Protecting group manipulation on D-glucosamine propane-1,3-diyl dithioacetal

Article abstract of DOI:10.1080/07328300701540183

d-glucosamine propane-1,3-diyl dithioacetal is a versatile synthetic building block, especially when being incorporated with the Corey-Seebach method. Hence, exploring compatible protecting group patterns on this compound mainly for use with the Corey-Seebach method is a fundamental work. Various protecting group strategies were applied. Typically, N-protection of d-glucosamine propane-1,3-diyl dithioacetal yielded N-phthaloyl, N-Boc, and N-Ac derivatives. On the N-Ac derivative, experiments differentiating 3,4- and 5,6-hydroxyls by basic stable protecting groups yielded useful intermediates. Selective protections of the 6-hydroxyl of the N-Ac derivative were also applied. The remaining secondary hydroxyls of the resulting N-Ac-6-O-acyl d-glucosamine propane-1,3-diyl dithioacetals could be methoxymethylated to tri-O-MOM derivatives or protected by a unique one-pot discriminating protection to form the N-acyl-6-O-acyl- 3,4-O-methylene-5-O-methoxymethyl d-glucosamine propane-1,3-diyl dithioacetals as useful intermediates.

Full text of DOI:10.1080/07328300701540183

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Protecting Group Manipulation on
d‐Glucosamine Propane‐1,3‐diyl Dithioacetal
Yue‐Lei Chen a b , Robin Leguijt c & Hartmut Redlich c
a Organisch‐Chemisches Institut der Westfälischen Wilhelms‐Universität
Münster , Münster, Germany
b NRW Graduate School of Chemistry , Münster, Germany
c Organisch‐Chemisches Institut der Westfälischen Wilhelms‐Universität
Münster , Münster, Germany
Published online: 31 Aug 2007.
To cite this article: Yue‐Lei Chen , Robin Leguijt & Hartmut Redlich (2007) Protecting Group Manipulation
on d‐Glucosamine Propane‐1,3‐diyl Dithioacetal , Journal of Carbohydrate Chemistry, 26:5-6, 279-303, DOI:
10.1080/07328300701540183
To link to this article: http://dx.doi.org/10.1080/07328300701540183
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Journal of Carbohydrate Chemistry, 26:279–303, 2007
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300701540183
Protecting Group
Manipulation
on D-Glucosamine Propane-
1,3-diyl Dithioacetal
Yue-Lei Chen
¨
¨
Organisch-Chemisches Institut der Westfalischen Wilhelms-Universitat Mu¨nster,
Mu¨nster, Germany and NRW Graduate School of Chemistry, Mu¨nster, Germany
Robin Leguijt and Hartmut Redlich
¨
¨
Organisch-Chemisches Institut der Westfalischen Wilhelms-Universitat Mu¨nster,
Mu¨nster Germany
D-glucosamine propane-1,3-diyl dithioacetal is a versatile synthetic building block,
especially when being incorporated with the Corey-Seebach method. Hence, exploring
compatible protecting group patterns on this compound mainly for use with the Corey-
Seebach method is a fundamental work. Various protecting group strategies were
applied. Typically, N-protection of D-glucosamine propane-1,3-diyl dithioacetal yielded
N-phthaloyl, N-Boc, and N-Ac derivatives. On the N-Ac derivative, experiments differen-
tiating 3,4- and 5,6-hydroxyls by basic stable protecting groups yielded useful intermedi-
ates. Selective protections of the 6-hydroxyl of the N-Ac derivative were also applied. The
remaining secondary hydroxyls of the resulting N-Ac-6-O-acyl D-glucosamine propane-
1,3-diyl dithioacetals could be methoxymethylated to tri-O-MOM derivatives or protected
by a unique one-pot discriminating protection to form the N-acyl-6-O-acyl- 3,4-O-methyl-
ene-5-O-methoxymethyl D-glucosamine propane-1,3-diyl dithioacetals as useful
intermediates.
Keywords D-Glucosamine propane-1,3-diyl dithioacetal, Protecting group, Selective
protection
Received February 2, 2006; accepted October 2, 2006.
This is part 5 of a series of work on the chemistry of propane-1,3-diyl dithioacetals of
carbohydrates; for the former parts, see references 2(c), 2(d), 2(e), 2(f), 3 in this paper.
Address correspondence to Hartmut Redlich, Organisch-Chemisches Institut der West-
¨
¨
falischen Wilhelms-Universitat Mu¨nster, Corrensstrabe 40, D-48149 Mu¨nster,
Germany. E-mail: redlich@uni-muenster.de
279

Y.-L. Chen et al.
280
Figure 1
INTRODUCTION
D-Glucosamine propane-1,3-diyl dithioacetal (1b, and compound 1a as its
hydrochloric salt, Fig. 1) has been known for a long time[1] and is a potential
precursor for the widely-used Corey-Seebach method.[2] However, to date,
there has been no report in this field except two papers[3] from our group,
which proved that with proper protecting groups, compound 1b serves as an
excellent precursor for the Corey-Seebach method and as a versatile building
block for natural product and bioactive compound synthesis. The congenital
amino group of compound 1b, on one hand, offers great advantage for
natural product and bioactive compound synthesis; on the other hand, it may
cause serious problems when extreme reaction conditions are used (i.e., with
BuLi in the Corey-Seebach method). Therefore, it is our first task to develop
a series of robust protecting group patterns (especially toward strong basic
conditions) on compound 1b for the later application in organic synthesis.
This will be reported herein.
RESULTS AND DISCUSSION
Direct isopropylidenation of hydrochloric salt (1a) according to the known pro-
cedure[1(b), 1(c)] gave the 3,4;5,6-di-O-isopropylidene derivative 2 in 71% yield.
The amino group on compound 2 was further converted to phthalimide 3 in
72% yield (Sch. 1). In later experiments using the Corey-Seebach method,[3]
the isopropylidene group was proved to be very stable, but the phthalimide
group was eliminated when the dithian anion was formed.
The free amine 1b, easily available by basifying compound 1a with
aqueous sodium hydroxide, allowed the protection first of the amino function
and then of the hydroxyls. By reacting compound 1b with phthalic anhydride
(Phth2O), di-tert-butyl dicarbonate (Boc2O), and acetic anhydride (Ac2O),
N-acyl compounds 4, 5, and 6 were prepared with good to excellent yields
(Sch. 2). Different N-protected derivative 4, 5, and 6 served as important
starting material for further protecting group manipulation on hydroxyls
and gave useful information during the exploration of their use in the Corey-
Seebach method.[3]

Manipulation of D-Glucosamine Propane
281
Scheme 1: Reagents and conditions: (a) 1,3-propane dithiol; (b) aqueous NaOH;
(c) 2,2-dimethoxy propane, p-toluenesulfonic acid (cat.), reflux; (d) phthalic anhydride,
pyridine.
Isopropylidenation of N-Boc derivative 5 with 2,2-dimethoxypropane cata-
lyzed by pyridinium p-toluenesulfonate (PPTS) and selective esterification of
the 6-hydroxyl gave compound 7 and 8 with the yield of 73% and 68%, respect-
ively (Sch. 3). The Boc protection is sensitive to acid but quite stable toward
nonaqueous base. In principle, the typical protecting group pattern can be
applied on N-Boc derivative 5 if no strong acid is involved. The model
compound 7 proved less efficient, though was still viable, for the Corey-
Seebach method.[3]
The main work was done on the N-acetyl derivative 6. This compound was
found to be the easiest to handle. It also tolerated various rigorous reaction con-
ditions including n-butyl lithium for the Corey-Seebach method as well as
strong Lewis acids.[3] Regioselective protection and deprotection of compound
Scheme 2: Reagents and conditions: (a) NaOMe, phthalic anhydride; (b) Boc2O, MeOH; (c)
Ac2O, MeOH; (d) Ac2O, pyridine, for analytical reson.

Y.-L. Chen et al.
282
Scheme 3: Reagents and conditions: (a) 2,2-dimethoxy propane, PPTS (cat.); (b) pivaloyl
chloride (PvCl), pyridine, DMF.
6 offers important intermediates for later synthesis[3(b)] and will be described in
detail as follows.
Of compound 6, the 3,4- and 5,6-hydroxyls could be protected simul-
taneously by isopropylidenation to give the 3,4;5,6-di-O-isopropylidene deriva-
tive 9 in 83% isolated yield. Kinetically controlled selective cleavage of the
5,6-O-isopropylidene group of compound 9 was realized by using 0.5 N HCl
or 80% acetic acid. The resulting compound 10 was acetylated to compound
10a for the convenience of analysis (Sch. 4).
Alternatively, the 5,6-hydroxyls of compound 6 allowed the selective protec-
tion by kinetically controlled isopropylidenation to give compound 11 at 68%
yield. The remaining unprotected hydroxyls on C-atom 3 and 4 were subjected
to further manipulation, for example, by 3,4-O-methoxymethylation to give
the 3,4-O-methoxymethyl (MOM) derivative 12 or by Ley’s O-butane diacetal
(BDA) formation[4] to give compound 14. The 5,6-O-isopropylidene on
compound 12 could be removed selectively by 80% aqueous acetic acid to give
compound 13 (Sch. 5). Attempts of removing isopropylidene acetal from
compound 14 under the same condition with 80% acetic acid were not successful
due to the initial cleavage of the methoxy group on the O-butane diacetal protec-
tion. All the above protecting groups are stable toward very basic conditions and
may be used as synthetic intermediates for the Corey-Seebach method.
Scheme 4: Reagents and conditions: (a) con. HCl, acetone; (b) 0.5N HCl or 80% HOAc.

