Dye-sensitized photooxygenation of 2,5-Bis(glycosyl)furans

Article abstract of DOI:10.2174/157017811795685027

The dye-sensitized photooxygenation of 2,5-bis(glycosyl)furans followed by warming up to r.t. provides 1,1'- linked disaccharides separated by a functionalized spacer. Asymmetrical disubstituted glycosyl furans give the corresponding Bayer-Villiger type-r

Full text of DOI:10.2174/157017811795685027

Letters in Organic Chemistry, 2011, 8, 309-314
309
Dye-Sensitized Photooxygenation of 2,5-Bis(glycosyl)furans
Flavio Cermola*, Maria R. Iesce, Anna Astarita and Monica Passananti
Dipartimento di Chimica Organica e Biochimica Università di Napoli Federico II, Complesso Universitario di M.
Sant’Angelo, Via Cinthia 4, 80126, Napoli, Italy
Received August 13, 2010: Revised December 29, 2010: Accepted March 25, 2011
Abstract: The dye-sensitized photooxygenation of 2,5-bis(glycosyl)furans followed by warming up to r.t. provides 1,1’-
linked disaccharides separated by a functionalized spacer. Asymmetrical disubstituted glycosyl furans give the
corresponding Bayer-Villiger type-rearranged products in a molar ratio depending on the sugars and the protecting
groups. The migratory aptitudes have been rationalized by both theoretical calculations and experimental data. The 1,1’-
disaccharides obtained are new sugar derivatives structurally related to some mimetics of Sialyl Lewis X.
Keywords: [4+2]-Cycloaddition, endoperoxides, glycosyl furans, glycosides, photooxygenation, singlet oxygen, thermal
rearrangement.
INTRODUCTION
spacer. These compounds are of interest because structurally
related to mimetics of Sialyl Lewis X (sLeX) [7], a
tetrasaccharide which has been recognized to be involved in
the initial step of inflammation response [7, 8]. Drug-design
studies have evidenced that the biological activity of some of
these mimetics is related to disaccharidic systems consisting
of 1,1’-Gal-Man separated by a suitable spacer [8a].
Coupling reactions between a glycosyl-donor and an
acceptor in the presence of a Lewis-acid as promoter
represent the most general synthetic approach to glycosides.
Many other pathways which make use of glycals as well as
of lactone sugars are also useful synthetic routes [1]. Most of
these procedures are based on the bond formation at the
anomeric centre which represents the key step of the whole
process. An alternative approach is based on building up the
desired aglycone through selective and suitable reactions that
are carried out on a pre-existent residue. Although this
strategy is of less general use, it could be useful when
coupling reactions could turn out unsuccessfully [1]. As part
of our research program, we are investigating on the use of
sugar-furans as building blocks for glycosides including
functionalized frameworks, heterocycles or privileged
structures as novel aglycones [2-5]. The approach is set up
on a [4+2]-cycloaddition of singlet oxygen to diene function
[6] of a glycosyl furan, e.g. 1, followed by appropriate
reactions on the related endoperoxide 2 (Scheme 1). By this
route, new glycosides [2, 3] and modified nucleosides [3-5]
have been synthesized. It has also been found that the
thermal stability of peroxides 2 is strictly dependent on the
position of the sugar on the bicycle [2-6]. Indeed, while
endoperoxides of 3-glycosyl furans are quite stable [4], those
of 2-glycosyl furans by warming up to r.t. quantitatively
rearrange to O-glycosides 3 through a Baeyer-Villiger
mechanism-type that occurs with a complete retention of the
configuration at the anomeric carbon (Scheme 1) [2-6].
R1
R1
1O2, -20 °C
O
O
O
O
O
2
1
R1
1O2, -20 °C
r.t.
R1
O
O
R1
O
O
O
O
2
3
1
Scheme 1.
RESULTS AND DISCUSSION
Preliminarily, the reactivity of singlet oxygen towards
2,5-bis(2’,3’,4’,6’-tetra-O-benzyl-D-glucopiranosyl)furan
(1aa), chosen as model of a disubstituted sugar-furan, was
examined. Furan 1aa was synthesized following the pathway
showed in Scheme 2 [9].
