Optimized synthesis of an orthogonally protected glucosamine

Article abstract of DOI:10.1055/s-2002-20962

Glucosamine hydrochloride was transformed into an orthogonally protected intermediate in seven steps and 34% overall yield. The synthesis includes an optimized preparation of N-phthaloyl-β-D-glucosamine tetraacetate, a commonly used precursor in carbohydrate chemistry.

Full text of DOI:10.1055/s-2002-20962

PAPER
487
Optimized Synthesis of an Orthogonally Protected Glucosamine
Synthesis
e
of an Ortho
s
gonally P
ú
rotected Gluc
s
osamine M. Hernández-Torres, Siong-Tern Liew, Jihane Achkar, Alexander Wei*
Department of Chemistry, Purdue University, 1393 Brown Building, West Lafayette, Indiana 47907-1393, USA
Fax +1(765)4940239; E-mail: alexwei@purdue.edu
Received 1 September 2001; revised 4 February 2002
Abstract: Glucosamine hydrochloride was transformed into an
orthogonally protected intermediate in seven steps and 34% over-
all yield. The synthesis includes an optimized preparation of N-
phthaloyl- -D-glucosamine tetraacetate, a commonly used precur-
sor in carbohydrate chemistry.
Keywords: carbohydrates, glucosamine, glycosides, orthogonal
protecting groups
Glucosamine derivatives are important intermediates in
the synthesis of oligosaccharides and glycoconjugates.1
Both natural and synthetic glucosamine-containing com-
pounds have demonstrated potent anticoagulation and im-
munomodulatory activity2 and are used clinically to treat
heart disease,3 arthritis,4 and kidney disorders.5 Recent
methodological advances in the solid-state synthesis of
complex carbohydrates6 are likely to increase demand for
the scalable preparation of monosaccharide precursors
with orthogonal protecting group systems. Although nu-
merous synthetic procedures exist, few are truly appropri-
ate for economic scale-up. Here we report an efficient and
scalable synthetic sequence of an orthogonally protected
glucosamine derivative (Scheme 1). Of particular note is
the efficient conversion of glucosamine to N-phthaloyl- -
D-glucosamine tetraacetate (1), a popular intermediate
first introduced by Baker in 1954.7
Scheme 1 Reagents and conditions: (a) (i) NaOMe, MeOH (ii)
Phth2O, Et3N (iii) Ac2O, pyridine (77%); (b) PhSH, TMSOTf, CH2Cl2
(76%); (c) NaOMe, 3:2 MeOH–CH2Cl2, –10 °C; (d) p-anisaldehyde
dimethyl acetal, CSA, toluene, 90 °C (80% yield over two steps); (e)
t-BuMe2SiCl, AgNO3, Et3N, CH2Cl2 (88%). MP = p-methoxyphenyl,
Phth = phthaloyl, TBS = tert-butyldimethylsilyl, CSA = camphorsul-
fonic acid
The preparation of 1 was adapted from a procedure de-
scribed by Lemieux and coworkers.8 Glucosamine hydro-
chloride was neutralized with one equivalent of freshly
prepared NaOMe, then treated directly with finely pow-
dered phthalic anhydride added in two portions with sub-
sequent addition of triethylamine and methanol to reduce
viscosity. A filtration step for removing sodium chloride
was deemed unnecessary and even undesirable, as the
neutral glucosamine itself was only partially soluble un-
der these conditions. However, efficient mechanical stir-
ring was found to be essential for complete conversion of
the amine to the intermediate phthalamate, to accelerate
the exchange rate of the reactants between the solid and
solution states and to maintain a small grain size to pre-
vent unreacted materials from being trapped in particulate
form. The crude product and salts were cooled and col-
lected by filtration and carefully dried under reduced pres-
sure, then resuspended in pyridine and treated with acetic
anhydride and stirred at room temperature, again with me-
chanical stirring. Pyridine was efficiently removed from
the reaction mixture by azeotropic distillation with tolu-
ene prior to aqueous extraction of the inorganic by-prod-
ucts, minimizing problems associated with waste
remediation and loss of product by inefficient partitioning
between the aqueous and organic phases. Recrystalliza-
tion from a binary (20:80) mixture of EtOAc and hexanes
yielded the desired tetraacetate in 77% yield as an 8:1
mixture of anomers, with 1 as the predominant isomer.
