Conformational evaluation of some 4-deoxyhex-4-enopyranose derivatives and their use in the preparation of a previously undescribed class of 3-thio-L-sorbopyranosides and their 6-C-methoxy analogues

Article abstract of DOI:10.1016/S0008-6215(02)00431-7

A new series of thio-substituted sugars were synthesised relying on the totally regio- and stereoselective cycloaddition of 4-deoxyhex-4-enopyranose derivatives to 'in situ' generated oxothiones. Conformational studies of the above unsaturated sugars showed a marked prevalence of the all-axial conformer.

Full text of DOI:10.1016/S0008-6215(02)00431-7

Carbohydrate Research 338 (2003) 123–132
www.elsevier.com/locate/carres
Conformational evaluation of some 4-deoxyhex-4-enopyranose
derivatives and their use in the preparation of a previously
undescribed class of 3-thio- -sorbopyranosides and their
L
6-C-methoxy analogues
Giuseppe Capozzi,a Giorgio Catelani,b,* Felicia D’Andrea,b Stefano Menichetti,c
Cristina Nativia,*
aCentro CNR ‘Chimica e Struttura Composti Eterociclici’, Dipartimento di Chimica Organica ‘Ugo Schiff’, Uni6ersita’ di Firenze,
6ia della Lastruccia, 13 I-50019 Sesto Fiorentino (FI), Italy
bDipartimento di Chimica Bioorganica e Biofarmacia, Uni6ersita’ di Pisa, 6ia Bonanno, 33 I-56126 Pisa, Italy
cDipartimento di Chimica Organica e Biologica, Uni6ersita’ di Messina, Salita Sperone, 31 I-98166 Messina, Italy
Received 17 May 2002; received in revised form 3 October 2002; accepted 20 October 2002
Abstract
A new series of thio-substituted sugars were synthesised relying on the totally regio- and stereoselective cycloaddition of
4-deoxyhex-4-enopyranose derivatives to ‘in situ’ generated oxothiones. Conformational studies of the above unsaturated sugars
showed a marked prevalence of the all-axial conformer. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Cycloadditions; Oxothiones; 4-Deoxyhex-4-enopyranose derivatives; 3-Thio-L-sorbopyranosides; Conformations
1. Introduction
tives, based on
a
reductive elimination from
ketopyranosyl bromides was devised by Ness and
Fletcher8 and subsequently improved by Lichtenthaler
Monosaccharide glycals constitute one of the most
useful classes of synthetic sugar intermediates, largely
employed in several types of transformations.1 The
versatile reactivity of the glycal’s C-1ꢀC-2 double bond
allows for the introduction of several functional groups
at both carbon atoms. Glycals have, for example, been
successfully used to introduce oxygen,2 nitrogen,3
sulfur4,5 or selenium6 at C-2 of the sugar skeleton.
Another attractive use of glycals as building blocks
regards the stereoselective synthesis of 2-deoxygly-
cosides, a widespread class of compounds, whose
preparation requires ‘tailored’ transformations.7 While
aldopyranose glycals are widely used intermediates,
their ketopyranose analogues were scarcely employed,
owing to the difficulties encountered in their synthe-
and co-workers.9 A synthesis of 1,5-anhydro-
L-threo-4-
deoxyhex-4-enitol derivatives of preparative value was
based on a conceptually different method, exploiting
the facile base promoted acetone elimination from 1,5-
anhydro-3,4-O-isopropylidene-
tives.10 Application of the same reaction to alkyl
3,4-O-isopropylidene- -galactopyranoside lead to a-L-
D-galactitol
deriva-
D
threo-4-deoxyhex-4-enopyranosides such as 2 (Scheme
1).11,12
We report here the conformational investigation of
unsaturated sugars 1–6 and their evaluation as electron
rich dienophiles in etherocycloadditions to a,a%-
dioxothiones and ortho-thioquinones to give a new
class of enantiomerically pure thiosugars.
sis.8,9 A satisfactory preparation of
D-fructal deriva-
2. Results and discussion
* Corresponding authors. Tel.: +39-055-2757630; fax: +
39-055-2476964
E-mail address: cristina.nativi@unifi.it (C. Nativi).
The preparation of 1 has been achieved in overall 72%
yield from 1,5-anhydro-D-galactitol through a previ-
0008-6215/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00431-7

124
G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
Scheme 1.
ously described sequence of acetonation, benzylation
and acetone elimination reactions;10 the 4-deoxyhex-4-
eno derivative 2 was obtained (Scheme 1) by the same
reaction sequence starting from methyl b-D-galactopy-
ranoside.11,12 Because the protection of the free hy-
droxyl group of 1 and 2 may alter the reactivity of the
enolic double bond, benzyl ethers 5 and 6 and acetates
3 and 4 were also prepared. Compounds 310 and 613
were previously described, whereas 4 and 5 were rou-
tinely prepared in high yield by reaction of 2 with acetic
anhydride in pyridine and of 1 with benzyl bromide,
KOH and 18-crown-6, respectively.
unsaturated pyranose derivatives,17,18 an evaluation of
the dependence of the axial preference on substituents
has, to the best of our knowledge, not yet been at-
tempted. The conformational analysis of compounds
1–6 could give, thus, some interesting informations
about this point. An estimate of the population of the
A and B conformers was made by comparing the
experimental vicinal coupling constants of the three
non-vinylic protons H-3, H-2 and H-1 with the corre-
sponding calculated values for the two limit conforma-
tions, applying the Karplus equation modified by
Altona19 to the dihedral angles obtained by molecular
mechanics calculations performed with the PC
MODEL program. The calculated and experimental
values of the coupling constants for compounds 1–6
are reported in Table 1. The conformational equi-
librium for all 1,5-anhydro-4-deoxyhex-4-enitols 1, 3
and 5 showed a marked preference (about 85%) for
conformer A. For the 4-deoxyhex-4-enopyranoside 2, a
similar population was inferred, despite the presence of
2.1. Conformational analysis of unsaturated sugars
Previous studies on the conformation of compound 310
and the structurally related hex-4-enopyranosyl
uronates,14,15 suggest that: i) compounds 1–6 exist as
an equilibrium between the two half-chair conforma-
2
1
tions H1(
L
) (A) and H2( ) (B); ii) a conformer with
L
all-axial sustituents, could substantially contribute to
the equilibrium, because of the so called ‘allylic
effect’ introduced by Ferrier in 196616 to explain the
pseudo-axial preference for allylic oxygenated sub-
stituents. Although this effect was occasionally invoked
to explain the conformational properties of various
Table 1
Conformational equilibrium for unsaturated derivatives 1–6 calculated from NMR data in CD3CN
Compound
J3,4
J2,3
J1,2
J1,3
%A (from J2,3
)
%A (from J1,2)
1
3
5
4.70
4.96
4.69
4.99
2.69
4.81
4.05
3.46
4.63
2.75
n.d.
2.87
3.0
2.09
8.49
3.03
3.52
4.39
1.77
8.65
3.97
1.51
1.69
1.57
–
n.d.
88
86
80
88
83
3.39
3.72
2.45
10.67
3.52
4.15
5.37
2.63
8.04
Calcd for A
Calcd for B
2
4
–
1.08
0.85
0.62
–
82
75
62
84
72
50
6
Calcd for A
Calcd for B
–

G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
125
Scheme 2.
an additional axial substituent at the anomeric position.