Owing to the high molecular symmetry, only one signal
of the two anomeric protons appeared in the proton spectrum
of 1aa which authenticates the ꢀ-configuration at both the
anomeric carbons [10]. The [4+2]-cycloaddition of singlet
oxygen to 1aa was performed in dichloromethane at -20 °C
and, despite the high steric hindrance offered by the two
sugar moieties, it was complete within 90 min (TLC). Then,
the solution was transferred to r.t. and, after 10 min,
Continuing with this project, the present study deals with
an investigation on the photooxygenation of novel 2,5-
bis(glycosyl)furans in order to gain information on the
thermal rearrangement of the corresponding 1,4-
cycloadducts and verify the use of the procedure for new
1,1’-linked disaccharides separated by a functionalized
1
analyzed by NMR spectroscopy. The H spectrum of the
*Address correspondence to this author at the Dipartimento di Chimica
Organica e Biochimica, Università di Napoli Federico II, Via Cintia 4,
80126 – Napoli, Italy; Tel: +39(0)81674331; Fax: +39(0)81674393;
E-mail: cermola@unina.it
crude mixture showed the quantitative formation of
compound 3aa that was spectroscopically characterized
(Scheme 3). In particular, according to the assigned
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

310 Letters in Organic Chemistry, 2011, Vol. 8, No. 5
Cermola et al.
OBn
OBn
OBn
O
O
O
Cl3CCN
O
BnO
BnO
BnO
BnO
BnO
BnO
CH2Cl2, ZnCl2
DBU
BnO
BnO
OH
BnO
O
CCl3
O
4a
(84%)
NH
1a
(78%)
4a
CH2Cl2
ZnCl2
OBn
OBn
O
BnO
BnO
BnO
OBn
OBn
O
BnO
O
1aa
(39%)
Scheme 2.
structure, the signal of the anomeric proton of the migrated
glucose is at ꢁ 6.41, a typical value for the anomeric protons
of O-glycosides [2-5].
Hence, the migratory aptitudes of the sugars in the
thermal rearrangements of endoperoxides 2 ab’ and 2ac’
appeared to be glucose > galactose > mannose. However,
photooxygenation of the bis(glycosyl)furan 1bc afforded a
mixture of the two derivatives 3bc-GAL and 3bc-MAN in ca.
1 : 1 molar ratio (Scheme 6), suggesting that steric effects of
the crowded protecting benzyl groups could have a role in
promoting the rearrangement.
OBn
OBn
O
BnO
BnO
BnO
OBn
OBn
O
1O2
BnO
OBn
1aa
-20 °C
O
O
O
Theoretical calculations by MMFF models were carried
out on acetylated glycosyl endoperoxides of monosubstituted
furans 2a’, 2b’ and 2c’, chosen as models. They showed that
the order of stability is 2a’ (Glu) < 2b’ (Gal) < 2c’ (Man)
and fits with the observed migratory aptitude glucose >
galactose > mannose (Fig. 1) [12]. A possible explanation
can be drawn by comparing the relationship between the
groups at C-1 and C-2 and at C-1 and C-4 in the
endoperoxide 2a’-c’. These are trans (C1/C2) in the most
stable 2c', cis (C1/C2) and trans (C1/C4) in 2b' and all cis in
the least stable 2a' (Fig. 1). The presence of encumbered
protecting groups (e.g. benzyl group) exalts (e.g. in 2ab’ and
2ac’) or overcomes (e.g. in 2bc) these differences.
2aa
r.t.
O
BnO
BnO
OBn
BnO
BnO
O
OBn
OBn
O
O
O
3aa
Scheme 3.
With the aim to support the steric control of the thermal
rearrangement, we have synthesized and photooxygenated
the glycosyl furans 1d and 1e, both ꢀ,ꢀ’-disubstitued with a
benzylated glucose and with a benzyl and a trityl group,
respectively (Scheme 7).