Manipulation of D-Glucosamine Propane
283
Scheme 5: Reagents and conditions: (a) 2-methoxypropene, p-toluenesulfonic acid (cat.);
(b) MOMCl, diisopropyl ethylamine; (c) 0.7N HCl; (d) 2,3-butadione, trimethoxy orthoformiate,
.
BF3 Et2O.
The differentiation of the primary and the secondary hydroxyls of
compound 6 is illustrated in Scheme 6.
Acetylation by Ac2O and benzoylation by BzCl of compound 6 produced
compounds 15 and 16 in moderate yield. However, the pivaloylating reaction
by pivaloyl chloride gave compound 17 in good yield. Furthermore, tritylation
gave compound 18 almost quantitatively (Table 1).
Scheme 6
Table 1: Selective acylation and tritylation of 6-O.
Reagent
Equiv.
T(8C)
Time
Product and yield
Ac2O
BzCl
BzCl
BzCl
PvCl
TrCl
2.1
25.0
1.1
1.0
1.0
210
0
1.5 h
30 sec
45 min
2.5 h
3 h
15, 68%
16, 52%, with 32% di-O-benzoyl product
16, 38%, with 28% di-O-benzoyl product
16, 48%, with no di-O-benzoyl product
17, 71%
0
215
250
rt
1.5
12 h
18, 95%

Y.-L. Chen et al.
284
Scheme 7
By treating compounds 15 and 16 with dimethoxymethane and phosphorus
pentoxide according to literature,[5] the 3,4,5-tri-O-methoxymethyl derivatives
19 and 21 were produced in moderate yields. Additionally, it was observed that
the 3,4-di-O-methylene derivatives[6] 20 and 22 were formed in a considerable
amount too (Sch. 7). Optimization with the aim to increase the ratio of
compounds 19 and 21 to compounds 20 and 22 failed.
However, the formation of the 3,4-di-O-methylene derivative could be
improved dramatically by applying boron trifluoride instead of diphosphopent-
oxide. Thus, compounds 22 and 23 were synthesized from compounds 16 and
17 in 69% and 75% yields, respectively (Sch. 8).
The compounds (19, 20, 21, 22, and 23), combining the base-sensitive 6-O-
ester protection and the base-resistant 3,4,5-O-acetal protections, were demon-
strated to be crucial intermediates, from which interesting natural product
analogs were synthesized.[3] Furthermore, the O-MOM group is generally
more labile (to acidic conditions) than the vicinal di-O-methylene group and
can be cleaved selectively. The vicinal di-O-methylene group can also be
opened in a regioselective way. Hence, the unique 3,4-di-O-methylene 5-O-
MOM protecting pattern on compounds 20, 22, and 23 should offer great
advantage during later synthetic applications.
Scheme 8

Manipulation of D-Glucosamine Propane
285
CONCLUSION
For the sake of exploring suitable protecting group patterns on D-glucosamine
propane-1,3-diyl dithioacetal (1b) for later synthetic applications (especially
for the Corey-Seebach method), various protecting group strategies, mainly
including base stable protections and regioselective protections as well as
deprotections, were tested. Three different protecting groups were applied on
the amino group to yield compound 4, 5, and 6, which made it possible to
install various O-protecting groups on the remaining free hydroxyls. Differen-
tiating protections on 3,4- and 5,6-hydroxyls, 3,4,5- and 6-hydroxyls, or 3,4- and
5-, and 6-hydroxyls were proved viable by acid or base stable protecting groups.
Most of them have the advantage of easy preparation and high yields. As it has
been known,[3] with proper protecting groups, D-glucosamine propane-1,3-diyl
dithioacetal (1b) is an excellent building block when being incorporated with
the Corey-Seebach procedure in natural product and bioactive compound
synthesis. The protecting group manipulation described above furnishes the
fundament for further exploration of the synthetic use of D-glucosamine
propane-1,3-diyl dithioacetal (1b).
EXPERIMENTAL
Nuclear magnetic resonance spectra were recorded on a Bruker AMX 300 or
400 spectrometer. The chemical shift is specified as d in ppm and the signal
of the solvent was used as the internal standard (CDCl3 1H: d ¼ 7.24 ppm,
1
13C: d ¼ 77.23 ppm, C6D6 1H: d ¼ 7.16 ppm, 13C: d ¼ 128.39 ppm, CD3OD H:
d ¼ 4.85 ppm, 13C: d ¼ 49.15 ppm). Electrospray ionization mass spectra (MS-
ESI) were recorded on a Quattro LCZ or on a MicroTof. MALDI-TOF spectra
were recorded on a REFLEX IV.
General Procedure for O-Acetylation
The compound with free hydroxyls was dissolved in a mixture of dry
pyridine and acetic anhydride (2:1 v/v). The reaction mixture was stirred at
rt until the compound was completely converted, which can take from hours
to several days (monitored by TLC). The reaction may be accelerated by the
addition of a catalytic amount of N,N-dimethyl aminopyridine (DMAP). The
solvent was then evaporated under reduced pressure and traces of pyridine
were removed by coevaporation with toluene. The crude product was purified
by extraction from water with CH2Cl2 and, if necessary, by column
chromatography.

Y.-L. Chen et al.
286
2-Amino-2-deoxy-D-glucose Propane-1,3-diyldithioacetal
Hydrochloride (1a)
D-Glucosamine hydrochloride (50.1 g, 0.23 mol) and 1,3-propanedithiol
(26.0 mL, 0.24 mol) were placed in a 1-L round-bottom flask with concentrated
hydrochloric acid (400 mL). The mixture was vigorously stirred at rt for 4 d and
subsequently the solvent was evaporated under reduced pressure. The remain-
ing solid was recrystallized by solving the solid in boiling water (20 mL) and
adding 300 mL of ethanol during cooling of the mixture. The dithian
compound 1a (49.3 g, 0.16 mmol, 70%) precipitated as a colorless crystalline
204 2 2068C). [a]2D0 ¼ 29.58 (c ¼ 1.00, H2O). (Lit.
[1(a)]
solid. mp: 2198C. (Lit.
[1(a)]
[a]1D6 ¼ 28.98 (c 1.45, H2O)).
Anal. Calcd. for C9H21ClNO4S2: C, 35.34; H, 6.59; N, 4.58. Found: C, 35.41;
H, 6.50; N, 4.43.
2-Amino-2-deoxy-D-glucose Propane-
1,3-diyldithioacetal (1b)
To a solution of the hydrochloride 1a (50.6 g, 0.17 mol) in boiling water
(150 mL) was added an aqueous solution of 3.3 N NaOH (50 mL, 0.17 mol). A
white solid precipitated, which dissolved again after the addition of water
(100 mL). During cooling of the solution the free amine compound 1b (39.3 g,
14.6 mmol, 86%) precipitated as a colorless crystalline solid. The yield was
extended to 92% by the recrystallization of the product that remained in the
filtrate. mp: 1748C. [a]2D0 ¼ 27.48 (c ¼ 1.00, H2O).
MS-ESI (þ) m/z ¼ 270.1 [M þ H]þ, 292.1 [M þ Na]þ.
Anal. calcd. for C9H19NO4S2: C, 40.13; H, 7.11; N, 5.20. Found: C, 39.93; H,
7.03; N, 5.07.
HRMS-ESI (þ): m/z found [M þ Na]þ 292.0649. C9H19NNaO4S2 requires
292.0648.
2-Amino-2-deoxy-3,4;5,6-di-O-isopropylidene-D-glucose
Propane-1,3-diyldi-thioacetal (2)
To a suspension of D-glucosamine 1,3-propane-diyl dithioacetal hydrochlo-
ride 1a (3.06 g, 10.0 mmol) in 2,2-dimethoxypropane (20 mL) was added p-
toluenesulfonic acid monohydrate (200 mg, 0.1 equiv.) at reflux temperature.
The reaction was followed by TLC (EtOAc) and quenched after 3 h with a satu-
rated aqueous sodium bicarbonate. After phase separation, the aqueous layer
was extracted with Et2O several times. The combined organic phases were
washed with water and dried over MgSO4, and the solvent was evaporated
under reduced pressure. The purification by MPLC (cyclohexane:EtOAc ¼ 7:1)

Manipulation of D-Glucosamine Propane
287
yielded the di-O-isopropylidene compound 2 (2.48 g, 7.1 mmol, 71%) as a yel-
lowish syrup. [a]2D0 ¼ þ0.78 (c ¼ 1.00, MeOH). [Lit.[1(b)]] þ 898 (c ¼ 1.3, CHCl3)].
1H NMR (C6D6, 300 MHz): d 4.04 (dd, J ¼ 7.9 Hz, J ¼ 1.7 Hz, 1H, H-3), 4.37
(dd, J ¼ 7.9 Hz, J ¼ 7.8 Hz, 1H, H-4), 4.04 (ddd, J ¼ 7.8 Hz, J ¼ 6.2 Hz,
J ¼ 4.5 Hz, 1H, H-5), 3.99 (dd, J ¼ 8.3 Hz, J ¼ 4.5 Hz, 1H, H-6a), 3.94 (dd,
J ¼ 8.3 Hz, J ¼ 6.2 Hz, 1H, H-6b), 3.91 (d, J ¼ 9.1 Hz, 1H, H-1), 3.34 (dd,
J ¼ 9.1 Hz, J ¼ 1.7 Hz, 1H, H-2), 2.59–2.42 (m, 2H, dithian-SCHax), 2.31–
2.19 (m, 2H, dithian-SCHeq), 1.59–1.48 (m, 2H, dithian-SCCH2CS), 1.50
(s, 2H, NH2), 1.38 (s, 3H, CH3-i-pr), 1.36 (s, 3H, CH3-i-pr), 1.33 (s, 3H, CH3-i-
pr), 1.23 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 75 MHz): d 110.0 (Cq-i-pr), 109.7 (Cq-i-pr), 80.4 (C-3), 78.8
(C-5), 78.4 (C-4), 68.5 (C-6), 54.2 (C-2), 52.9 (C-1), 28.5 (dithian-SCH2C), 28.2
(CH3-i-pr), 27.8 (dithian-SCH2C), 27.5 (dithian-SCCH2CS), 27.3 (CH3-i-pr),
26.4 (CH3-i-pr), 25.9 (CH3-i-pr).
MS-ESI (þ): m/z ¼ 350.2 [M þ H]þ, 372.2 [M þ Na]þ, 388 [M þ K]þ.
HRMS-ESI (þ): m/z found [M þ H]þ 350.1434. C15H27NNaO4S2 requires
350.1454.
2-Deoxy-3,4;5,6-di-O-isopropylidene-2-phthalimido-
D-glucose Propane-1,3-diyldithioacetal (3)
Phthalic anhydride (305 mg, 2.06 mmol) was added to a solution of the di-O-
isopropylidene derivative 2 (719 mg, 2.06 mmol) in 20 mL dry pyridine. The
reaction mixture was stirred overnight at rt. Another portion of phthalic anhy-
dride (305 mg, 2.06 mmol) was added and the reaction mixture was stirred until
TLC showed a complete conversion. Acetic anhydride was then added and again
the reaction mixture was stirred until TLC showed the complete conversion to a
higher running product. The solvent was then evaporated under reduced
pressure and coevaporated with toluene. The purification of the remaining
syrup by chromatography (cyclohexane:EtOAc ¼ 10:1) yielded the N-phthali-
mide protected product 3 (716 mg, 1.49 mmol, 72%) as colorless crystals (from
cyclohexane and EtOAc. mp: 109 2 1108C; [a]2D0 ¼ 264.08 (c ¼ 1.00, CHCl3).
1H NMR (C6D6, 300 MHz): d 7.53 (dd, J ¼ 5.5 Hz, J ¼ 3.0 Hz, 2H, H-Phth),
6.88 (dd, J ¼ 5.5 Hz, J ¼ 3.0 Hz, 2H, H-Phth), 5.42 (dd, J ¼ 7.5 Hz, J ¼ 2.1 Hz,
1H, H-3), 5.38 (d, J ¼ 2.3 Hz, 1H, H-2), 5.34 (broad s, 1H, H-1), 4.14 (ddd,
J ¼ 7.4 Hz, J ¼ 6.3 Hz, J ¼ 5.4 Hz, 1H, H-5), 4.04 (dd, J ¼ 7.4 Hz, J ¼ 7.5 Hz,
1H, H-4), 4.02 (d, J ¼ 5.4 Hz, 1H, H-6a), 4.02 (d, J ¼ 6.3 Hz, 1H, H-6b),
The H6a and H6b in this compound are very close to each other; therefore,
the J value for them could not be determined. 2.87 (ddd, J ¼ 13.5 Hz,
J ¼ 10.2 Hz, J ¼ 2.9 Hz, 1H, dithian-SCHax-a), 2.70 (ddd, J ¼ 13.6 Hz,
J ¼ 10.2 Hz, J ¼ 2.8 Hz, 1H, dithian-SCHax-b), 2.15 (ddd, J ¼ 14.4 Hz,
J ¼ 6.4 Hz, J ¼ 3.1 Hz, 1H, dithian-SCHeq-a), 2.03 (ddd, J ¼ 14.1 Hz,
J ¼ 6.4 Hz, J ¼ 3.0 Hz, 1H, dithian-SCHeq-b), 1.72 (s, 3H, CH3-i-pr),