The anomeric mixture of glycosyl tetraacetates were most
efficiently converted to -thiophenyl glycoside 2 using
trimethylsilyl triflate (TMSOTf) as a Lewis acid.9 Less
expensive Lewis acids such as BF3 Et2O have also been
used as catalysts for glycosylation10 but the reaction times
are much slower. Dissolution of the tetraacetates in anhy-
drous CH2Cl2 and treatment with 1.2 equivalents of
TMSOTf at ambient temperature produced the desired
compound 2 in 7 hours. It is worth mentioning that the -
acetate 1 is considerably more reactive than the -anomer;
we have observed that glycosyl tetraacetates with lower /
ratios can require 1–3 days for complete conversion. Re-
Synthesis 2002, No. 4, 15 03 2002. Article Identifier:
1437-210X,E;2002,0,04,0487,0490,ftx,en;M14101SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

488
J. M. Hernández-Torres et al.
PAPER
crystallization after aqueous workup was again accom-
plished using a binary mixture of EtOAc and hexanes to
yield compound 2 in 76% yield.
Triacetate 2 could be chemoselectively saponified to triol
3 by treatment with NaOMe in a 60:40 mixture of MeOH–
CH2Cl2 at –20 to –10 °C.11 Methanolysis did not proceed
at an appreciable rate for temperatures below –20 °C,
whereas the phthalimide group was susceptible to partial
cleavage for reaction temperatures above 0 °C. The reac-
tion mixture was neutralized by passage through an ion-
exchange resin packed in methanol. The crude triol was
dried under reduced pressure, then resuspended in anhy-
drous toluene and treated with p-anisaldehyde dimethyl
acetal and a catalytic amount of camphorsulfonic acid at
reflux with azeotropic removal of methanol.12 Attempts to
recrystallize the product from aqueous ethanol at –20 °C
were inefficient and yielded crystalline solids which melt-
ed below room temperature.13 Therefore, the product was
purified by silica gel chromatography to yield the desired
anisylidene acetal 4 in 80% yield over two steps. Protec-
tion of the sterically hindered O-3 as a tert-butyldimethyl-
silyl (TBS) ether was achieved most economically with
the corresponding chloride assisted by AgNO3.14 The re-
action was conducted in CH2Cl2 at room temperature us-
ing Et3N as a base and protected from light to prevent
photoactivated degradation. The silver salts were re-
moved by filtration through Celite prior to aqueous work-
up, and crystallization was accomplished using a binary
mixture of EtOAc and hexanes to yield the fully protected
intermediate 5 in 88% yield.
Scheme 2 Reagents and conditions: (a) (i) BH3 THF, TMSOTf,
CH2Cl2, –25 to 0 °C (96%); (b) allyl chloroformate, Et3N, DMAP,
CH2Cl2 (87%) AOC = allyloxycarbonyl, MP = p-methoxyphenyl,
Phth = phthaloyl, PMB = p-methoxybenzyl, TBS = tert-butyldime-
thylsilyl
acquired from thin films on NaCl plates using a Nicolet Nexus 670
spectrometer. Optical rotations were obtained at r.t. with a Rudolph
AUTOPOL III polarimeter. Mass spectra were obtained using a
Hewlett-Packard 5989B or a Finnigan 4000 mass spectrometer. El-
emental analyses were performed in the Department of Chemistry,
Purdue University.
