Dde as a protecting group for carbohydrate synthesis

Article abstract of DOI:10.1080/07328300500388685

Oligosaccharide synthesis using aminosugars requires the presence of a suitable amino protecting group. A number of protecting groups are currently used, and while many display favorable properties, most agents available still suffer from certain disadvan

Full text of DOI:10.1080/07328300500388685

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Dde as a Protecting Group for Carbohydrate
Synthesis
Laurent Bornaghi a , Guyla Dekany a , Nicholas B. Drinnan a , Stephen Taylor
a , Istvan Toth a b & Michael L. West a
a Alchemia Pty Ltd, Upper Mt Gravatt, Queensland, Australia
b The Department of Pharmacy, University of Queensland, St Lucia,
Queensland, Australia
Published online: 21 Aug 2006.
To cite this article: Laurent Bornaghi , Guyla Dekany , Nicholas B. Drinnan , Stephen Taylor , Istvan Toth
& Michael L. West (2006) Dde as a Protecting Group for Carbohydrate Synthesis, Journal of Carbohydrate
Chemistry, 25:1, 1-18, DOI: 10.1080/07328300500388685
To link to this article: http://dx.doi.org/10.1080/07328300500388685
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Journal of Carbohydrate Chemistry, 25:1–18, 2006
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300500388685
Dde as a Protecting Group
for Carbohydrate Synthesis
Laurent Bornaghi, Guyla Dekany, Nicholas B. Drinnan,
and Stephen Taylor
Alchemia Pty Ltd, Upper Mt Gravatt, Queensland, Australia
Istvan Toth
Alchemia Pty Ltd, Upper Mt Gravatt, Queensland, Australia and The Department
of Pharmacy, University of Queensland, St Lucia, Queensland, Australia
Michael L. West
Alchemia Pty Ltd, Upper Mt Gravatt, Queensland, Australia
Oligosaccharide synthesis using aminosugars requires the presence of a suitable amino
protecting group. A number of protecting groups are currently used, and while many
display favorable properties, most agents available still suffer from certain disadvan-
tages. This report details the use of a hydrazine labile aminosugar protecting group,
N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl] (Dde), which can be introduced
and removed in a facile and cost-effective manner.
Keywords Carbohydrates, Vinylogous amides, Protecting group
INTRODUCTION
Aminosugars are important constituents of various glycoconjugates and
biologically relevant oligosaccharides.[1] Examples include peptidoglycans,
mucopolysaccharides, glycopeptides and proteins, oligosaccharides of human
milk, and blood group determinants. Aminosugars are also often encountered
in bacterial and tumor-associated carbohydrate antigens.[2]
There have been various methods reported for the formation of 2-deoxy
2-N-protected carbohydrate donors for the synthesis of 1,2-trans-glycosides.
Received March 9, 2005; accepted October 4, 2005.
Address correspondence to Michael L. West, Alchemia Pty Ltd, PO Box 6242, Upper Mt
Gravatt, Queensland, Australia 4122. E-mail: mwest@alchemia.com.au
1

L. Bornaghi et al.
2
2-Deoxyphthalimido donors were the most commonly used in 1980s.[3] More
recently, tetrachlorophthaloyl (TCP),[4] pentenoyl,[5] dithiasuccinoyl (Dts),[6]
allyloxycarbonyl (Alloc),[7,8] 2,2,2-trichloroethyloxycarbonyl (Troc),[9] N,N-
diacetyl,[10] 2,5-dimethylpyrrole,[11] and dimethylmaleoyl (DMM)[12] protection
has been used for 1,2-trans-glycosylation of aminosugars.
There has been to date an absence of suitable N-protecting groups for 1,2-
cis-glycosylation of aminosugars. The azide group has proven effective as a
masked nonparticipating amino functionality, thereby allowing the synthesis
of 1,2-cis-linked 2-amino-2-deoxy glycosides.[13] However, there are various
problems associated with the preparation of 2-azido-2-deoxy sugars.[14–19]
Other nonparticipating groups that have been reported include 2,4-dinitrophe-
nyl and p-methoxybenzylimino, both of which result in loss of the desired
product.[20]
In solid-phase peptide synthesis (SPPS), N-[1-(4,4-dimethyl-2,6-dioxocyclo-
hex-1-ylidene)ethyl] (Dde) has been used effectively as a lysine side chain
amino protecting group.[21] Further, a derivatized Dde group has demonstrated
efficacy as a linker for both solid-phase carbohydrate and peptide synthesis.[22]
With similar structural characteristics to Dde, the recently reported (1,3-
dimethyl-2,4,6(1H,3H,5H)-trioxopyrimidine-5-ylidene)methyl (DTPM) pro-
tecting group has displayed some nonparticipating characteristics.[23]
Herein, we report the investigations in our laboratory directed toward
determining the efficacy of the Dde group as an amino sugar protecting
group. Furthermore, a short study on the potential nonparticipating effect of
the Dde group for the synthesis of amino-sugar containing glycoconjugates
has been carried out.[24]
RESULTS AND DISCUSSION
Dde Protection of Aminosugars
Generally, Dde-type vinylogous amide protection of aminosugars can be
achieved in good yield by refluxing an unprotected aminosugar with the com-
mercially available 2-acetyldimedone in alcohol. If required, secondary and
tertiary bases can catalyse the reaction. Typically, glucosamine hydrochloride
was Dde protected by refluxing with 2-acetyldimedone in methanol to give
compound 1 (Sch. 1).
As mentioned, it was of interest to examine the stability of the Dde
protecting group to common carbohydrate chemistries, as well as the protect-
ing group’s influence on the outcome of various glycosylation reactions. To
this end several suitably protected Dde-containing donor sugars were syn-
thesized. Compound 1 was acetylated with acetic anhydride in pyridine to
give glucopyranose 2 as a crystalline solid in 86% yield. Peracetate 2 was