Then, the asymmetrically disubstituted sugar-furans
1ab’, 1ac’ and 1bc were synthesized by using the ꢀ-1b’, ꢀ-
1c’ and ꢀ-1b furans as glycosyl acceptors, respectively, and
4a and 4c as the donors (Scheme 4) [11]. All of them were
obtained as ꢀ-anomers at the newly formed stereocentres.
When the reactions were complete, each solution was
transferred to r.t. and analyzed by H NMR in C6D6 [13].
1
The three 2,5-bis(glycosyl)furans were photooxygenated
in dichloromethane at -20 °C as above for 1aa. After the
completion of the reaction each crude mixture was
transferred to r.t. and, after 10 min, spectroscopically
analyzed. For 1ab’ the 1H NMR spectrum showed the
presence of the two disaccharides 3ab’-GLU and 3ab’-GAL
in ca. 2 : 1 molar ratio, deriving from the diastereoisomeric
endoperoxides 2ab’ by migration of the glucose and
galactose unit, respectively (Scheme 5). The reaction of 1ac’
afforded compounds 3ac’-GLU and 3ac’-MAN, in ca 6: 1
molar ratio (Scheme 5).
The spectra showed that for the endoperoxide 2d only
migration of the sugar occurs leading to 3d-GLU, while 2e
leads to 3e-GLU and 3e-TRITYL in ca. 1 : 1 molar ratio,
evidencing that migration of sugar competes with that of the
particularly encumbered trityl group (Scheme 8).
EXPERIMENTAL
The spectra were recorded on the crude products at 500
MHz for [1H] and 125 MHz for [13C]. The carbons

Dye-Sensitized Photooxygenation of 2,5-Bis(glycosyl)furans
Letters in Organic Chemistry, 2011, Vol. 8, No. 5
311
OAc
OAc
OBn
OBn
AcO
OAc
O
O
O
AcO
AcO
AcO
AcO
BnO
BnO
O
O
O
1b'
1b
1c'
OBn
OBn
CH2Cl2
SnCl4
OBn
O
OBn
4a
CH2Cl2
ZnCl2
4a
CH2Cl2
ZnCl2
Cl3C
O
NH
4c
OBn
OBn
OBn
O
OAc
OAc
OBn
OBn
OBn
AcO
OAc
O
O
O
AcO
O
BnO
BnO
BnO
BnO
OAc
OBn
OBn
OAc
OAc
O
O
BnO
BnO
O
BnO
BnO
O
1bc
1ab'
1ac'
(40%)
(32%)
(25%)
Scheme 4.
Scheme 5.
Scheme 6.
1ab'
1O2
1ac'
1O2
-20 °C
-20 °C
OAc
OAc
OBn
OBn
BnO
AcO
OAc
O
O
AcO
BnO
BnO
BnO
BnO
OAc
OAc
O
O
OAc
BnO
O
O
O
O
O
O
2ac'
r.t.
2ab'
r.t.
2 : 1
3ab'-GLU
3ab'-GAL
3ac'-GLU
3ac'-MAN
6 : 1
1bc
1O2
-20 °C
OBn
OBn
OBn
OBn
O
OBn
OBn
O
BnO
BnO
O
O
O
2bc
r.t.
3bc-GAL
3bc-MAN
1 : 1

312 Letters in Organic Chemistry, 2011, Vol. 8, No. 5
Cermola et al.
AcO
3
OAc
OAc
4
OAc
1,4-trans
OAc
O
2
4
4
O
O
1,2-trans
AcO
AcO
AcO
2
2
3
3
1
1
1
AcO
AcO
AcO
AcO
1,4-cis
1,4-cis
1,2-cis
O
O
O
1,2-cis
O
O
O
O
O
O
2c'
2a'
2b'
RR-2c' (336.18 KJ/mol)
[SS-2c' (338.60 KJ/mol)]
RR-2a' (341.61 KJ/mol)
[SS-2a' (349.90 KJ/mol)]
RR-2b' (339.85 KJ/mol)
[SS-2b' (347.65 KJ/mol)]
Fig. (1). Interactions of C1/C2 and C1/C4 groups and energies of sugar endoperoxides 2a', 2b' and 2c' by MMFF models [12].