Y.-L. Chen et al.
288
1.57–1.39 (m, 2H, dithian-SCCH2CS), 1.31 (s, 3H, CH3-i-pr), 1.29 (s, 3H, CH3-i-
pr), 1.26 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 75 MHz): d 179.4 (CO-Phth), 179.3 (CO-Phth), 134.2 (2C,
CH-Phth), 131.5 (2C, Cq-Phth), 123.7 (2C, CH-Phth), 110.7 (Cq-i-pr), 110.6 (Cq-
i-pr), 80.2 (C-4), 79.4 (C-3), 78.3 (C-5), 68.4 (C-6), 54.7 (C-2), 43.5 (C-1), 27.7 (2C,
CH3-i-pr), 27.1 (dithian-SCH2C), 26.5 (dithian-SCH2C), 26.0 (2C, CH3-i-pr),
25.9 (dithian-SCCH2CS).
MS-ESI (þ) m/z ¼ 502.6 [M þ Na]þ.
Anal. calcd. for C23H29NO6S2: C, 57.60; H, 6.09; N, 2.92. Found: C, 57.63; H,
5.96; N, 2.75.
HRMS-ESI (þ): m/z found [M þ Na]þ 502.1301. C23H29NNaO6S2 requires
502.1329.
3,4,5,6-Tetra-O-acetyl-2-deoxy-2-phthalimido-D-glucose
Propane-1,3-diyldithioacetal (4a)
Sodium methylate (0.89 g, 16.5 mmol) was added to a solution of D-glucosa-
mine dithioacetal hydrochloride 1a (5.00 g, 16.4 mmol) in MeOH (160 mL) at
408C, after which a white solid precipitated. After 30 min of stirring, phthalic
anhydride (2.67 g, 18.0 mmol) was added and the white precipitate slowly dis-
solved again. After 45 min TLC (EtOH) analysis showed that no starting
material remained and another portion of phthalic anhydride (2.67 g,
18.0 mmol) was added. The reaction mixture was stirred overnight at rt and
subsequently the solvent was evaporated. Compound 4 was crystallized from
ethyl acetate and analyzed by its peracetylated derivative 4a, produced accord-
ing to the general O-acetylation procedure. The combined two steps yielded 4a
6.13 g (10.8 mmol, 66%) as colorless crystals (from cyclohexane and EtOAc. mp:
162 2 1638C; [a]D20 ¼ 230.08 (c ¼ 1.00, CHCl3).
1H NMR (CDCl3, 300 MHz): d 7.80 (broad s, 2H, H-Phth), 7.70 (dd,
J ¼ 5.5 Hz, J ¼ 3.1 Hz, 2H, H-Phth), 6.07 (dd, J ¼ 3.1 Hz, J ¼ 2.5 Hz, 1H,
H-3), 5.49 (dd, J ¼ 8.4 Hz, J ¼ 3.1 Hz, 1H, H-4), 5.06 (ddd, J ¼ 8.3 Hz,
J ¼ 5.4 Hz, J ¼ 2.9 Hz, 1H, H-5), 4.80 (dd, J ¼ 11.6 Hz, J ¼ 2.5 Hz, 1H, H-2),
4.47 (d, J ¼ 11.6 Hz, 1H, H-1), 4.17 (dd, J ¼ 12.4 Hz, J ¼ 2.9 Hz, 1H, H-6a),
4.05 (dd, J ¼ 12.5 Hz, J ¼ 5.4 Hz, 1H, H-6b), 3.15 (ddd, J ¼ 14.3 Hz,
J ¼ 11.3 Hz, J ¼ 2.9 Hz, 1H, dithian-SCHax-a), 2.73 (ddd, J ¼ 14.2 Hz,
J ¼ 11.3 Hz, J ¼ 2.8 Hz, 1H, dithian-SCHax-b), 2.64–2.56 (broad m, 1H,
dithian-SCHeq-a), 2.34–2.26 (broad m, 1H, dithian-SCHeq-b), 2.04 (s, 3H, Me-
OAc), 2.02 (s, 3H, Me-OAc), 2.02–1.97 (m, 2H, dithian-SCCH2CS), 2.00
(s, 3H, Me-OAc), 1.92 (s, 3H, Me-OAc).
13C NMR (CDCl3, 75 MHz): d 170.8 (OC55O), 170.7 (OC55O), 170.3
(OC55O), 170.1 (OC55O), 168.3 (2C, O55C-Phth), 134.4 (2C, CH-Phth), 131.6
(2C, Cq-Phth), 123.6 (2C, CH-Phth), 72.1 (C-4), 68.7 (C-5), 68.0 (C-3), 62.1

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(C-6), 52.0 (C-1), 42.6 (C-2), 25.2 (dithian-SCH2C), 25.0 (dithian-SCH2C), 24.5
(dithian-SCCH2CS), 21.2 (Me-OAc), 21.0 (Me-OAc), 20.8 (2C, Me-OAc).
MS-ESI (þ): m/z ¼ 590 [M þ Na]þ.
Anal. calcd. for C25H29NO10S2: C, 52.90; H, 5.15; N, 2.47. Found: C, 52.85;
H, 4.80; N, 2.29.
HRMS-ESI (þ): m/z found [M þ Na]þ 590.1080. C25H29NNaO10S2 requires
590.1125.
2-tert-Butoxycarbonylamino-2-deoxy-D-glucose Propane-
1,3-diyldithioacetal (5)
Compound 1b (0.5 g, 1.85 mmol) was suspended in 10 mL dry MeOH and
di-tert-butyl dicarbonate (0.6 g, 2.75 mmol) was added at rt. The reaction
mixture was then stirred overnight. All volatile components were removed
under vacuum, and the remained solid was recrystallized from ethyl acetate
to give compound 5 (0.57 g, 1.35 mmol, 83%) as a white solid. mp:
135.8 2 136.98C; [a]2D0 ¼ 28.98 (c ¼ 1.00, MeOH).
1H NMR (CDCl3 þ DMSO-d6, 400 MHz): d 5.44 (d, 1H, NH), 4.25 (brs, 2H,
H-6), 4.14 (m, 2H, H-2 and H-1), 3.74 (m, 1H, H-3), 3.69 (m, 1H, H-4), 3.62
(m, 1H, H-5), 3.3–4.5 (br, 4H, OH), 2.95 (m, 2H, dithian), 2.72 (m, 2H,
dithian), 2.01 (m, 1H, dithian), 1.91 (m, 1H, dithian), 1.44 (s, 9H, Me-Boc).
13C NMR (CDCl3 þ DMSO-d6, 100 MHz): d 152.2 (CO-Boc), 79.2 (Me3C-
Boc), 73.2 (C-5), 72.0 (C-4), 69.2 (C-6), 63.5 (C-3), 54.7 (C-2), 48.4 (C-1), 28.2
(3C, Me-Boc), 27.9 (2C, dithian), 25.5 (dithian).
MS-ESI (þ): m/z ¼ 392.1 [M þ Na]þ.
Anal. calcd. for C14H27NO6S2: C, 45.51; H, 7.37; N, 3.79. Found: C, 45.52; H,
7.26; N, 3.61.
2-Acetamido-2-deoxy-D-glucose Propane-1,3-
diyldithioacetal (6)
To a suspension of the free amine compound 1b (26.9 g, 0.10 mol) in MeOH
(800 mL) was added acetic anhydride (45 mL, 4.8 mol). The reaction was
followed by TLC (EtOH) and after 1.5 h of stirring at rt the solution was
filtered. Evaporation of the solvent under reduced pressure yielded the N-
acetylated compound 6 (29.4 g, 94.6 mmol, 95%) as a white solid. mp:
16721688C; [a]2D0 ¼ þ1.28 (c ¼ 1.00, H2O).
NMR spectroscopic data were recorded from the O-peracetylated derivative.
1H NMR (C6D6, 300 MHz): d 5.98 (dd, J ¼ 5.1 Hz, J ¼ 5.0 Hz, 1H, H-3), 5.88
(d, J ¼ 10.2 Hz, 1H, NHC ¼ O), 5.78 (dd, J ¼ 7.0 Hz, J ¼ 4.7 Hz, 1H, H-4), 5.50
(ddd, J ¼ 7.0 Hz, J ¼ 6.0 Hz, J ¼ 3.1 Hz, 1H, H-5), 5.06 (ddd, J ¼ 10.2 Hz,
J ¼ 6.7 Hz, J ¼ 5.3 Hz, 1H, H-2), 4.46 (dd, J ¼ 12.4 Hz, J ¼ 3.1 Hz, 1H,
H-6a), 4.18 (dd, J ¼ 12.4 Hz, J ¼ 6.0 Hz, 1H, H-6b), 4.14 (d, J ¼ 6.7 Hz, 1H,
H-1), 2.75 (m, 2H, dithian-SCHax), 2.38–2.67 (m, 2H, dithian-SCHeq), 1.83