Instead, when the allylic substituent was an acetoxy
(compound 4) or a benzyloxy (compound 6), the popu-
lation of conformer A decreased to about 75 and 55%,
respectively.
HOMO of the dienophile and the LUMO of the a,a%-
dioxotiones.22
Reactions were generally performed by adding to a
solution of enol ether in chloroform, the phthalimido
derivative and a weak base such as pyridine and heating
the solution to 60 °C. Cycloadditions were all quite
slow; the required refluxing time ranged from four days
(cycloadduct 18, see Section 3) to ten days (cycload-
ducts 15, 23 and 24). Compounds 3 and 4 (see Scheme
1) could not be used as dienophiles because the electron
withdrawing acetyl group made the reaction very
sluggish.23
These results indicate that allylic hydroxy, acetoxy or
benzyloxy groups (see 1, 3 and 5) determine an
analogous prevalence of the A conformer. The 1,3-diax-
ial steric effect between the allylic and the anomeric
substituents in the 4-deoxyhex-4-enopyranoside series
was, in the case of alcohol 2, completely counterbal-
anced by a combination of the anomeric and the allylic
effects and, likely, by the presence of a stabilising
intramolecular H-bond between the OH and the OMe
groups. In the absence of this latter interaction, (i.e.
compounds 4 and 6), a larger amount of the B con-
former is observed, raising to about 50% for the more
sterically demanding benzyloxy group.
The described cycloadditions showed outstanding se-
lectivities: all reactions occurred with a complete
chemo-,20 regio-20 and stereoselectivity, giving isomeri-
cally pure products. Moreover, the stereochemical out-
come appeared to be independent of the nature of the
substituents R and X on dienophiles (see Scheme 2).
The regio- and stereochemistry of cycloadducts 15–24
2.2. Synthesis of the cycloadducts
1
were unambiguously determined by H NMR analysis:
indeed, d H-3 (15 and 17) or H-4 (16, 18–24) clearly
Cycloaddition of 1, 2, 5 and 6 to the a,a%-dioxothiones
7–9 and ortho-thioquinone 10 which, in turn, were
generated in situ by the base treatment of the parent
phthalimide derivatives 11–14,20,21 gave compounds
15–24, as depicted in Scheme 2.
indicate the presence of a geminal sulfur atom, and J3,4
,
3
are typical diaxial J coupling constants. In the case of
oxothione 8, the complete chemoselectivity,20 due to the
exclusive participation of the ketone carbonyl, was
confirmed by the presence of the ester signal in the 13C
NMR spectrum.
These cycloadditions are inverse electron-demand
Diels-Alder reactions which typically involve the

126
G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
The formation of cycloadducts 15–24 as single
As already reported for related 1,4-oxathiines,5 re-
duction of 18 with LiAlH4 in THF at room temperature
afforded the corresponding allylic alcohol 27 (Scheme
3). Under oxidation conditions (m-CPBA, CH2Cl2,
r.t.), 23 gave the corresponding sulfoxide 28 with com-
plete diasteroselectivity.27
In conclusion, in this paper we reported conforma-
tional studies of 4-deoxyhex-4-eno derivatives 1–6. An
equilibrium between two half-chair forms A and B was
inferred with prevalence for the all-axial (A), con-
former. The prevalence of A was explained taking into
account the steric and anomeric effects as well as the
less familiar allylic effect. An evaluation of the depen-
dence of the latter on different types of substituents was
also estimated. Compounds 1,2,5,6 were successfully
cycloadded with oxothiones 7–10, to give a new class
of enantiomerically pure thiosubstituted sugars. A pre-
liminary investigation of the chemical behaviour of this
class of thiosugars highlighted their potentials as pre-
cursors of non-natural thio-substituted- or deoxy-
carbohydrates.
stereoisomers can be ascribed to a fast interconversion
between A and B with respect to the reaction times (see
Section 3), and assuming that the attack of the oxoth-
iones occurs from the bottom-face (anti to the allylic
substituents) of the presumably more reactive B, in
agreement with the general rule24 predicting that in
all-equatorial glycal series a bottom-site attack is
preferred.25
Although conformer A is more abundant, no correla-
tion between the stereoselectivity of the reaction of
thiones with glycals and their conformational prefer-
ences can be likely expected.25,26 As a matter of fact, the
product distribution is not determined by the distribu-
tion of the ground state conformers (see Curtin-Ham-
mett principle) but by the relative transition states
energy.
2.3. Reactivity of cycloadducts
Further investigations on these interesting building-
blocks are currently in progress in our laboratories.
Compounds 15–24 represent a new class of thiosubsti-
tuted sugars, efficiently and selectively obtained by
cycloaddition of 4-deoxyhex-4-eno derivatives to oxoth-
iones, which are promising building blocks for the
synthesis of carbohydrate derivatives. With this in mind
we carried out a preliminary investigation on the reac-
tivity which, to our knowledge, has not been reported
up to date.
3. Experimental
3.1. General methods
Although analogies with previously reported cycload-
ducts of related oxathiines was observed, unexpected
differences raised the interest in these new class of
thiosugars. Treatment of 16 and 18 with Raney nickel
in wet THF at room temperature afforded derivatives
25 and 26, respectively with a small amount of com-
pounds 2 (8%, from 16) and 6 (9%, from 18). Under
reducing desulfurisation conditions compounds 16 and
18 underwent the expected desulfurisation but also the
unpredictable21,23 reduction of the conjugated double
bond. Different reaction conditions (EtOH as solvent,
at r.t. or 60 °C) increased the amount of 2 and 6. No
reaction was observed instead with cycloadducts 17 and
24.
Solvents were purified and dried according to standard
procedures. All reactions were performed under nitro-
gen in dry solvents unless otherwise stated. TLC was
performed on glass-backed Silica Gel (Macherey-Nagel,
Durasil-25-UV254). Detection was effected by treatment
with a solution of vanillin (3 g) and H2SO4 (4 mL) in
EtOH (250 mL). Flash chromatography was carried out
on silica gel (Macherey-Nagel, 60M). CHCl3 was
washed with water and dried with CaCl2 before use.
Optical rotations were determined at 25 °C with a Jasco
DIP-370 polarimeter (1 dm cell). NMR spectra were
recorded with a Varian Gemini 2000 (200 MHz) and a
Bruker AM 500 (500 MHz) instruments, using CDCl3
1
as solvent for H NMR and 13C NMR (dH=7.26 and
Scheme 3.

G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
127
dC=77.0, respectively, as reference). Melting point are
3.3. Methyl 3-O-acetyl-2,6-di-O-benzyl-4-deoxy-a-
threo-hex-4-enopyranoside (4)
L-
uncorrected and were recorded with a Bu¨chi 510 ap-
paratus. Elemental analyses were performed with a
Perkin–Elmer Elementary Analyser 2400 Series II.
Compounds 1 and 3 were prepared according to Ref.
10 and compounds 2 and 6 according to Refs. 12 and
13, respectively. In the preparation of 1, the overall
yield from 1,5-anhydro-galactitol was improved to 72%
operating without purification of the intermediates.