TBAI, BnBr
TBAI, (Ph)3CCl
-78 °C 0 °C
Ph
Ph
-78 °C
0 °C
Li
O
O
O
Ph
Ph
4a
CH2Cl2
ZnCl2
4a
CH2Cl2
ZnCl2
BuLi, THF
-78 °C
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
O
Ph
Ph
Ph
Ph
1d
(70%)
1e
(58%)
Scheme 7.
OBn
O
BnO
BnO
1O2
r.t.
BnO
1d
2d
O
O
O
-20 °C
Ph
3d-GLU
OBn
OBn
O
O
BnO
BnO
1O2
BnO
BnO
r.t.
1e
2e
+
-20 °C
BnO
BnO
O
O
O
O
Ph
O
Ph
O
Ph
Ph
Ph
3e-GLU
3e-TRITYL
Ph
Scheme 8.

Dye-Sensitized Photooxygenation of 2,5-Bis(glycosyl)furans
Letters in Organic Chemistry, 2011, Vol. 8, No. 5
313
multiplicity was evidenced by DEPT experiments. The
proton couplings were evidenced by 1H-1H COSY
experiments. The heteronuclear chemical shift correlations
were determined by HMQC (optimized for 1JHC, 140 Hz) and
(2 d, 2 H, J= 12.2 Hz, CH2Ph), 4.50 and 4.80 (2 d, 2 H, J=
10.9 Hz, CH2Ph), 4.64 (s, 2 H, CH2Ph), 4.83 and 4.95 (2 d, 2
H, J= 10.9 Hz, CH2Ph), 5.12 (d, 1 H, J= 6.0 Hz, H-1’), 5.94
(d, 1 H, J= 3.3 Hz, H-3), 6.46 (d, 1 H, J= 3.3 Hz, H-4), 7.22-
7.78 (m, 25 H, 5 C6H5); 13C NMR (CDCl3) ꢀ= 34.6, 68.8,
70.1, 72.7, 73.0, 73.4, 74.9, 75.5, 78.0, 79.6, 82.7, 106.8,
112.5, 126.4, 127.6, 127.7, 127.9, 128.3, 128.4, 128.7, 138.0,
138.1, 138.2, 138.4, 138.8, 149.4, 154.8. Anal. Calcd. For
C45H44O6: C, 79.39; H, 6.51. Found: C, 79.31; H, 6.48.
1
HMBC (optimized for JHC, 8 Hz) pulse sequences. The
solvents used for the reactions were anhydrous. Reagent-
grade commercially available reagents were used. Analytical
TLC was performed on plates with 0.2 mm film thickness.
Spots were visualized by UV light and by spraying with
EtOH-H2SO4 (95: 5) followed by heating for 5 min at 110
°C. Silica gel (0063-0.2 mm), was used for column
chromatography.
Synthesis of 1e
To
a
stirred solution of 2,3,4,6-tetra-O-benzyl-
glucopyranosyl-1-O-trichloroacetimidate (4a) (0.5 mmol) in
dry CH2Cl2 (0.26 M) under argon and in the presence of
molecular sieves, 2-triylfuran [15] (0.6 mmol) and,
successively, a dichloromethane solution of ZnCl2 (1 M, 2.6
mL) was added. The resulting mixture was stirred at room
temperature for 4 h. The reaction was then quenched by
saturated solution of NaHCO3 (10 mL). The organic layer
was separated and the aqueous layer was extracted with
CHCl3 (3 x 10 mL). The combined organic extracts were
washed with brine and dried over anhydrous MgSO4. After
filtration the solvent was removed under reduced pressure.
Silica gel chromatography using n-hexane/diethyl ether (9 :
1, v/v) as eluent afforded 1e in 58% yield.