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(s, 3H, Me-OAc), 1.81 (s, 3H, Me-OAc), 1.79 (s, 3H, Me-OAc), 1.75 (s, 3H, Me-
OAc), 1.74 (s, 3H, Me-NAc), 1.53-1.45 (m, 2H, dithian-SCCH2CS).
13C NMR (C6D6, 75 MHz): d 170.7 (OC55O), 170.6 (OC55O), 170.5 (OC55O),
170.4 (OC55O), 170.0 (NC55O), 71.1 (C-4), 71.0 (C-5), 70.1 (C-3), 62.4 (C-6), 51.7
(C-2), 48.4 (C-1), 28.7 (dithian-SCH2C), 28.4 (dithian-SCH2C), 26.0 (dithian-
SCCH2CS), 23.1 (Me-NAc), 20.9 (Me-OAc), 20.9 (Me-OAc), 20.7 (Me-OAc),
20.7 (Me-OAc).
MS-ESI: m/z ¼ 334.1 [M þ Na]þ, 645.2 [2M þ Na]þ.
HRMS-ESI (þ): m/z calcd for C11H21NNaO5S2: 334.0753, found [M þ Na]þ:
334.0712.
Anal. calcd. for C11H21NO5S2: C, 42.42; H, 6.80; N, 4.50. Found: C, 42.43; H,
6.76; N, 4.39.
2-tert-Butoxycarbonylamino-2-deoxy-3,4;5,6-di-O-
isopropylidene-D-glucose Propane-1,3-
diyldithioacetal (7)
Compound 5 (3.50 g, 9.47 mmol) was mixed with dry DMF 10 mL, dry
acetone 50 mL, and 2,2-dimethoxy propane 200 mL. Then 50 mg pyridinium
p-toluene sulfonate was added to the mixture. The resulting solution was
stirred overnight. Then the solvent was removed under vacuum and the
remained syrup was purified by MPLC to give compound 7 (3.10 g,
6.90 mmol, 73%) as a white solid. mp: 127.02128.28C; [a]2D0 ¼ 217.88
(c ¼ 1.00, MeOH).
1H NMR (CDCl3, 400 MHz): d 4.97 (d, J ¼ 10.2 Hz, 1H, NH), 4.66 (pseudo-
d, J ¼ 7.88 Hz, 1H, H-3), 4.34 (pseudo-t, J ¼ 9.9 Hz, 1H, H-2), 4.13 (m, 2H,
H-6), 3.99 (m, 1H, H-5), 3.81 (d, J ¼ 9.2 Hz, 1H, H-1), 3.71 (m, 1H, H-4), 3.15
(m, 1H, H-dithian), 2.99 (m, 1H, H-dithian), 2.65 (m, 2H, H-dithian), 2.01
(m, 2H, H-dithian), 1.49 (s, 3H, CH3-i-pr), 1.41 (s, 3H, CH3-i-pr), 1.45 (s, 9H,
Me-Boc), 1.37 (s, 3H, CH3-i-pr), 1.35 (s, 3H, CH3-i-pr).
13C NMR (CDCl3, 100 MHz): d 155.6 (CO-Boc), 109.9 (Cq-i-pr), 109.5 (Cq-i-
pr), 79.4 (Me3C-Boc), 78.3 (C-4), 78.1 (C-3), 77.0 (C-6), 67.4 (C-5), 51.6 (C-2),
48.0 (C-1), 28.2 (3C, CH3-Boc), 27.5 (CH3-i-pr), 26.9 (dithian-SCCH2CS), 26.8
(2C, dithian-SCH2), 26.5 (CH3-i-pr), 25.4 (CH3-i-pr), 24.2 (CH3-i-pr).
HRMS-ESI (þ): m/z found [M þ Na] þ 472.1798. C20H35NNaO6S2 requires
472.1804.
2-tert-Butoxycarbonylamino-6-O-pivaloyl-2-deoxy-D-
glucose Propane-1,3-diyldithioacetal (8)
Compound 5 (50 mg, 0.135 mmol) was dissolved in dry pyridine 1.0 mL and
cooled to 08C with stirring. Pivaloyl chloride (0.025 mL, 0.203 mmol, 1.5equiv.)

Manipulation of D-Glucosamine Propane
291
in 0.5 mL dry DMF was added dropwise to the above solution. The stirring was
kept for 1 more h at 08C and MeOH was added to quench the reaction. All
volatile components were removed under vacuum, and the remained syrup
was purified by MPLC (EtOAc:cyclohexane ¼ 1:5) to give compound 8
(41 mg, 0.092 mmol, 68%) as a white solid. mp: 155.02156.58C; [a]2D0 ¼ þ1.08
(c ¼ 1.00, MeOH).
1H NMR (CDCl3, 400 MHz): d 5.29 (d, J ¼ 7.2 Hz, 1H, NH), 4.30 (m, 2H,
H-6), 4.27 (brs, 1H, H-3), 4.21 (m, 2H, H-2 and H-1), 3.89 (dd, J ¼ 5.0 Hz,
J ¼ 10.5 Hz, 1H, H-5), 3.63 (dd, J ¼ 5.0 Hz, J ¼ 6.5 Hz, 1H, H-4), 2.94
(m, 2H, H-dithian), 2.77 (m, 2H, H-dithian), 2.06 (m, 1H, H-dithian), 1.92
(m, 1H, H-dithian), 1.45 (s, 9H, Me-Pv), 1.22 (s, 9H, Boc).
13C NMR (CDCl3, 100 MHz): d 179.1 (CO-Pv), 156.9 (CO-Boc), 80.2 (Me3C
-Boc), 72.1 (C-4), 71.4 (C-5), 70.2 (C-3), 66.1 (C-6), 55.5 (C-2), 48.7 (C-1), 39.0
(Me3C-Pv), 28.7 (C-dithian), 28.6 (C-dithian), 28.4 (3C, Me-Pv), 27.3 (3C, Me-
Boc), 25.7 (C-dithian).
MS-ESI (þ): m/z ¼ 476.2 [M þ Na]þ.
Anal. calcd. for C19H35NO7S2: C, 50.31; H, 7.78; N, 3.09. Found: C, 50.67; H,
7.78; N, 2.90.
2-Acetamido-2-deoxy-3,4;5,6-di-O-isopropylidene-D-
glucose Propane-1,3-diyldithioacetal (9)
Concentrated hydrochloric acid (2 mL) was added to a suspension of the
dithian compound 6 (3.0 g, 9.6 mmol) in dry acetone (300 mL). After 3 h of
vigorous stirring at rt the reaction mixture was poured into a saturated
aqueous sodium bicarbonate solution and the organic solvent was evaporated
under reduced pressure. The suspension was extracted with CH2Cl2 several
times and the combined organic layers were washed once with water. Drying
the solution over MgSO4 and evaporation of the solvent under reduced
pressure yielded the di-O-isopropylidene protected compound 9 (3.1 g,
8.0 mmol, 83%) as a pale yellow solid. Further purification is possible by recrys-
tallization from a cyclohexane-EtOAc mixture, yielding large colorless crystals.
mp: 14121428C; [a]D20 ¼ 238.18 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 400 MHz): d 5.48 (d, J ¼ 10.1 Hz, 1H, NHC55O), 5.09 (ddd,
J ¼ 10.2 Hz, J ¼ 10.1 Hz, J ¼ 0.8 Hz, 1H, H-2), 5.04 (dd, J ¼ 8.1 Hz,
J ¼ 0.7 Hz, 1H, H-3), 4.05 (ddd, J ¼ 7.8 Hz, J ¼ 7.7 Hz, J ¼ 4.2 Hz, 1H, H-5),
4.04 (dd, J ¼ 10.1 Hz, J ¼ 4.2 Hz, 1H, H-6a), 3.93 (dd, J ¼ 10.1 Hz,
J ¼ 7.8 Hz, 1H, H-6b), 3.79 (dd, J ¼ 7.7 Hz, J ¼ 7.7 Hz, 1H, H-4), 3.76
(d, J ¼ 9.8 Hz, 1H, H-1), 3.06 (ddd, J ¼ 13.9 Hz, J ¼ 10.2 Hz, J ¼ 2.7 Hz, 1H,
dithian-SCHax-a), 2.87 (ddd, J ¼ 13.7 Hz, J ¼ 10.1 Hz, J ¼ 2.7 Hz, 1H,
dithian-SCHax-b), 2.21 (ddd, J ¼ 14.6 Hz, J ¼ 6.7 Hz, J ¼ 2.9 Hz, 1H,
dithian-SCHeq), 2.18 (ddd, J ¼ 14.4 Hz, J ¼ 6.7 Hz, J ¼ 2.9 Hz, 1H, dithian-

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SCHeq), 1.70–1.60 (m, 1H, dithian-SCCH2CS), 1.65 (s, 3H, CH3-i-pr), 1.62
(s, 3H, Me-NAc), 1.55–1.47 (m, 1H, dithian-SCCH2CS), 1.30 (s, 3H, CH3-i-
pr), 1.28 (s, 3H, CH3-i-pr), 1.25 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 100 MHz): d 169.5 (NC55O), 110.7 (Cq-i-pr), 109.9 (Cq-i-pr),
79.5 (C-4), 79.2 (C-3), 78.1 (C-5), 68.1 (C-6), 50.4 (C-2), 48.1 (C-1), 27.6 (dithian-
SCH2C), 27.5 (CH3-i-pr), 27.5 (CH3-i-pr), 27.3 (CH3-i-pr), 26.8 (dithian-
SCH2C), 26.1 (dithian-SCCH2CS), 25.7 (CH3-i-pr), 23.2 (Me-NAc).
MS-ESI (þ): m/z ¼ 392.3 [M þ H]þ, 414.2 [M þ Na]þ.
Anal. calcd. for C17H29NO5S2: C, 52.15; H, 7.47; N, 3.58. Found: C, 52.36; H,
7.30; N, 3.39.
HRMS-ESI (þ): m/z found [M þ Na]þ 414.1331. C17H29NNaO5S2 requires
414.1385.
2-Acetamido-5,6-di-O-acetyl-2-deoxy-3,4-O-isopropylidene-
D-glucose Propane -1,3-diyldithioacetal (10a)
Method A: To a solution of the di-O-isopropylidene derivative 9 (630 mg,
1.6 mmol) was added 0.5 N hydrochloric acid (10 mL, 5 mmol). The reaction
was followed by TLC (EtOAc) and after 4.5 h the reaction was quenched with
aqueous sodium bicarbonate. The solvent was then evaporated under
reduced pressure and the remaining syrup was put in water and extracted
with CH2Cl2 (3 ꢀ 20 mL). The combined organic phases were dried with
MgSO4 and filtered, and the solvent was evaporated under reduced pressure.
Purification by MPLC (EtOAc) yielded the 5,6-dihydroxy derivative 10
(355 mg, 1.0 mmol, 63%) as a colorless syrup. The analysis was performed on
5,6-di-O-acetyl derivative 10a, produced according to the general O-acetylation
procedure.
Method B: A solution of the di-O-isopropylidene derivative 9 (393 mg,
1.0 mmol) in 80% aqueous acetic acid (10 mL) was heated to 508C. After 1.5 h
a TLC analysis showed complete conversion and the solvent was evaporated
under reduced pressure. O-Acetylation of the remaining crude 10 according
to the general procedure and purification by MPLC (cyclohexane/EtOAc, 1:1)
yielded the di-O-acetyl derivative 10a (320 mg, 0.76 mmol, 76%) as a colorless
syrup. The analysis was again performed on compound 10a and gave the same
result as in method A.
[a]2D0 ¼ 21.68 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 300 MHz): d 5.63 (d, J ¼ 10.0 Hz, 1H, NHC55O), 5.48 (ddd,
J ¼ 7.7 Hz, J ¼ 6.1 Hz, J ¼ 3.2 Hz, 1H, H-5), 4.89 (dd, J ¼ 7.9 Hz, J ¼ 1.0 Hz,
1H, H-3), 4.80 (ddd, J ¼ 10.1 Hz, J ¼ 9.1 Hz, J ¼ 1.1 Hz, 1H, H-2), 4.72 (dd,
J ¼ 12.1 Hz, J ¼ 3.2 Hz, 1H, H-6a), 4.15 (dd, J ¼ 12.1 Hz, J ¼ 6.1 Hz, 1H,
H-6b), 4.01 (dd, J ¼ 7.8 Hz, J ¼ 7.8 Hz, 1H, H-4), 3.89 (d, J ¼ 9.2 Hz, 1H,
H-1), 2.79–2.61 (m, 2H, dithian-SCHax), 2.26–2.14 (m, 2H, dithian-SCHeq),