NMR data for 2, previously reported in C6D6,12 were
now determined in CD3CN solution and are as follow:
1H NMR (200 MHz, CD3CN): d 3.44 (3 H, s, CH3O),
3.63 (ddd, 1 H, J2,3 3.0 Hz, J2,4 1.1 Hz, H-2), 3.93 (m,
1 H, J3,6% 0.8 Hz, H-6%), 3.94 (m, 1 H, J3,4 4.8 Hz, H-3),
3.95 (m, 1 H, J3,6 0.9 Hz, H-6), 4.67 (s, 2 H, CH2ꢀBn),
4.70 (s, 2 H, CH2ꢀBn), 5.07 (dd, 1 H, J1,2 3.5 Hz, J1,3
1.1 Hz, H-1), 5.11 (m, 1 H, J4,6 0.7 Hz, J4,6% 0.6 Hz,
H-4), 7.29–7.38 (m, 10 H, CHꢀAr); 13C NMR (50
MHz, CD3CN): d 56.6 (CH3O), 64.5 (C-3), 70.2 (C-6),
70.2, 72.5 (2 CH2ꢀBn), 77.7 (C-2), 100.4 (C-1), 103.5
(C-4), 127.8–130.2 (10 CꢀAr); 139.4 (2 Cq); 148.5 (C-
5).
A solution of 2 (600 mg, 1.68 mmol) in pyridine (8 mL)
and acetic anhydride (4 mL) was left 5 h at room
temperature, then co-evaporated three times with tolu-
ene (3×10 mL). The residue was purified by flash
column chromatography on silica gel (4:1 hexane–
EtOAc+0.1% Et3N) to give pure 4 (621 mg, 93%) as a
1
syrup; [a]D +13.20° (c 1.30, CHCl3), H NMR (200
MHz, CD3CN) d: 1.97 (s, 3 H, CH3CO), 3.45 (s, 3 H,
OCH3), 3.67 (ddd, 1 H, J2,3 3.5 Hz, J2,4 1.0 Hz, H-2),
3.94 (m, 1 H, J3,6 0.9 Hz, J4,6 0.8 Hz, H-6), 3.94 (m, 1
H, J4,6% 0.8 Hz, J3,6% 0.9 Hz, H-6%), 4.52 (s, 2 H,
CH2ꢀBn), 4.72 (s, 2 H, CH2ꢀBn), 4.98 (dd, 1 H, J1,2 4.2
Hz, J1,3 0.8 Hz, H-1), 5.00 (ddd, 1 H, J3,4 4.0 Hz, H-4),
5.21 (m, 1 H, H-3); 13C NMR (50 MHz, CD3CN) d:
21.3 (CH3CO), 56.9 (OCH3), 67.6 (C-3), 69.9 (C-6),
70.9, and 73.2 (2 CH2ꢀBn), 76.1 (C-2), 99.0 (C-4), 101.0
(C-1), 128.5–129.3 (10 CHꢀAr), 139.2, and 139.3 (2
Cq), 148.1 (C-5), 169.6 (CꢁO); Anal. Calcd for
C23H26O6: C, 69.33; H, 6.58. Found: C, 69.57; H, 7.00.
3.2. 1,5-Anhydro-2,3,6-tri-O-benzyl-4-deoxy- -threo-
hex-4-enitol (5)
L
3.4. 1{(4S,5S)-1,5-Anhydro-2,3-di-O-benzyl-4-deoxy-L-
threo-hexitol[3,2-b]-2-methyl-1,4-oxathiin-3-yl}ethanone
(15)
To a solution of 1 (953 mg, 2.92 mmol) in THF
containing 0.5% of water (7.0 mL), 18-crown-6 (35 mg,
0.13 mmol) and powdered KOH (650 mg) were added;
the mixture was stirred 20 min at room temperature
then treated with benzyl bromide (0.6 mL, 5.04 mmol).
The reaction mixture was stirred at room temperature
until TLC analysis (1:1 hexane–EtOAc) revealed the
complete disappearance of 1 (4 h). Excess benzyl bro-
mide was destroyed by addition of MeOH (15 mL) and
stirring at room temperature for 10 min, the solvents
were concentrated under diminished pressure, the
residue taken up in CH2Cl2 (50 mL), washed with H2O
(3×25 mL) and the dried organic phase was concen-
trated under diminished pressure. The crude residue
(1.60 g) was submitted to flash column chromatography
on silica gel (9:1 hexane–EtOAc+0.1% Et3N), to give
pure 5 (1.11 g, 91%) as a syrup; [a]D= +101.54° (c
1.30, CHCl3); 1H NMR (200 MHz, CD3CN) d: 3.70 (m,
1 H, J2,3 3.0 Hz, J2,4 1.4 Hz, H-2), 3.87 (m, 1 H, J1,3 1.6
Hz, H-3), 3.92 (m, 1 H, J4,6 0.7 Hz, H-6), 3.92 (m, 1 H,
J4,6% 0.7 Hz, H-6%), 3.93 (m, 1 H, J1%,2 1.9 Hz, H-1%), 4.21
(ddd, 1 H, J1,1% 11.7 Hz, J1,2 3.7 Hz, H-1), 4.49 (s, 2 H,
CH2ꢀBn), 4.56, and 4.60 (AB system, 2 H, JAB 11.9 Hz,
CH2ꢀBn), 4.58, and 4.63 (AB system, 2 H, JAB 11.8 Hz,
CH2ꢀBn), 5.07 (m, 1 H, J3,4 4.7 Hz, H-4), 7.28–7.37 (m,
15 H, CHꢀAr.); 13C NMR (50 MHz, CD3CN) d: 65.1
(C-6), 70.5 (C-1), 70.6 (C-3), 70.6, 71.7, and 72.7 (3
CH2ꢀBn), 73.7 (C-2), 98.3 (C-4), 127.9–129.3 (15
CHꢀAr), 139.5, 139.5, and 140.0 (3 Cq), 154.6 (C-5);
Anal. Calcd for C27H28O4: C, 77.86; H, 6.78. Found: C,
77.98; H, 6.82.