Dde as a Protecting Group
3
Scheme 1: Conditions: i. 2-Acetyldimedone/MeOH (78%).
treated with 45% HBr/AcOH at rt to give the solid glycosyl bromide 3 in good
yield. Bromosugar 3 was also found to be a stable crystalline solid at rt. Bromo-
sugar 3 was refluxed in acetone with thiourea to give the isothiouronium salt 4.
Under phase-transfer conditions uronium salt 4 was treated with Na2S2O5
followed by reaction with methyl iodide (MeI) in methanol to give thiomethyl
glycoside 5. In an alternative sequence, peracetate 2 was converted with piper-
idine to hemiacetal 6. Subsequent treatment of hemiacetal 6 with trichloroace-
tonitrile in the presence of 1,8-diazabicyclo(5.4.0)-undec-7-ene (DBU) gave the
trichloroacetimidate 7 in an a/b ratio of 12/1 (Sch. 2).
The stability of the Dde group to other common protecting group manipula-
tions was also examined (Sch. 3). Under Zemplen conditions, thioglycoside 5
was converted to triol 8 in good yield. Experience in our laboratories has
shown that the Dde group shows far greater stability to Zemplen conditions
than, for example, the phthalimido group. Treatment of 8 with a,a-dimethoxy-
toluene (a,a-DMT) and catalytic p-toluenesulphonic acid (p-TsOH) in aceto-
nitrile provided benzylidene protected 9, which was further derivatized by
reaction with biphenylcarbonylchloride to give the fully protected derivative
10. The benzylidene ring of derivative 10 was then cleaved with p-TsOH in
MeCN/MeOH to give diol 11. Triol 8 was also treated with t-butyldiphenylsi-
lylchloride in the presence of imidazole to give diol 12. Similarly, triol 8 was
treated with trityl chloride in pyridine to give compound 13. Triol 8 was then
regenerated from compounds 12 and 13 by treatment with tetrabutylammo-
niumfluoride and p-TsOH, respectively.
Glycosylation Studies with Dde Protected Aminosugars
Introductory glycosylation studies were carried out with the previously
formed Dde-protected donor sugars: peracetate 2, bromosugar 3, thioglycoside 5,

L. Bornaghi et al.
4
Scheme 2: Conditions: i. Ac2O/Py; ii. HBr/AcOH, DCM; iii. Thiourea, Acetone; iv. Na2S2O5, 1,2-
DCE; v. K2CO3, Acetone/Water, MeI; vi. Piperidine, DMF; vii. Trichloroacetonitrile, DBU.
and trichloroacetimidate 7 and 3 acceptors (methanol, 4-phenylbenzylalcohol,
and 1,2-3,4-di-O-isopropylidene-a-D-galactopyranose). Surprisingly, sugars 2
and 5 were unable to be activated using standard conditions and were recov-
ered after the coupling reaction (Sch. 4). Although a disappointing result,
this failure to activate thiomethyl glycosides does open up interesting opportu-
nities in armed/disarmed-type glycosylations, whereby the Dde group is
employed to effectively mask a thiomethylglycoside leaving group.
More successful glycosylations were carried out with the Dde-protected
bromosugar and trichloroacetimidate. Bromosugar 3 was reacted with 4-phe-
nylbenzylalcohol, methanol, and 1,2-3,4-di-O-isopropylidene-a-D-galactopyra-
nose employing silver triflate as a promoter. Similarly, trichloroacetimidate 7
was reacted with 4-phenylbenzylalcohol and 1,2-3,4-di-O-isopropylidene-a-D-
galactopyranose under borontrifluorideetherate activation (Sch. 5, results
provided in Table 1).
Results in Table 1 indicate that there is considerable nonparticipating
characteristics to both Dde donor sugars 3 and 7.

Dde as a Protecting Group
5
Scheme 3: Conditions: i. NaOMe/MeOH; ii. a,a-DMT, MeCN, p-TsOH; iii.
Biphenylcarbonylchloride, DMAP, 1,2-DCE; iv. MeCN/MeOH, p-TsOH; v. TBDPS-Cl, Imidazole,
1,2-DCE; vi. TBAF, THF; vii. Trityl chloride, Pyridine; viii. p-TsOH, MeCN, MeOH.
So far only methanol, di-O-isopropylidene-D-galactose, and a benzylic
alcohol have been successfully employed as glycosylation acceptors. Some
less reactive acceptors such as compound 9 were trialed without success.
Experiments with less reactive acceptors were typically low yielding (ꢀ15%)
with an a/b ratio favoring 1,2-trans-glycoside formation.
Deprotection of Dde-Protected Aminosugars
The Dde group is labile to ammonia, hydrazine, and primary amines (etha-
nolamine, ethylenediamine, n-butylamine, hydroxylamine, etc.) at rt. The Dde
group also exhibits some lability toward aqueous hydroxides and under some
conditions is susceptible to alkylation. Unwanted alkylation of the Dde group
was shown to deactivate it to the conditions required for cleavage. The

L. Bornaghi et al.
6
Scheme 4: Conditions: [a] (i) SnCl4 or (ii) TMSOTf and primary or secondary alcohol acceptor,
[b] (i) DMTST or (ii) DMTSB or (iii) MeOTf and primary or secondary alcohol acceptor.
Scheme 5: Glycosylation reactions.

Dde as a Protecting Group
Table 1: Results of glycosylations with Dde protected aminosugar donors.
7
Entry
Donors
Acceptors
Methanol
4-Phenylbenzylalcohol
1,2-3,4-di-O-
Products
Yields
a/b Ratio
1
2
3
3
3
3
14a/b
15a/b
16a/b
81
72
86
13 : 1
7 : 10
1 : 1.75
Isopropylidene-a-D-
galactopyranose
4-Phenylbenzylalcohol
1,2-3,4-Di-O-
4
5
7
7
15a/b
16a/b
74
48
2 : 3
1 : 2
isopropylidene-a-D-
galactopyranose
following scheme (Sch. 6) provides an example of Dde cleavage by treatment
with ammonia/methanol solution, resulting in amines 17 and 18 in high yield.
CONCLUSION
The results of our investigations have shown that the Dde-protecting group is
stable to a wide range of carbohydrate chemistries. The excellent crystalline
characteristics that the Dde group imparts to carbohydrate building blocks
and the ease of its introduction and cleavage make it an ideal protecting
group for the facile synthesis of monosaccharide donor sugars and derivatives.
At this stage the capabilities of Dde as a nonparticipating group for the syn-
thesis of 1,2-cis-glycosidic linkages have not been comprehensively explored;
however, initial results indicate that in most cases the 1,2-trans-glycoside i.e.
Scheme 6: Conditions: i. MeOH/NaOMe; ii. NH3/MeOH.

