Photoinduced electron-transfer α-deoxygenation of aldonolactones. Efficient synthesis of 2-deoxy-d-arabino-hexono-1,4-lactone

Article abstract of DOI:10.1016/j.carres.2006.04.012

A photoinduced electron-transfer (PET) reaction was used for the deoxygenation at C-2 of aldonolactones derivatized as 2-O-[3-(trifluoromethyl)benzoyl] or benzoyl esters. By irradiation of different d-galactono- and d-glucono-1,4-derivatives, with a 450 W

Full text of DOI:10.1016/j.carres.2006.04.012

Carbohydrate Research 341 (2006) 1788–1795
Photoinduced electron-transfer a-deoxygenation of
aldonolactones. Efficient synthesis of 2-deoxy-D-arabino
hexono-1,4-lactone
Andrea Bordoni, Rosa M. de Lederkremer and Carla Marino*
CIHIDECAR (CONICET), Departamento de Quı´mica Orga´nica, Facultad de Ciencias Exactas y Naturales,
Universidad de Buenos Aires, Pabello´n II, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Received 2 March 2006; received in revised form 29 March 2006; accepted 13 April 2006
Available online 11 May 2006
Abstract—A photoinduced electron-transfer (PET) reaction was used for the deoxygenation at C-2 of aldonolactones derivatized as
2-O-[3-(trifluoromethyl)benzoyl] or benzoyl esters. By irradiation of different D-galactono- and D-glucono-1,4-derivatives, with a
450 W lamp, using 9-methylcarbazole as photosensitizer, the corresponding 2-deoxy-D-lyxo- and 2-deoxy-D-arabino-hexono-1,4-lac-
tones were efficiently obtained.
Ó 2006 Elsevier Ltd. All rights reserved.
Keywords: Deoxy sugars; Aldonolactone photodeoxygenation; 2-Deoxy-D-arabino-1,4-lactone; 2-Deoxy-D-lyxono-1,4-lactone
1. Introduction
using 9-methylcarbazole as the photosensitizer (Scheme
1).1 This reaction was first used for the synthesis of 2-
deoxyribonucleosides6–8 and for the deoxygenation of a
disaccharide analogue of moenomycin A.9 Surprisingly,
the reaction conditions necessary for the deoxygenation
of compound 1a were extremely mild compared with
those required for the ribonucleosides. While such deriv-
atives needed several hours of irradiation at 400 W,6,8 the
lactone derivative 1a was deoxygenated in 1 h using a 120-
W medium-pressure lamp.1 The effectiveness of this reac-
tion on lactone derivatives should be due to the stabiliza-
tion of the intermediate radical by the vicinal carbonyl
group.
In connection with our project on the specificity of the
enzyme, exo-b-D-galactofuranosidase, we developed strat-
egies for the synthesis of 2-, 3-, and 6-deoxygenated
galactofuranosides in order to establish the importance
of each hydroxyl group in the interaction with the
enzyme.1–3 We showed that the exo-b-D-galactofuranosi-
dase (EC 3.2.1.146) from Penicillium fellutanum has a
strict selectivity for the glycon structure and that the
hydroxyl groups at C-2, C-3, and C-6 of the substrate
are essential for the interaction with the enzyme. For
the synthesis of the deoxygenated analogues, we have
used D-galactono-1,4-lactone, a convenient precursor
of the furanosic sugar, which offers the possibility of reg-
ioselective acylation.4,5 Particularly, for the synthesis of
2-deoxy-D-lyxo-hexofuranosides (2-deoxy-D-galactofur-
anosides), the deoxygenation step was performed via a
photoinduced electron-transfer (PET) reaction on 2-O-
[3-(trifluoromethyl)benzoyl]-D-galactono-1,4-lactone (1a)
O
O
OR2
OR2
hυ
O
O
MCZ, MgClO
4
OR1
OR2
OR2
CH2OR2
CH2OR2
1a R1 = COC6H4(3-CF3), R2 = H
1b R1 = COC6H4(3-CF3), R2 = Bz
1c R1 = R2 = Bz
2a R2 = H
2b R2 = Bz
*
Corresponding author. Tel./fax: +54 11 4576 3352; e-mail: cmarino@
qo.fcen.uba.ar
Scheme 1.