To a solution of compound 1 (80 mg, 0.24 mmol) in
CHCl3 (3 mL), 82 mg (0.29 mmol) of phthalimide
derivative 11 and 21 mL (0.29 mmol) of pyridine were
added at room temperature. The reaction mixture was
heated to 60 °C and kept at this temperature for 10
days. After this time it was cooled to room tempera-
ture, diluted with CH2Cl2 (5 mL), washed with a satu-
rated NH4Cl solution (2×) and H2O (1×) and the
organic layer dried over Na2SO4. Evaporation of the
solvent afforded a crude product (223 mg) which was
purified by flash column chromatography on silica gel
(6:1 hexane–EtOAc) to give 15 (56 mg, 50%) as glassy
solid. 1H NMR (200 MHz, CDCl3) d: 2.27 (s, 3 H,
CH3ꢀCꢁC), 2.31 (s, 3 H, CH3ꢀCO), 2.81 (bs, 1 H, OH),
3.32–3.37 (m, 1 H, H-2), 3.46 (B part of an AB system,
1 H, JAB 10.2 Hz, H-6), 3.58–3.64 (m, 3 H, H-1ax,
H-1eq, and H-3), 3.86 (A part of an AB system, 1 H,
JAB 10.2 Hz, H-6%), 3.88–3.93 (m, 1 H, H-4), 4.52, and
4.69 (AB system, 2 H, JAB 12.0 Hz, CH2ꢀBn), 4.69, and
4.80 (AB system, 2 H, JAB 11.8 Hz, CH2ꢀBn), 7.26–
7.36 (m, 10 H, 10 CHꢀAr); 13C NMR (50 MHz, CDCl3)
d: 21.7 (CH3ꢀCO), 30.2 (CH3ꢀCꢁC), 41.6 (C-1), 62.1,
70.0, 71.5, 73.4, 74.1 (C-3, C-4, C-2, 2 CH2ꢀBn), 100.4
(C-5), 101.6 (SCꢁC), 127.8, 128.0, 128.3, 128.5 (10
CHꢀAr), 137.3, 137.8 (2 Cq), 159.0 (SCꢁC), 195.4
(CꢁO). Acetylation of 15 under standard conditions
afforded the corresponding acetyl derivative quantita-
1
tively; [a]D= −71.57° (c 0.17, CHCl3); H NMR (200
MHz, C6D6) d: 1.57 (s, 3 H, CH3ꢀAc), 2.01 (s, 3 H,

128
G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
CH3ꢀCꢁC), 2.09 (s, 3 H, CH3ꢀCꢁO), 3.18–3.31 (m, 1
H, H-2), 3.30 (B part of an AB system, 1 H, JAB 10.0
Hz, H-6), 3.38 (d, 1 H, J3,4 10.6 Hz, H-4), 3.53–3.62
(m, 2 H, H-1ax, and H-1eq), 3.78 (A part of an AB
system, 1 H, JAB 10.0 Hz, H-6%), 4.04 (as, 2 H,
CH2ꢀBn), 4.14, and 4.27 (AB system, 2 H, JAB 12.2 Hz,
CH2ꢀBn), 5.28 (dd, 1 H, J2,3 10.4 Hz, J3,4 10.6 Hz,
H-3), 7.24–7.35 (m, 10 H, 10 CHꢀAr); 13C NMR (50
MHz, CDCl3) d: 20.9 (CH3ꢀAc), 21.5 (CH3ꢀCO), 30.3
(CH3ꢀCꢁC), 38.8 (C-1), 62.1, 69.6, 71.6, 73.0, 74.2, and
75.3 (C-2, C-3, C-4, C-6, and 2 CH2ꢀBn), 100.6, 102.0,
127.6, 127.8, 127.87, 127.9, 128.4, and 128.4 (10
CHꢀAr), 137.2, and 137.6 (2 Cq), 158.2 (SCꢁC), 169.7
(COꢀAc), 195.9 (CꢁO); Anal. Calcd for C27H30O7S: C,
65.04; H, 6.06. Found: C, 65.29; H, 6.00.
ture was heated to 60 °C for 10 days, then cooled to
room temperature, diluted with CH2Cl2 (3 mL), washed
with a saturated NH4Cl solution (2×) and water (1×)
and dried over Na2SO4. After concentration, the crude
product (62 mg) was purified by flash column chro-
matography on silica gel (CHCl3) to give 17 (15.7 mg,
1
60%) as colourless oil; [a]D −8.89° (c 0.10, CHCl3); H
NMR (200 MHz, CDCl3) d: 2.30 (s, 3 H, CH3), 2.50 (s,
3 H, CH3ꢀCO), 3.41–3.71 (m, 5H, H-1ax, H-1eq, H-2,
CH2-6), 3.86–3.94 (m, 1 H, H-3), 3.89 (d, 1 H, J3,4 10.2
Hz, H-4), 4.59 (AB system, 2 H, JAB 11.2 Hz, CH2ꢀBn),
4.68 (AB system, 2 H, JAB 11.2 Hz, CH2ꢀBn), 4.86 (AB
system, 2 H, JAB 10.6 Hz, CH2ꢀBn), 7.28–7.42 (m, 15
H, 15CHꢀAr); 13C NMR (50 MHz, CDCl3) d: 21.6
(CH3ꢀCO), 30.1 (CH3ꢀCꢁC), 40.6 (C-1), 62.2, 71.5,
73.4, 74.1, 76.6, and 78.2 (C-2, C-3, C-4, and 3
CH2ꢀBn), 100.8 (C-5), 102.1 (SCꢁC), 127.1, 127.4,
127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.4, 128.4,
and 128.5 (15 CHꢀAr), 137.3, 137.8, and 138.0 (3 Cq),
158.7 (SCꢁC); 195.6 (CꢁO); Anal. Calcd for C32H34O6S:
C, 70.31; H, 6.27. Found: C, 70.42; H, 6.01.
3.5. 1-{Methyl (4S,5R)-2,6-di-O-benzyl-4-deoxy-a-L-
threo-hexopyranosid[4,5-b]-2-methyl-1,4-oxathiin-3-yl}-
ethanone (16)
To a solution of 2 (200 mg, 0.56 mmol) in 3 mL of
CHCl3, 248.9 mg (0.9 mmol) of phthalimide derivative
11 and 35.4 ml (0.45 mmol) of pyridine were added. The
reaction mixture was heated at 60 °C for 7 days, after
this time the heating was stopped and the mixture
diluted with CH2Cl2 (3 mL), washed with saturated
NH4Cl solution (2×) and water (1×) and dried over
Na2SO4. The organic layer was concentrated and the
crude product (630 mg) was purified by flash column
chromatography on silica gel (4:1 hexane–EtOAc) to
give 16 (140 mg, 51%) and unreacted glycal 2 (30 mg,
60%) as a yellow oil; [a]D −16.99° (c 1.12, CHCl3);
nmax (thin film) 3031 (m), 2923 (s), 1673 (s, CꢁO), 1563
3.7. 1-{Methyl (4S,5R)-2,3,6-tri-O-benzyl-4-deoxy-a-L-
threo-hexopyranosid[4,5-b]-2-methyl-1,4-oxathiin-3-yl}-
ethanone (18)
To a solution of 6 (200 mg, 0.45 mmol) in 3 mL of
CHCl3, 174.5 mg (0.63 mmol) of phthalimide derivative
11 and 28.4 ml (0.36 mmol) of pyridine were added. The
reaction mixture was heated to 60 °C. After 93 h the
heating was stopped and the mixture was diluted with
CH2Cl2 (15 mL), washed with saturated NH4Cl solu-
tion (2×) and water (1×) and dried over Na2SO4. The
organic layer was concentrated to give 288 mg of crude
product which was purified by flash column chromatog-
raphy on silica gel (CH2Cl2) affording the cycloadduct
18 (224 mg, 86%) as yellow oil; [a]D −144.81° (c 0.14,
CHCl3); nmax (thin film) 3031 (m), 2913 (s), 1673 (s,
1
(s, CꢁC) cm−1; H NMR (200 MHz, C6D6) d: 2.14 (s,
3 H, CH3), 2.27 (s, 3 H, CH3CꢁO), 3.34 (s, 3 H, CH3O),
3.39–3.67 (m, 4 H, H-2, H-3, and CH2-6), 3.90 (d, 1 H,
J3,4 10.2 Hz, H-4), 4.46 (AB system, 2 H, JAB 12.0 Hz,
CH2ꢀBn), 4.73 (B part of an AB system, 1 H, JAB 11.4
Hz, CHBꢀBn), 4.82 (d, 1 H, J1,2 8.0 Hz, H-1), 4.96 (A
part of an AB system, 1 H, JAB 11.8 Hz CHAꢀBn),
7.11–7.42 (m, 10 H, 10CHꢀAr); 13C NMR (50 MHz,
CDCl3) d: 21.7 (CH3CꢁO), 30.1 (CH3ꢀCꢁ), 40.0 (C-6),
57.3 (CH3O), 68.3, 71.2, 74.0, 74.7, and 81.4 (C-2, C-3,
C-4, and 2 CH2ꢀBn), 99.8, and 100.6 (C-1, and C-5),
101.8 (SCꢁC); 127.9, 128.0, 128.1, 128.4, and 128.6 (10
CHꢀBn), 137.4, and 138.1 (2 Cq), 158.3 (SCꢁC); 195.6
(CꢁO); Anal. Calcd for C26H30O7S: C, 64.18; H, 6.21.