L. Bornaghi et al.
8
the beta anomer formed preferentially. The complete deactivation of thioglyco-
side donor sugars by Dde was unexpected but may prove to be useful in the
coupling of complex oligosaccharides to aglycons and supports. Similarly,
such deactivation may prove useful in the synthesis of repeating oligosacchar-
ide motifs. So far the Dde group has proven to be a valuable tool in carbo-
hydrate synthesis.
EXPERIMENTAL
General Methods
Purification was achieved by flash chromatography on silica gel (0.0404-
0.063 mm, Amicon), using mobile phases as stated. Reaction progress was mon-
itored by thin layer chromatography (TLC) on Kiesegel 60 F254 (Merck) using
mobile phases as stated with detection by UV light and/or charring with 5%
sulfuric acid. Solvents were evaporated under reduced pressure with a rotary
evaporator. 1H NMR and COSY spectra were obtained with a Bruker AM
500 instrument operating at a field of 500 MHz, a Brucker ARX 500 MHz, or
a Varian Mercury 400 broadband spectrometer (internal standard Me4Si,
d ¼ 0.00). Chemical shifts are reported in ppm (d) referenced from solvent.
Mass spectra were run with a VG analytical ZAB-SE instrument using fast
atom bombardment (FAB) techniques 220 kV Csþ ion bombardment, with
2 mL of appropriate matrix, either 3-nitrobenzyl alcohol or thioglycerol with
NaI (MeOH) solution, added when necessary to produce natriated species
when no protonated molecular ions were observed, or on a PE SCIEX API
3000 MS SHIMADZU SLC/LC-10A HPLC gradient system.
2-Deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-
ylidene)ethyl]-D-glucopyranose (1)
To a mixture of sodium (143 mg, 6.21 mmol) completely dissolved in anhy-
drous methanol (30 mL), was added D-glucosamine hydrochloride (1.34 g,
6.21 mmol). The reaction mixture was stirred at rt for 5 min. 2-Acetyldimedone
(1.69 g, 9.32 mmol) was added, and the reaction mixture was refluxed for 5 h.
The reaction mixture was cooled and the product was precipitated by the
addition of ether (200 mL) and collected by filtration to yield 1 as single
anomer (1.66 g, 78%). Rf 0.37 (MeCN/H2O 10:0.5); 1H NMR (D2O) d 5.12
(d, 1H, J1,2 3.6 Hz, H-1), 3.60 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b), 2.38,
2.36 (2s, 3H, CH3), 2.28, 2.27 (2s, 4H, 2 CH2), 0.85 (s, 6H, 2 CH3). HRMS
(TOF) Calcd for C16H25NO17: 343.1631. Found: 344.1676 [M þ H]þ.

Dde as a Protecting Group
9
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-a-D-glucopyranose (2)
A mixture of 1 (1.55 g, 4.51 mmol), pyridine (11 mL), and acetic anhydride
(20 mL) was stirred at rt overnight. The reaction mixture was evaporated,
and the product crystallized from MeOH (10 mL,–158C) to afford 2 (1.95 g,
1
86%). Rf 0.35 (Hexane/EtOAc 1 : 1); H NMR (CDCl3) d 13.70 (d, 1H, NH),
6.22 (d, 1H, J1,2 3.8 Hz, H-1), 5.44 (t, 1H, J3,4 9.9 Hz, H-3), 5.19 (t, 1H, J4,5
10.0 Hz, H-4), 4.39 (dd, 1H, J6a,6b 12.2 Hz, H-6b), 4.25 (m, 1H, J5,6a 1.2 Hz,
J5,6b 3.9 Hz, H-5), 4.13 (dd, 1H, J2,3 9.8 Hz, H-2), 4.06 (dd, 1H, J6a,6b 12.2 Hz,
H-6a), 2.58 (s, 3H, CH3–C(NH–)55C,), 2.35 (s, 4H, 2 CH2), 2.09, 2.03, 1.97
(3s, 9H, 3 CH3 acetyl), 1.00 (s, 6H, 2 CH3); HRMS (TOF) Calcd for
C24H33NO11: 511.2054. Found: 512.2145 [M þ H]þ.
3,4,6-Tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-a-D-glucopyranosyl
bromide (3)
A mixture of 2 (2 g, 3.9 mmol) in DCM (5 mL) and HBr in acetic acid (45%)
(5.0 mL) was stirred at rt for 1 h. The reaction mixture was diluted with cold
CH2Cl2 (50 mL), and washed with cold H2O (50 mL), cold saturated NaHCO3
solution (50 mL), and cold H2O (50 mL). The organic phase was dried over
MgSO4 and evaporated to afford 3 (1.88 g, 91%); Rf 0.35 (hexane/EtOAc 1 : 1);
1H NMR (CDCl3) d 13.83 (d, 1H, NH), 6.45 (d, 1H, J1,2 3.7 Hz, H-1), 5.55
(t, 1H, J3,4 9.7 Hz, H-3), 5.23 (t, 1H, J4,5 9.9 Hz, H-4), 4.41 (m, 2H, H-6b, H-2),
4.26 (m, 1H, J5,6a 1.3 Hz, J5,6b 4.0 Hz, H-5), 4.14 (dd, 1H, J6a,6b 11.9 Hz,
H-6b), 4.09 (dd, 1H, H-6a), 2.62 (s, 3H, CH3–C(NH–)55C,), 2.41 (s, 4H,
2 ꢀ CH2), 2.11, 2.04, 1.96 (3s, 9H, 3 CH3 acetyl), 1.02 (s, 6H, 2 ꢀ CH3);
HRMS (TOF) Calcd for C22H29BrNO9: 531.3767. Found: 532.1146 [M þ H]þ.
Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-1-thio-b-D-
glucopyranoside (5)
Thiourea (280 mg, 3.37 mmol) was added to a solution of 3 (2.05 g,
3.85 mmol) in acetone (10 mL). The mixture was refluxed for 30 min and then
concentrated. The residue was purified by column chromatography (CHCl3/
MeOH, 5:1) yielding S-[3,4,6-tri-O-acetyl-2-Deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-b-D-glucopyranosyl]-isothiouronium bromide 4
(1.72 g, 85%); Rf 0.46 (CHCl3/MeOH 5:1). To 4 (1.7 g, 3.25 mmol) was added a
solution of Na2S2O5 (538 mg, 0.225 mmol) in water (0.2 mL) and 1,2-dichlor-
oethane (0.24 mL). The reaction mixture was kept under reflux at 858C for
20 min. After dilution with CH2Cl2 (5 mL) the layers were separated. The

