Stereoselective (2-naphthyl)methylation of sugar hydroxyls by the hydrogenolysis of diastereoisomeric dioxolane-type (2-naphthyl)methylene acetals

Article abstract of DOI:10.1016/S0008-6215(02)00180-5

The cis axial/equatorial OH groups of methyl α-L- and ethyl 1-thio-α-L-rhamnopyranoside, 1,6-anhydro-β-D-mannopyranose, and 1,6-anhydro-β-D-galactopyranose were reacted with 2-naphthaldehyde dimethyl acetal to diastereomeric dioxolane-type 2,3-O-(2-naphth

Full text of DOI:10.1016/S0008-6215(02)00180-5

Carbohydrate Research 337 (2002) 1941–1951
www.elsevier.com/locate/carres
Stereoselective (2-naphthyl)methylation of sugar hydroxyls by the
hydrogenolysis of diastereoisomeric dioxolane-type
(2-naphthyl)methylene acetals
Aniko´ Borba´s,a Zolta´n B. Szabo´,a La´szlo´ Szila´gyi,b Attila Be´nyei,c Andra´s Lipta´ka,d,*
aResearch Group for Carbohydrates of the Hungarian Academy of Sciences, Debrecen, PO Box 55, H-4010 Hungary
bDepartment of Organic Chemistry, Faculty of Science, Uni6ersity of Debrecen, Debrecen, PO Box 20, H-4010 Hungary
cInstitute of Physical Chemistry, Faculty of Science, Uni6ersity of Debrecen, Debrecen, PO Box 7, H-4010 Hungary
dDepartment of Biochemistry, Faculty of Science, Uni6ersity of Debrecen, Debrecen, PO Box 55, H-4010 Hungary
Received 18 April 2002; accepted 1 July 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
The cis axial/equatorial OH groups of methyl a-
and 1,6-anhydro-b- -galactopyranose were reacted with 2-naphthaldehyde dimethyl acetal to diastereomeric dioxolane-type
2,3-O-(2-naphthyl)methylene or 3,4-O-(2-naphthyl)methylene acetals. The glycosides yielded the exo- and endo-isomers in nearly
1:1 ratio, 1,6-anhydro-b- -mannopyranose gave predominantly the endo-, and 1,6-anhydro-b- -galactopyranose exclusively
L
- and ethyl 1-thio-a-
L
-rhamnopyranoside, 1,6-anhydro-b-D-mannopyranose,
D
D
D
endo-isomer. The acetals and some of their fully protected derivatives bearing benzyl or tert-butyldimethylsilyl groups were
hydrogenolised with AlH3 (3LiAlH4-AlCl3) or with Me3N·BH3–AlCl3 reagents. The endo-isomers were cleaved by both reagents
to give axial NAP ethers, the exo-isomers of pyranosides furnished equatorial NAP ethers. However, the exo-isomers of pyranoses
gave irregular axial ethers with a \30-fold enhancement of the reaction rates with respect to the endo-isomer. © 2002 Elsevier
Science Ltd. All rights reserved.
1. Introduction
O-4 leading to intermediary carbocations which are
subsequently reduced to the hydroxy/ether derivatives.
From a preparative point of view, among the readily
available hydroxy/ether derivatives the O-benzyl,16,17
Although enormous progress has been made during
the last two decades, the synthesis of complex oligosac-
charides still remains difficult.1 Conventional syntheses
of the building blocks often require multiple protection
and deprotection of various hydroxyl groups.2 The
introduction of acetals3–5 and their transformation into
hydroxy/ether derivatives are the most often used pro-
cedures. Reduction of dioxane type acetals of hexopy-
ranosides with different mixed hydrides6–11 result
mainly in 4-O-alkyl/6-OH hexopyranosides, and the
other type of solvents or reagents8,9,12–15 give 6-O-alkyl/
4-OH derivatives. The regioselectivity of the methods
are attributed to preferential complexation at O-6 or
O-(p-methoxy)benzyl16
and
O-(2-naphthyl)methyl
(NAP)18 ethers are the most important. These can be
obtained by the hydrogenolysis of 4,6-O-benzyli-
dene,16,17 4,6-O-(p-methoxy)benzylidene16 and 4,6-O-
(2-naphthyl)methylene18–21 acetals of hexopyranosides.
3,5-O-Benzylidene-xylofuranosides22 were also cleaved
with the LiAlH4–AlCl3 reagent to give 5-O-benzyl
ethers.
In the case of the dioxolane type acetals of hexo-23
and pentopyranosides,24 the direction of the ring-cleav-
age reaction is determined by the configuration of the
acetalic carbon. Equatorial ethers are obtained from the
exo-(alkyl, aryl)-acetals; however, the endo-isomers re-
act in an opposite way and the products are the axial
ethers. This is a general rule and it was verified for all
of the reagents above.25
* Corresponding author. Tel.: +36 52 512 900; fax: +36
52 512 913
E-mail address: liptaka@tigris.klte.hu (A. Lipta´k).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00180-5

1942
A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
Most recently there have been some promising suc-
was also carried out, as described for the preparation of
2exo- and 2endo-compounds, to afford the crystalline
7exo (41%) and 7endo (47%) compounds (Scheme 1).
cessful applications of sugar NAP ethers, mainly in the
field of the synthesis of complex oligosaccharides.26–35
Therefore, it was interesting to study the possibility of
their preparation through the hydrogenolysis of both
diastereomers of the hitherto unknown dioxolane type
(2-naphthyl)methylene acetals.19
Acetalisation of 1,6-anhydro-b-
D
-galactopyranose38
-rhamnopyran-
(8) required the same conditions as the
L
osides but only a single isomer was detected in the
reaction mixture. It proved to be the endo-isomer
(9endo) which was acetylated (“10endo) and benzy-
lated (“11endo); all of the three substances are crys-
talline. Compound 11endo was isomerised in
dichloromethane with 0.05 equivalent of AlCl3, and
after 2 h, the 11exo:11endo ratio was 1:2.36 (l: 6.40
ppm and l: 5.93 ppm).