0008-6215/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.04.012

A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
1789
The development of specific deoxygenation methods
HO
HO
O
O
for sugars is important for the preparation of biologi-
cally important sugars from readily available precursors.
Among a variety of methods for carbohydrate deoxy-
genation, tin radical cleavage of thiono esters developed
by Barton and McCombie has been widely used.10 How-
ever, avoiding the use of reagents based on tin hydrides
and thiocarbonyl compounds is desirable from the envi-
ronmental and economical point of view, and an alter-
native procedure has been recently developed.11
We have now optimized the PET reaction for other
derivatives of D-galactono- and extended the reaction
to derivatives of D-glucono-1,4-lactone with the aim
to establish an efficient protocol for deoxygenation at
C-2.
O
O
H
iii
i, ii
OR2
O
O
O
OR1
R1 = R2 = H
OH
4
3
5a R1 = COC6H4(3-CF3), R2 = H
5b R1 = Bz, R2 = H
6
R1 = R2 = COC6H4(3-CF3)
HO
HO
HO
HO
O
O
iv
R2
R2
O
O
O
O
OR1
7a R1 = COC6H4(3-CF3), R2 = H
7b R1 = Bz, R2 = H
9
R2 = H
10 R2 = COC6H4(3-CF3)
2. Result and discussion
8
R1 = R2 = COC6H4(3-CF3)
2.1. Preparation of partially acylated derivatives of
D-galactono- and D-glucono-1,4-lactones
Scheme 2. Reagents and conditions: (i) 2,2-dimethoxypropane–ace-
tone, H+; (ii) (3-CF3)C6H4COCl or BzCl, Py, 0 °C; (iii) 4:1 AcOH–
H2O, 65 °C; (iv) 9-methylcarbazole, Mg(ClO4)2, 9:1 n-PrOH–H2O, hm.
D-Galactono-1,4-lactone derivatives 1a–c (Scheme 1) were
prepared as previously reported.1,12 The photochemical
deoxygenation of partially protected derivatives of D-
glucono-1,5-lactone was unsuccessful because complex
mixtures were obtained in which open-chain, and 1,4-
and 1,5-lactone derivatives were present, as observed by
FTIR and NMR spectroscopy. The contraction to
the1,4-lactone isomers was the predominant reaction.
We then studied the photoinduced deoxygenation reac-
tion using derivatives of the more stable 1,4-lactone 3, ob-
tainedby refluxing asolution ofcommercial 1,5-lactone in
2-methoxyethanol–HCl.13
The 2,6-disubtituted derivatives of aldohexonolac-
tones are easily obtained due to the enhanced reactivity
of the HO-6, primary, and the HO-2, activated by the
vicinal carbonyl lactone group.4 Thus, treatment of 3
with 2.2 equiv of 3-(trifluoromethyl)benzoyl chloride
led to derivative 11 (Scheme 3), isolated from the crude
mixture as a crystalline product from toluene in 51%
yield. The structure of 11 was confirmed on the basis
of the NMR data (Tables 1 and 2). The signal for H-2
was shifted downfield (4.52 to 5.65 ppm) in comparison
to that of lactone 3.
All the derivatives of lactone 3 were prepared at low
temperature, and acylations were performed under
mildly basic conditions in order to minimize b-elimina-
tion reactions.14 For the synthesis of monoacylated
derivatives 7a and 7b (Scheme 2), the sequence previ-
ously used for analogue 1a was applied.1 Treatment of
lactone 3 with 2,2-dimethoxypropane in acetone with
H2SO4 as catalyst gave a better yield (85%) than that
previously reported for compound 4 (Scheme 2).13
Treatment of 4 with 1.2 equiv of either 3-(trifluoro-
methyl)benzoyl or benzoylchloride afforded compounds
5a or 5b, while with an excess of reagent, compound 6
was obtained. NMR spectroscopic data for compounds
5a,b and 6 are shown in Tables 1 and 2. Doublets corre-
sponding to H-2 are the lowest field signals for 5a,b. For
compound 6, the signal corresponding to H-3 was
shifted from 4.74 to 6.11 ppm, in comparison with 5a,
as effect of acylation at HO-3.