L. Bornaghi et al.
10
organic phase was washed with water (3 mL), dried over MgSO4, concentrated
under reduced pressure, and purified by column chromatography (ether/
MeOH 10 : 1) to yield the thioglycoside precursor to 5 (1.41 g, 87%). Then to a
solution of the thioglycoside (1.17 mg, 2.4 mmol) in acetone (2.5 mL) was
added K2CO3 (400 mg) in water (2.5 mL), followed by methyliodide (370 mg,
2.6 mmol). After 2 h the reaction mixture was concentrated under reduced
pressure and dissolved in CH2Cl2 (50 mL) and the layers were separated.
The organic phase was washed twice with water (50 mL), dried over MgSO4,
and evaporated. The residue was purified by chromatography (EtOAc/pet-
roleum ether 2 : 1) to yield 5 (947 mg, 58%); Rf 0.44 (EtOAc/petroleum ether
1
2 : 1); H NMR (CDCl3) d 13.96 (d, 1H, NH), 5.24 (t, 1H, J3,4 9.4 Hz, H-3), 5.09
(t, 1H, J4,5 9.8 Hz, H-4), 4.64 (d, 1H, J1,2 10.0 Hz, H-1), 4.30 (dd, 1H, J1,2
9.8 Hz, H-2), 4.01 (m, 3H, H-6a, H-6b, H-5), 2.60 (s, 3H, CH3–C(NH–)55C,),
2.42 (s, 4H, 2 CH2), 2.20 (s, 3H, SCH3), 2.09, 2.02, 1.96 (3s, 9H, 3 AcO), 1.03
(s, 6H, 2 CH3). HRMS (TOF) Calcd for C23H33NO9S: 499.1876. Found:
500.1917 [M þ H]þ.
3,4,6-Tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-a-D-glucopyranose (6)
To a solution of 2 (0.5 g 0.98 mmol) in dry DMF (10 mL), piperidine
(0.13 mL) was added. The reaction mixture was stirred at rt overnight, then
concentrated under vacuum. The crude mixture was purified by chromato-
graphy (EtOAc/petroleum ether 2 : 1) to yield 6 (340 mg, 74%); Rf 0.44
1
(CHCl3/EtOAc 1 : 1); H NMR (CDCl3) d 13.81 (d, 1H, NH), 5.49 (t, 1H, J3,4
9.6 Hz, H-3), 5.28 (d, 1H, J1,2 3.3 Hz, H-1), 5.11 (t, 1H, J4,5 9.9 Hz, H-4),
4.42 (dd, 1H, J2,3 9.7 Hz, H-2), 4.39 (dd, 1H, J6a,6b 12.2 Hz, H-6b), 4.33 (dd,
1H, H-6a), 4.25 (m, 1H, J5,6a 1.2 Hz, J5,6b 3.9 Hz, H-5), 2.59 (s, 3H, CH3–
C(NH–)55C,), 2.37 (s, 4H, 2 CH2), 2.10, 2.03, 1.96 (3s, 9H, 3 CH3 acetyl),
1.01 (s, 6H, 2 CH3). HRMS (TOF) Calcd for C22H31NO10: 469.1948. Found:
470.1984 [M þ H]þ.
2-Deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-
ylidene)ethyl]-3,4,6-tri-O-acetyl-a,b-D-glucopyranosyl
trichloroacetimidate (7)
A mixture of 6 (1.7 g, 3.62 mmol) and trichloroacetonitrile (2.2 mL,
21.74 mmol) in CH2Cl2 (12 mL) was cooled to 08C and 1,8-diazabicyclo(5.4.0)-
undec-7-ene (108 mL, 0.72 mmol) added. The reaction mixture was stirred at
08C for 1.5 h and at rt for 2 h. The solution was evaporated, and the residue
purified by column chromatography yielding 7 (880 mg, 40%, a : b, 12 : 1);
Rf 0.61 (CHCl3/EtOAc 1 : 1); 1H NMR (CDCl3) d 13.74 (d, 1H, NH), 8.85,
(s, 1H, NH), 6.48 (d, 1H, J1,2 3.5 Hz, H-1), 5.55 (t, 1H, J3,4 10.0 Hz, H-3), 5.24