1,3,4,6-Tetra-O-acetyl-2-phthalimido-2-deoxy- -D-glucopyra-
noside (1)
A 1 M NaOMe solution was prepared by adding Na metal (5.33 g,
0.232 mol) in small pieces to MeOH (Mallinckrodt, ChromAR
HPLC, 232 mL) at –5 °C in a 500 mL round-bottomed flask
equipped with a reflux condensor, which was swirled until the metal
had been completely consumed. This was slowly added at 0 °C to a
1 L round-bottomed flask containing glucosamine hydrochloride
(50 g, 0.232 mol). The reaction mixture was mechanically agitated
for 2 h at r.t. using a stirring rod with a tapered Teflon blade, then
treated with finely ground phthalic anhydride (19 g, 0.128 mol) and
mechanically stirred for another 45 min. The mixture was charged
with a second portion of phthalic anhydride (19 g, 0.128 mol), Et3N
(35.5 mL, 0.255 mol), and MeOH (230 mL) and vigorously stirred
for another 24 h, during which it slowly changed from a milky white
solution to a thick yellow paste. The intermediate phthalamate (and
salts) were precipitated as a white solid by cooling the mixture to –
20 °C for 4 h. These were filtered and thoroughly washed with cold
MeOH, then dried overnight under reduced pressure. The solid was
redispersed in pyridine (Mallinckrodt, 500 mL) with vigorous me-
chanical stirring and cooled to –5 °C, followed by treatment with
Ac2O (Mallinckrodt, 330 mL). The mixture was mechanically
stirred at r.t. for 48 h, during which it slowly changed from a trans-
lucent white to an opaque yellow solution. Cold EtOH (100 mL)
was slowly added to the mixture to quench the excess Ac2O, which
was then reduced by rotary evaporation. This was redispersed in tol-
uene (3 100 mL) and concentrated several times for the azeotropic
removal of pyridine. The remaining slurry was redissolved in
CHCl3 (1 L) and washed with distilled H2O (4 250 mL) and brine
(250 mL), then dried (Na2SO4) and evaporated to dryness. The
crude product was dissolved in minimal amount of hot EtOAc (100
mL), then diluted with hexanes (400 mL) and left to cool at –5 °C.
The recrystallized product was collected by filtration, washed with
cold hexanes, and dried to yield the desired tetraacetate as an 8:1
mixture of anomers (85.3 g, 77%). Comparison of the 1H NMR sig-
nals (CDCl3, 300 MHz) with the values in the literature18 confirmed
1 as the major -isomer; mp 94–95 °C.
Glucosamine derivative 5 is a versatile intermediate; it
can be directly activated for glycosylation15 or converted
to the C-4 or C-6 p-methoxybenzyl (PMB) ether by regi-
oselective cleavage of the 4,6-anisylidene (Scheme 2).
16
Treatment of 5 with BH3 THF and TMSOTf in CH2Cl2
yielded the C-4 ether 6 in 96% yield after silica gel chro-
matography. The primary alcohol was then protected as
an allyloxycarbonate (AOC) using allyl chloroformate
and Et3N assisted by 4-dimethylaminopyridine in
CH2Cl2;17 purification by silica gel chromatography yield-
ed the orthogonally protected glucosamine 7 in 87% yield.
In summary, we have reported a scalable, seven-step syn-
thesis of an orthogonally protected glucosamine, with an
overall yield of 34% or an average yield of 86% per step.
We anticipate that efficient synthetic routes to carbohy-
drate precursors such as the one reported here will be im-
portant for the large-scale synthesis of complex
carbohydrates and glycoconjugates.
All starting materials and reagents were obtained from commercial
sources and used as received unless otherwise noted. Hexanes were
purified by fractional distillation; CH2Cl2 and toluene were freshly
distilled from CaH2; THF was freshly distilled from sodium ben-
zophenone ketyl. Silica gel chromatography was performed with
ICN SiliTech 32-63 D. Melting points were determined using a cap-
illary tube apparatus and are uncorrected. 1H and 13C NMR spectra
were obtained using a Varian spectrometer operating at 300 MHz
and 75 MHz, respectively. Chemical shifts are reported in ppm with
the residual solvent peak as an internal reference. IR spectra were
Synthesis 2002, No. 4, 487–490 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of an Orthogonally Protected Glucosamine
489
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-1-thio- -D-
glucopyranoside (2)
Phenyl 3-O-(tert-Butyldimethylsilyl)-4,6-O-(p-methoxybenzyl-
idene)-2-deoxy-2-phthalimido-1-thio- -D-glucopyranoside (5)
Anisylidene acetal 4 (1.5 g, 2.9 mmol) was dissolved in anhyd
CH2Cl2 (10 mL) in an oven-dried 25 mL round-bottomed flask.