2. Results and discussion
To investigate the formation of dioxolane type (2-
naphthyl)methylene acetals, two sets of starting com-
Transformation of 1,6-anhydro-b-D-mannopyran-
pounds were selected:
1,6-anhydro-hexopyranoses.
Methyl a-
-rhamnopyranoside36 (1) was reacted with
L-rhamnopyranosides and
ose39 (12) into the diastereoisomeric 2,3-O-(2-naph-
thyl)methylene acetals required a prolonged reaction
time (5 days) and both isomers were isolated in crys-
talline form where the 13endo-isomer dominated
(13endo:13exo=6:1). This mixture was converted into
the 4-O-acetyl derivatives (14endo and 14exo). Com-
pound 13endo was benzylated to 15endo. The 15endo
diastereomer was converted into 15exo by isomerisa-
tion, and the ratio was 1.2:1 in favour of the endo-iso-
L
2-naphthaldehyde dimethyl acetal in the presence of
p-toluenesulfonic acid (pTSA), and two diastereoiso-
meric forms of methyl 2,3-O-(2-naphthyl)methylene-a-
L
-rhamnopyranoside (2exo and 2endo)19 were obtained.
The exo-isomer (42%) crystallised spontaneously, and
in the mother liquor a ꢀ2:1 ratio of the 2exo and
1
2endo isomers was detected by H NMR (2exo: l=
1
mer as shown by H-NMR measurements. Despite the
6.30 ppm; and 2endo: l=6.03 ppm). Following acety-
lation of this mixture, the 4-O-acetyl derivatives were
isolated in crystalline form (3exo and 3endo). Similarly,
treatment of the mixture of the 2exo/2endo-isomers
with benzyl bromide/NaH in DMF solution gave the
crystalline 4exo-isomer, and the syrupy 4endo-com-
pound was obtained after column chromatographic
purification. Deacetylation of compound 3endo yielded
the 2endo derivative as a syrup. Compound 2exo was
converted into 4-OTBDMS-ether (5exo) by treatment
with tert-butyldimethylsilyl chloride in the presence of
imidazole. Since the protected thioglycosides are useful
not only as glycosyl acceptors but also as glycosyl
fact that the endo-isomers of the 1,6-anhydro-2,3/3,4-
O-(2-naphthyl)methylene-b-D-hexopyranoses are steri-
cally extremely crowded, surprisingly they are the
kinetic products, and the ratio of the two isomeric pairs
in the equilibrium proves that the endo-isomers are
more stable than the exo compounds (Scheme 2).
Comparison of the conditions of the ring-cleavage of
benzylidene acetals to those of the (2-naphthyl)-
methylene acetals revails that the latters require essen-
tially milder conditions: the (2-naphthyl)methylene ac-
etals can be opened by AlH3 (3LiAlH4–AlCl3) instead
of AlClH2 (LiAlH4–AlCl3), the reaction time varies
between 5 min to 2–3 hours at room temperature.
Treatment of the exo-isomers of the methyl 2,3-O-(2-
donors, treatment of ethyl 1-thio-a-L-rhamno-
pyranoside37 (6) with 2-naphthaldehyde dimethyl acetal
naphthyl)methylene-a-L-rhamnopyranoside derivatives
(2exo, 4exo and 5exo) with alane resulted in the 3-
ONAP ethers (16–18) with isolated yields of 90, 93 and
93%. However, the endo-isomers (2endo, 4endo) were
cleaved to the 2-ONAP ethers (19 and 20) with a yield
of 90 and 92%. Ring-opening proceeded with a com-
plete stereoselectivity: the exo-isomers furnished equa-
torial O-NAP ethers, and the endo-isomers gave axial
O-NAP ethers. The high stereoselectivity can be ex-
plained by two factors: under low temperature and in
the presence of a soft Lewis acid (AlH3) no isomeriza-
tion was observed. The same reaction with high
stereoselectivity were observed also in the case of the
ethyl 2,3-O-(napthyl)methylene-1-thio-a-L-rhamnopy-
ranoside isomers (7exo and 7endo) affording ethyl 3-O-
(2-naphthyl)methyl- (21) and ethyl 2-O-(2-naphthyl)-
Scheme 1. Synthesis of dioxolane-type (2-naphthyl)methylene
acetals of rhamnopyranosides. Reaction conditions: (a) 2-
naphthaldehyde dimethyl acetal, TsOH, DMF; (b) acetic
anhydride, pyridine; (c) benzyl bromide, NaH, DMF.
methyl-1-thio-a- -rhamnopyranoside (22).
L

A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
1943
Scheme 2. Synthesis of dioxolane-type (2-naphthyl)methylene acetals of 1,6-anhydro-hexopyranoses. Reaction conditions: (a)
2-naphthaldehyde dimethyl acetal, TsOH, DMF; (b) acetic anhydride, pyridine; (c) benzyl bromide, NaH, DMF; (d) AlCl3,
CH2Cl2.