Signals for C-2 and C-6 were shifted downfield with
respect to those of lactone 3, and signals corresponding
to the b-carbon atoms (C-1,3 and 5) were shifted upfield
on acylation of HO-2 and 6, in accordance with previous
reports.4
1
Compound 11 was acetylated to afford 12. The H
NMR spectrum of 12 showed significant downfield
shifts (>1 ppm) for the H-3,5 signals with respect to
11, as expected for acylation of HO-3 and HO-5.
Treatment of 3 with an excess of 3-(trifluoro-
methyl)benzoylchloride led to peracylated derivative 15
1
(Scheme 4). The H NMR spectrum of 15 was com-
pletely assigned and resembled that of the per-O-acetyl-
ated analogue. The signal for H-3 was the lowest-field
signal (Table 1), as previously observed.15
2.2. Photoinduced deoxygenation of aldonolactone
derivatives
Treatment of 5a,b and 6 with acetic acid led to
compounds 7a,b and 8 (Scheme 2). The corresponding
upfield shift of the signals for H-6, 60, and 5 were
Saito et al. have studied the photoinduced electron-
transfer (PET) deoxygenation of alcohols derivatized
1
observed in the H NMR spectra (Table 1).

1790
A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
Table 1. 1H NMR (500 MHz) chemical shifts and JH,H coupling constants value for compounds 5–16
Compd
H-2
(J2,3
5.42
H-20
H-3
(J3,4
4.74
H-4
(J4,5
4.65
H-5
(J5,6
4.51
H-6
ðJ6;6
4.22
H-60
0
0
0
)
ðJ2 ;3
Þ
(J2,2
)
)
)
)
Þ
ðJ5;6 Þ
5aa
5ba
6a
4.11
(4.6)
(4.6)
(6.0)
(7.3)
(6.5)
(9.1)
5.42
(3.8)
4.69
(5.7)
4.65
(7.2)
4.49
(6.3)
4.20
(9.1)
4.10
(4.9)
5.99
(6.6)
6.11
(6.8)
4.90
(8.1)
4.51
(6.5)
4.21
(9.1)
4.06
(5.1)
7aa
7bb
8a
5.62
(5.6)
4.86d
—
4.73d
—
4.18
(3.7)
3.93
(11.6)
3.88
(5.1)
5.29
(8.8)
3.99d
3.77d
4.14
(2.2)
3.73
(12.4)
3.66
(3.1)
5.90
(4.9)
6.07
(6.0)
5.02
(7.6)
(4.12)
(3.6)
(3.85)
(11.1)
3.89
(5.1)
9c
3.01
(5.3)
2.53
2.79
4.66
(3.6)
4.44
(9.2)
3.98
(2.7)
3.80
(12.2)
3.66
(5.3)
(<0.5)
(<0.5)
(18.3)
(18.3)
10a
11a
12a
13a
14a
15a
16a
3.07
(5.4)
5.92
(3.6)
4.62
(9.4)
3.98
(2.8)
3.92
(11.7)
3.85
(4.5)
5.65
(5.9)
4.89
(6.9)
4.79
(ꢀ6.2)
5.17
(8.2)
4.47
(3.7)
4.72
(12.1)
4.68
(6.1)
5.52
(3.7)
5.84
(5.8)
5.60
(2.9)
4.87
(12.4)
4.47
(5.5)
2.76
(5.9)
2.63
2.60
4.76
(2.6)
4.81
(12.3)
4.58
(4.9)
4.39e
(—)
4.39e
(4.9)
(0.5)
(17.9)
(18.3)
2.94
(5.5)
5.67
(3.6)
4.74
(9.5)
5.49
(2.2)
4.89
(12.5)
4.43
(5.2)
(<0.5)
5.96
(6.04)
6.26
(6.8)
5.49
(9.3)
5.97
(2.9)
5.06
(12.5)
4.66
(5.1)
3.14
(5.9)
2.86
5.99
(4.2)
5.11
(7.6)
5.91
(2.6)
5.05
(12.6)
4.98
(4.9)
(1.2)
(18.6)
a CDCl3.
b Me2SO-d6.
c D2O.
d Interchangeable.
e Center of a complex multiplet.