Et3N (0.69 mL, 4.9 mmol) was added and the reaction mixture was
stirred for 10 min at r.t., under argon. AgNO3 (0.74 g, 4.3 mmol)
was added and the reaction flask was covered with aluminum foil
(to prevent photoactivated degradation) and stirred for 15 min, then
treated with tert-butyldimethylchlorosilane (TBSCl, 0.66 g, 4.3
mmol). A white precipitate of AgCl was observed immediately. The
mixture was stirred at r.t. for 18 h, then filtered through Celite into
a sat. aq solution of NaHCO3 (10 mL). The aqueous phase was sep-
arated and extracted with additional CH2Cl2 (2 7 mL). The com-
bined organic phases were then washed with brine (7 mL), dried
(Na2SO4), and concentrated by rotary evaporation. The crude prod-
uct was dissolved in a minimum amount of hot EtOAc (5 mL), then
diluted with hexanes (20 mL) and cooled to 0 °C overnight. The re-
crystallized product was collected by filtration, washed with cold
10% EtOAc in hexanes and dried to yield the desired compound 5
as white crystals (1.62 g, 88%); mp 176.0 0.5 °C; [ ]D +26.8 (c =
0.81, CHCl3).
An oven-dried 1 L round-bottomed flask was charged with tetraac-
etate 1 (43.25 g, 90.9 mmol), thiophenol (Aldrich, 28 mL, 272.8
mmol), and anhyd CH2Cl2 (430 mL). The mixture was treated with
freshly distilled TMSOTf (20 mL, 109.2 mmol) at r.t. and stirred for
7 h under argon. The mixture was then quenched with a sat. aq so-
lution of NaHCO3 (400 mL) and separated. The aqueous layer was
extracted with additional CH2Cl2 (2 100 mL); the combined or-
ganic phases were then washed with brine (250 mL), dried
(Na2SO4), and concentrated by rotary evaporation equipped with a
bleach trap. The crude product was dissolved in a minimum amount
of hot EtOAc (65 mL), then diluted with hexanes (200 mL) and
cooled to 0 °C. The recrystallized product was collected by filtra-
tion, washed with cold 10% EtOAc in hexanes, and dried to yield
the desired thiophenyl glycoside 2 (36.5 g, 76%). Comparison of the
1H NMR signals (CDCl3, 300 MHz) with the values in the
literature19 confirmed the identity of 2; mp 145.0 0.5 °C.
Phenyl 4,6-O-(p-Methoxybenzylidene)-2-deoxy-2-phthalimido-
1-thio- -D-glucopyranoside (4)
To a 100 mL round-bottomed flask was added the triacetate 2 (8.5
g, 16.1 mmol) and a 3:2 mixture of MeOH–CH2Cl2 (Mallinckrodt,
80.0 mL). The mixture was cooled to –20 °C, treated with a 0.3 M
NaOMe solution in MeOH (21.3 mL, 6.4 mmol) and stirred for 10
min, then warmed to –10 °C and stirred for 2 h. The reaction mix-
ture was warmed to 0 ºC and passed through an ion-exchange resin
(Dowex 50WX8-100) packed with MeOH. The crude triol was con-
centrated by rotary evaporation and dried under vacuum overnight
in a 250 mL round-bottomed flask, then suspended in anhyd toluene
(Mallinckrodt, 80 mL). p-Anisaldehyde dimethyl acetal (Avocado,
3.3 mL, 19.4 mmol) and camphorsulfonic acid (0.86 g, 3.7 mmol)
were also added and the mixture was stirred at 90 °C for 3 h in a
flask equipped with a Dean–Stark apparatus. The temperature was
increased to 120 °C and refluxed until 2 mL of MeOH–toluene
azeotrope had been collected, then cooled to r.t. The mixture was
quenched with a sat. aq solution of NaHCO3 (100 mL) and diluted
with EtOAc (60 mL). The aqueous layer was separated and extract-
ed with additional EtOAc (2 50 mL). The combined organic phas-
es were then washed with brine (50 mL), dried (Na2SO4), and
concentrated by rotary evaporation. The product was purified by sil-
ica gel chromatography using a 10–50% EtOAc–hexanes gradient
to yield the desired anisylidene acetal 4 as a white solid (6.75 g,
80% overall yield); mp 182.0 0.5 °C; [ ]D +32.9 (c = 1.02,
CHCl3).
IR (film): 1772, 1711, 1617, 1515, 1472, 1385, 1247, 1171, 1142,
1117, 1092, 856, 722 cm–1.