Dde as a Protecting Group
11
(t, 1H, J4,5 10.0 Hz, H-4), 4.26 (m, 4H, H-2, H-6a, H-6b, H-5), 2.67 (s, 3H, CH3–
C(NH–)55C,), 2.36 (s, 4H, 2 CH2), 2.11, 2.08, 2.00 (3s, 9H, 3 CH3 acetyl), 1.02,
1.04 (2 ꢀ s, 6H, 2 ꢀ CH3). HRMS (TOF) Calcd for C24H31Cl3N2O10: 613.8816.
Found: 614.8947 [M þ H]þ.
Methyl 2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-
ylidene)ethyl]-1-thio-b-D-glucopyranoside (8)
Sodium (10 mg, 0.44 mmoL) was reacted with anhydrous MeOH (25 mL),
and then to the solution was added compound 5 (720 mg, 1.44 mmoL). The
reaction mixture was stirred at rt overnight and then neutralized to pH 7
using Amberlite resin IR 120 (Hþ). The resin was filtered out and the residue
was concentrated under vacuum to yield compound 8 as a white powder
(496 mg, 92%). Rf 0.1 (EtOAc/petroleum ethers 4 : 1); 1H NMR (CDCl3) d
13.64 (d, 1H, NH), 4.68 (d, 1H, J1,2 9.8 Hz, H-1), 3.85 (t, 1H, J2,3 8.9 Hz, H-2),
3.79 (dd, 1H, J5,6a 1.3 Hz, J6a,6b 11.4, Hz, H-6a), 3.62 (dd, 1H, J5,6b 3.8 Hz
H-6b), 3.59 (t, 1H, J3,4 9.7 Hz, H-3), 3.41 (m, 2H, H-4, H-5), 2.41 (s, 1H,
SCH3), 2.31 (s, 4H, 2 CH2), 2.07 (s, 3H, CH3–C(NH–)55C,), 0.88 (2 ꢀ s, 6H,
2 ꢀ CH3). HRMS (TOF) Calcd for C17H27NO6S: 373.1559. Found: 374.1602
[M þ H]þ; [a]D—193.218C (c ¼ 1.00, MeOH).
Methyl 4,6-O-benzylidene-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-1-thio-b-D-
glucopyranoside (9)
Compound 8 (1 g, 2.68 mmol) and p-TsOH (10 mg, 52.6 mmol) were dis-
solved in dry acetonitrile (10 mL) and heated to 608C. After equilibrium was
reached a,a-dimethoxytoluene (600 mg, 4.02 mmol) was added to the reaction
flask. The reaction was stirred at 608C for 12 h after which additional
p-TsOH (10 mg, 52.6 mmol) and a,a-dimethoxytoluene (200 mg, 1.34 mmol)
were added to the reaction mixture. After a further 6 h the reaction mixture
was neutralized with triethylamine (250 mL) and the solvent removed in
vacuo. The reaction mixture was taken up in EtOAc (100 mL) and washed
with saturated NaHCO3 solution (3 ꢀ 100 mL). The organic layer was dried
over Na2SO4 and the solvent removed in vacuo. The residue was purified by
column chromatography (EtOAc/Petroleum ether 1:1) to afford compound 9
1
(900 mg, 81%); Rf 0.55 (EtOAc/Petroleum ether 2:1), HNMR d 13.78 (d, 1H,
NH), 5.59 (s, 1-H, Ar-CH), 4.58 (d, 1H, J1,2 9.6 Hz, H-1), 4.42 (dd, 1H, J4,5
10.5 Hz, H-4), 3.92 (m, 2H, H-6a, H-6b), 3.81 (t, 1H, J3,4 10.2 Hz, H-3), 3.64
(t, 1H, J2,3 9.0 Hz, H-2), 3.60 (m, 1H, J5,6a 1.4 Hz, J5,6b 3.6 Hz, H-5), 2.67
(s, 3H, CH3–C(NH–)55C,), 2.38 (s, 3H, 2 ꢀ CH2), 2.23 (s, 3H, S-CH3), 1.05
(s, 6H, 2 ꢀ CH3). HRMS (TOF) Calcd for C24H31NO6S: 461.1872. Found:
462.1895 [M þ H] þ; [a]D–177.958C (c ¼ 1.00, MeOH).

L. Bornaghi et al.
12
Methyl 4,6-O-benzylidene-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-3-O-(4-phenylbenzoyl)-
1-thio-b-D-glucopyranoside (10)
A
solution of biphenylcarbonylchloride (667 mg, 3.1 mmol) and
4-dimethylaminopyridine (378 mg, 3.1 mmol) in dry 1,2-DCE (5 mL) was
stirred at rt for 10 min. Compound 9 (1.3 g, 2.8 mmol) was added portion-
wise. The mixture was stirred at rt for 40 min and then cooled in a water
and ice bath. The resultant suspension was filtered, the filtrate and
diluted with DCM (25 mL) and washed with saturated KHSO4 solution
(200 mL) and water (200 mL). The organic phase was dried over MgSO4
and the solvent removed in vacuo. The residue was crystallized from
dichloromethane, diethylether to give 10 (1.5 g, 84%), Rf 0.60 (EtOAc/
petroleum ether 1 : 1), 1H NMR d 13.84 (d, 1H, NH), 8.27 (m, 2H, Ar-BP),
7.63 (m, 5H, Ar-BP), 7.47 (m, 2H, Ar-BP), 7.41 (m, 2H, Ar), 7.33 (m, 3H,
Ar), 5.66 (t, 1H, J3,4 9.6 Hz, H-3), 5.57 (s, 1H, benzylidene), 4.76 (d, 1H,
J1,2 9.9 Hz, H-1), 4.48 (dd, 1H, J4,5 9.5 Hz, H-4), 4.20 (dd, 1H, J2,3 9.8 Hz,
H-2), 3.91 (2 ꢀ t, 2H, H-6a, H-6b), 3.76 (m, 1H, H-5), 2.60 (s, 3H, CH3–
C(NH–)55C,), 2.38 (s, 3H, 2 ꢀ CH2), 2.28 (s, 3H, S–CH3), 1.03, 0.96
(2 ꢀ s, 4H, 2 ꢀ CH2). HRMS (TOF) Calcd for C37H39NO7S: 641.2512.
Found: 642.2525 [M þ H]þ; [a]D –139.878C (c ¼ 1.04, MeOH).
Methyl 2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-
ylidene)ethyl]-3-O-(4-phenylbenzoyl)-1-thio-b-D-
glucopyranoside (11)
A mixture of 10 (1 g, 1.56 mmol) in acetonitrile/methanol (24 mL, 1/1)
with a catalytic amount of p-TsOH (5 mg) was stirred at 1008C for 24 h.
The reaction mixture was cooled to rt, and concentrated in vacuo and any
trace solvents removed by coevaporation with toluene (25 mL). The
residue was taken up with DCM (25 mL) and washed two times with satu-
rated NaHCO3 solution (250 mL) and saturated brine solution (250 mL). The
organic phase was dried over MgSO4 and the solvent removed in vacuo to
give a white solid 11, (810 mg, 94%), Rf 0.09 (EtOAc/petroleum ether
3 : 1), 1H–NMR d 13.91 (d, 1H, NH), 8.02 (m, 2H, Ar), 7.63 (m, 5H, Ar),
7.49 (m, 2H, Ar), 5.38 (t, 1H, J3,4 9.5 Hz, H-3), 4.75 (d, 1H, J1,2 9.9 Hz,
H-1), 4.12 (dd, 1H, J4,5 9.3 Hz, H-4), 4.05 (dd, 1H, J6a,6b 9.7 Hz, H-6a),
4.97 (m, 2H, H-2, H-6b), 3.66 (m, 1H, J5,6a 1.3 Hz, J5,6b 2.9 Hz H-5), 2.64
(s, 3H, CH3–C(NH–)55C,), 2.35 (s, 3H, 2 ꢀ CH2), 2.27 (s, 3H, S–CH3),
1.01, 0.91 (2 ꢀ s, 4H, 2 ꢀ .CH2). HRMS (TOF) Calcd for C30H35NO7S:
553.2206. Found: 554.2182 [M þ H]þ.