Manipulation of D-Glucosamine Propane
293
1.96 (s, 3H, Me-NAc), 1.75 (s, 3H, Me-OAc), 1.65 (s, 3H, Me-OAc), 1.56–1.49
(m, 2H, dithian-SCCH2CS), 1.28 (s, 3H, CH3-i-pr), 1.25 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 75 MHz): d 170.4 (C55O), 170.2 (C55O), 169.8 C55O),
110.4 (Cq-i-pr), 78.6 (C-4), 76.6 (C-3), 72.6 (C-5), 63.5 (C-6), 51.1 (C-2),
48.3 (C-1), 30.5 (CH3-i-pr), 28.2 (CH3-i-pr), 27.4 (dithian-SCH2C), 27.0
(dithian-SCH2C), 26.0 (dithian-SCCH2CS), 23.0 (Me-NAc), 21.1 (Me-OAc),
20.7 (Me-OAc).
MS-ESI (þ): m/z ¼ 436.2 [M þ H]þ, 458.2 [M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 458.1289. C18H29NNaO7S2 requires
458.1278.
Anal. calcd. for C18H29NO7S2: C, 49.64; H, 6.71; N, 3.22. Found: C, 49.81; H,
6.49; N, 3.06.
2-Acetamido-3,4-di-O-acetyl-2-deoxy-5,6-O-isopropylidene-
D-glucose Propane- 1,3-diyldithioacetal (11a)
To a solution of acetamido derivative 6 (6.10 g, 16.5 mmol) and 2-methoxy-
propene (3.0 mL, 30.0 mmol) in DMF (250 mL) was added p-toluenesulfonic
acid monohydrate (210 mg, 1.1 mmol) at 08C. After stirring for 1 h the
reaction was quenched with concentrated aqueous NH3. The solvent was evap-
orated under reduced pressure and codistilled with toluene. The purification of
the remaining syrup by MPLC (cyclohexane:EtOAc ¼ 1:2) yielded the 5,6-O-
isopropylidene derivative 11 (3.93 g, 11.2 mmol, 68%) as a colorless syrup.
The analysis was performed on 3,4-di-O-acetyl derivative 11a, produced
according to the general O-acetylation procedure. mp: 10021028C;
[a]2D0 ¼ 211.18 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 400 MHz): d 5.95 (dd, J ¼ 5.3 Hz, J ¼ 4.9 Hz, 1H, H-3), 5.85
(d, J ¼ 10.0 Hz, 1H, NHC55O), 5.55 (dd, J ¼ 6.6 Hz, J ¼ 4.9 Hz, 1H, H-4), 5.07
(ddd, J ¼ 10.2 Hz, J ¼ 6.6 Hz, J ¼ 5.4 Hz, 1H, H-2), 4.30 (ddd, J ¼ 6.6 Hz,
J ¼ 6.4 Hz, J ¼ 5.3 Hz, 1H, H-5), 4.20 (d, J ¼ 6.6 Hz, 1H, H-1), 3.95 (dd,
J ¼ 8.6 Hz, J ¼ 5.3 Hz, 1H, H-6a), 3.86 (dd, J ¼ 8.6 Hz, J ¼ 6.3 Hz, 1H,
H-6b), 2.66–2.60 (m, 1H, dithian-SCHax-a), 2.56–2.50 (m, 1H, dithian-
SCHax-b), 2.33–2.25 (m, 2H, dithian-SCHeq), 1.76 (s, 3H, Me-OAc), 1.75
(s, 3H, Me-OAc), 1.66 (s, 3H, Me-NAc), 1.48 (s, 3H, CH3-i-pr), 1.47–1.42
(m, 2H, dithian-SCCH2CS), 1.24 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 100 MHz): d 170.4 (OC55O), 169.9 (2C, OC55O/NC55O),
110.3 (Cq-i-pr), 75.6 (C-5), 72.2 (C-3), 72.1 (C-4), 66.6 (C-6), 51.9 (C-2), 49.0
(C-1), 28.8 (dithian-SCH2C), 28.6 (dithian-SCH2C), 27.2 (CH3-i-pr), 26.0
(dithian-SCCH2CS), 25.8 (CH3-i-pr), 23.0 (Me-NAc), 20.7 (2C, Me-OAc).
MS-ESI (þ): m/z ¼ 436.1 [M þ H]þ, 458.1 [M þ Na]þ, 893.3 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 458.1273. C18H29NNaO7S2 requires
458.1278.

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2-Acetamido-2-deoxy-5,6-O-isopropylidene-3,4-di-O-
methoxy-methyl-D-glucose propane-1,3-
diyldithioacetal (12)
To a solution of the 5,6-O-isopropylidene derivative 11 (2.26 g, 6.4 mmol) in
DIPEA (9.5 mL, 64.3 mmol) and dry CH2Cl2 (15 mL) was added methoxy-
methyl chloride (1.3 mL, 14.0 mmol). The reaction mixture was heated to
reflux temperature for 5 h and was stirred overnight at rt. TLC (EtOAc)
analysis indicated that the reaction was not complete and therefore an
additional portion of methoxymethyl chloride (1.3 mL, 14.0 mmol) was added.
The reaction was quenched with MeOH and the solvent was evaporated
under reduced pressure. The remaining syrup was put in a glass filter filled
with silica gel and washed with EtOAc. The purification by MPLC
(cyclohexane:EtOAc ¼ 8:1) yielded the 3,4-di-O-methoxymethyl derivative 12
(1.99 g, 4.6 mmol, 72%) as a colorless syrup. [a]2D0 ¼ þ3.98 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 300 MHz): d 5.95 (d, J ¼ 9.6 Hz, 1H, NHC ¼ O), 4.89 (dd,
J ¼ 9.6 Hz, J ¼ 9.0 Hz, 1H, H-2), 4.71 (dd, J ¼ 13.6 Hz, J ¼ 6.4 Hz, 2H,
OCH2O), 4.68 (dd, J ¼ 19.1 Hz, J ¼ 6.6 Hz, 2H, OCH2O), 4.50 (d, J ¼ 6.4 Hz,
1H, H-3), 4.35 (dd, J ¼ 12.9 Hz, J ¼ 6.4 Hz, 1H, H-4), 4.10–4.04 (m, 2H),
4.01–3.95 (m, 2H), 3.18 (s, 3H, OCH3), 3.17 (s, 3H, OCH3), 3.02
(ddd, J ¼ 13.6 Hz, J ¼ 9.5 Hz, J ¼ 2.9 Hz, 1H, dithian-SCHax-a), 2.72
(ddd, J ¼ 13.6 Hz, J ¼ 9.5 Hz, J ¼ 2.7 Hz, 1H, dithian-SCHax-b), 2.26 (ddd,
J ¼ 14.1 Hz, J ¼ 6.9 Hz, J ¼ 2.9 Hz, 1H, dithian-SCHeq-a), 2.16 (ddd,
J ¼ 14.0 Hz, J ¼ 7.0 Hz, J ¼ 2.7 Hz, 1H, dithian-SCHeq-b), 1.70 (s, 3H, Me-
NAc), 1.65–1.49 (m, 2H, dithian-SCCH2CS), 1.46 (s, 3H, CH3-i-pr), 1.30
(s, 3H, CH3-i-pr).
13C NMR (C6D6, 75 MHz): d 170.0 (NC55O), 109.9 (Cq-i-pr), 199.3 (OC55O),
198.3 (OC55O), 78.9 (OCH3), 78.4 (OCH3), 76.9 (C-4), 67.6 (C-3), 60.6 (C-5), 56.7
(C-6), 51.6 (C-2), 48.2 (C-1), 30.0 (dithian-SCH2C), 28.5 (dithian-SCH2C), 27.3
(dithian-SCCH2CS), 26.4 (CH3-i-pr), 26.1 (CH3-i-pr), 23.4 (Me-NAc).
MS-ESI (þ): m/z ¼ 440.3 [M þ H]þ, 462.3 [M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 462.1550. C18H33NNaO7S2 requires
462.1591.
Anal. calcd. for C18H33NO7S2: C, 49.18; H, 7.57; N, 3.19. Found: C, 49.01; H,
7.65; N, 3.05.
2-Acetamido-2-deoxy-5,6-di-O-acetyl-3,4-di-O-methoxy-
methyl-D-glucose Pro-pane-1,3-diyldithioacetal (13a)
To a solution of 5,6-O-isopropylidene derivative 12 (2.05 g, 4.7 mmol) in
acetone (20 mL) was added 0.7 N hydrochloric acid (31 mL). The reaction
mixture was stirred at rt and followed by TLC (EtOAc). After the complete con-
version the reaction was quenched with sat. NaHCO3 solution (40 mL) and the

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reaction mixture was extracted with CH2Cl2 five times. The combined organic
phase was evaporated under reduced pressure and the remaining syrup as
crude compound 13 was O-acetylated according to the general procedure.
The purification by MPLC (cyclohexane:EtOAc ¼ 1:2) yielded the 5,6-di-O-
acetyl derivative 13a (801 mg, 2.0 mmol, 43%) as colorless syrup.
[a]2D0 ¼ þ338 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 400 MHz) d 6.17 (d, J ¼ 10.0 Hz, 1H, NHC55O), 5.48 (ddd,
J ¼ 7.8 Hz, J ¼ 3.3 Hz, J ¼ 3.2 Hz, 1H, H-5), 4.85 (dd, J ¼ 10.0 Hz, J ¼ 9.4 Hz,
1H, H-2), 4.68 (d, J ¼ 6.1 Hz, 1H, 3-OCH2O), 4.65 (d, J ¼ 6.7 Hz, 1H,
4-OCH2O), 4.65 (d, J ¼ 6.1 Hz, 1H, 3-OCH2O), 4.55 (d, J ¼ 6.7 Hz, 1H,
4-OCH2O), 4.53 (d, J ¼ 7.5 Hz, 1H, H-3), 4.60 (dd, J ¼ 12.1 Hz, J ¼ 3.4 Hz,
1H, H-6a), 4.31 (dd, J ¼ 12.1 Hz, J ¼ 7.9 Hz, 1H, H-6b), 4.11 (dd, J ¼ 7.5 Hz,
J ¼ 3.3 Hz, 1H, H-4), 3.94 (d, J ¼ 9.5 Hz, 1H, H-1), 3.22 (s, 3H, 4-OCH3), 3.18
(s, 3H, 3-OCH3), 3.12–3.08 (m, 1H, dithian-SCHax-a), 3.01–2.93 (m, 1H,
dithian-SCHax-b), 2.30–2.24 (m, 2H, dithian-SCHeq), 1.88 (s, 3H, Me-NAc),
1.81 (s, 3H, Me-5-OAc), 1.77 (s, 3H, Me-6-OAc), 1.72–1.57 (m, 2H, dithian-
SCCH2CS).
13C NMR (C6D6, 100 MHz) d 170.6 (NC55O), 170.6 (6-OC55O), 170.1 (5-
OC55O), 99.3 (3-OCH2O), 98.1 (4-OCH2O), 78.6 (C-4), 78.1 (C-3), 72.3 (C-5),
62.8 (C-6), 56.6 (3-OCH3), 56.3 (4-OCH3), 51.3 (C-2), 47.0 (C-1), 27.7 (dithian-
SCH2C), 26.8 (dithian-SCH2C), 26.1 (dithian-SCCH2CS), 23.3 (Me-NAc), 21.1
(Me-OAc), 20.8 (Me-OAc).
MS-ESI (þ) m/z ¼ 484.2 [M þ H]þ, 506.2 [M þ Na]þ, 989.3 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 506.1458. C19H33NNaO9S2 requires
506.1489.
2-Acetamido-2-deoxy-3,4-O-(30,40-dimethoxy butane-30,40-
diyl)-5,6-O-isopropy-lidene-D-glucose Propane-1,3-
diyldithioacetal (14)
To a solution of the 5,6-O-isopropylidene derivative 11 (354.8 mg,
1.0 mmol), 2,3-butadione (0.10 mL, 1.1 mmol), and trimethoxy orthoformiate
.
(0.44 mL, 4.0 mmol) in dry MeOH (3 mL) was added BF3 Et2O (0.3 l,
0.1 mmol). After stirring at rt overnight, the yellow solution disappeared and
the solvent was evaporated under reduced pressure. The purification by
MPLC (cyclohexane:EtOAc ¼ 3:1) yielded the 3,4-O-BDA derivative 14
(201 mg, 0.43 mmol, 43%) as a colorless syrup. [a]2D0 ¼ 213.68 (c ¼ 1.00,
MeOH).
1H NMR (C6D6, 300 MHz): d 5.82 (d, J ¼ 9.9 Hz, 1H, NHC55O), 4.97 (dd,
J ¼ 9.9 Hz, J ¼ 9.3 Hz, 1H, H-2), 4.92 (d, J ¼ 10.1 Hz, 1H, H-3), 4.16 (ddd,
J ¼ 10.1 Hz, J ¼ 7.4 Hz, J ¼ 3.9 Hz, 1H, H-5), 3.91 (d, J ¼ 9.3 Hz, 1H, H-1),
3.86–3.73 (m, 3H, H-4/6), 3.28 (s, 3H, OCH3), 3.05 (s, 3H, OCH3), 3.01–2.92
(m, 1H, dithian-SCHax-a), 2.80–2.71 (m, 1H, dithian-SCHax-b), 2.30–2.14