1H NMR (300 MHz, CDCl3): = 7.73–7.88 (m, 4 H, ArH), 7.23–
7.41 (m, 7 H, ArH), 6.89 (d, 2 H, J = 8.7 Hz, ArH), 5.67 (d, 1 H,
J = 10.7 Hz, H-1), 5.48 (s, 1 H, CHPMP), 4.63 (t, 1 H, J = 9.3 Hz,
H-3), 4.37 (dd, 1 H, J = 4.4, 9.9 Hz, H-6a), 4.32 (t, 1 H, J = 9.9 Hz,
H-2), 3.77–3.83 (m, 4 H, H-6e, OCH3), 3.71 (ddd, 1 H, J = 4.4, 9.2,
9.8 Hz, H-5), 3.56 (t, 1 H, J = 8.9 Hz, H-4), 0.57 [s, 9 H,
C(CH3)3], –0.14 (s, 3 H, SiCH3), –0.30 (s, 3 H, SiCH3).
13C NMR (75 MHz, CDCl3): = 160.05 (1 C, Carom–OCH3), 134.22,
132.28, 132.14, 131.68, 129.59, 128.90, 127.88, 127.64, 123.61,
123.22, 113.46 (17 C, C and CH arom), 101.89 (1C, Cacetal), 84.37
(1C, C-1), 82.39, 70.66, 70.58, 68.60, 56.66, 55.21 (6 C, C-
2,3,4,5,6, OCH3), 25.36 [3 C, C(CH3)3], 17.69 [1 C, C(CH3)3], –4.16
(1 C, SiCH3), –5.39 (1 C, SiCH3).
ESI-MS: m/z = 634 (M + H).
Anal. Calcd for C34H39NO7SSi: C, 64.43; H, 6.20; N, 2.21. Found:
C, 64.28; H, 6.15; N, 2.19.
Phenyl 3-O-(tert-Butyldimethylsilyl)-4-O-(p-methoxybenzyl)-2-
deoxy-2-phthalimido-1-thio- -D-glucopyranoside (6)
Compound 5 (151 mg, 0.24 mmol) was dissolved in anhyd CH2Cl2
(1.0 mL) in an oven-dried 25 mL round-bottomed flask. The reac-
tion mixture was cooled to –20 °C under argon and treated with bo-
rane–THF (2.4 mL of a 1 M solution in THF). The mixture was
stirred at –20 °C for 15 min, then treated with TMSOTf (0.07 mL of
a 2 M solution in CH2Cl2) and warmed to 0 °C over a period of 30
min. The mixture was stirred at 0 °C for an additional 4 h, cooled to
–15 °C and treated with Et3N (0.2 mL), then quenched by the drop-
wise addition of MeOH (3 mL) until effervescence ceased. The
mixture was warmed to r.t. and concentrated by rotary evaporation
to dryness. The product was purified by silica gel chromatography
using a 20–40% EtOAc–hexanes gradient to yield the desired O-6
alcohol 6 as a white crystalline solid (145 mg, 96%); mp 166.0 0.5
°C; [ ]D +48.0 (c = 1.03, CHCl3).
IR (film): 3474, 1774, 1713, 1614, 1519, 1387, 1250, 1091, 752,
720, 688 cm–1.
1H NMR (300 MHz, CDCl3): = 7.73–7.89 (m, 4 H, ArH), 7.36–
7.42 (m, 7 H, ArH), 6.90 (d, 2 H, J = 8.7 Hz, ArH), 5.70 (d, 1 H,
J = 10.5 Hz, H-1), 5.52 (s, 1 H, CH-PMP), 4.65 (dd, 1 H, J = 2.9,
9.8 Hz, H-3), 4.39 (dd, 1 H, J = 4.6, 10.2 Hz, H-6a), 4.32 (t, 1 H,
J = 10.2 Hz, H-2), 3.77–3.84 (m, 4 H, H-6e, OCH3), 3.70 (ddd, 1 H,
J = 4.5, 9.3, 9.8 Hz, H-5), 3.58 (t, 1 H, J = 9.0 Hz, H-4), 2.54 (d,
1 H, J = 3.3 Hz, OH).
13C NMR (75 MHz, CDCl3): = 160.29 (1 C, Carom–OCH3), 134.20,
132.59, 131.78, 131.57, 129.34, 128.93, 128.07, 127.62, 123.81,
123.34, 113.72 (17 C, C and CH arom), 101.86 (1 C, Cacetal), 84.25
(1 C, C-1), 81.81, 70.27, 69.68, 68.51, 55.49, 55.28 (6 C, C-
2,3,4,5,6, OCH3).