Dde as a Protecting Group
13
Methyl 6-tert-butyldiphenylsilyl-2-deoxy-2-N-[1-(4,4-
dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-1-thio-b-D-
glucopyranoside (12)
To a solution of compound 8 (1 g, 2.7 mmol) in 1,2-DCE (12 mL) was added
TBDPSCl (411 mg, 1.5 mmol) and DMAP (183 mg, 1.5 mmol). The reaction
mixture was stirred at 808C for 24 h and then cooled in a water and ice bath.
The resultant suspension was filtered and the filtrate diluted with DCM
(25 mL) and washed twice with saturated KHSO4 solution (20 mL) and water
(20 mL). The organic phase was dried over MgSO4 and the solvent removed
in vacuo. The residue was purified by column chromatography (EtOAc/
petroleum ether 3 : 1) to afford compound 12 (1.11 mg, 68%). Rf 0.62 (EtOAc/
1
Toluene 3 : 1), H-NMR d 13.88 (d, 1H, NH), 7.70 (m, 4H, Ar), 7.43 (m, 6H,
Ar), 4.45 (d, 1H, J1,2 9.6 Hz, H-1), 3.95 (m, 2H, H-6b, H-6b), 3.77 (dd, 1H, J2,3
9.5 Hz, H-2), 3.76 (t, 1H, J4,5 9.8 Hz, H-4), 3.66 (t, 1H, J3,4 9.5 Hz, H-3), 3.48
(m, 1H, H-5), 2.62 (s, 3H, CH3–C(NH–)55C,), 2.21 (s, 3H, S–CH3), 1.07
(s, 9H, C–(CH3)3), 1.03 (s, 4H, 2 ꢀ .CH2), 0.03 (s, 6H, 2 ꢀ CH3). HRMS
(TOF) Calcd for C33H45NO6Ssi: 611.2835. Found: 612.2815 [M þ H]þ; [a]D–
94.238C (c ¼ 1.00, MeOH).
Methyl 2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-
ylidene)ethyl]-6-O-trityl-1-thio-b-D-glucopyranoside
(13)
Compound 8 (250 mg, 0.669 mmol) was dissolved in anhydrous pyridine
(10 mL) and stirred with trityl chloride (560 mg, 2 mmol) at 508C for 48
hours. The solvent was evaporated and trace amounts of pyridine
removed by coevaporation with toluene (20 mL). The crude product was
dissolved in CHCl3 (50 mL) and washed with H2O (50 mL), 10% citric acid
solution (50 mL), saturated NaHCO3 solution (50 mL) and saturated
brine solution (50 mL). The aqueous washings were back extracted with
CHCl3 (50 mL) and the organic layers combined, dried over MgSO4,
filtered, and evaporated to dryness. The residue was chromatographed
(EtOAc/toluene 3:1) to yield the desired product 13 (270 mg, 65%). Rf 0.25
(EtOAc/toluene 3 : 1), 1H-NMR d 13.68 (d, 1H, NH), 7.38 (m, 4H, Ar),
7.19 (m, 1H, Ar), 4.32 (d, 1H, J1,2 9.6 Hz, H-1), 3.74 (dd, 1H, J2,3 9.8 Hz,
H-2), 3.56 (m, 2H, H-3, H-4), 4.38 (m, 3H, H-5, H-6a, H-6b), 2.56 (s, 3H,
CH3–C(NH–)55C,), 2.28 (s, 3H, 2 ꢀ CH2), 2.12 (s, 3H, S-CH3), 1.50
(s, 9H, C–(CH3)3), 0.97 (s, 4H, 2 ꢀ .CH2). HRMS (TOF) Calcd for
C33H45NO6SSi: 611.2835. Found: 612.2815 [M þ H]þ; [a]D–153,698C
(c ¼ 1.01, MeOH).