Synthesis of 2,5-bis(glucosyl)furan 1aa
To
glucopyranosyl-1-O-trichloroacetimidate (4a) (0.5 mmol) in
a
stirred solution of 2,3,4,6-tetra-O-benzyl-
dry CH2Cl2 (0.26 M) under argon and in the presence of
2-(2’,3’,4’,6’-tetra-O-benzyl-ꢀ-D-
molecular
sieves,
glucopyranosyl)furan (1a) (3 mmol) and, successively, a
dichloromethane solution of ZnCl2 (1 M, 2.6 mL) were
added. The resulting mixture was stirred at room temperature
for 24 h. The reaction was then quenched by saturated
solution of NaHCO3 (10 mL). The organic layer was
separated and the aqueous layer was extracted with CHCl3 (3
x 10 mL). The combined organic extracts were washed with
brine and dried over anhydrous MgSO4. After filtration the
solvent was removed under reduced pressure. Silica gel
chromatography using benzene/diethyl ether (9 : 1, v/v) as
eluent afforded 1aa in 35% yield.
1e: oil; 1H NMR (CDCl3) ꢀ= 3.33-3.65 (m, 4 H, H-4’, H-
5’, H-6’a, H-6’b); 3.92 (dd, 1 H, , J= 9.0, 5.6 Hz, H-2’), 4.05
(t, 1 H, J= 9.0 Hz, H-3’), 4.40 and 4.42 (2 d, 2 H, J= 12.0
Hz, CH2Ph), 4.50 and 4.55 (2 d, 2 H, J= 11.9 Hz, CH2Ph),
4.65 (s, 2 H, CH2Ph), 4.70 and 4.78 (2 d, 2 H, J= 10.8 Hz,
CH2Ph), 5.09 (d, 1 H, J= 5.6 Hz, H-1’), 6.08 (d, 1 H, J= 3.0
Hz, H-3), 6.45 (d, 1 H, J= 3.0 Hz, H-4), 7.05-7.50 (m, 35 H,
7 x C6H5); 13C NMR (CDCl3) ꢀ= 68.8, 70.0, 72.9, 73.4, 74.2,
74.8, 75.6, 77.7, 79.8, 82.9, 99.3, 111.4, 111.9, 126.5, 127.5,
127.6, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 130.3, 138.1,
138.2, 138.3, 138.5, 138.8, 139.9, 150.9, 159. Anal. Calcd.
For C57H52O6: C, 82.18; H, 6.29. Found: C, 82.07; H, 6.20.
1
1aa: oil; H NMR (CDCl3) ꢀ= 3.45-3.64 (m, 6 H, H-5’,
H-6’a, H-6’b), 3.72 (m, 2 H, H-4’), 3.95 (dd, 2 H, J= 8.5, 6.4
Hz, H-2’), 4.28 (t, 2 H, J= 8.5 Hz, H-3’), 4.33 (d, 2 H, J=
12.1 Hz, CH2Ph), 4.49 (2 d, 4 H, J= 11.6 Hz, CH2Ph); 4.62
(s, 4 H, CH2Ph), 4.79-4.82 (m, 4 H, CH2Ph), 4.93 (d, 2 H, J=
11.6 Hz, CH2Ph), 5.14 (d, 2 H, J= 6.4 Hz, H-1’), 6.50 (s, 2
H, H-3, H-4), 7.18-7.78 (m, 40 H, 8 C6H5); 13C NMR
(CDCl3) ꢀ= 68.3, 70.0, 72.3, 73.3, 75.1, 75.6, 77.9, 79.4,
83.1, 112.4, 127.0-129.0, 139.1, 139.2, 139.5, 139.7, 151.3.
Anal. Calcd. For C72H72O11: C, 77.67; H, 6.52. Found: C,
77.56; H, 6.43.