IR (film): 3479, 1776, 1711, 1613, 1514, 1387, 1249, 1109, 1087,
1034, 838, 754, 720 cm–1.
ESI-MS: m/z = 520 (M + H).
1H NMR (300 MHz, CDCl3): = 7.69–7.82 (m, 4 H, ArH), 7.18–
7.31 (m, 7 H, ArH), 6.84 (d, 2 H, J = 8.54 Hz, ArH), 5.61 (d, 1 H,
J = 10.5 Hz, H1), 4.74 (d, 1 H, J = 11.3 Hz, benzyl-H), 4.55 (d, 1 H,
J = 11.4 Hz, benzyl-H), 4.45 (t, 1 H, J = 9.5 Hz, H-3), 4.21 (t, 1 H,
J = 10.2 Hz, H-2), 3.80–3.86 (m, 1 H, H-6a), 3.75 (s, 3 H, OCH3),
3.59–3.67 (m, 1 H, H-5), 3.50–3.58 (m, 1 H, H-6e), 3.46 (t, 1 H,
Anal. Calcd for C28H25NO7S: C, 64.73; H, 4.85; N, 2.70. Found: C,
64.68; H, 4.88; N, 2.64.
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J. M. Hernández-Torres et al.
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J = 9.6 Hz, H-4), 1.89 (t, 1 H, J = 6.8 Hz, OH), 0.69 [s, 9 H,
C(CH3)3], –0.05 (s, 3 H, SiCH3), –0.47 (s, 3 H, SiCH3).
Acknowledgements
This work was supported by the American Chemical Society Petro-
leum Research Foundation (33341-G4, 36069-AC1), the American
Heart Association Midwest Affiliates (30399Z), the American
Cancer Society (IRG-58-006-41), and the Purdue Research Found-
ation and Sloan Foundation in the form of fellowships to J. A. and
J. M. H.-T.
13C NMR (75 MHz, CDCl3): = 159.11 (1 C, Carom–OCH3), 134.24,
132.20, 132.12, 130.08, 128.92, 128.90, 127.83, 123.54, 113.76 (17
C, C and CH arom), 83.39 (1 C, C-1), 79.61, 79.37, 74.46, 73.30,
62.01, 56.74, 55.21 (7 C, C-2,3,4,5,6, OCH3, C benzyl), 25.63 [3 C,
C(CH3)3], 17.60 [1 C, C(CH3)3], –4.11 (1 C, SiCH3), –4.68 (1 C,
SiCH3).
ESI–MS: m/z = 658 (M + Na).
References
Anal. Calcd for C34H41NO7SSi: C, 64.22; H, 6.50; N, 2.20. Found:
C, 64.36; H, 6.52; N, 2.18.
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noside (7)
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Compound 6 (89.6 mg, 0.14 mmol) was dissolved in anhyd CH2Cl2
(1.5 mL) in an oven-dried 5 mL pear-shape flask. 4-Dimethylami-
nopyridine (DMAP, 171 mg, 1.4 mmol) and Et3N (0.18 mL, 1.8
mmol) were added and the reaction mixture was cooled to 0 °C with
stirring under argon. Allyl chloroformate (0.22 mL, 2.1 mmol) was
added and the mixture was warmed to r.t. and stirred for 3 h. The
mixture was quenched with a sat. aq solution of NaHCO3 (4 mL)
and diluted with CH2Cl2 (1 mL). The aqueous phase was extracted
with additional CH2Cl2 (2 2 mL). The combined organic phases
were then washed with brine (4 mL), dried (Na2SO4), and concen-
trated by rotary evaporation. The product was purified by silica gel
chromatography using a 20–40% EtOAc–hexanes gradient to afford
the desired compound 7 as a yellow oil (87.8 mg, 87%); [ ]D +53.5
(c = 0.99, CHCl3).