Found: C, 63.69; H, 6.14.
1
CꢁO), 1563 (s, CꢁC) cm−1; H NMR (500 MHz, C6D6)
d: 1.99 (s, 3 H, CH3), 2.20 (s, 3 H, CH3CꢁO), 3.24 (s, 3
H, CH3ꢀO), 3.43 (B part of an AB system, 1 H, JAB
10.5 Hz, CHBꢀBn), 3.45–3.54 (m, 2 H, H-2, and H-3),
3.60 (A part of an AB system, 1 H, JAB 10.5 Hz,
CHAꢀBn), 3.82 (d, 1 H, J3,4 10.0 Hz, H-4), 4.33 (AB
system, 2 H, JAB 12.0 Hz, CH2ꢀBn), 4.54 (B part of an
AB system, 1 H, JAB 11.2 Hz, CHBꢀBn), 4.68–4.83 (m,
3 H, CH2ꢀBn, and H-1), 4.74 (d, 1 H, J1,2 8.0 Hz, H-1),
4.82 (A part of an AB system, 1 H, JAB 11.5 Hz,
CHAꢀBn), 6.96–7.28 (m, 15 H, CHꢀBn); 13C NMR (50
MHz, C6D6) d: 21.2 (CH3ꢀCꢁO), 29.6 (CH3), 41.0
(C-6), 56.6 (CH3O), 71.59, 73.79, 74.81, 76.29, 76.52,
and 82.79 (C-2, C-3, C-4, and 3 CH2ꢀBn), 100.05, and
101.21 (C-1, and C-5), 102.34, 127.30, 127.55, 127.77,
128.39; 138.02, 138.75, and 138.86 (3 Cq), 157.49, and
194.08 (CꢁO); Anal. Calcd for C33H36O7S: C, 68.73; H,
6.29. Found: C, 68.69; H, 6.61.
3.6. 1{(4S,5S)-1,5-Anhydro-2,3,6-tri-O-benzyl-4-deoxy-
L-threo-hexitol[3,2-b]-2-methyl-1,4-oxathiin-3-yl}-
ethanone (17)
A solution of 5 (20 mg, 0.05 mmol) in 1.5 mL of CHCl3
was treated with 24 mg (0.09 mmol) of phthalimide
derivative 11 and pyridine (3.03 ml). The reaction mix-

G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
129
3.8. Ethyl 1-{methyl (4S,5R)-2,6-di-O-benzyl-4-deoxy-
a- -threo-hexopyranosid[4,5-b]-2-methyl-1,4-oxatiin-
3-yl}formate (19)
127.7, 128.0, 128.2, and 128.3 (15 CHꢀBn), 137.7,
138.0, and 138.2 (3 Cq), 158.7 (SCꢁC); 165.1 (OCꢁO).
L
3.10. Methyl (4S,5R)-2,6-di-O-benzyl-4-deoxy-a-
threo-hexopyranosid[4,5-b]-3-benzoyl-2-phenyl-
1,4-oxathiin (21)
L-
To a solution of 2 (50 mg, 0.14 mmol) in 3 mL of
CHCl3, 77.36 mg (0.25 mmol) of phthalimide derivative
12 and 11.09 ml (0.14 mmol) of pyridine were added.
The mixture was heated to 60 °C for 9 days and after
this time the heating was stopped and the reaction
diluted with CH2Cl2 (10 mL), washed with a saturated
NH4Cl solution (2×) and water (1×) and dried over
Na2SO4. After concentration, the crude product (180
mg) was purified by flash column chromatography on
silica gel (3:1 hexane–EtOAc) to give 19 (35 mg, 48%);
[a]D +9.13° (c 0.15, CHCl3); 1H NMR (500 MHz,
CDCl3) d: 1.30 (t, 3 H, J 7.2 Hz, CH3CH2O), 2.30 (s, 3
H, CH3ꢀCꢁC), 3.41 (d, 1 H, J3,4 11.1 Hz, H-4), 3.53–
3.57 (m, 4 H, CH3O, CH-6), 3.81–3.90 (m, 3 H, H-1,
H-2, and CH-6%), 4.13–4.26 (m, 3 H, H-3, and
CH3CH2O), 4.63 (B part of an AB system, 1 H, JAB
11.8 Hz, CHBꢀBn); 4.68 (AB system, 2 H, JAB 11.8 Hz,
CH2ꢀBn), 4.76 (A part of an AB system, 1 H, JAB 11.8
Hz, CHAꢀBn), 5.07 (s, 1 H, OH), 7.28–7.37 (m, 10 H,
10 CHꢀAr); 13C NMR (50 MHz, CDCl3) d: 14.2
(CH3CH2O), 21.4 (CH3CꢁC), 34.5 (C-6), 55.8 (CH3O),
61.0 (CH3CH2O), 71.1, 72.2, 74.1, and 75.0 (C-2, C-3,
C-4, and 2 CH2ꢀBn), 97.4, and 98.9 (C-1, and C-5),
99.7 (SCꢁC); 127.4, 127.5, 127.9, 128.2, and 128.5 (10
CHꢀAr), 137.3, and 137.9 (2 Cq), 157.67 (SCꢁC);
164.92 (OCꢁO); Anal. Calcd for C27H32O8S: C, 62.77;
H, 6.24. Found: C, 62.80; H, 6.13.
A solution of 2 (100 mg, 0.28 mmol) in 3 mL CHCl3
was treated with 202.3 mg (0.50 mmol) of phthalimide
derivative 13 and 22.0 mL (0.28 mmol) of pyridine. The
reaction mixture was heated to 60 °C for 7 days then
cooled to room temperature, diluted with CH2Cl2 (15
mL), washed with a saturated NH4Cl solution (2×)
and water (1×) and dried over Na2SO4. The crude
product (280 mg) obtained after concentration, was
purified by flash column chromatography on silica gel
(3:1 hexane–EtOAc) to give 21 (80 mg, 47%) as a pale
yellow oil; [a]D −53.44° (c 0.18, CHCl3); 1H NMR
(200 MHz, C6D6) d: 3.23 (s, 3 H, CH3O), 3.48 (dd, 1 H,
J1,2 8.0 Hz, J2,3 9.2 Hz, H-2), 3.56 (B part of an AB
system, 1 H, JAB 10.6 Hz, CH-6), 3.83–3.93 (m, 1 H,
H-3), 3.91 (d, 1H, J3,4 10.4 Hz, H-4), 4.13 (A part of an
AB system, 1 H, JAB 10.6 Hz, CH-6%), 4.26 (s, 1 H,
OH), 4.54 (s, 2 H, CH2ꢀBn), 4.75 (B part of an AB
system, 1 H, JAB 11.0 Hz, CHBꢀBn), 4.89 (A part of an
AB system, 1 H, JAB 11.0 Hz, CHAꢀBn), 4.93 (d, 1 H,
J1,2 8.0 Hz, H-1), 6.72–6.83 (m, 5 H), 7.06–7.36 (m, 13
H), 7.70–7.75 (m, 2 H); 13C NMR (50 MHz, C6D6) d:
44.1 (C-6), 57.0 (CH3O), 70.3, 71.9, 74.2, 75.0, and 82.4
(C-2, C-3, C-4, and 2 CH2ꢀBn), 100.5, and 101.4 (C-1,
and C-5), 105.8 (SCꢁC); 127.0, 127.5, 128.2, 128.5,
128.6, 129.3, 129.5, 129.8, 132.3, and 133.5 (20
CHꢀAr.), 135.5, 138.1, 138.3, 139.3, and 153.5 (SCꢁC),
193.82 (CꢁO); Anal. Calcd for C36H34O7S: C, 70.80; H,
5.61. Found: C, 70.74; H, 5.92.
3.9. Ethyl 1-{methyl (4S,5R)-2,3,6-tri-O-benzyl-4-de-
oxy-a- -threo-hexopyranosid[4,5-b]-2-methyl-1,4-
L
oxatiin-3-yl}formate (20)
To a solution of 6 (100 mg, 0.22 mmol) in 3 mL of
CHCl3, 82.6 mg (0.26 mmol) of phthalimide derivative
12 and 17.7 ml (0.22 mmol) of pyridine were added and
the mixture was heated to 60 °C for 5 days. After this
time, the heating was stopped and the reaction mixture
was diluted with CH2Cl2 (10 mL), washed with satu-
rated NH4Cl (2×) and water (1×) and dried over
Na2SO4. After concentration the crude product (250
mg) was purified by flash column chromatography on
silica gel (5:1 hexane–EtOAc) to give 20 (55 mg, 42%)
3.11. Methyl (4S,5R)-2,3,6-tri-O-benzyl-4-deoxy-a-
threo-hexopyranosid[4,5-b]-3-benzoyl-2-phenyl-1,4-
oxathiin (22)
L-
A solution of 6 (100 mg, 0.22 mmol) in 2 mL CHCl3
was treated with 162.0 mg (0.40 mmol) of phthalimide
derivative 13 and 17.7 mL (0.22 mmol) of pyridine. The
reaction mixture was heated to 60 °C for 6 days then
cooled to room temperature, diluted with CH2Cl2 (3
mL), washed with a saturated NH4Cl solution (2×)
and water (1×) and dried over Na2SO4. After concen-
tration, the crude product (300 mg) was purified by
flash column chromatography on silica gel (7:1 hex-
ane–EtOAc) to afford cycloadduct 22 (65.0 mg, 48%)
as yellowish oil; [a]D −77.03° (c 0.16, CHCl3); 1H
NMR (200 MHz, C6D6) d: 3.32 (s, 3 H, CH3O), 3.69
(at, 1 H, J1,2 7.8 Hz, H-2), 3.81 (d, 1 H, J3,4 10.6 Hz,
H-4), 3.99 (B part of an AB syst., 1 H, JAB 10.2 Hz,
CH-6), 4.13 (dd, 1 H, J2,3 10.8 Hz, J3,4 10.6 Hz, H-3),
4.26 (A part of an AB syst., 1 H, JAB 10.2 Hz, CH-6%),
1
as colourless oil; H NMR (200 MHz, CDCl3) d: 1.30
(t, 3 H, J 7.0 Hz, CH3CH2O), 2.33 (s, 3 H, CH3ꢀCꢁC),
3.37–3.77 (m, 7 H, H-2, H-3, CH3O, and CH2-6), 3.90
(d, 1 H, J3,4 10.6 Hz, H-4), 4.21 (q, 2 H, J 7.2 Hz,
CH3CH2O), 4.54–4.87 (m, 7 H, 3 CH2ꢀBn, and H-1),
7.25–7.38 (m, 15 H, 15 CHꢀAr); 13C NMR (50 MHz,
CDCl3) d: 14.2 (CH3CH2O), 21.1 (CH3ꢀCꢁC), 41.1
(C-6), 57.3 (CH3O), 61.0 (CH3CH2O), 71.2, 74.0, 75.0,
76.4, 76.5, and 82.4 (C-2, C-3, C-4, and 3 CH2ꢀBn),
99.9, and 101.0 (C-1, and C-5), 101.8 (SCꢁC); 127.6,

130
G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
4.61 (s, 2 H, CH2ꢀBn), 4.75 (B part of an AB syst., 1 H,
JAB 11.4 Hz, CHBꢀBn), 4.98 (A part of an AB syst., 1
H, JAB 11.2 Hz, CHAꢀBn), 5.04 (d, 1 H, J1,2 8.0 Hz,
H-1), 5.15 (B part of an AB syst., 1 H, JAB 9.8 Hz,
CHBꢀBn), 5.30 (A part of an AB syst., 1 H, JAB 9.8 Hz,
CHAꢀBn), 6.81–6.92 (m, 5 H), 7.11–7.58 (m, 18 H),
7.80–7.85 (m, 2 H); 13C NMR (50 MHz, CDCl3) d:
42.4 (C-6), 57.4 (CH3O), 71.0, 74.1, 75.2, 77.4, 82.7
(C-2, C-3, C-4, 3 CH2ꢀBn), 93.2, 100.0 (C-1, C-5), 101.2
(SCꢁC); 127.21, 127.92, 127.97, 128.05, 128.25, 128.45,
128.50, 128.74, 128.85, 129.41, 132.51 (25 CHꢀAr.),
135.58, 137.51, 137.69, 138.04, 138.19 (5 Cq), 153.19
(SCꢁC); 185.84 (CꢁO); Anal. Calcd for C43H40O7S: C,
73.69; H, 5.76. Found: C, 73.89; H, 6.25.
then it was cooled to room temperature and treated
with an additional amount of phthalimide derivative 14
(37.4 mg, 0.11 mmol). The heating (60 °C) was main-
tained for 6 additional days. After this time, the mix-
ture was cooled to room temperature, diluted with
CH2Cl2 (10 mL), washed with a saturated NH4Cl solu-
tion (2×) and water (1×) and dried over Na2SO4. The
crude product (450 mg) was purified by flash column
chromatography on silica gel (6:1 hexane–EtOAc) to
give 24 (121.4 mg, 66%) as colourless oil; [a]D −68.22°
1
(c 0.14, CHCl3); H NMR (200 MHz, CDCl3) d: 3.51–
3.82 (m, 7 H, H-2, H-3, CH2-6, CH3O), 4.02 (d, 1 H,
J3,4 10.6 Hz, H-4), 4.58–4.76 (m, 6 H, 3 CH2ꢀBn), 4.92
(d, 1 H, J1,2 10.6 Hz, H-1), 7.06 (d, 1 H, J 9.0 Hz,
CHꢀAr.), 7.23–7.59 (m, 18 H, 3 CHꢀAr., 15 CHꢀBn),
7.77 (d, 1 H, J 7.7 Hz, CHꢀAr.), 7.95 (d, 1 H, J 7.6 Hz,
CHꢀAr.); 13C NMR (50 MHz, CDCl3) d: 41.4 (C-6),
57.4 (CH3O), 71.3, 74.0, 75.0, 76.7, 77.3, 82.8 (C-2, C-3,
C-4, 3 CH2ꢀBn), 98.8 (C-5), 101.0 (C-1), 107.4 (SCꢁC);
119.2, 123.0, 124.6, 126.7, 126.8, 127.7, 127.8, 128.1,
128.2, 128.3, 128.4 (15 CHꢀBn, 6 CHꢀAr.), 129.6, 131.3
(2CqꢀAr.), 137.9, 138.1, 138.3 (3 CqꢀBn), 148.9
(SCꢁC); Anal. Calcd for C38H36O6S: C, 73.53; H, 5.85.