General Procedure of Dye-Sensitized Photooxygenation
A 0.02 M solution of furan 1 (0.25 mmol) in dry CH2Cl2
was irradiated at -20 °C with a halogen lamp (650 W) in the
presence of methylene blue (MB, 1 x 10-3 mmol), while dry
oxygen was bubbled through the solution. The progress of
the reaction was checked by periodically monitoring the
Synthesis of 1d
To
a
stirred solution of 2,3,4,6-tetra-O-benzyl-
glucopyranosyl-1-O-trichloroacetimidate (4a) (0.5 mmol) in
dry CH2Cl2 (0.26 M) under argon and in the presence of
molecular sieves, 2-benzylfuran [14] (0.6 mmol) and,
successively, a dichloromethane solution of ZnCl2 (1 M, 2.6
mL) was added. The resulting mixture was stirred at room
temperature for 4 h. The reaction was then quenched by
saturated solution of NaHCO3 (10 mL). The organic layer
was separated and the aqueous layer was extracted with
CHCl3 (3 x 10 mL). The combined organic extracts were
washed with brine and dried over anhydrous MgSO4. After
filtration the solvent was removed under reduced pressure.
Silica gel chromatography using n-hexane/diethyl ether (9 :
1, v/v) as eluent afforded 1d in 70% yield.
1
disappearance of starting material by TLC, or H NMR.
When the reaction was complete, the crude mixture was
transferred to r.t. After 10 min, the solvent was removed
under reduced pressure and the residue was filtered from
diethyl ether to remove MB. After removal of diethyl ether,
the residue was analysed by NMR spectroscopy.
Photooxygenation of 1aa
1
3aa: H NMR (CDCl3) ꢀ= 3.58-3.84 (m, 10 H, H-6a, H-
6b, H-4, H-5, H-2), 3.87 (t, 1 H, J= 7.7 Hz, H-3), 3.98 (t, 1 H,
J= 8.2 Hz, H-3), 4.30 and 4.94 (2 d, 2 H, J= 12.0 Hz,
CH2Ph), 4.40-4.85 (m, 14 H, CH2Ph), 4.94 (d, 1 H, J= 12.0
Hz, 7 CH2Ph), 5.91 (d, 1 H, J= 12.2 Hz, CH=), 6.41 (d, 1 H,
J= 3.6 Hz, H-1O-glu), 6.58 (d, 1 H, J= 12.2 Hz, CH=), 7.10-
1d: oil; 1H NMR (CDCl3) ꢀ= 3.53-3.70 (m, 4 H, H-4’, H-
5’, H-6’a, H-6’b), 3.92 (dd, 1 H, J= 9.4, 6.0 Hz, H-2’), 3.97
(s, 2 H, CH2Ph), 4.17 (t, 1 H, J= 9.4 Hz, H-3’), 4.45 and 4.58

314 Letters in Organic Chemistry, 2011, Vol. 8, No. 5
Cermola et al.
7.40 (m, 40 H, 8 C6H5). Anal. Calcd. For C72H72O13: C,
75.50; H, 6.34. Found: C, 75.33; H, 6.22.
SUPPLEMENTARY MATERIAL
Supplementary material is available on the publishers
Web site along with the published article.
Photooxygenation of 1d
REFERENCES
3d-GLU: 1 H NMR (C6D6) ꢀ= 3.56 (dd, 1 H, , J= 7.4, 3.5
Hz, H-2), 3.60-3.78 (m, 4 H, CH2Ph and H-6a, H-6b), 3.90 (t,
1 H, J= 7.4 Hz, H-3), 4.05-4.15 (m, 2 H, H-4 and H-5), 4.31
and 4.42 (2 d, 2 H, J= 12.0 Hz, CH2Ph), 4.35 and 4.47 (2 d, 2
H, J= 11.0 Hz, CH2Ph), 4.83 and 4.93 (2 d, 2 H, J= 11.5 Hz,
CH2Ph), 4.66 and 4.97 (2 d, 2 H, J= 12.0 Hz, CH2Ph), 5.56
(d, 1 H, J= 12.4 Hz, CH=), 5.79 (d, 1 H, J= 12.4 Hz, CH=),
6.65 (d, 1 H, J= 3.5 Hz, H-1), 7.0-7.40 (m, 25 H, 5 x C6H5).