(7) Baker, B. R.; Joseph, J. P.; Schaub, R. E.; Williams, J. H. J.
Org. Chem. 1954, 19, 1786.
(8) Lemieux, R. U.; Takeda, T.; Chung, B. Y. In ACS
Symposium Series, Vol. 39; El Khadem, H. S., Ed.;
American Chemical Society: Washington, 1975, 90–115.
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IR (film): 1750, 1715, 1613, 1514, 1387, 1250, 1090, 961, 839, 721
cm–1.
1H NMR (300 MHz, CDCl3): = 7.75–7.90 (m, 4 H, ArH), 7.21–
7.41 (m, 7 H, ArH), 6.93 (d, 2 H, J = 8.7 Hz, ArH), 5.92–6.05 (m, 1
H, H2C=CHCH2) 5.61 (d, 1 H, J = 10.5 Hz, H-1), 5.41 (dq, 1 H, J =
1.4, 17.1 Hz, HCH=CHCH2), 5.32 (dq, 1 H, J = 1.2, 10.4 Hz,
HCH=CHCH2), 4.84 (d, 1 H, J = 11.3 Hz, benzyl-H), 4.67 (d, 2 H,
J = 5.7 Hz, C=CHCH2O) 4.48–4.54 (m, 3 H, benzyl-H, H-3, H-6a),
4.28 (t, 1 H, J = 10.1 Hz, H-2), 4.21 (t, 1 H, J = 6.5 Hz, H-6e), 3.83
(s, 3 H, OCH3), 3.73–3.78 (m, 1 H, H-5), 3.54 (t, 1 H, J = 9.8 Hz,
H-4), 0.77 [s, 9 H, C(CH3)3], 0.02 (s, 3 H, SiCH3), –0.41 (s, 3 H,
SiCH3).
(11) El-Sokkary, R. I.; Silwanis, B. A.; Nashed, M. A.; Paulsen,
H. Carbohydr. Res. 1990, 203, 319.
(12) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov,
T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734.
(13) Wong and co-workers have reported that the corresponding
p-tolyl thioglycoside could be recrystallized straight
forwardly from EtOH.12
(14) (a) Hardinger, S. A.; Wijaya, N. Tetrahedron Lett. 1993, 34,
3821. (b) Ogilvie, K. K.; Hakimelahi, G. H. Carbohydr. Res.
1983, 115, 234.
13C NMR (75 MHz, CDCl3): = 159.22 (1 C, Carom–OCH3), 154.69
[1 C, O–C(O)–O], 134.22, 132.41, 132.19, 131.50, 129.75, 128.99,
128.76, 127.77, 123.27, 118.97, 113.83 (19 C, C and CH arom,
(15) Kihlberg, J. O.; Leigh, D. A.; Bundle, D. R. J. Org. Chem.
1990, 55, 2860.
(16) Jiang, L.; Chan, T.-H. Tetrahedron Lett. 1998, 39, 355.
(17) (a) Hayakawa, Y.; Kato, H.; Uchiyama, M.; Kajino, H.;
Noyori, R. J. Org. Chem. 1986, 51, 2400. (b) Allainmat,
M.; L’Haridon, P.; Toupet, L.; Plusquellec, D. Synthesis
1990, 27.
(18) Horton, D.; Hughes, J. B.; Jewell, J. S.; Philips, K. D.;
Turner, W. N. J. Org. Chem. 1967, 32, 1073.
(19) Jain, R. K.; Matta, K. L. Carbohydr. Res. 1992, 226, 91.
C
allylic), 83.38 (1 C, C-1), 79.47, 77.07, 74.72, 73.54, 68.58, 66.44,
56.46, 55.23 (8 C, C-2,3,4,5,6, OCH3, =CHCH2O, Cbenzyl), 29.66,
25.65 [3 C, C(CH3)3], 17.60 [1 C, C(CH3)3], –4.14 (1 C, SiCH3),
–4.58 (1 C, SiCH3). ESI–MS: m/z = 742 (M + Na).
Anal. Calcd for C38H45NO9SSi: C, 63.40; H, 6.30; N, 1.95. Found:
C, 63.72; H, 6.48; N, 1.87.
Synthesis 2002, No. 4, 487–490 ISSN 0039-7881 © Thieme Stuttgart · New York