Found: C, 73.20; H, 6.22.
3.12. Methyl (4S,5R)-2,6-di-O-benzyl-4-deoxy-a-L-
threo-hexopyranosid[4,5-b]naphtho[1,2-e]-1,4-oxathiin
(23)
A solution of 2 (100 mg, 0.28 mmol) in 2 mL of CHCl3
was treated with 108 mg (0.33 mmol) of phthalimide
derivative 14 and 17.75 mL (0.22 mmol) of pyridine.
The reaction mixture was heated to 60 °C for 8 days
then cooled to room temperature and treated with an
additional amount of 14 (89 mg, 0.28 mmol). The
heating (60 °C) was maintained for 2 additional days.
After this time, the mixture was diluted with CH2Cl2
(10 mL), washed with a saturated NH4Cl solution (2×)
and water (1×) and dried over Na2SO4. The organic
layer was concentrated and the crude product obtained
(268 mg) was purified by flash column chromatography
on silica gel (2:1 hexane–EtOAc) to give 23 (72 mg,
48%) as a colourless oil; [a]D −90.92° (c 0.14, CHCl3);
1H NMR (200 MHz, CDCl3) d: 2.15 (bs, 1 H, OH),
3.41–3.50 (m, 1 H, H-2), 3.64–3.72 (m, 6 H, H-3,
CH2-6, CH3O), 3.98 (d, 1 H, J3,4 10.6 Hz, H-4), 4.58–
4.94 (m, 4 H, 2 CH2ꢀBn), 4.95 (d, 1 H, J1,2 8.4 Hz,
H-1), 7.03 (d, 1 H, J 9.2 Hz, CHꢀAr.), 7.24–7.57 (m, 13
H, 3 CHꢀAr., 10 CHꢀBn), 7.75 (d, 1 H, J 7.6 Hz,
CHꢀAr.), 7.92 (d, 1 H, J 8.4 Hz, CHꢀAr.); 13C NMR
(50 MHz, CDCl3) d: 41.8 (C-6), 57.4 (CH3O), 69.5,
71.3, 74.0, 74.6, 81.8 (C-2, C-3, C-4, 2 CH2ꢀBn), 98.5
(C-5), 100.6 (C-1), 106.5 (SCꢁC); 119.2, 123.1, 124.6,
126.8, 126.9, 127.8, 127.8, 128.0, 128.4, 128.5 (10
CHꢀBn, 6 CHꢀAr.), 129.6, 131.2 (2 CqꢀAr.), 137.8,
138.3 (2 CqꢀBn), 148.8 (SCꢁC); Anal. Calcd for
C31H30O6S: C, 70.17; H, 5.70. Found: C, 70.06; H, 5.78.
3.14. 4-{Methyl (5S)-2,6-di-O-benzyl-4-deoxy-a-
threo-hexopyranosid-5-O-yl}pentan-2-one (25)
L-
To a solution of 16 (60 mg, 0.12 mmol) in 2 mL THF,
0.8 mL of Raney-Ni (W-2) in THF were added; the
suspension was vigorously stirred at room temperature
for 8 h, after this time a second amount of Raney-Ni
(0.2 mL in THF) was added and the stirring kept for
additional 12 h. The reaction mixture was then diluted
with CH2Cl2 (10 mL) and filtered over Celite®. The
solvent was evaporated under diminished pressure and
the crude obtained (43 mg) was purified by flash
column chromatography on silica gel (2:1 eluant hex-
ane–EtOAc) to give 25 (18 mg, 32%) as glassy oil and
a recovered amount of glycal 2 (12%); [a]D +1.2° (c
1
0.28, CHCl3); H NMR (200 MHz, CDCl3) d: 1.24 (d,
3 H, J 6.2 Hz, CH3ꢀCHO), 1.53 (B part of an ABX
syst., 1 H, JAB and JBX 16.2 Hz CHB-4), 2.06 (s, 3 H,
CH3ꢀCO), 2.36 (B part of an ABX syst., 1 H, JAB 13.2
Hz, JBX 4.8 Hz, CHBꢀCꢁO), 2.50 (A part of an ABX
syst., 1 H, JAB 16.0 Hz, JBX 7.8 Hz, CHA-4), 2.77 (A
part of an ABX syst., 1 H, JAB 13.2 Hz, JAX 4.4 Hz,
CHAꢀCꢁO), 3.12 (at, 1 H, J1,2 8.0 Hz, H-2), 3.31 (B
part of an AB syst., 1 H, JAB 10.2 Hz, CHB-6), 3.35 (s,
3 H, CH3ꢀO), 3.68 (A part of an AB syst., 1 H, JAB
10.2 Hz, CHA-6), 3.89–4.04 (m, 1 H, H-3), 4.38–4.47
(m, 1 H, CHꢀCH3), 4.52 (s, 2 H, CH2ꢀBn), 4.61 (B part
of an AB syst., 1 H, JAB 11.2 Hz, CHBꢀBn), 4.68 (d, 1
H, J1,2 7.8 Hz, H-1), 4.93 (A part of an AB syst., 1 H,
JAB 11.2 Hz, CHAꢀBn), 7.29–7.36 (m, 10 H, 10
CHꢀAr.); 13C NMR (50 MHz, CDCl3) d: 22.4
3.13. Methyl (4S,5R)-2,3,6-tri-O-benzyl-4-deoxy-a-L-
threo-hexopyranosid[4,5-b]naphtho[1,2-e]-1,4-oxathiin
(24)
To a solution of 6 (130 mg, 0.29 mmol) in 3 mL of
CHCl3, 108 mg (0.29 mmol) of phthalimide derivative
14 and 18.4 mL (0.23 mmol) of pyridine were added.
The reaction mixture was heated to 60 °C for 4 days

G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
131
(CH3ꢀCO), 30.4 (CH3ꢀCHO), 39.7 (C-4), 51.8
(CH3ꢀO), 56.8 (CHꢀO), 64.5 (CH2ꢀCO), 67.2, 71.7,
73.4, 74.4, 83.7, (C-2, C-3, C-6, 2 CH2ꢀBn), 99.7, 100.9
(C-1, C-5), 125.4, 127.7, 128.0, 128.4, 128.5, (10
CHꢀAr), 137.4, 138.4 (2Cq), 207.2 (CꢁO); Anal. Calcd
for C26H34O7: C, 68.10; H, 7.47. Found: C, 67.91; H,
6.68.
mg) which was purified by flash column chromatogra-
phy (5:1 hexane–EtOAc) to give 27 (15 mg, 53%) as
colourless oil; [a]D −184.16° (c 0.14, CHCl3); 1H NMR
(200 MHz, CDCl3) d: 1.93 (s, 3 H, CH3ꢀCꢁC), 3.44–
3.65 (m, 7 H, H-2, H-3, CH3ꢀO, CH2-6), 3.90 (d, 1 H,
J3,4 10.6 Hz, H-4), 4.09 (AB syst., 2 H, JAB 12.8 Hz,
CH2ꢀOH), 4.56–4.93 (m, 7 H, 3 CH2ꢀBn, H-1), 5.30 (s,
1 H, OH), 7.26–7.37 (m, 15 H, 15 CHꢀAr.); 13C NMR
(50 MHz, CDCl3) d: 17.7 (CH3ꢀCꢁ), 41.6 (C-6), 57.2
(CH3ꢀO), 62.0, 70.9, 73.8, 75.0, 76.8, 82.8 (C-2, C-3,
C-4, 3 CH2ꢀBn), 98.2, 98.5, (C-5, C-1), 100.7 (SCꢁC),
127.5, 127.7, 128.1, 128.2, 128.3 (15CHꢀAr.), 137.8,
138.7 (3Cq), 144.8 (SCꢁC); Anal. Calcd for C32H36O7S:
C, 68.06; H, 6.43. Found: C, 68.33; H, 6.43.