Compounds 2exo, 4exo and 5exo were treated with
the Me3N·BH3–AlCl3 (4 equiv) reagent; the reaction
was complete after 3 hours at room temperature and
resulted in the same compounds (16–18) as with the
alane reagent. The yields are also comparable to those
of the alane-mediated reactions.
acetals. A probable explanation is that in the first case
a very soft Lewis acid, AlH3 is the electrophile, but it is
a very hard hydride donor. In other words, the rate of
the isomerisation is low, but the reduction is a fast
process. The hydrogenolysis of the benzylidene acetals
requires AlH2Cl which enhances the rate of the isomeri-
Cleavage of compounds 11endo and 15endo was
stereoselective and fast reaction (84% isolated yield of
23 after 15 min, 89% yield of 24 after 3 h). The
hydrogenolysis of the exo-isomers was studied with a
mixture of the 11exo:11endo (1:2.36) isomers and that
of the 15exo:15endo (1:1.2) isomers. The first reaction
required 7 hours and gave only a single product: com-
pound 23 was a characteristic cleavage product for the
11endo- but irregular for the 11exo-isomer. A com-
pletely similar reaction proceeded in the second reac-
tion, resulting exclusively in the axial O-NAP ether
again which was the regular cleavage product for the
15endo, but irregular for the 15exo-compound (Scheme
3). Similar irrregularities were also observed earlier for
some benzylidene derivatives.40–42
We suppose that the hydrogenolysis, as well as the
isomerisation of the dioxolane type benzylidene and
(2-naphthyl)methylene acetals have common intermedi-
ates and these are the oxocarbonium ions. We assume
that (i) the electrophylic attacks occur at different oxy-
gens of the dioxolane skeleton; (ii) the reduction of the
oxocarbonium ions is a faster reaction than the cleav-
age of the dioxolane ring.43,44
Scheme 3. Hydrogenolysis of dioxolane-type (2-naphthyl)-
methylene acetals of rhamnopyranosides and 1,6-anhydro-
hexopyranoses. Reaction conditions: (a) AlH3, CH2Cl2–Et2O,
r.t.; (b) Me3N·BH3–AlCl3, THF, r.t.
In the case of dioxolane type (2-naphthyl)methylene
acetals the stereoselectivity of the hydrogenolysis of the
endo-isomers is higher than in the case of benzylidene

1944
A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
Fig. 1. X-ray structure of the methyl 4-O-acetyl-2,3-endo-benzylidene-a-L-rhamnopyranoside
Fig. 2. X-ray structure of the methyl 4-O-acetyl-2,3-exo-benzylidene-a-
L
-rhamnopyranoside.
sation but decreases the rate of the reduction. X-ray
crystallographic studies were performed on various
endo and exo diastereoisomeric compounds in the
rhamnopyranoside (methyl 4-O-acetyl-exo-45 and
twist-like conformation in the endo-isomer. The angle
of the planes of C2-C3-O3 and C8-O3-C3 for the endo
isomers is in the region of 7–16°, while in the exo
isomers it is in the region of 37–41°. The corresponding
values for the C2-O2-C3 and O2-C8-O3 planes are
34-41°, and 0.6–12° for the endo and exo isomers,
respectively. This means that the C8-O3-C3-C2 atoms
are coplanar in the endo isomers, and the O2-C2-C3-O3
atoms are coplanar in the exo isomers. Detailed results
methyl 4-O-acetyl-endo-2,3-O-benzylidene-a-L-rhamno-
pyranoside45) and mannopyranose (14exo and 15endo)
series46 (Figs. 1–4). The main result of these investiga-
tions is that the dioxolane ring always adopts an envel-
ope conformation in the exo-isomer, while it has a

A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
1945
cannot be the oxygen located at the carbon atom below
or above the plane of the envelope. These observations
suggest that the place of the attack of the reagent, or in
other words, the electrophile on the oxygen depends on
the conformation of the non-bonded electron pairs of
the oxygen of the dioxolane-type skeleton. For more
details on the hydrogenolysis of the dioxolane type
acetal, investigations are under way in our laboratory.
of the crystallographic studies will be published
elsewhere.
Figs. 1–4 represent the conformation of the four
studied molecules. In the case of both isomers the
reagent (AlH3) attacks at the oxygen located in the
middle of the plane of the envelope or the twist skele-
ton. In the case of the exo-isomers the site of the attack
Fig. 3. X-ray structure of 14exo.
Fig. 4. X-ray structure of 15endo.

1946
A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
3. Experimental
The filtrate was a chromatographically unseparable
mixture of the exo and endo isomers. Compound 2exo:
mp 107–108 °C (white needles); [h]D −2.4 (c 0.28,
CHCl3); Rf 0.25 (7:3 hexane–EtOAc); H NMR l (200
MHz, CDCl3) 7.91–7.41 (7H, m, aromatic), 6.30 (1H,
s, H acetalic), 4.93 (1H, s, H-1), 4.45 (1H, dd, J2,3=5.2,
General methods.—Optical rotations were measured
at room temperature with a Perkin-Elmer 241 auto-
matic polarimeter. Melting points were determined on a
Kofler hot-stage apparatus and are uncorrected. TLC
was performed on Kieselgel 60 F254 (Merck) with detec-
tion by charring with 50% aqueous sulfuric acid.
Column chromatography was performed on Silica Gel
60 (E. Merck 0.062–0.200 nm). The organic solutions
were dried over MgSO4, and concentrated in vacuum.
1
J3,4=7.5, H-3), 4.14 (1H, d, H-2), 3.53-3.80 (2H, m,
H-4, H-5), 3.37 (3H, s, OCH3), 2.79 (1H, d, J4H,OH
=
4.1, 4-OH), 1.36 (3H, d, J=6.0, CH3-6); 13C NMR l
(50 MHz, CDCl3) 135.8 (2×), 133.6, 132.8, (Cq, aro-
matic), 128.4–123.4 (CH, aromatic), 103.1 (C acetalic),
98.0 (C-1), 79.6 (C-3), 75.4 (C-2), 71.9 (C-4), 65.3 (C-5),
54.9 (OCH3), 17.4 (C-6). Anal. Calcd for C18H20O5: C
68.34; H 6.37. Found: C 68.31; H 6.35.