as benzoate esters using 9-methylcarbazole (MCZ) in
stoichiometric amounts as photosensitizer.16 The reac-
tion took place efficiently with 3-(trifluoromethyl)benzo-
ates as substrates in 9:1 i-PrOH–H2O as solvent. The
reaction mechanism, the influence of the solvent, and
the role of MgClO4, have been studied.6–8,16
The reaction was successfully used for the deoxygen-
ation of ribonucleosides at positions 20 or 30, depending
on the derivative used, and it has been used as the key
step in a stereocontrolled de novo synthesis of 20-deoxy-
nucleosides.6 Irradiation times between 7 and 15 h were
required for conversion of the starting material into the
deoxygenated photoproducts, which were isolated from
the photolysis reaction in 44–73% yield. They improved
the method by using synthetic 3,6-dimethyl-9-ethylcar-
bazole (DMECZ) as the electron donor. This photosen-
sitizer showed both turnover and improved reactivity.
When used at levels of 10–15 mol %, the deoxygenated
products resulted after 2 h of irradiation.7
In our previous work for the synthesis of 2-deoxy-D-
lyxo-hexono-1,4-lactone (2a, Scheme 1), derivative 1a
was irradiated during 1 h with a 120-W lamp in the pres-
ence of MCZ at 10 mol %. Compound 2a was obtained
in 88% yield (Table 3, entry 1). Deoxygenation of the
peracylated derivative 1b, required 3 h of irradiation
for consumption of the starting lactone (as monitored
by TLC). However, a complex reaction mixture was
obtained due to the long reaction time, from which
compound 2b was isolated by column chromatography
in low yield (Table 3, entry 2).1
The reaction was improved by using a 450-W lamp,
which allowed one to diminish the irradiation time, min-
imizing decomposition. Under these conditions, we ob-
served complete disappearance of the starting lactones

A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
Table 2. 13C NMR chemical shifts (125 or 50 MHz) for compounds 5–16
1791
Compd
C-1
C-2
C-3
C-4
C-5
C-6
5aa
5ba
6a
169.7
170.2
168.1
170.7
171.5
168.8
180.1
173.8
169.2
169.1
171.5
172.9
170.6
172.3
75.5
75.4
73.3
75.2
74.4
73.8
39.5
36.8
76.1
72.7
38.3
36.4
72.4
36.2
73.4d
73.3d
72.7d
72.1d
72.2d
72.3
68.6d
71.4d
73.1d
70.8d
67.9d
68.3d
71.8d
69.9d
79.9
80.3
77.6
79.2
79.9
77.6
83.5
80.4
78.1
76.4
81.4
78.3
74.6
78.0
72.2d
72.2d
71.8d
71.2d
71.4d
71.0
68.4d
68.0d
70.3d
67.6d
66.9d
67.0d
69.0d
68.6d
66.6
66.6
66.6
62.9
62.5
62.8
63.7
63.4
66.3
63.2
60.5
63.6
63.2
63.6
7aa
7bb
8a
9c
10a
11a
12a
13a
14a
15a
16a
a CDCl3.
b Me2SO-d6.
c D2O.
d Interchangeable.
OCOC6H4(3-CF3)
O
OCOC6H4(3-CF3)
RO
RO
RO
RO
R1O
R1O
O
OR
O
OR
O
hυ
O
O
R1
O
R1
i
iii
O
O
O
3
MCZ, MgClO
4
OR
OCOC6H4(3-CF3)
11 R1 = H
16
15
13 R1 = H
14 R1 = Ac
R = COC6H4(3-CF3)
ii
12 R1 = Ac
Scheme 4.
Scheme 3. Reagents and conditions: (i) 2.2 equiv (3-CF3)C6H4COCl,
Py, 0 °C; (ii) 1:1 Ac2O, Py, 0 °C; (iii) 9-methylcarbazole, Mg(ClO4)2,
9:1 n-PrOH–H2O, hm.
methyl)benzoyl esters at 400 W.16 In lactone derivatives,
we now observed that the 2,6-substituted derivative 11
was selectively deoxygenated at C-2 upon only 3 min
of irradiation due to the assistance of the carbonyl
group (Scheme 3 and Table 3, entry 9). Recovery of
compound 13 from the column chromatography was
low (23%); thus acetylation was performed (compound
12) previous to photodeoxygenation, which consider-
ably improved the yield (14, 67%, Table 3, entry 10).
