben zyl)-â-D-glu cop yr a n osid e (4-O-
Hz), 3.30 (s, 3 H), 3.15 (s, 3 H), 1.60 (s, 3 H); 13C NMR (75
MHz, C6D6) δ 169.3, 159.7, 139.5, 139.1, 130.8, 129.1, 128.5,
128.4, 127.9, 127.8, 127.5, 114.0, 98.2, 80.8, 79.5, 75.1, 73.4,
73.0, 71.6, 70.1, 69.5, 54.9, 54.7, 20.4; IR (thin film) 1744, 1613,
1
a cetyl 3j). H NMR (300 MHz, CDCl3) δ 7.39 (d, 2 H, J ) 7.8
Hz), 7.20 (d, 2 H, J ) 8.4 Hz), 7.05 (d, 2 H, J ) 7.5 Hz), 6.85
(d, 2 H, J ) 8.4 Hz), 5.93 (m, 1 H), 5.56 (d, 1 H, J ) 5.4 Hz),
5.34 (d, 1 H, J ) 17.4 Hz), 5.27 (d, 1 H, J ) 10.5 Hz), 5.18 (t,
1 H, J ) 9.5 Hz), 5.08 (t, 1 H, J ) 9.5 Hz), 4.66 (d, 2 H, J )
4.8 Hz), 4.54 (m, 1 H), 4.46 (d, 1 H, J ) 11.4 Hz), 4.32 (d, 1 H,
J ) 11.7 Hz), 4.06 (dd, 1 H, J ) 5.7, 10.2 Hz), 3.80 (s, 3 H),
3.51 (d, 2 H, J ) 3.6 Hz), 2.32 (s, 3 H), 1.96 (s, 3 H); 13C NMR
(125 MHz, CDCl3) δ 169.4, 159.2, 154.1, 138.2, 132.8, 131.1,
129.8, 129.4, 118.9, 113.6, 86.9, 76.2, 73.0, 69.5, 68.9, 68.8, 67.6,
61.6, 55.2, 29.6, 21.0, 20.5; IR (thin film) 2109, 1777, 1744,
1719, 1612, 1514, 1467, 1385, 1302, 1249, 1073, 1032, 753, 720,
1514, 1497, 1455, 1369, 1234, 1163, 1101, 1046, 739, 698 cm-1
;
[R]20 +54.1 (c 1.03, C6H6); ESI-MS m/z 559 [M + Na]+.
D
Meth yl 6-O-Acetyl-2,3-O-d iben zyl-4-O-(p-m eth oxyben -
zyl)-r-D-glu cop yr a n osid e (6-O-a cetyl 5b). 1H NMR (300
MHz, C6D6) δ 7.36 (m, 2 H), 7.05-7.23 (m, 10 H), 6.75 (m, 2
H), 5.03 (d, 1 H, J ) 11.7 Hz), 4.86 (d, 1 H, J ) 11.1 Hz), 4.82
(d, 1 H, J ) 11.7 Hz), 4.60 (s, 1 H), 4.56 (d, 1 H, J ) 10.5 Hz),
4.49 (d, 1 H, J ) 12.3 Hz), 4.44 (dd, 1 H, J ) 2.1, 11.7 Hz),
4.40 (d, 1 H, J ) 11.7 Hz), 4.33 (dd, 1 H, J ) 4.8, 11.7 Hz),
4.23 (t, 1 H, J ) 9.2 Hz), 3.89 (m, 1 H), 3.57 (t, 1 H, J ) 9.6
Hz), 3.51 (dd, 1 H, J ) 3.3, 9.6 Hz), 3.27 (s, 3 H), 3.09 (s, 3 H),
1.60 (s, 3 H); 13C NMR (75 MHz, C6D6) δ 169.9, 159.8, 139.7,
139.0, 130.9, 130.0, 128.5, 128.4, 114.0, 98.2, 82.4, 81.0, 77.4,
75.6, 74.6, 72.9, 69.2, 63.4, 54.9, 54.7, 30.2, 20.4; IR (thin film)
1741, 1612, 1514, 1497, 1455, 1364, 1249, 1071, 1030, 739, 698
699 cm-1; [R]20 +65.4 (c 0.55, CHCl3); ESI-MS m/z 581 [M +
D
Na]+.
Th iotolyl 4-O-Acetyl-2,3-O-isopr opyliden e-6-O-(p-m eth -
oxyben zyl)-â-D-glu cop yr a n osid e (4-O-a cetyl 3k ). 1H NMR
(300 MHz, C6D6) δ 7.65 (d, 2 H, J ) 8.1 Hz), 7.24 (d, 2 H, J )
8.1 Hz), 6.83 (d, 2 H, J ) 7.8 Hz), 6.78 (d, 2 H, J ) 8.7 Hz),
5.40 (t, 1 H, J ) 9.5 Hz), 4.60 (d, 1 H, J ) 9.3 Hz), 4.37 (d, 1
H, J ) 11.7 Hz), 4.32 (d, 1 H, J ) 11.7 Hz), 3.53-3.66 (m, 3
H), 3.44 (t, 1 H, J ) 9.2 Hz), 3.41 (m, 1 H), 3.29 (s, 3 H), 1.99
(s, 3 H), 1.53 (s, 3 H), 1.33 (s, 3 H), 1.20 (s, 3 H); 13C NMR (75
MHz, C6D6) δ 168.9, 159.8, 138.3, 134.4, 130.7, 129.8, 129.7,
114.0, 111.2, 85.1, 80.8, 78.8, 75.7, 73.4, 70.3, 69.3, 54.7, 26.7,
26.6, 21.0, 20.3; IR (thin film) 1748, 1613, 1514, 1493, 1456,
cm-1; [R]20 +34.1 (c 1.02, C6H6); ESI-MS m/z 559 [M + Na]+.