1
The H (200, 360 and 500 MHz) and 13C NMR (50.3,
90.54, 125.76 MHz) spectra were recorded with Bruker
WP-200SY, Bruker AM-360 and Bruker DRX-500
spectrometers for solutions in CDCl3. Internal refer-
Deacetylation of compound 3endo afforded the title
compound 2endo, as a colorless syrup; [h]D −23.1 (c
1
ences: TMS (0.00 ppm for H), CDCl3 (77.00 ppm for
1
13C). Single crystals of 14exo (from EtOAc-nhexane)
and 15endo (from EtOH) suitable for X-ray diffraction
measurement was obtained after recrystallization. X-ray
diffraction data were collected at 293(1) K, Enraf Non-
ius MACH3 diffractometer, Mo Ka radiation u=
0.29, CHCl3); Rf 0.25 (7:3 hexane–EtOAc). H NMR l
(200 MHz, CDCl3) 7.89–7.41 (7H, m, aromatic), 6.03
(1H, s, H acetalic), 5.01 (1H, s, H-1), 4.25 (1H, m, H-3),
4.14 (1H, d, J2,3=2.1, H-2), 3.73-3.45 (2H, m, H-4,
H-5), 3.39 (3H, s, OCH3), 3.14 (1H, br.s, 4-OH), 1.26
(3H, d, J=6.0, CH3-6); 13C NMR d (50 MHz, CDCl3)
135.7-123.4 (C aromatic), 104.1 (C acetalic), 98.0 (C-1),
78.1 (C-3), 77.8 (C-2), 74.3 (C-4), 65.8 (C-5), 54.9
(OCH3), 17.3 (C-6). Anal. Calcd for C18H20O5: C 68.34;
H 6.37. Found: C 68.30; H 6.34.
,
0.71073 A.
General method A for the hydrogenolysis of (2-naph-
thyl)methylene acetals of hexopyranosides with LiAlH4-
AlCl3 to get compounds 16–24.—To a stirred solution
of the starting acetal compound (1 mmol) and LiAlH4
(3 equiv) in dry CH2Cl2:Et2O (2:1, 6 mL) AlCl3 in Et2O
(1 equiv in 3 mL) was added dropwise at room temper-
ature. After complete conversion (10–15 min) 1–2 mL
of EtOAc and 1–3 drops of water were added, the
mixture was diluted with ethyl–acetate, washed with
water (3×25 mL), dried and concentrated. The residue
Methyl 4-O-acetyl-2,3-O-(2-naphthyl)methylene-h-L-
rhamnopyranoside (3endo, 3exo).—To a solution of the
isomeric mixture of 2exo and 2endo (500 mg, 1.5 mmol)
in dry pyridine (2 mL), acetic anhydride (1 mL) was
added. After usual work-up procedure the title com-
pounds were separated by column chromatography (7:3
hexane–EtOAc) yielding 250 mg (46%) of 3endo (Rf
0.42) and 230 mg (43%) of 3exo (Rf 0.50). Compound
3endo crystallized from EtOH, mp 122–123 °C (white
was
purified
by
crystallization
or
column
chromatography.
General method B for the hydrogenolysis of (2-naph-
thyl)methylene acetals of hexopyranosides with
Me3N.BH3-AlCl3 to get compounds 16–18.—The mix-
1
crystals); [h]D +49.3 (c 0.25, CHCl3); H NMR l (200
MHz, CDCl3) 7.95–7.80 (4H, m, aromatic), 7.57–7.41
(3H, m, aromatic), 6.07 (1H, s, H acetalic), 5.04 (1H,
dd, J3,4=7, J4,5=10, H-4), 5.04 (1H, s, H-1), 4.40 (1H,
t, J2,3=7, H-3), 4.27 (1H, d, H-2), 3.81 (1H, m, H-5),
3.40 (3H, s, OCH3), 2.11 (3H, s, Ac), 1.20 (3H, d,
J=6.0, CH3-6); 13C NMR d (50 MHz, CDCl3) 169.9
(CO), 133.9–124.0 (C aromatic), 104.8 (C acetalic), 97.8
(C-1), 78.2 (C-3), 75.6 (C-2), 75.0 (C-4), 63.7 (C-5), 54.9
(OCH3), 21.0 (Ac), 17.0 (C-6). Anal. Calcd for
C20H22O6: C 67.03; H 6.19. Found: C 66.97; H 6.15.
Compound 3exo crystallized from EtOH, mp 136–
,
ture of the starting acetal compound (1 mmol), 4 A
molecular sieves (200 mg) and Me3N.BH3 (4 equiv) in
dry THF (10 mL) was stirred for 30 min at room
temperature, then AlCl3 (4 equiv) was added. After
complete conversion (2–3 h) the mixture was filtered
through a layer of Celite, diluted with CH2Cl2, washed
with water, dried, concentrated and co-evaporated 3
times with MeOH.
Methyl 2,3-O-(2-naphthyl)methylene-h-L-rhamnopy-
ranoside (2endo, 2exo).—To a solution of compound 1
(1.78 g, 10 mmol) in dry DMF (5 mL) 2-naphthalde-
hyde dimethyl acetal (2.6 g, 13 mmol) and catalytic
amount of p-toluenesulfonic acid were added. The reac-
tion mixture was stirred at room temperature for 24 h,
then neutralized with triethylamine and evaporated in
vacuo. The residue was dissolved in dichloromethane,
washed with water (3×50 mL), dried and evaporated.
The crude product was crystallized from nhexane–
EtOAc to afford the title compound 2exo (1.35 g, 42%).