L. Bornaghi et al.
14
Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-a,b-D-glucopyranoside
(14a, 14b)
To a solution of 3 (60 mg, 0.11 mmol) in dichloromethane (5 mL–158C), was
added silver trifluoromethanesulphonate (43 mg, 0.16 mmol) in MeOH (1 mL).
The reaction mixture was stirred overnight and filtered and the filtrate evap-
orated. The residue was washed with saturated NaHCO3 solution, dried over
MgSO4, and evaporated. The residue was purified by chromatography to
yield methyl 3,4,6-tri-O-acetyl- 2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclo-
hex-1-ylidene)ethyl]-a-D-glucopyranoside 14a (40 mg, 75%); Rf 0.35 (hexane/
1
EtOAc, 1 : 1); H NMR (CDCl3) d 13.55 (d, 1H, NH), 5.40 (t, 1H, J3,4 9.7 Hz,
H-3), 5.08 (t, 1H, J4,5 9.7 Hz, H-4), 4.82 (d, 1H, J1,2 3.4 Hz, H-1), 4.32 (dd, 1H,
J2,3 9.4 Hz, H-2), 4.12 (m, 3H, H-5, H-6a, H-6b), 3.53 (s, 3H, OCH3), 2.58
(s, 3H, CH3–C(NH–)55C,), 2.41 (s, 4H, 2 CH2), 2.11, 2.02, 1.94 (3s, 9H,
3 ꢀ CH3 acetyl), 1.02 (s, 6H, 2 ꢀ CH3), and methyl 3,4,6-tri-O-acetyl-2-deoxy-
2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-b-D-glucopyranoside
1
14b (3 mg, 6%); Rf 0.33 (Hexane/EtOAc 1:1); H NMR (CDCl3) d 13.84 (d, 1H,
NH), 5.20 (t, 1H, J3,4 9.8 Hz, H-3), 5.09 (t, 1H, J4,5 9.9 Hz, H-4), 4.41 (d, 1H, J1,2
8.2 Hz, H-1), 4.32 (dd, 1H, J2,3 9.8 Hz, H-2), 4.09 (m, H, H-6a), 3.95 (m, 1H,
H-6b), 3.75 (m, 1H, H-5), 3.48 (s, 3H, OCH3), 2.57 (s, 3H, CH3), 2.37 (s, 4H, 2
CH2), 2.09, 2.03, 1.96 (3s, 9H, 3 CH3(O)–), 1.02 (s, 6H, 2 ꢀ CH3). HRMS
(TOF) Calcd for C23H33NO10: 483.2104. Found: 484.2145 [M þ H]þ.
4-Phenylbenzyl-3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-
dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-a/b-D-
glucopyranoside (15a, 15b)
From donor 3: Under an atmosphere of nitrogen compound 3 (200 mg,
˚
376 mmmol), 4-phenylbenzyl alcohol (66 mg, 358 mmol) and 4 A molecular sieves
(200 mg) were combined in anhydrous DCM (2mL). The reagents were stirred
at rt for 4 h and cooled to 08C, at which time silver triflate (138 mg, 537 mmol)
was added. The reaction mixture was allowed to return to rt and stirred for a
further 1.5 h. The reaction was neutralized by the addition of solid NaHCO3,
diluted with chloroform (50 mL), filtered through Celite, washed with saturated
NaHCO3 solution (2 ꢀ 50 mL) and saturated brine solution (50 mL), and dried
over MgSO4. The organic phase was evaporated and the resulting residue
purified by column chromatography (1,2-DCE/EtOAc 6 : 1) to yield 4-phenylben-
zyl
3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylide-
ne)ethyl]-a/b-D-glucopyranoside (15a, 15b) as a white solid (170 mg, 72%, (a:b,
7 : 10), Rf 0.35 (DCE-EtOAc 7-3). A small amount of each anomer could be
purified: 1H NMR (4-phenylbenzyl 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-
dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-a-D-glucopyranoside) 15a, (CDCl3)

Dde as a Protecting Group
15
d 13.72 (d, 1H, NH), 7.43 (m, 9H, Ar), 5.48 (t, 1H, J3,4 9.3 Hz, H-3), 5.12 (t, 1H, J4,5
9.6 Hz, H-4), 5.00 (d, 1H, J1,2 3.5 Hz, H-1), 4.80 (2 ꢀ d, 2H, CH2-Ar), 4.34
(dd, 1H, J6a,6b 9.9 Hz, H-6a), 4.14 (m, 3H, H-2, H-5, H-6b), 2.57 (s, 3H, CH3–
C(NH–)55C,), 2.19 (s, 4H, 2 ꢀ CH2), 2.14, 2.04, 1.97 (3 ꢀ s, 9H, 3 ꢀ CH3(CO)-),
1.06 (s, 6H, 2 ꢀ CH3); (4-phenylbenzyl 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-
dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-b-D-glucopyranoside) 15b, (CDCl3) d
13.85 (d, 1H, NH), 7.44 (m, 9H, Ar), 5.25 (t, 1H, J3,4 9.4 Hz, H-3), 5.15 (t, 1H,
J
4,5 9.6 Hz, H-4), 4.8 (2d, 2H, CH2-Ar), 4.62, (d, 1H, J1,2 8.3 Hz, H-1), 4.37, (dd,
1H, J6a,6b 12.3 Hz, H-6a), 4.21 (dd, 1H, H-6b), 4.06 (m, 1H, J2,3 9.8 Hz, H-2),
3.77 (m, 1H, J5,6a 2.1 Hz, J5,6b 4.5 Hz, H-5), 2.63 (s, 3H, CH3–C(NH–)55C,),
2.35 (s, 4H, 2 ꢀ CH2), 2.14, 2.05, 1.99, (3s, 9H, 3 ꢀ CH3(CO)), 1.05 (s, 6H,
2 ꢀ CH3). HRMS (TOF) Calcd for C35H41NO10: 635.2730. Found: 636.2796
[M þ H]þ.
From donor 7: Under an atmosphere of nitrogen compound 7 (100 mg,
˚
163 mmol), 4-phenylbenzyl alcohol (45 mg, 245 mmol) and 4 A molecular
sieves (150 mg) were combined in anhydrous DCM (1.5 mL). The reaction
mixture was stirred at rt for 1 h; the reaction mixture was then cooled to 08C
and TMSOTf (10 mL, 543 mmol) was added. The reaction mixture was
allowed to return to rt and stirred for a further 2 h. The reaction was
neutralized with triethylamine, diluted with chloroform (50 mL), filtered
through Celite, washed with saturated NaHCO3 solution (2 ꢀ 50 mL), and
dried over MgSO4. The organic phase was evaporated and the
resulting residue chromatographed (DCE/EtOAc 6:1) to yield 4-phenylbenzyl
3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-
ethyl]-a/b-D-glucopyranoside as a white solid (76 mg; 74% (a:b, 2:3); Rf 0.35
(DCE-EtOAc 7:3). HRMS (TOF) and 1H-NMR (CDCl3), see experiment 15
above.
3,4,6-Tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-
dioxocyclohex-1-ylidene)ethyl]-a/b-D-glucopyranosyl-
(1 ! 6)-1,2-3,4-di-O-isopropylidene galactopyranoside
(16a/16b)
From donor 3: Compound 3 (300 mg, 56.4 mmol), 1,2-3,4-di-O-isopropyli-
˚
dene galactopyranose (100 mg, 37.6 mmol), and 4 A molecular sieves (350 mg)
were combined under nitrogen in DCM (5 mL) and stirred at rt for 2 h. The
reaction was cooled in a dry ice/acetone bath silver triflate (193 mg,
75.2 mmol) was added, and the resulting mixture stirred for 1.5 h. NaHCO3
(s) was added and the mixture diluted with chloroform (50 mL), filtered
through Celite, washed with saturated NaHCO3 solution (2 ꢀ 50 mL) and satu-
rated brine solution (50 mL) and dried over MgSO4. The organic phase was
evaporated and the resulting residue chromatographed (DCE/EtOAc 7 : 3) to