The carbonyl-assisting effect for the PET reaction on
secondary hydroxyl groups could be confirmed by selec-
tive deoxygenation at C-2 of derivative 8 to give 10
(Scheme 3 and Table 3, entry 11). Moreover, when the
other secondary OH groups are substituted as in com-
pound 15, the 2-O-(3-trifluoromethyl)benzoyl group is
selectively deoxygenated (Table 3, entry 12). This fea-
ture of the PET reaction is not shared by the Barton–
McCombie deoxygenation, by which a bis-xanthate
would give a C-2–C-3 olefin.19
in 3 min. Thus, photolysis of compound 1b afforded
selectively 2b in 73% yield (Table 3, entry 3), and com-
plete deoxygenation of 1a occurred in a comparable
yield (Table 3, entry 4).
With the purpose of comparing the efficiency between
benzoyl and 3-(trifluoromethyl)benzoyl groups as subti-
tuents for the deoxygenation reaction, derivative 1c12
(Scheme 1) was also irradiated. Entry 5 (Table 3) shows
that the reaction requires longer irradiation times with
benzoyl than with 3-(trifluoromethyl)benzoyl esters.
However, the less expensive benzoyl esters can be satis-
factorily used to obtain derivatives like 2b.
For deoxygenation of the 2-O-benzoylated derivative
7b (Scheme 2), more than 6 min were required (Table
3, entries 6 and 7), whereas the 3-(trifluoromethyl)-
benzoyl analogue 7a showed total conversion to 9 in
3 min (Table 3, entry 8). Lactone 9 was previously pre-
pared in several steps from tri-O-acetyl-D-glucal,17 and
later it was isolated in very low yield from the c-radio-
lysis products of D-glucose.18
The identity of compounds 9, 10, 13, 14, and 16 was
established on the basis of their NMR spectra. The pres-
ence of two doublets of doublets at high fields (d 3.00
and 2.50, Table 1), with a large Jgem (ꢀ18.0 Hz) in the
1H NMR spectra, and the signal corresponding to the
deoxy function (C-2) at ꢀ39.0 ppm in the 13C NMR
spectra (Table 2), were diagnostic for deoxygenation.
Saito et al. reported that secondary OH could be
selectively reduced in the presence of primary OH, upon
15 h irradiation of the corresponding 3-(trifluoro-

1792
A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
Table 3. Photoinduced deoxygenation of aldono-1,4-lactone derivatives
Entry
1
Compd
Product
Watts
120
Time (min)
60
Conversiona (%)
Yieldb (%)
O
OH
O
OH
O
O
100
881
OCOC6H4(3-CF3)
OH
CH2OH
OH
CH2OH
2a
1a
O
OBz
O
OBz
O
O
201
OCOC6H4(3-CF3)
OBz
CH2OBz
2
120
180
100
OBz
CH2OBz
1b
2b
3
4
1b
1a
2b
450
450
3
3
100
100
73
76
2a
O
OBz
O
OBz
O
O
OBz
5
450
10
68
36
OBz
OBz
CH2OBz
CH2OBz
1c
2b
HO
HO
O
6
7
8
9
450
450
450
3
6
3
16
68
10
46
70
O
OH
OBz
7b
7b
9
9
HO
HO
O
OH
O
100
OCOC6H4(3-CF3)
7a
OCOC6H4(3-CF3)
O
OCOC6H4(3-CF3)
O
HO
HO
O
9
450
3
100
23
OH
O
OH
OCOC6H4(3-CF3)
11
13
OCOC6H4(3-CF3)
O
OCOC6H4(3-CF3)
O
AcO
AcO
O
10
OAc
450
3
100
67
O
OAc
OCOC6H4(3-CF3)
14
12

A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
1793
Table 3 (continued)
Entry
Compd
Product
Watts
450
Time (min)
Conversiona (%)
Yieldb (%)
HO
HO
HO
HO
O
O
OR2
O
OR2
11
3
100
59
O
OR1
10
8 R = COC6H4(3-CF3)
RO
RO
RO
RO
O
OR
O
OR
O
O
12
450
3
100
78
OR
15 R = COC6H4(3-CF3)
16
a Conversion was determined by NMR spectroscopy.
b Yield refers to isolated pure products after column chromatography.