1
137 °C (white needles); [h]D −6.6 (c 0.27, CHCl3); H
NMR l (200 MHz, CDCl3) 7.95–7.76 (4H, m, aro-
matic), 7.57–7.43 (3H, m, aromatic), 6.38 (1H, s, H
acetalic), 5.08 (1H, dd, J3,4=8, J4,5=10, H-4), 4.99
(1H, s, H-1), 4.54 (1H, dd, J2,3=5.5, H-3), 4.21 (1H, d,
H-2), 3.81 (1H, m, H-5), 3.39 (3H, s, OCH3), 2.14 (3H,
s, Ac), 1.26 (3H, d, J=6.0, CH3-6); 13C NMR d (50
MHz, CDCl3) 170.2 (CO), 135.5–123.5 (C aromatic),
103.1 (C acetalic), 98.0 (C-1), 77.2 (C-3), 75.6 (C-2),

A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
1947
71.6 (C-4), 63.5 (C-5), 54.9 (OCH3), 20.9 (Ac), 17.0
(C-6). Anal. Calcd for C20H22O6: C 67.03; H 6.19.
Found: C 67.09; H 6.21.
126.2, 125.4, 123.6 (CH, aromatic), 102.7 (C-acetalic),
98.1 (C-1), 80.5 (C-3), 75.8, 72.8 (C-2, C-4), 65.6 (C-5),
54.8 (OCH3), 25.9 (But), 18.3 (CH3-6), 18.1 (But-Cq),
−3.8, −4.5 (Si–CH3). Anal. Calcd for C24H34O5Si: C
66.94; H 7.96. Found: C 66.90; H 8.01.
Methyl 4-O-benzyl-2,3-O-(2-naphthyl)methylene-h-
L
-rhamnopyranoside (4endo, 4exo).—To a solution of
the isomeric mixture of 2exo and 2endo (500 mg, 1.5
mmol) in dry DMF (3 mL), 80% NaH was added at
0 °C (70 mg, 2.25 mmol) and stirred for 30 min. Then
benzyl bromide (0.26 mL, 2.25 mmol) was added to the
mixture and stirred for 2 h. After the usual work-up
procedure the title compounds were separated by
column chromatography (7:3 hexane–EtOAc) yielding
270 mg (44%) of 4endo (Rf 0.40) and 260 mg (43%) of
4exo (Rf 0.46). Compound 4endo isolated as colorless
Ethyl
2,3-O-(2-naphthyl)methylene-1-thio-h-L-
rhamnopyranoside (7endo, 7exo).—Compound 6 (700
mg, 3.3 mmol) was converted to compound 7 in a
similar manner as described for the synthesis of 2. The
title compounds were purified by column chromatogra-
phy (7:3 hexane–EtOAc) yielding 535 mg (47%) of
7endo (Rf 0.49) and 470 mg (41%) of 7exo (Rf 0.41).
Compound 7endo crystallized from EtOAc-nhexane,
mp 102–104 °C (white crystals); [h]D −144.3 (c 0.24,
1
syrup, [h]D −21.3 (c 0.34, CHCl3); H NMR l (200
1
CHCl3); H NMR l (200 MHz, CDCl3) 7.90–7.79 (4H,
MHz, CDCl3) 7.91–7.20 (12H, m, aromatic), 6.08 (1H,
s, acetalic), 5.22 (1H, d, J=11.7, CH2a), 5.04 (1H, s,
H-1), 4.82 (1H, d, CH2b), 4.45 (1H, t, J=6.8, H-3),
4.27 (1H, d, H-2), 3.75 (1H, m, H-5), 3.39 (3H, s,
OCH3), 3.34 (1H, m, H-4), 1.27 (3H, d, J=6.0, CH3-6);
13C NMR l (50 MHz, CDCl3) 138.0-123.9 (C aro-
matic), 104.1 (C acetalic), 97.9 (C-1), 81.0 (C-4), 78.4
(2×, C-2, C-3), 72.6 (CH2), 64.3 (C-5), 54.8 (OCH3),
17.8 (C-6). Anal. Calcd for C25H26O5: C 73.87; H 6.45.
Found: C 73.98; H 6.40.
m, aromatic), 7.55–7.45 (3H, m, aromatic), 6.01 (1H, s,
H acetalic), 5.68 (1H, s, H-1), 4.23 (1H, d, J2,3=5.9,
H-2), 4.21 (1H, dd, J3,4=10.5, H-3), 4. (1H, m, H-5),
3.45 (1H, m, H-4), 2.72 (1H, d, J4H,OH=4.1, 4-OH),
2.61 (2H, m, SCH2CH3), 1.30 (3H, t, J=7.0,
SCH2CH3), 1.21 (3H, d, J=6.0, CH3-6); 13C NMR d
(50 MHz, CDCl3) 134.3-123.6 (C aromatic), 104.0 (C
acetalic), 79.2 (C-1), 79.1 (C-3), 78.0 (C-2), 75.5 (C-4),
65.9 (C-5), 24.4 (SCH2CH3), 17.0 (C-6), 14.6
(SCH2CH3). Anal. Calcd for C19H22O4S: C 65.87; H
6.40; S 9.25. Found: C 65.01; H 6.45; S 9.34.
Compound 4exo crystallized from EtOH, mp 70–
1
71 °C (white needles); [h]D −69.7 (c 0.44, CHCl3); H
Compound 7exo crystallized from EtOH, mp 135–
137 °C (white needles); [h]D −111.4 (c 0.34, CHCl3);1H
NMR l (200 MHz, CDCl3) 7.91–7.75 (4H, m, aro-
matic), 7.52–7.48 (3H, m, aromatic), 6.30 (1H, s, H
acetalic), 5.60 (1H, s, H-1), 5.04 (1H, dd, J2,3=5.1,
NMR l (500 MHz, CDCl3) 7.91–7.20 (12H, m, aro-
matic), 6.14 (1H, s, acetalic), 4.93 (1H, d, J=11.7,
CH2a), 4.89 (1H, s, H-1), 4.71 (1H, d, CH2b), 4.60 (1H,
t, J=5.1, H-3), 4.13 (1H, d, J=5.1, H-2), 3.71 (1H, m,
H-5), 3.35 (1H, m, H-4), 3.31 (3H, s, OCH3), 1.30 (3H,
d, J=6.0, CH3-6); 13C NMR d (125 MHz, CDCl3)
138.1, 135.9, 133.8, 132.9 (Cq, aromatic), 128.5, 128.3
(2x), 128.2 (2x), 128.1 (2x), 127.7, 126.5, 126.3, 125.8,
123.6 (CH, aromatic), 103.0 (C acetalic), 98.0 (C-1),
79.9 (C-3), 77.7 (C-4), 75.6 (C-2), 72.9 (CH2), 64.1
(C-5), 54.9 (OCH3), 17.9 (C-6). Anal. Calcd for
C25H26O5: C 73.87; H 6.45. Found: C 73.91; H 6.41.