D
Meth yl 6-O-Acetyl-2,3,4-O-tr iben zyl-â-D-glu cop yr a n o-
sid e (6-O-a cetyl 7). 1H NMR (300 MHz, C6D6) δ 7.33 (m, 4
H), 7.24 (m, 2 H), 7.02-7.19 (m, 9 H), 5.01 (d, 1 H, J ) 11.1
Hz), 4.97 (d, 1 H, J ) 11.4 Hz), 4.80 (d, 1 H, J ) 10.5 Hz), 4.77
(d, 1 H, J ) 10.2 Hz), 4.68 (d, 1 H, J ) 11.4 Hz), 4.47 (d, 1 H,
J ) 11.1 Hz), 4.42 (dd, 1 H, J ) 2.4, 12.0 Hz), 4.28 (dd, 1 H,
J ) 4.8, 12.0 Hz), 4.13 (d, 1 H, J ) 7.5 Hz), 3.64 (t, 1 H, J )
9.0 Hz), 3.54 (t, 1 H, J ) 7.9 Hz), 3.52 (t, 1 H, J ) 9.3 Hz),
3.28 (s, 3 H), 3.27 (m, 1 H), 1.60 (s, 3 H); 13C NMR (75 MHz,
C6D6) δ 169.9, 139.4, 139.3, 138.7, 128.6, 128.5, 105.0, 85.0,
82.6, 77.7, 75.5, 74.9, 74.6, 73.2, 63.2, 56.5, 20.3; IR (thin film)
1372, 1240, 1173, 1151, 1038, 833, 782 cm-1; [R]20 -11.8 (c
D
0.67, C6H6); ESI-MS m/z 511 [M + Na]+.
4-O-Acetyl-3-O-ben zyl-6-O-(p-m eth oxyben zyl)-â-D-glu -
ca l (4-O-a cetyl 3l). 1H NMR (300 MHz, C6D6) δ 7.28 (m, 2
H), 7.07-7.19 (m, 5 H), 6.74 (d, 2 H, J ) 8.7 Hz), 6.27 (d, 1 H,
J ) 6.3 Hz), 5.54 (t, 1 H, J ) 4.1 Hz), 4.71 (t, 1 H, J ) 5.1 Hz),
4.49 (d, 1 H, J ) 12.6 Hz), 4.45 (d, 1 H, J ) 12.6 Hz), 4.38 (dd,
1 H, J ) 5.1, 10.5 Hz), 4.30 (d, 1 H, J ) 11.7 Hz), 4.26 (d, 1 H,
J ) 11.7 Hz), 3.90 (t, 1 H, J ) 3.9 Hz), 3.77 (dd, 1 H, J ) 6.0,
10.5 Hz), 3.73 (dd, 1 H, J ) 5.7, 10.2 Hz), 3.28 (s, 3 H), 1.58 (s,
3 H); 13C NMR (75 MHz, C6D6) δ 169.3, 159.7, 144.8, 139.0,
130.6, 129.5, 114.0, 75.5, 73.1, 70.3, 69.9, 68.3, 68.1, 54.7, 20.5;
IR (thin film) 1740, 1650, 1613, 1514, 1456, 1369, 1245, 1102,
1743, 1497, 1454, 1364, 1237, 1070, 1029, 737, 699 cm-1; [R]20
D
+25.4 (c 0.95, C6H6); ESI-MS m/z 529 [M + Na]+.
Ack n ow led gm en t. The authors gratefully acknowl-
edge financial support from the American Cancer
Society (03-135-01-CDD), the American Heart Associa-
tion (30399Z), and the National Institutes of Health
(EB-001777-01). Support from the Purdue Cancer Cen-
ter is gratefully acknowledged. We thank Dr. Fabien
Boulineau for providing several of the anisylidene
acetals for our studies.
1036, 819, 739, 699 cm-1; [R]20 -11.7 (c 0.63, C6H6); ESI-MS
D
m/z 421 [M + Na]+.
Meth yl 4-O-Acetyl-2,3-O-d iben zyl-6-O-(p-m eth oxyben -
zyl)-r-D-glu cop yr a n osid e (4-O-a cetyl 5a ). 1H NMR (300
MHz, C6D6) δ 7.27 (m, 6 H), 7.01-7.12 (m, 6 H), 6.77 (m, 2 H),
5.40 (t, 1 H, J ) 9.8 Hz), 4.86 (d, 1 H, J ) 12.0 Hz), 4.63 (d, 1
H, J ) 12.0 Hz), 5.59 (d, 1 H, J ) 3.3 Hz), 4.44 (d, 1 H, J )
12.0 Hz), 4.36 (s, 2 H), 4.32 (d, 1 H, J ) 12.6 Hz), 4.15 (t, 1 H,
J ) 9.5 Hz), 4.00 (m, 1 H), 3.62 (dd, 1 H, J ) 3.3, 10.2 Hz),
3.56 (dd, 1 H, J ) 5.4, 10.5 Hz), 3.47 (dd, 1 H, J ) 3.3, 9.6
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
acetylated 4-O- and 6-O-PMB ethers 2a -l, 3a -l, 5a , 5b, and
7. This material is available free of charge via the Internet at
http://pubs.acs.org.
J O048999M
J . Org. Chem, Vol. 69, No. 21, 2004 7211