In conclusion, the PET deoxygenation reaction on
aldonolactones that are conveniently derivatized allows
selective deoxygenation at C-2. Conditions for the deoxy-
genation of D-glucono and D-galactono-1,4-lactone
derivatives were optimized, and the selectivity for the
vicinal position to the carbonyl group was confirmed.
The effectiveness of this strategy lies in the easy prepara-
tion of partially substituted aldonolactones, together
with the carbonyl-assisting effect for the PET reaction.
The unique reactivity of the aldonolactone allows for
the 9-methylcarbazole (MCZ) to turn over, and it can
be used in 10 mol %. The 2-deoxy-aldonolactones are
good precursors for the synthesis of 2-deoxy sugar deriv-
atives that are useful for studies on enzyme inhibition.1
rotations were measured with a Perkin–Elmer 343 polar-
imeter, using cells with a path length of 1 dm.
3.2. Materials
D-Glucono-1,5-lactone and 3-(trifluoromethyl)benzoyl-
chloride were purchased from Sigma–Aldrich. D-Glu-
cono-1,4-lactone was prepared by refluxing D-glucono-1,
5-lactone in HCl–2-methoxyethanol as described,13
although the use of basic lead carbonate for the neutral-
ization was avoided; mp 134–135 °C, lit.13 131–134 °C,
[a]D +67 (c 1, water); lit.13 +65.5. 5,6-Di-O-isopropylid-
ene-D-glucono-1,4-lactone (4) was obtained in 83% yield
by treatment of lactone 3 with 2,2-dimethoxypropane
and sulfuric acid as catalyst: mp 108–110; lit.13 107–
110 °C; [a]D +80 (c 1, acetone); lit.13 +84.
3. Experimental
3.3. 5,6-Di-O-isopropylidene-2-O-[3-(trifluoromethyl)-
benzoyl]-D-glucono-1,4-lactone (5a)
3.1. General procedures
Thin-layer chromatography (TLC) was performed on
0.2-mm Silica Gel 60 F254 (Merck) aluminum-backed
plates. Detection was effected by exposure to UV light
and by spraying with 10% (v/v) H2SO4 in EtOH, and
charring. Column chromatography was performed on
Silica Gel 60 (200–400 mesh, E. Merck). NMR spectra
were recorded with a Bruker AC 200 spectrometer at
200 MHz (1H) and 50 MHz (13C) or with a Bruker
AM 500 spectrometer at 500 MHz (1H) and 125 MHz
(13C). The assignments are listed in Tables 1 and 2.
High-resolution mass spectra (HRMS) were recorded
on a VG ZAB2SE (1996) high-resolution mass spec-
trometer, outfitted with an Opus V3.1 and DEC 3000
Alpha Station. Melting points were determined with a
Fisher–Johns apparatus and are uncorrected. Optical
To a solution of 5,6-di-O-isopropylidene-D-glucono-1,4-
lactone (4, 1.28 g, 5.86 mmol) in CH2Cl2 (20 mL) con-
taining pyridine (2 mL), cooled to 0 °C, was added 3-
(trifluoromethyl)benzoylchloride (1.06 mL, 7.01 mmol)
in four aliquots during 2 h. The solution was stirred
for an additional 0.5 h at 0 °C, and then for 1 h at rt.
The solution was diluted with CH2Cl2 and washed with
HCl (5%), water, NaHCO3 (ss), and water, dried
(NaSO4), and concentrated. TLC analysis of the syrup
showed a main product of Rf 0.41 (3:1 toluene–EtOAc),
which was purified by column chromatography (20:1
toluene–EtOAc). Evaporation of the corresponding
fractions afforded compound 5a (1.64, 72%) that gave
[a]D +55 (c 1, CHCl3). Anal. Calcd for C17H17F3O7: C
52.31; H 4.39. Found C 52.27, H 4.34.

1794
A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
3.4. 5,6-Di-O-isopropylidene-2,3-di-O-[3-(trifluoro-
methyl)benzoyl]-D-glucono-1,4-lactone (6)
homogeneous (Rf 0.55, 3:2 toluene–EtOAc). By recrys-
tallization from CHCl3, compound 11 gave mp 141–
142 °C, [a]D +77 (c 1, acetone). Anal. Calcd
for C22H16F6O8: C 50.59; H 3.09. Found C 50.52; H
3.24.