J3,4=7.5, H-3), 4.23 (1H, d, H-2), 4.18 (1H, m, H-5),
3.64 (1H, m, H-4), 2.79 (1H, d, J4H,OH=4.5, 4-OH),
2.60 (2H, m, SCH2CH3), 1.35 (3H, d, J=6.0, CH3-6);
1.28 (3H, t, J=7.0, SCH2CH3), 13C NMR l (50 MHz,
CDCl3) 135.7–123.4 (C aromatic), 103.4 (C acetalic),
79.6 (C-1), 79.5 (C-3), 76.3 (C-2), 72.5 (C-4), 65.7 (C-5),
24.4 (SCH2CH3), 17.3 (C-6), 14.6 (SCH2CH3). Anal.
Calcd for C19H22O4S: C 65.87; H 6.40; S 9.25. Found:
C 65.97; H 6.44; S 9.33.
Methyl
4-O-tert-butyldimethylsilyl-2,3-O-(2-naph-
thyl)methylene-h-
L
-rhamnopyranoside (5exo).—To
a
solution of 2exo (316 mg, 1 mmol) in dry DMF (3 mL),
tert-butyldimethylsilyl chloride (210 mg, 1.2 mmol) and
imidazole (163 mg, 2.4 mmol) were added and the
mixture stirred overnight. After usual work-up proce-
dure the title compound was purified by column chro-
matography (8:2 hexane–EtOAc, Rf 0.68) yielding 330
mg (77%) of 5exo, as colorless syrup, [h]D −14.8 (c
0.37, CHCl3); 1H NMR l (360 MHz, CDCl3) 7.95–7.40
(7H, m, aromatic), 6.25 (1H, s, acetalic), 4.93 (1H, br.s,
H-1), 4.36 (1H, dd, J=7.3, 5.2, H-3), 4.13 (1H, d,
J=5.2, H-2), 3.66 (1H, m, H-5), 3.53 (1H, dd, J=9.3,
7.3, H-4), 3.37 (3H, s, OCH3), 1.32 (3H, d, J=6.1,
CH3-6), 0.91 (9H, s, But), 0.19 (3H, s, Si–CH3), 0.14
(3H, s, Si–CH3); 13C NMR d (90 MHz, CDCl3) 136.2,
133.8, 133.0 (Cq, aromatic), 128.4, 128.3, 127.7, 126.4,
1,6 - Anhydro - 3,4 - O - (2 - naphthyl)methylene - i - D-
galactopyranose (9endo).—Compound 8 (2.1 g, 13.2
mmol) was converted to compound 9 in a similar
manner as described for the synthesis of 2. After 24 h
TLC showed 70% conversion (7:3 hexane–EtOAc, Rf
0.49), the mixture was worked up and the solid crude
product was crystallized from EtOAc yielding 2.18 g
(55%) of 9endo: mp 260–262 °C (white needles); [h]D
+8.23 (c 0.12, CHCl3); 1H NMR l (200 MHz,
CDCl3+Me3OD) 7.81–7.34 (7H, m, aromatic), 5.87
(1H, s, H acetalic), 5.42; 13C NMR l (50 MHz,
CDCl3+Me3OD) 103.2 (C acetalic), 100.1 (C-1), 74.3,
71.2, 70.4, 63.8 (C-2,3,4,5), 63.3 (C-6). Anal. Calcd for
C17H16O5: C 67.99; H 5.37. Found: C 68.04; H 5.31.

1948
A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
2-O-Acetyl-1,6-anhydro-3,4-O-(2-naphthyl)methyl-
ene-i- -galactopyranose (10endo).—To a solution of
etalic), 99.3 (C-1), 78.7, 75.9 (C-3, 5), 71.6, 69. 2 (C-2,
4), 64.4 (C-6). Anal. Calcd for C17H16O5: C 67.99; H
5.37. Found: C 68.01; H 5.33.
D
9endo (600 mg, 1.9 mmol) in dry pyridine (5 mL), acetic
anhydride (3 mL) was added. After usual work-up
procedure the solid residue was crystallized from
EtOAc yielding 600 mg of 10endo (90%) as white
Compound 13exo crystallized from EtOH, mp 123–
124 °C (white needles); [h]D −43.5 (c 0.33, CHCl3); (Rf
0.30, 9:1 dichloromethane-acetone); 1H NMR l (200
MHz, CDCl3) 7.98–7.41 (7H, m, aromatic), 6.49 (1H,
s, H acetalic), 5.59 (1H, d, J=2.5, H-1); 13C NMR l
(50 MHz, CDCl3) 136.7-123.3 (C aromatic), 105.1 (C
acetalic), 99.9 (C-1), 76.3, 75.8, 73.4, 69.2 (C-2, 3, 4, 5),
64.9 (C-6). Anal. Calcd for C17H16O5: C 67.99; H 5.37.
Found: C 66.71; H 5.32.