3.15. 4-{Methyl (5S)-2,3,6-tri-O-benzyl-4-deoxy-a-
threo-hexopyranosid-5-O-yl}pentan-2-one (26)
L-
A solution of 18 (70 mg, 0.12 mmol) in 2 mL THF was
treated with 0.8 mL of commercially available Raney-
nickel;28 the suspension was vigorously stirred at room
temperature for 12 h, after this time a second amount
of Raney-Ni (0.2 mL in THF) was added and the
stirring kept for additional 12 h. After this time the
reaction mixture was diluted with CH2Cl2 (10 mL) and
filtered over Celite®. After evaporation of the solvent,
the crude product (62 mg) was purified by flash column
chromatography on silica gel (4:1 hexane–EtOAc) to
give 26 (21.5 mg, 32%) and 14 mg (26%) of 6; [a]D20
3.17. Methyl (4S,5R)-2,6-di-O-benzyl-4-thio-a- -threo-
L
hexopyranosid[4,5-b]naphtho[1,2-e]-S-oxo-1,4-oxathiin
(28)
A solution of 23 (50 mg, 0.102 mmol) in 1 mL of
CH2Cl2 was cooled to −15 °C and treated with a
solution of mCPBA (23.1 mg, 0.133 mmol) in 1.5 mL
CH2Cl2. After 45 min, the reaction was complete; it was
washed with a 10% Na2S2O3 solution (1×) and with a
saturated NaHCO3 solution (2×); the organic layer
was dried over Na2SO4 and evaporated under dimin-
ished pressure. The crude (56 mg) was purified by flash
column chromatography on silica gel (5:1 hexane–
EtOAc) to give 28 (25 mg, 45%) as glassy solid; [a]D=
1
+21.30° (c 0.13, CHCl3); H NMR (200 MHz, CDCl3)
d: 1.23 (d, 3 H, J 5.8 Hz, CH3ꢀCH), 1.55 (m, 1 H,
CH2-4), 2.04 (s, 3 H, CH3ꢀCO), 2.41–2.55 (m, 2 H,
CHꢀCO, CH2-4), 2.77 (A part of an ABX syst., 1 H,
JAB 16.0 Hz, JBX 4.4 Hz, CHAꢀCO), 3.31 (B part of an
AB syst., 1 H, JAB 10.2 Hz, CHB-6), 3.31 (dd, 1 H, J1,2
9.4, J2,3 7.6 Hz, H-2), 3.53 (s, 3 H, CH3ꢀO), 3.69 (A
part of an AB syst., 1 H, JAB 10.2 Hz, CHA-6), 3.82–
3.95 (m, 1 H, H-3), 4.36–4.45 (m, 1 H, CHꢀCH3), 4.52
(s, 2 H, CH2ꢀBn), 4.67 (AB syst., 2 H, JAB 11.8 Hz,
CH2ꢀBn), 4.69 (d, 1 H, J1,2 9.4 Hz, H-1), 4.80 (AB syst.,
2 H, JAB 11.0 Hz, CH2ꢀBn), 7.28–7.36 (m, 15 H, 15
CHꢀAr.); 13C NMR (50 MHz, CDCl3) d: 22.3
(CH3ꢀCO), 29.7 (CH3ꢀCHO), 38.5 (C-4), 51.8
(CH3ꢀO), 57.0 (CHꢀO), 64.6 (CH2ꢀCO), 71.6, 72.5,
73.5, 74.9, 75.5, 83.2 (C-2, C-3, C-6, 3 CH2ꢀBn), 99.6
(C-1), 101.2 (C-5), 127.5, 127.6, 127.7, 128.0, 128.1,
128.3, 128.4 (15CHꢀAr), 137.4, 138.7 (3Cq), 207.4
(CꢁO); Anal. Calcd for C33H40O7: C, 72.24; H, 7.35.
Found: C, 72.60; H, 7.50.
1
+56.69° (c 0.12, CHCl3); H NMR (200 MHz, CDCl3)
d: 3.51–3.72 (m, 6 H, H-2, CH2-6, CH3ꢀO), 4.12 (d, 1
H, J3,4 10.2 Hz, H-4), 4.45 (A part of an AB syst., 1 H,
JAB 11.8 Hz, CHAꢀBn), 4.55 (B part of an AB syst., 1
H, JAB 12.2 Hz, CHBꢀBn), 4.77–4.93 (m, 3 H, H-3,
CH2ꢀBn), 5.04 (d, 1 H, J1,2 8.0 Hz, H-1), 5.24 (d, 1 H,
J 1,4 Hz, OH), 7.04 (d, 1 H, J 9.0 Hz, CHꢀAr.),
7.07–7.81 (m, 13 H, 13 CHꢀAr.), 7.88 (d, 1 H, J 9.2
Hz, CHꢀAr.), 8.39 (d, 1 H, J 8.2 Hz, CHꢀAr.); 13C
NMR (50 MHz, CDCl3) d: 53.1 (C-6), 57.5 (CH3ꢀO),
71.6, 72.2, 74.0, 75.3; 81.7 (C-2, C-3, C-4, 2 CH2ꢀBn),
100.1 (C-5), 100.4 (C-1), 113.01 (SCꢁC), 118.4, 123.9,
125.2, 127.7, 127.9, 128.1, 128.3, 128.4, 134.4 (16
CHꢀBn), 130.2, 131.6 (2 Cq), 136.6, 138.3 (2Cq), 149.0
(SCꢁC); Anal. Calcd for C26H34O7: C, 68.12; H, 5.53.
Found: C, 68.19; H, 5.90.
3.16. Methyl (4S,5R)-2,3,6-tri-O-benzyl-4-deoxy-a-L-
threo-hexopyranosid[4,5-b]-2-methyl-3-hydroxymethyl-
1,4-oxathiin (27)
A solution of 18 (30 mg, 0.05 mmol) in 1 mL of dry
THF was cooled to 0 °C and treated with LiAlH4 (2.8
mg, 0.07 mmol). After 15 min, a saturated solution (2
mL) was added at 0 °C and the aqueous phase was
extracted with CH2Cl2 (2×). The combined organic
layers were washed with a saturated NH4Cl solution
(1×), dried over Na2SO4 filtered and concentrated
under diminished pressure to give a crude product (48
Acknowledgements
This work was carried out in the framework of the
National Project ‘Stereoselezione in Sintesi Organica—
Metodologie e Applicazioni’ supported by the Minis-
tero dell’Universita’
Tecnologica, Rome and by the Universities of Florence
and Pisa.
e della Ricerca Scientifica e

132
G. Capozzi et al. / Carbohydrate Research 338 (2003) 123–132
H. B.; Dietrich, C. P. J. Carbohydr. Chem. 1993, 12,
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