Compound 6 was synthesized as described for 5a, but
using 17.6 mmol (2.65 mL) of 3-(trifluoromethyl)benz-
oylchloride for 1.28 g (5.86 mmol) of compound 4. The
syrup obtained (2.99 g, 98%) gave [a]D +96 (c 1, Cl3CH).
Anal. Calcd for C25H20F6O8: C 52.67; H 2.56. Found: C
52.86; H 2.89.
3.9. 3,5-Di-O-acetyl-2,6-di-O-[3-(trifluoromethyl)-
benzoyl]-D-glucono-1,4-lactone (12)
To a solution of 11 (0.30 g, 0.59 mmol) in dried pyridine
(0.5 mL), cooled at 0 °C, Ac2O (0.5 mL) was added.
After 1.5 h of stirring at 0 °C, the solution was poured
into ice-water and treated as usual. Compound 12 was
obtained as a homogeneous syrup (0.34 g, 94%) of Rf
0.49 (9:1.5 toluene–EtOAc). After purification by col-
umn chromatography (toluene) it gave [a]D +70 (c 1,
acetone). Anal. Calcd for C26H20F6O10: C 51.50; H
3.32. Found: C 51.35; H 3.20.
3.5. 2-O-[3-(Trifluoromethyl)benzoyl]-D-glucono-1,4-
lactone (7a)
Crude compound 5a (2.24 g, 5.74 mmol) was treated
with 4:1 AcOH–water (41 mL) for 1.5 h at 65 °C. The
solvent was evaporated under reduced pressure, and
the acid was eliminated by several coevaporations with
water and toluene. The syrup obtained was purified by
column chromatography (10:1 toluene–EtOAc) and
fractions of Rf 0.55 (EtOAc) (1.45 g, 72%) gave [a]D
3.10. 2,3,5,6-Tetra-O-[3-(trifluoromethyl)benzoyl]-D-
glucono-1,4-lactone (15)
+76 (c 1, acetone). Anal. Calcd for C14H13F3O7
C
48.01, H 3.74. Found: C 48.25; H 3.93.
To a solution of D-glucono-1,4-lactone (3, 0.60 g,
3.37 mmol) in CH2Cl2 (6.0 mL), pyridine (3.0 mL),
and 3-(trifluoromethyl)benzoyl chloride (2.54 mL,
16.8 mmol) were added, and the solution was stirred
for 2 h at 0 °C. The solution was diluted with CH2Cl2
and treated as usual. After column chromatography
(9:1 toluene–EtOAc), fractions of Rf 0.53 were evapo-
rated and characterized as compound 15 (1.17 g,
40%), [a]D +16 (c 1, CHCl3). Anal. Calcd for
C38H20F12O10: C 52.67; H 2.56. Found: C 52.86; H
2.89.
3.6. 2-O-Benzoyl-D-glucono-1,4-lactone (7b)
5,6-Di-O-isopropylidene-D-glucono-1,4-lactone (4, 1.28 g,
5.86 mmol) was treated with benzoyl chloride (0.81 mL,
7.01 mmol) as described for the preparation of 5a, and
immediately after the workup, the crude product was
treated with 4:1 AcOH–water (41 mL) for 1.5 h at
65 °C. After the evaporation of the solvent and several
coevaporations with water and toluene, the syrup ob-
tained was crystallized from 7:3 EtOAc–toluene. Recrys-
tallization from the same solvent gave 0.95 g (58%)
of 2-O-benzoyl-D-glucono-1,4-lactone (7b): mp 130–
131.5 °C, [a]D +89 (c 1, acetone). Anal. Calcd for
C13H14O7: C 55.32; H 5.00. Found: C 55.33; H 5.09.