1
needles; [h]D +78.4 (c 0.49, CHCl3); H NMR l (500
MHz, CDCl3) 7.98–7.41 (7H, m, aromatic), 5.99 (1H,
s, H acetalic), 5.51 (1H, s, H-1), 5.13 (1H, s, H-2), 4.54
(2H, m, H-3, H-5), 4.13 (1H, d, J=4.0, H-4), 4.08 (1H,
d, J=7.0, H-6a), 3.35 (1H, d, H-6b), 2.12 (3H, s, Ac);
13C NMR d (125 MHz, CDCl3) 133.5–123.2 (C aro-
matic), 102.8 (C acetalic), 98.6 (C-1), 75.7 (C-4), 71.9
(C-3), 70.5 (C-2), 69.1 (C-5), 63.3 (C-6) 20.6 (Ac). Anal.
Calcd for C19H18O6: C 66.66; H 5.30. Found: C 66.81;
H 5.34.
4-O-Acetyl-1,6-anhydro-2,3-O-(2-naphthyl)methyl-
ene-i- -mannopyranose (14endo, 14exo).—The iso-
D
meric mixture of 13exo and 13endo (300 mg, 1.0 mmol)
was converted to compound 14endo and 14exo in a
similar manner as described for the synthesis of 3.
Compound 14endo crystallized from EtOAc-nhexane,
mp 160–162 °C (white crystals); [h]D −111.5 (c 0.37,
CHCl3); (Rf 0.23, 9:1 dichloromethane-acetone); 1H
NMR l (500 MHz, CDCl3) 7.95–7.76 (4H, m, aro-
matic), 7.58–7.41 (3H, m, aromatic), 5.98 (1H, s, H
acetalic), 5.51 (1H, s, H-1), 5.10 (1H, s, H-4), 4.68 (1H,
m, H-5), 4.21 (2H, m, H-2, H-3), 4.10 (1H, m, H-6a),
3.85 (1H, m, H-6b), 2.18 (3H, s, Ac); 13C NMR l (125
MHz, CDCl3) 133.9–124.1 (C aromatic), 104.5 (C ac-
etalic), 98.8 (C-1), 75.7 (C-3), 73.1 (C-5), 71.3 (C-2),
70.8 (C-4), 64.4 (C-6) 20.7 (Ac). Anal. Calcd for
C19H18O6: C 66.66; H 5.30. Found: C 66.81; H 5.34.
Compound 14exo crystallized from EtOH, mp 83–
85 °C (white needles); [h]D +61.2 (c 0.29, CHCl3); (Rf
0.30, 9:1 dichloromethane-acetone); Anal. Calcd for
C19H18O6: C 66.66; H 5.30. Found: C 66.73; H 5.26.
1,6-Anhydro-4-O-benzyl-2,3-O-(2-naphthyl)methyl-
1,6-Anhydro-2-O-benzyl-3,4-O-(2-naphthyl)methyl-
ene-i- -galactopyranose (11endo).—To a solution of
D
9endo (300 mg, 1.0 mmol) in dry DMF (3 mL), 80%
NaH was added at 0 °C (45 mg, 1.5 mmol) and stirred
for 30 min. Then benzyl bromide (0.15 mL, 1.2 mmol)
was added to the mixture and stirred for 2 h. After
usual work-up procedure the residue was crystallized
from EtOH yielding 340 mg (87%) of 11endo, as white
needles: mp 128–130 °C [h]D +32.7 (c 0.26, CHCl3);
1H NMR l (200 MHz, CDCl3) 8.08–7.35 (12H, m,
aromatic), 5.93 (1H, s, H acetalic), 5.54 (1H, s, H-1),
4.83 (1H, d, J=12.0, CH2a), 4.70 (1H, d, J=12.0,
CH2b) 4.65 (2H, m, H-4, 5), 4.38 (1H, d, J3,4=7.0,
H–3), 4.16 (1H, d, J=7.0, H-6a), 3.88 (1H, s, H-2),
3.54 (1H, dd, J5,6=7.0, H-6b), 3.81 (1H, s, H-5); 13C
NMR d (50 MHz, CDCl3) 137.2-123.4 (C aromatic),
102.9 (C acetalic), 99.8 (C-1), 76.6, 76.1, 72.1, 69.7 (C-2,
3, 4, 5), 72.2 (CH2), 64.6 (C-6). Anal. Calcd for
C24H22O5: C 73.83; H 5.68. Found: C 73.81; H 5.64.
ene-i- -mannopyranose (15endo).—Compound 13
D
1,6 - Anhydro - 2,3 - O - (2 - naphthyl)methylene - i -
D
-
endo (200 mg, 0.67 mmol) was converted to compound
15endo in a similar manner as described for the synthe-
sis of 11endo. Compound 15endo crystallized from
EtOH, mp 130–13 1°C (white needles); [h]D +55.2 (c
0.34, CHCl3); 1H NMR l (500 MHz, CDCl3) 8.01–7.21
(12H, m, aromatic), 5.93 (1H, s, H acetalic), 5.59 (1H,
d, J=2.9, H-1), 4.78 (1H, d, J=12.0, CH2a), 4.69 (1H,
mannopyranose (13endo, 13exo).—To a solution of
compound 12 (1.2 g, 7.4 mmol) in dry DMF (3 mL)
2-naphthaldehyde dimethyl acetal (1.9 g, 9.6 mmol) and
catalytic amount of p-toluenesulfonic acid were added,
and the mixture was stirred at room temperature. After
24 h TLC showed 50% conversion. The mixture stirred
for
4
days, TLC showed 80% conversion (9:1
d, J=12.0, CH2b) 4.71 (1H, s, H-4), 4.38 (1H, d, J2,3=
dichloromethane-acetone), the mixture was worked up
and the solid crude product was crystallized from
EtOH yielding 1.0 g of 13endo. The filtrate, containing
the isomeric mixture of the title compounds was evapo-
rated and separated by column chromatography (9:1
dichloromethane-acetone) yielding 200 mg of 13endo
(over all yield 55%) and 200 mg of 13exo (9.2%).