Y.-L. Chen et al.
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(m, 2H, dithian-SCHeq), 1.69 (s, 3H, Me-NAc), 1.66–1.52 (m, 2H, dithian-
SCCH2CS), 1.35 (s, 3H, CH3-i-pr), 1.31 (s, 3H, CH3-i-pr), 1.31 (s, 3H, CH3-i-
pr), 1.29 (s, 3H, CH3-i-pr).
13C NMR (C6D6, 75 MHz): d 169.8 (NC55O), 110.2 (Cq-i-pr), 99.8 (Cq-BDA),
98.8 (Cq-BDA), 78.8 (C-4), 78.1 (C-3), 70.0 (C-5), 62.0 (C-6), 51.1 (C-1), 48.4 (C-
2), 48.3 (OMe), 48.0 (OMe), 28.1 (dithian-SCH2C), 27.6 (dithian-SCH2C), 27.4
(CH3-i-pr), 27.3 (dithian-SCCH2CS), 26.1 (CH3-i-pr), 23.1 (Me-NAc), 18.3
(CCH3-BDA), 18.2 (CCH3-BDA).
MS-MALDI (þ): m/z ¼ 488.1 [M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 488.1737. C20H35NNaO7S2 requires
488.1747.
2-Acetamido-6-O-acetyl-2-deoxy-D-glucose Propane-
1,3-diyldithioacetal (15)
A solution of the acetamido derivative 6 (311 mg, 1.0 mmol) in dry pyridine
(5 mL) was cooled to 2108C. Then acetic anhydride (0.2 mL, 2.1 mmol) was
added slowly to the reaction mixture and after 1.5 h of stirring the reaction
was quenched with EtOH. The solvent was evaporated under reduced
pressure and coevaporated with toluene several times. Purification by MPLC
(toluene:EtOH ¼ 4:1) yielded the 6-O-acetyl derivative 15 (240 mg,
0.68 mmol, 68%) as a colorless syrup. [a]2D0 ¼ 22.78 (c ¼ 1.00, MeOH).
1H NMR (CDCl3/CD3OD, 400 MHz): d 6.77 (d, J ¼ 9.6 Hz, 1H, NHC55O),
4.56 (ddd, J ¼ 9.6 Hz, J ¼ 7.7 Hz, J ¼ 3.3 Hz, 1H, H-2), 4.26 (dd, J ¼ 11.6 Hz,
J ¼ 2.8 Hz, 1H, H-6a), 4.21 (dd, J ¼ 4.1 Hz, J ¼ 3.3 Hz, 1H, H-3), 4.12 (dd,
J ¼ 11.6 Hz, J ¼ 6.6 Hz, 1H, H-6b), 4.10 (d, J ¼ 7.7 Hz, 1H, H-1), 3.81 (ddd,
J ¼ 6.6 Hz, J ¼ 6.6 Hz, J ¼ 2.8 Hz, 1H, H-5), 3.51 (dd, J ¼ 6.2 Hz, J ¼ 4.8 Hz,
1H, H-4), 3.32 (broad s, 3H, OH), 2.89–2.84 (m, 2H, dithian-SCHax), 2.73–2.64
(m, 2H, dithian-SCHeq), 2.04 (s, 3H, Me-NAc), 2.04–1.94 (m, 1H, dithian-
SCCH2CS), 1.98 (s, 3H, Me-OAc), 1.89–1.81 (m, 1H, dithian-SCCH2CS).
13C NMR (CDCl3, 75 MHz): d 172.3 (NC55O), 172.0 (OC55O), 72.5 (C-4),
70.5 (C-5), 69.5 (C-3), 66.0 (C-6), 53.8 (C-2), 48.1 (C-1), 28.6 (dithian-SCH2C),
28.5 (dithian-SCH2C), 25.7 (dithian-SCCH2CS), 23.0 (Me-NAc), 21.0 (Me-OAc).
MS-ESI (þ): m/z ¼ 376.2 [M þ Na]þ, 729.3 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ H]þ 376.0847. C13H23NNaO6S2 requires
376.0859.
2-Acetamido-6-O-benzoyl-2-deoxy-D-glucose Propane-
1,3-diyldithioacetal (16)
The acetamido compound 6 (12.64 g, 40.6 mmol) was dissolved in dry
pyridine (200 mL) and the solution was cooled to 2158C. Then a solution of

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297
benzoyl chloride (4.7 mL, 40.6 mmol) in dry pyridine (20 mL) was added slowly
over a period of 45 min. After 2.5 h the reaction was quenched with 100 mL
MeOH and the solvent was evaporated under reduced pressure. The purifi-
cation by MPLC (toluene: EtOH ¼ 9:1) yielded the 6-O-benzoate product 16
(8.11 g, 19.5 mmol, 48%) as a white solid. mp: 15521568C; [a]2D0 ¼ þ1.18
(c ¼ 1.00, MeOH).
1H NMR (CDCl3/CD3OD, 400 MHz): d 7.99 (d, J ¼ 8.3 Hz, 2H, Hortho-Bz),
7.48 (m, 1H, Hpara-Bz), 7.35 (dd, J ¼ 7.7 Hz, 2H, Hmeta-Bz), 6.74 (weak d,
J ¼ 9.5 Hz, 1H, NHC ¼ O), 4.48 (dd, J ¼ 11.7 Hz, J ¼ 2.7 Hz, 1H, H-6a), 4.43
(dd, J ¼ 7.9 Hz, J ¼ 3.1 Hz, 1H, H-2), 4.40 (dd, J ¼ 11.6 Hz, J ¼ 6.2 Hz, 1H,
H-6b), 4.26 (dd, J ¼ 4.6 Hz, J ¼ 3.1 Hz, 1H, H-3), 4.07 (d, J ¼ 7.9 Hz, 1H,
H-1), 3.89 (ddd, J ¼ 6.4 Hz, J ¼ 6.4 Hz, J ¼ 3.2 Hz, 1H, H-5), 3.56 (dd,
J ¼ 6.8 Hz, J ¼ 4.6 Hz, 1H, H-4), 2.86–2.81 (m, 2H, dithian-SCHax), 2.68–
2.58 (m, 2H, dithian-SCHeq), 2.02–1.90 (m, 1H, dithian-SCCH2CS), 1.95
1
(s, 3H, Me-NAc), 1.87–1.77 (m, 1H, dithian-SCCH2CS). H-Signals from the
amide and hydroxy protons are weakened due to a fast proton exchange with
CD3OD.
13C NMR (CDCl3/CD3OD, 100 MHz): d 172.3 (NC55O), 167.3 (OC55O),
133.2 (Cpara-Bz), 129.8 (2C, Cortho-Bz), 128.4 (2C, Cmeta-Bz), 72.1 (C-4), 70.9
(C-5), 69.6 (C-3), 66.5 (C-6), 53.8 (C-2), 47.9 (C-1), 28.4 (dithian-SCH2C), 28.3
(dithian-SCH2C), 25.6 (dithian-SCCH2CS), 22.9 (Me-NAc).
MS-ESI (þ): m/z ¼ 438.2 [M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 438.1058. C18H25NO6S2Na requires
438.1016.
Anal. calcd. for C18H25NO6S2: C, 52.03; H, 6.06; N, 3.37. Found: C, 51.86; H,
6.05; N, 3.29.
2-Acetamido-6-O-pivaloyl-2-deoxy-D-glucose Propane-
1,3-diyldithioacetal (17)
The acetamido compound 6 (1.50 g, 4.8 mmol) was dissolved in 20 mL
pyridine and 5 mL DMF and cooled to 2508C; a solution of pivaloyl chloride
(0.6 mL, 4.9 mmol) in 5 mL DMF was added dropwise during a period of 2 h.
The reaction mixture was kept stirring at this temperature for another 1 h
before methanol was added to quench the reaction and the mixture was
warmed to rt. All volatile components were then removed under reduced
pressure and a small amount of ethanol was added to the residue. The
product precipitated out by seeding. A small amount of water was added to
this slurry. The mixture was stirred and filtered. The resulted white solid
was collected, dried, and weighed to yield 1.35 g (71%) compound 17. mp:
95.1296.28C. [a]2D0 ¼ 26.48 (c ¼ 1.00, methanol).
1H NMR (CDCl3/CD3OD, 400 MHz): d 6.72 (d, J ¼ 9.3 Hz, 1H, NH), 4.72
(ddd, J ¼ 3.1 Hz, J ¼ 7.9 Hz, J ¼ 9.3 Hz, 1H, H-2), 4.44 (m, 3H, H-3, H-6),