3.11. Photochemical deoxygenation. General procedure
In a custom-made Pyrex reaction vessel equipped with a
cold finger, a solution containing 0.75 mmol of the sub-
strate, Mg(ClO4)2 (66 mg, 0.3 mM), and 9-methylcarb-
azole (13 mg, 0.075 mmol) in 500 mL of 10% deionized
water–2-PrOH was degassed by bubbling UHP Ar
through the solution for 30 min. The solution was
photolyzed with a 450-W, medium-pressure lamp
(kexc > 300 nm), while the temperature was maintained
at 25 °C with a circulating water bath. Alternatively, a
120-W lamp was used. After irradiation for the times
indicated in Table 3 the solvent was removed under re-
duced pressure and the residue was treated as described
in each case. TLC examination showed the deoxygen-
ated product, and faster moving components (Rf 0.95
and 0.65, 1:1 toluene–EtOAc) corresponding to 9-meth-
ylcarbazole and a photoproduct of 9-methylcarbazole.
2-Deoxy-D-lyxo-hexono-1,4-lactone (2a) and 3,5,6-tri-
O-benzoyl-2-deoxy-D-lyxo-hexono-1,4-lactone (2b) were
obtained as previously reported,1 but using a 400-W
lamp (Table 3).
3.7. 2,3-Di-O-[3-(trifluoromethyl)benzoyl]-D-glucono-1,4-
lactone (8)
Compound 8 was obtained from 6 as described for 7a; Rf
0.38 (1:1 toluene–EtOAc), 85% yield. Anal. Calcd for
C22H16F6O8: C 50.59; H 3.09. Found: C 50.64; H 3.38.
3.8. 2,6-Di-O-[3-(trifluoromethyl)benzoyl]-D-glucono-1,4-
lactone (11)
Compound 11 was prepared as previously described for
2,6-di-O-benzoyl-D-galactono-1,4-lactone.4 To a stirred
solution of D-glucono-1,4-lactone (0.63 g, 3.5 mmol) in
dry pyridine (5.0 mL), cooled in an ice-water bath, 3-
(trifluoromethyl)benzoyl chloride (1.30 mL, 8.6 mmol)
was added in four aliquots during 2 h and treated as
usual. Treatment of the syrup with toluene gave crystal-
line compound 11 (0.93 g, 51%) chromatographically

A. Bordoni et al. / Carbohydrate Research 341 (2006) 1788–1795
1795
The following compounds were obtained.
fluoromethyl)benzoyl]-D-arabino-hexono-1,4-lactone (16)
in 78% yield (0.40 g), [a]D ꢁ83 (c 1, CHCl3). HRFABMS
(positive ion): calcd for C30H19F9O8 [M+H]+, m/z
679.1009; found, m/z 679.1018.
3.11.1. 2-Deoxy-D-arabino-hexono-1,4-lactone (9). The
photolyzed solution from 7a (0.26 g) was evaporated,
partitioned between water and CH2Cl2, and the aqueous
phase was concentrated. Column chromatography puri-
fication afforded 0.08 g (70%) of 2-deoxy-D-arabino-hex-
ono-1,4-lactone (9), Rf 0.32 (9:1 EtOAc–MeOH), [a]D
+58 (c 1, water), lit.17 +68. HRFABMS (positive ion):
calcd for C6H10O5, [M+NH4]+, m/z 180.0914, found
m/z 180.0878.
Acknowledgements
´
This work was supported by grants from Fundacion
Antorchas, Universidad de Buenos Aires, and Agencia
´
´
´
Nacional de Promocion Cientıfica y Tecnologica. R.
M. de Lederkremer and C. Marino are research mem-
bers of CONICET, and A. Bordoni was supported by
a fellowship from CONICET.
Compound 9 was also obtained from 7b (0.21g) in
46% yield.
3.11.2. 2-Deoxy-3-O-[3-(trifluoromethyl)benzoyl]-D-ara-
bino-hexono-1,4-lactone (10). The photolyzed solution
from compound 8 (0.39 g) was purified by column chro-
matography (6:4 toluene–EtOAc), and fractions of Rf
0.23 (1:2 toluene–EtOAc) afforded 0.15 g (59%) of 2-
deoxy-3-O-[3-(trifluoromethyl)benzoyl]-D-arabino-hexono-
1,4-lactone (10): [a]D +3 (c 1, acetone). HRFABMS
(positive ion): calcd for C14H13F3O6, [M+H]+, m/z
352.1002, found m/z 352.1014.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2006.04.012.
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