L. Bornaghi et al.
16
yield 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)
ethyl]-a/b-D-glucopyranosyl-(1 ! 6)-1,2-3,4-di-O-isopropylidene-a-D-galacto-
pyranose (16a/16b) as a white solid (230 mg, 86%, a:b; 1:1.75), Rf 0.35 (DCE/
EtOAc 7 : 3). Only a small amount of pure anomer b could be purified: 1H NMR
(CDCl3) for 16b, d 13.85 (d, 1H, NH) 5.38 (d, 1H, J1,2 5.0 Hz, H-1) 5.26 (t, 1-H,
J3 ,4 9.8 Hz, H-30), 5.11 (t, 1H, J4 ,5 5.0 Hz, H-40), 4.55 (d, 1H, J
7.6, H-10),
0
0
0
0
0
0
1 ,2
4.55 (m, 1H, H-3), 4.36 (dd, 1H, J6a,6b 12.0 Hz, H-6a0), 4.26 (m, 1H, H-2), 4.12
(m, 2H, H-4, H-6b0), 4.02 (dd, 1H, J6a,6b 11.1 Hz, H-6a), 3.99 (m, 1H, H-20),
3.83 (m, 1H, H-5), 3.75 (m, 1H, H-50), 3.60 (dd, 1H, H-6b), 2.60 (s, 3H, CH3–
C(NH–)55C,) 2.40, 2.33 (2 ꢀ d, 4H, 2 ꢀ CH2), 2.11, 2.04, 1.98 (3 ꢀ s, 9H,
CH3(CO)–), 1.44, 1.42, 1.31, 1.28 (4 ꢀ s, 12H, 4 ꢀ CH3), 1.04, 1.01 (2 ꢀ s, 6H,
2 ꢀ CH3). HRMS (TOF) Calcd for C34H49NO15: 711.3102. Found: 712.3151
[M þ H]þ. Only 16b could be purified as a pure compound.
From donor 7: Under an atmosphere of nitrogen, compound 7 (185 mg,
302 mmol), 1,2-3,4-di-O-isopropylidene-a-D-galactopyranose (118 mg, 4.54 mmol),
˚
and 4 A molecular sieves (400 mg) were combined in DCM (5 mL) and stirred
at rt for 1 h. The reaction mixture was cooled to 08C, at which time TMSOTf
(20 mL, 110 mmol) was added. The resulting mixture was allowed to return to
ambient temperature and stirred for 2 h. Pyridine (2 mL) and acetic anhydride
(1 mL) were added and the reaction mixture stirred for a further 30 min. The
solvent was removed in vacuo and the resulting residue azeotropically dried
with toluene (2 ꢀ 30 mL). The residue was then taken up in chloroform
(50 mL), filtered through Celite, washed with saturated NaHCO3 solution
(2 ꢀ 50 mL), and dried over MgSO4. The organic phase was evaporated
and the resulting residue was purified by column chromatography (DCE/
EtOAc 7 : 3) to yield 3,4,6-tri-O-acetyl-2-deoxy-2-N-[1-(4,4-dimethyl-2,6-dioxo-
cyclohex-1-ylidene)ethyl]-a/b-D-glucopyranosyl-(1 ! 6)-1,2-3,4-di-O-isopropy-
lidene galactopyranoside (16a, 16b) as a white film (104 mg, 48% (a/b; 1:2); Rf
1
0.35 (DCE/EtOAc 7:3). For H-NMR and HRMS (TOF), see above.
Methyl 2-amino-2-deoxy-1-thio-b-D-glucopyranoside (17)
A mixture of compound 5 (12.03 g, 24.1 mmol) and NaOMe (100 mg,
1.85 mmol) in dry methanol (100 mL) was stirred at rt overnight. The reaction
mixture was neutralized with Amberlite IR 120 (Hþ), filtered, and evaporated.
The residue was dissolved in NH3/MeOH and stirred at 458C for 2 h. The
reaction mixture was reduced in vacuo and the resultant oil evaporated from
benzene/ethanol (1 : 1, 3 ꢀ 150 mL). Crystallisation from ethanol/ether
yielded compound 17 (4.61 g, 92%); Rf 0.21 (MeCN : H2O, 9 : 1), 1H NMR
(CDCl3) d 4.22 (d, 1H, J1,2 9.6 Hz, H-1), 2.20 (s, 3H, CH3), 2.65 (t, 1H, J2,3
8.6 Hz, H-2), 3.63 (dd, 1H, J4,5 9.0 Hz, H-4), 3.87 (apparent d, 1H, H-3), 3.27
(m, 3H, H-5, H-6a, H-6b). HRMS (TOF) Calcd for C7H15NO4S: 209.0724.
Found: 210.0712 [M þ H]þ.

Dde as a Protecting Group
17
Methyl 2-amino-2-deoxy-4,6-O-benzylidene-1-thio-b-D-
glucopyranoside (18)
To a solution of aqueous ammonia in methanol (150 mL, 28% aqueous
ammonia/MeOH, 1 : 1) was added compound 9 (5.30 g, 11.50 mmol). The sus-
pension was stirred at rt overnight. The precipitate was collected and
washed with diethylether and the washings discarded. The reaction mother
liquor concentrated, azeotroped with toluene (3 ꢀ 100 mL), and suspended in
diethyl ether (300 mL) and stirred for 2 h. The solid was collected and
combined with the earlier precipitate to afford compound 18 (3.4 g, 99.5%); Rf
1
0.4 (MeCN/H2O 10 : 1); H–NMR d 7.41 (m, 5H, Ar), 5.60 (s, 1-H, Ar-CH),
4.35 (d, 1H, J1,2 9.8 Hz H-1), 4.19 (dd, 1H, J4,5 10.3 Hz, H-4), 3.70 (m, 1H,
H-3), 3.44 (m, 2H, H-6a, H-6b), 3.31 (m, 1H, J5,6a 1.8 Hz, J5,6b 4.1 Hz, H-5),
2.61 (t, 1H, J2,3 8.9 Hz, H-2), 2.12 (s, 3-H, S–CH3). HRMS (TOF) Calcd for
C14H19NO4S: 297.1035. Found: 298.1088 [M þ H]þ.
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