Y.-L. Chen et al.
298
4.33 (d, J ¼ 7.9 Hz, 1H, H-1), 4.02–3.96 (m, 1H, H-5), 3.70 (dd, J ¼ 4.6 Hz, 1H,
J ¼ 7.2 Hz, H-4), 3.13–3.05 (m, 2H, dithian), 2.94–2.82 (m, 2H, dithian), 2.20
(s, 3H, Me-NAc), 2.13–2.02 (m, 2H, dithian), 1.36 (s, 9H, Me-Pv).
13C NMR (CD3Cl, 100 MHz): d 178.6 (CO-Pv), 171.3 (CO-Ac), 71.5 (C-5),
71.0 (C-4), 69.7 (C-3), 65.7 (C-6), 53.5 (C-2), 47.5 (C-1), 38.5 (Me3C-Pv), 28.0
(dithian), 27.8 (dithian), 26.8 (3C, Me-Pv), 25.2 (dithian), 22.8 (Me-NAc).
MS-ESI (þ) m/z ¼ 418.1385 [M þ Na]þ.
Anal. calcd. for C16H29NO6S2: C, 48.59; H, 7.39; N, 3.54. Found: C, 48.65; H,
7.79; N, 3.09.
2-Acetamido-2-deoxy-6-O-trityl-D-glucose Propane-
1,3-diyldithioacetal (18)
To a solution of the acetamido derivative 6 (1.56 g, 5.0 mmol) and DMAP
(cat. amount) in dry pyridine (20 mL) was added trityl chloride (2.11 g,
7.5 mmol) in portions. The reaction mixture was stirred overnight at rt and
after TLC (toluene: EtOH ¼ 4:1) analysis indicated the complete conversion,
the reaction was quenched with water. Extraction with CH2Cl2 (3 ꢀ 20 mL),
evaporation of the solvent under reduced pressure, and purification by
MPLC (toluene:EtOH ¼ 1:19) yielded the 6-O-trityl derivative 18 (2.52 g,
4.6 mmol, 91%) as a colorless syrup. [a]2D0 ¼ 22.48 (c ¼ 1.00, MeOH).
NMR spectroscopic data were recorded from the O-acetylated compound,
which was produced by the general O-acetylation protocol.
1H NMR (CD3Cl, 400 MHz): d 7.34 (broad m, 6H, Harom), 7.21 (broad m, 6H,
H
arom), 7.15 (broad m, 3H, Harom), 5.68 (d, J ¼ 10.0 Hz, 1H, NHC ¼ O), 5.57 (dd,
J ¼ 8.5 Hz, J ¼ 3.4 Hz, 1H, H-4), 5.39 (dd, J ¼ 6.9 Hz, J ¼ 3.4 Hz, 1H, H-3),
5.07 (ddd, J ¼ 8.4 Hz, J ¼ 4.6 Hz, J ¼ 2.6 Hz, 1H, H-5), 4.48 (ddd,
J ¼ 10.1 Hz, J ¼ 6.6 Hz, J ¼ 5.2 Hz, 1H, H-2), 4.25 (d, J ¼ 5.0 Hz, 1H, H-1),
3.20 (dd, J ¼ 10.6 Hz, J ¼ 2.6 Hz, 1H, H-6a), 2.97 (dd, J ¼ 10.6 Hz,
J ¼ 4.6 Hz, 1H, H-6b), 2.92–2.85 (m, 2H, dithian-SCHax), 2.77–2.72 (m, 2H,
dithian-SCHeq), 2.05 (s, 3H, OCOCH3), 2.04–1.98 (m, 1H, dithian-SCCH2CS-
a), 1.94 (s, 3H, OCOCH3), 1.93 (s, 3H, NCOCH3), 1.86–1.79 (m, 1H, dithian-
SCCH2CS-b), 1.75 (s, 3H, OCOCH3).
13C NMR (CD3Cl, 100 MHz): d 170.6 (OC55O), 170.1 (NC55O), 170.0
(OC55O), 169.9 (OC55O), 143.5 (3C, Cq,arom-Tr), 128.8 (6C, CHarom-Tr), 127.9
(6C, CHarom-Tr), 127.2 (3C, CHarom-Tr), 86.8 (OCPh3), 70.4 (C-3), 70.2 (C-5),
68.9 (C-4), 61.8 (C-6), 51.9 (C-2), 49.3 (C-1), 29.8 (dithian-SCH2C), 29.7
(dithian-SCH2C), 25.8 (dithian-SCCH2CS), 23.3 (Me-NAc), 21.1 (Me-OAc),
20.8 (Me-OAc), 20.7 (Me-OAc).
MS-ESI (þ): m/z ¼ 576.4 [M þ Na]þ, 1129.7 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 576.1802. C30H35NNaO5S2 requires
576.1849.

Manipulation of D-Glucosamine Propane
299
2-Acetamido-6-O-acetyl-2-deoxy-3,4,5-tri-O-
methoxymethyl-D-glucose Propane-
1,3-diyldithioacetal (19)
To a mixture of diphosphopentoxide (31 g, 0.22 mol) in dry dimethoxy-
methane (300 mL) was added dropwise a solution of 6-O-acetate 15 (11.63 g,
32.9 mmol) in dry dioxane (40.0 mL) at reflux temperature. After 1 h of
stirring at reflux temperature a TLC analysis showed the complete conversion
and the reaction was quenched with a saturated NaHCO3 solution until pH .7.
The phases were separated and the aqueous phase was extracted with CH2Cl2
three times. The combined organic phases were washed with water, dried over
MgSO4, and filtrated. The solvent was evaporated under reduced pressure and
purification by MPLC (cyclohexane:EtOAc ¼ 5:3) yielded the 3,4,5-tri-O-
methoxy-methyl derivative 19 (5.29 g, 10.9 mmol, 33%) and the 5-O-methoxy-
methyl-3,4-O-methylene derivative 20 (860 mg, 2.1 mmol, 6%) both as colorless
syrup.
Compound 19: [a]2D0 ¼ þ27.28 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 400 MHz): d 5.86 (d, J ¼ 10.1 Hz, 1H, NHC55O), 4.68
(d, J ¼ 6.2 Hz, 1H, 3-OCH2O), 4.64 (d, J ¼ 6.1 Hz, 1H, 3-OCH2O), 4.63
(d, J ¼ 6.6 Hz, 1H, 4-OCH2O), 4.61 (d, J ¼ 6.6 Hz, 1H, 4-OCH2O), 4.61
(d, J ¼ 6.7 Hz, 1H, 5-OCH2O), 4.54 (d, J ¼ 6.7 Hz, 1H, 5-OCH2O), 4.43 (dd,
J ¼ 10.1 Hz, J ¼ 10.1 Hz, 1H, H-2), 4.24 (d, J ¼ 8.1 Hz, 1H, H-3), 4.21 (dd,
J ¼ 11.9 Hz, J ¼ 4.2 Hz, 1H, H-6a), 4.11 (dd, J ¼ 11.8 Hz, J ¼ 7.3 Hz, 1H,
H-6b), 3.92 (ddd, J ¼ 7.3 Hz, J ¼ 4.1 Hz, J ¼ 2.8 Hz, 1H, H-5), 3.74 (dd,
J ¼ 8.1 Hz, J ¼ 2.4 Hz, 1H, H-4), 3.72 (d, J ¼ 9.6 Hz, 1H, H-1), 3.30 (s, 6H,
OCH3), 3.29 (s, 3H, OCH3), 3.03–2.91 (m, 2H, dithian-SCHax), 2.53–2.42
(m, 2H, dithian-SCHeq), 1.98 (s, 3H, Me-OAc), 1.94 (s, 3H, Me-NAc), 1.92–
1.87 (m, 2H, dithian-SCCH2CS).
13C NMR (C6D6, 100 MHz): d 170.7 (OC55O), 170.1 (NC55O), 98.8 (3-
OCH2O), 97.5 (4-OCH2O), 96.3 (5-OCH2O), 78.8 (C-4), 76.8 (C-3), 75.6 (C-5),
63.5 (C-6), 56.5 (OCH3), 56.0 (OCH3), 55.7 (OCH3), 50.9 (C-2), 46.0 (C-1), 27.0
(dithian-SCH2C), 26.2 (dithian-SCH2C), 25.4 (dithian-SCCH2CS), 23.1 (Me-
NAc), 20.9 (Me-OAc).
MS-ESI (þ) m/z ¼ 486.2 [M þ H]þ, 508.2 [M þ Na]þ, 993.3 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 508.1682. C19H35NNaO9S2 requires
508.1645.
2-Acetamido-6-O-acetyl-2-deoxy-5-O-methoxymethyl-3,4-O-
methylene-D-glucose Propane-1,3-diyldithioacetal (20)
See procedure for the synthesis of 19.
[a]2D0 ¼ þ20.98 (c ¼ 1.00, MeOH).