Anal. Calcd. For C45H44O8: C, 75.82; H, 6.22. Found: C,
75.69; H, 6.11.
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to E-selectin, J. Am. Chem. Soc., 1996, 118, 9265-9270; b) Cheng,
X.; Khan, N.; Mootoo, D. R. Synthesis of the C-glycoside analogue
of a novel Sialyl Lewis X mimetic, J. Org. Chem., 2000, 65, 2544-
2547.
Photooxygenation of 1e
1
3e-GLU and 3e-TRITYL: H NMR (C6D6) (selected
signals) ꢀ= 5.53 (d, 1 H, J= 11.9 Hz, CH= of 3e-GLU), 5.71
(d, 1 H, J= 12.4 Hz, CH= of 3e-TRITYL), 6.08 (d, 1 H, J=
11.9 Hz, CH= of 3e-GLU), 6.32 (d, 1 H, J= 12.4 Hz, CH= of
3e-TRITYL), 6.74 (d, 1 H, J= 3.6 Hz, H-1). Anal. Calcd. For
C57H52O8: C, 79.14; H, 6.06. Found: C, 79.01; H, 5.96.
CONCLUSION
The work has highlighted that the Bayer-Villiger
rearrangement of endo-peroxides of 2,5-diglycosyl furans
leads quantitatively to O-glycosides and depends on steric
effects. In particular, the migratory aptitudes of the sugars
depend on the stereochemistry of the chosen sugars and by
the steric requirements of the protecting groups. Both
theoretical and experimental data indicate that it is possible
to drive the migration of a selected sugar by using suitable
protecting groups.
[9]
The ꢀ-glucosyl furan 1a used as the acceptor has been synthesized
by a reported procedure: Schmidt, R. R.; Effenberger, G. O-
Glycosyl imidates. 29. Reaction of O-(glucopyranosyl) imidates
with electron-rich heterocycles. Synthesis of C-glucosides, Liebigs
Ann. Chem. 1987, 10, 825-831.
The coupling constant is the same of that of the 2-glucosyl furan 1a
(3JH1,H2= 6.4 Hz).
It is used a, b, c, for benzylated glucose, mannose and galactose
sugars, respectively, and a’, b’, c’ for the corresponding acetylated
ones. The acceptors 1b’, 1c’ and 1b were prepared by coupling
between furan and the imidates 4b’, 4c’ and 4b, respectively.
[10]
[11]
Disaccharides 1,1'-linked by a spacer of 5 atoms have
been obtained which are new sugar derivatives structurally
related to some mimetics of Sialyl Lewis X. The efforts are
now directed to achieve pure compounds 3 which will be
deprotected and submitted to biological screening directed to
highlight biological activity.
While 1c’ was obtainded only as ꢀ-anomer, 1b’ was formed as a ꢀ
: ꢀ mixture in ca. 1 : 2 molar ratio, probably due to the
neighboring-group participation of the acetyl at the C2 after the
removal of the leaving group.
Theoretical calculations were performed by SPARTAN '08
Quantum Mechanics Program.
The NMR spectra were recorded in C6D6 to avoid also little extent
of hydrolysis or cis/trans-isomerization of products which could be
caused by the acidity of the CDCl3.
[12]
[13]
[14]
[15]
Wu, H.-J. and Lin, C.-C. First Exclusive Regioselective
Fragmentation of Primary Ozonides Controlled by Remote
ACKNOWLEDGEMENTS
Financial support from the Ministero dell’Università e
della Ricerca (MIUR, PRIN 2008) is gratefully
acknowledged. NMR experiments were run at the Centro di
Metodologie Chimico-Fisiche, Universita` di Napoli
Federico II.
Carbonyl Groups and
a New Method for Determining the
Regiochemistry of Carbonyl Oxide Formation, J. Org. Chem.,
1996, 61, 3820-3828.
2-Tritylfuran has been prepared following the same procedure [14]
used for 2-benzylfuran.