Y.-L. Chen et al.
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1H NMR (CDCl3, 400 MHz): d 5.91 (d, J ¼ 9.8 Hz, 1H, NHC55O), 5.03 (s, 1H,
3-OCH2O-4), 4.88 (s, 1H, 3-OCH2O-4), 4.71 (d, J ¼ 6.8 Hz, 1H, 5-OCH2OMe), 4.65
(d, J ¼ 6.8 Hz, 1H, 5-OCH2OMe), 4.62 (d, J ¼ 6.2 Hz, J ¼ 0.9 Hz, 1H, H-3), 4.52
(ddd, J ¼ 9.8 Hz, J ¼ 8.6 Hz, J ¼ 1.0 Hz, 1H, H-2), 4.38 (dd, J ¼ 12.0 Hz,
J ¼ 4.1 Hz, 1H, H-6a), 4.07 (dd, J ¼ 12.0 Hz, J ¼ 4.8 Hz, 1H, H-6b), 3.98
(d, J ¼ 8.6 Hz, 1H, H-1), 3.90 (ddd, J ¼ 6.2 Hz, J ¼ 4.8 Hz, J ¼ 4.1 Hz, 1H,
H-5), 3.79 (dd, J ¼ 6.2 Hz, J ¼ 6.2 Hz, 1H, H-4), 3.35 (s, 3H, OCH3), 2.98–2.87
(m, 2H, dithian-SCHax), 2.70–2.62 (m, 2H, dithian-SCHeq), 2.06 (s, 3H, Me-
OAc), 2.04–1.90 (m, 2H, dithian-SCCH2CS), 2.01 (s, 3H, Me-NAc).
13C NMR (CDCl3, 100 MHz): d 170.9 (OC55O), 170.5 (NC55O), 96.4 (5-
OCH2OMe), 95.7 (3-OCH2O-4), 77.1 (C-4), 76.9 (C-3), 75.0 (C-5), 63.1 (C-6),
56.2 (OCH3), 51.7 (C-2), 48.4 (C-1), 28.5 (dithian-SCH2C), 28.1 (dithian-
SCH2C), 25.6 (dithian-SCCH2CS), 23.3 (Me-NAc), 21.0 (Me-OAc).
MS-ESI (þ) m/z ¼ 410.1 [M þ H]þ, 432.1 [M þ Na]þ, 841.2 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 432.1101. C16H27NNaO7S2 requires
432.1121.
2-Acetamido-6-O-benzoyl-2-deoxy-3,4,5-tri-O-
methoxymethyl-D-glucose Propane-
1,3-diyldithioacetal (21)
An experiment similar to the preparation of 21 and 22 was carried out on
compound 16, with the cosolvent as DMF instead of dioxane. After purification,
it yielded compound 21 (41%) and 22 (13%).
Compound 21: [a]2D0 ¼ þ28.88 (c ¼ 1.00, MeOH).
1H NMR (CDCl3, 400 MHz): d 8.03 (dd, J ¼ 8.1 Hz, J ¼ 1.4 Hz, 2H, Hortho
-
Bz), 7.51 (dddd, J ¼ 8.1 Hz, J ¼ 7.5 Hz, J ¼ 1.4 Hz, J ¼ 1.4 Hz, 1H, Hpara-Bz),
7.39 (dd, J ¼ 7.5 Hz, J ¼ 1.4 Hz, 2H, Hmeta-Bz), 5.88 (d, J ¼ 10.2 Hz, 1H,
NHC ¼ O), 4.77 (d, J ¼ 6.2 Hz, 1H, OCH2O), 4.74 (d, J ¼ 6.5 Hz, 1H,
OCH2O), 4.73 (d, J ¼ 6.7 Hz, 1H, OCH2O), 4.72 (d, J ¼ 6.1 Hz, 1H, OCH2O),
4.71 (d, J ¼ 6.5 Hz, 1H, OCH2O), 4.67 (d, J ¼ 6.7 Hz, 1H, OCH2O), 4.95 (ddd,
J ¼ 10.2 Hz, J ¼ 9.8 Hz, J ¼ 0.8 Hz, 1H, H-2), 4.53 (dd, J ¼ 12.1 Hz,
J ¼ 3.5 Hz, 1H, H-6a), 4.46 (dd, J ¼ 12.1 Hz, J ¼ 7.1 Hz, 1H, H-6b), 4.37 (dd,
J ¼ 8.1 Hz, J ¼ 0.8 Hz, 1H, H-3), 4.12 (ddd, J ¼ 7.1 Hz, J ¼ 3.5 Hz,
J ¼ 2.9 Hz, 1H, H-5), 3.90 (dd, J ¼ 8.1 Hz, J ¼ 2.9 Hz, 1H, H-4), 3.80
(d, J ¼ 9.8 Hz, 1H, H-1), 3.37 (s, 3H, OCH3), 3.36 (s, 3H, OCH3), 3.32 (s, 3H,
OCH3), 3.11–2.97 (m, 2H, dithian-SCHax), 2.55–2.48 (m, 2H, dithian-SCHeq),
2.00 (s, 3H, Me-NAc), 1.98–1.92 (m, 2H, dithian-SCCH2CS).
13C NMR (CDCl3, 100 MHz): d 170.1 (NC55O), 166.4 (OC55O), 133.1 (Cpara
-
Bz), 129.8 (Cq-Bz), 130.2 (2C, Cortho-Bz), 128.4 (2C, Cmeta-Bz), 98.9 (OCH2O),
97.6 (OCH2O), 96.5 (OCH2O), 78.6 (OCH3), 77.1 (OCH3), 76.2 (OCH3), 64.5
(C-4), 56.6 (C-3), 56.2 (C-5), 55.9 (C-6), 51.1 (C-2), 46.2 (C-1), 27.2 (dithian-
SCH2C), 26.4 (dithian-SCH2C), 25.6 (dithian-SCCH2CS), 23.3 (Me-NAc).

Manipulation of D-Glucosamine Propane
301
MS-ESI (þ): m/z ¼ 548.2 [M þ H]þ, 570.2 [M þ Na]þ, 1117.4 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 570.1786. C24H37NNaO9S2 requires
570.1802.
2-Acetamido-6-O-benzoyl-2-deoxy-5-O-methoxymethyl-3,4-
O-methylene-D-glucose Propane-1,3-diyldithioacetal (22)
Method A: See the preparation of compound 21.
Method B: To a mixture of 6-O-benzoate 16 (121 mg, 0.29 mmol) in
.
dimethoxymethane (3.0 mL) was added dropwise BF3 Et2O at rt (0.16 mL,
1.3 mmol). The solid immediately dissolved and the solution was stirred over-
night at rt. The reaction was quenched with a saturated NaHCO3 solution.
The mixture was extracted with Et2O (3 ꢀ 4 mL) and the combined organic
phases were washed with water. Evaporation of the solvent under reduced
pressure yielded the 5-O-methoxymethyl-3,4-O-methylene derivative 22
(95 mg, 0.20 mmol, 69%) as a colorless syrup. [a]2D0 ¼ þ22.48 (c ¼ 1.00, MeOH).
1H NMR (C6D6, 400 MHz): d 8.27–8.25 (m, 2H, Hortho-benzoyl), 7.19–7.16
(m, 3H, H-benzoyl), 5.84 (d, J ¼ 10.0 Hz, 1H, NHC ¼ O), 4.97 (dd, J ¼ 10.0 Hz,
J ¼ 9.7 Hz, J ¼ 0.9 Hz, 1H, H-2), 4.94 (d, J ¼ 6.5 Hz, J ¼ 0.9 Hz, 1H, H-3), 4.89
(s, 1H, 3-OCH2O-4), 4.76 (dd, J ¼ 12.0 Hz, J ¼ 3.4 Hz, 1H, H-6a), 4.75 (s, 1H,
3-OCH2O-4), 4.70 (d, J ¼ 6.7 Hz, 1H, 5-OCH2OCH3), 4.61 (d, J ¼ 6.7 Hz, 1H,
5-OCH2OCH3), 4.51 (dd, J ¼ 12.0 Hz, J ¼ 4.8 Hz, 1H, H-6b), 4.18 (dd,
J ¼ 6.9 Hz, J ¼ 6.5 Hz, 1H, H-4), 3.98 (ddd, J ¼ 6.9 Hz, J ¼ 4.8 Hz,
J ¼ 3.4 Hz, 1H, H-5), 3.94 (d, J ¼ 9.7 Hz, 1H, H-1), 3.20 (s, 3H, OCH3), 2.91
(ddd, J ¼ 14.0 Hz, J ¼ 9.4 Hz, J ¼ 2.7 Hz, 1H, dithian-SCHax-a), 2.70 (ddd,
J ¼ 13.9 Hz, J ¼ 9.4 Hz, J ¼ 2.7 Hz, 1H, dithian-SCHax-b), 2.24 (ddd,
J ¼ 14.1 Hz, J ¼ 7.2 Hz, J ¼ 2.8 Hz, 1H, dithian-SCHeq-a), 2.18 (ddd,
J ¼ 14.1 Hz, J ¼ 7.1 Hz, J ¼ 2.8 Hz, 1H, dithian-SCHeq-b), 1.69 (s, 3H, Me-
NAc), 1.65–1.50 (m, 2H, dithian-SCCH2CS).
13C NMR (C6D6, 100 MHz): d 170.4 (NC55O), 166.6 (OC55O), 133.4 (Cpara
-
Bz), 131.0 (Cq-Bz), 130.5 (2C, Cortho-Bz), 129.0 (2C, Cmeta-Bz), 96.9 (5-
OCH2OCH3), 96.0 (3-OCH2O-4), 78.2 (C-3), 77.5 (C-4), 76.1 (C-5), 64.4 (C-6),
56.2 (OCH3), 51.8 (C-2), 47.7 (C-1), 27.7 (dithian-SCH2C), 27.1 (dithian-
SCH2C), 26.0 (dithian-SCCH2CS), 23.1 (Me-NAc).
MS-ESI (þ) m/z ¼ 494.3 [M þ Na]þ, 965.5 [2M þ Na]þ.
HRMS-ESI (þ): m/z found [M þ Na]þ 494.1258. C21H29NNaO7S2 requires
494.1278.
2-Acetamido-6-O-pivaloyl-2-deoxy-5-O-methoxymethyl-3,4-
O-methylene-D-glucose Propane-1,3-diyldithioacetal (23)
6-O-Pivaloyl derivative 17 (1.00 g, 2.5 mmol) was added into 20 mL dichlor-
.
omethane and 8 mL dimethoxymethane, and then BF3 Et2O (2.0 mL,

Y.-L. Chen et al.
302
15.8 mmol) was added. The reaction mixture was stirred at rt for 1 h. Saturated
aqueous sodium bicarbonate was then added to quench the reaction. The two
phases were separated and the water phase was washed with ether. The
combined organic phase was washed with brine and concentrated under
reduced pressure. The residue was purified by silica gel column
(dichloromethane:methanol ¼ 50:1) to yield 0.86 g (75%) product 23 as a color-
less oil. [a]2D0 ¼ þ5.58 (c ¼ 1.00, chloroform).
1H NMR (C6D6, 400 MHz): d 5.80 (d, J ¼ 9.8 Hz, 1H, NH), 5.03 (s, 1H,
3-OCH2O-4), 4.85 (s, 1H, 3-OCH2O-4), 4.74 (d, J ¼ 6.8 Hz, 1H, OCH2O-
MOM), 4.62 (d, J ¼ 6.8 Hz, 1H, OCH2O-MOM), 4.58 (dd, J ¼ 1.3 Hz,
J ¼ 6.0 Hz, 1H, H-3), 4.53 (ddd, J ¼ 1.3 Hz, J ¼ 8.5 Hz, J ¼ 9.8 Hz, 1H, H-2),
4.36 (dd, J ¼ 3.5 Hz, J ¼ 12.1 Hz, 1H, H-6), 4.10 (dd, J ¼ 4.4 Hz, J ¼ 12.1 Hz,
1H, H-6), 3.94 (d, J ¼ 8.5 Hz, 1H, H-1), 3.82 (ddd, J ¼ 3.5 Hz, J ¼ 4.4 Hz,
J ¼ 7.5 Hz, 1H, H-5), 3.76 (dd, J ¼ 6.0 Hz, J ¼ 7.5 Hz, 1H, H-4), 3.35 (s, 3H,
CH3-MOM), 2.99–2.87 (m, 2H, dithian), 2.67–2.60 (m, 2H, dithian), 1.98
(s, 3H, Me-NAc), 1.96–1.87 (m, 2H, dithian), 1.15 (s, 9H, Me-Pv).
13C NMR (C6D6, 100 MHz): d 178.0 (CO-Pv), 170.0 (CO-NAc), 96.1 (3,4-O-
methylene), 95.4 (OCH2O-MOM), 77.4 (C-3), 76.5 (C-4), 75.1 (C-5), 63.0 (C-6),
56.1 (CH3-MOM), 51.6 (C-2), 48.1 (C-1), 38.8 (Me3C-Pv), 28.2 (dithian), 27.8
(dithian), 27.0 (3C, Me-Pv), 25.5 (dithian), 23.1 (Me-NAc).
MS-ESI (þ) m/z ¼ 474.1615 (M þ Naþ).
Anal. calcd. for C19H33NO7S2: C, 50.53; H, 7.37; N, 3.10. Found: C, 50.58; H,
7.46; N, 3.00.
ACKNOWLEDGMENTS
The work was supported by the Deutsche Forschungsgemeinschaft (R.L.) and
NRW Graduate School of Chemistry (Y.-L.C.). We thank Marcus Daniel for his
kind assistance during the manuscript preparation.
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