Compound 13endo: mp 220–221 °C (white needles);
[h]D −78.6 (c 0.11, CHCl3); (Rf 0.23, 9:1
dichloromethane-acetone); 1H NMR d (200 MHz,
CDCl3) 7.98–7.81 (7H, m, aromatic), 5.95 (1H, s, H
acetalic), 5.56 (1H, d, J=1.5, H-1); 13C NMR l (50
MHz, CDCl3) 134.1–124.4 (C aromatic), 104.8 (C ac-
7.0, H-3), 4.31 (1H, dd, H-2), 4.00 (1H, d, J=7.5,
H-6a), 3.87 (1H, d, H-6b), 3.81 (1H, s, H-5); 13C NMR
l (125 MHz, CDCl3) 137.0-124.3 (C aromatic), 104.6
(C acetalic), 98.9 (C-1), 75.7 2× (C-3, 5), 73.7 (C-4),
71.7 (C-2), 71.5 (CH2), 64.6 (C-6). Anal. Calcd for
C24H22O5: C 73.83; H 5.68. Found: C 73.74; H 5.61.
Methyl
3-O-(2-naphthyl)methyl-h-L-rhamnopyran-
oside (16).—Compound 2exo (220 mg, 0.7 mmol) was
converted to 16 following the general method A. The
solid crude product was crystallized from EtOAc-nhex-
ane yielding 200 mg (90%) of 16: mp 74–76 °C (white
needles); [h]D −17.0 (c 0.27, CHCl3); (Compound 2exo
was also converted to 16 following the general method

A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
1949
1
B, with a yield of 90%). H NMR d (500 MHz, CDCl3)
crude product was purified by column chromatography
7.85–7.41 (7H, m, aromatic), 4.83 (1H, d, J=11.8,
CH2a), 4.70 (1H, d, J=11.8, CH2b), 4.68 (1H, br.s,
H-1), 4.02 (1H, br.s, H-2), 3.67 (1H, m, H-3), 3.61 (1H,
m, H-5), 3.57 (1H, m, H-4), 3.32 (3H, s, OCH3), 2.50
(1H, d, J=2.3, OH-2), 2.32 (1H, d, J=2.5, OH-3),
1.30 (3H, d, J=6.1, CH3-6); 13C NMR d (125 MHz,
CDCl3) 135.1, 133.2, 133.1 (Cq, aromatic), 128.6, 127.9,
127.7, 126.8, 126.3, 125.6 (CH, aromatic), 100.4 (C-1),
79.8 (C-3), 71.7 (CH2), 71.6 (C-4), 67.8 (C-2), 67.5
(C-5), 54.8 (OCH3), 17.6 (C-6). Anal. Calcd for
C18H22O5: C 67.91; H 6.97. Found: C 68.04; H 6.95.
(4:1 dichloromethane-acetone) yielding 200 mg (90%) of
1
19 as a colorless syrup; [h]D +15.8 (c 0.53, CHCl3); H
NMR l (500 MHz, CDCl3) 7.85–7.40 (7H, m, aro-
matic), 4.84 (d, 1H, 11.9, CH2a), 4.66 (1H, br.s, H-1),
4.66 (1H, d, CH2b), 3.70–3.75 (2H, m, H-2, H-3), 3.58
(1H, m, H-5), 3.45 (1H, t, J=9.0, H-4), 3.30 (3H, s,
OCH3), 1.31 (3H, d, J=6.1, CH3-6); 13C NMR d (125
MHz, CDCl3) 135.0, 133.2, 133.0 (Cq, aromatic), 128.4,
127.9, 127.7, 126.8, 126.2, 126.0, 125.7 (CH, aromatic),
99.1 (C-1), 78.1 (C-2), 73.8 (C-4), 73.1 (CH2), 71.5
(C-3), 67.7 (C-5), 54.7 (OCH3), 17.6 (CH3-6). Anal.
Calcd for C18H22O5: C 67.91; H 6.97. Found: C 68.07;
H 6.93.
Methyl
4-O-benzyl-3-O-(2-naphthyl)methyl-h-L-
rhamnopyranoside (17).—Compound 4exo (86 mg, 0.2
mmol) was converted to 17 following the general
method A. The crude product was purified by column
chromatography (7:3 hexane-EtOAc) yielding 80 mg
(93%) of 17 as a colorless syrup; [h]D −30.3 (c 0.33,
CHCl3); (Compound 4exo was also converted to 17
following the general method B, with a yield of 91%).
1H NMR l (200 MHz, CDCl3) 7.75–7.23 (12H, m,
aromatic), 4.91 (1H, d, J=11.5, CH2a), 4.81 (2H, s,
CH2), 4.69 (1H, d, J1,2=1.5, H-1), 4.64 (1H, d, CH2b),
4.05 (1H, m, H-2), 3.87 (1H, dd, J2,3=3.5, J3,4=9.1,
H-3), 3.71 (1H, m, H-5), 3.48 (1H, t, J4,5=9.1, H-4),
3.32 (3H, s, OCH3), 2.63 (1H, d, J2H,OH=2.0, 2-OH),
1.33 (3H, d, J=6.0, CH3-6); 13C NMR d (50 MHz,
CDCl3) 138.1-125.7 (C aromatic), 100.0 (C-1), 79.9
(2×, C-3, C-4), 75.3(CH2-NAP), 72.0 (CH2Ph), 68.4
(C-2), 54.7 (OCH3), 17.8 (C-6). Anal. Calcd for
C25H28O5: C 73.51; H 6.91. Found: C 73.38; H 6.88.
Methyl
4-O-benzyl-2-O-(2-naphthyl)methyl-h-L-
rhamnopyranoside (20).—Compound 4endo (130 mg,
0.32 mmol) was converted to 20 following the general
method A. The crude product was purified by column
chromatography (7:3 hexane–EtOAc) yielding 120 mg
(92%) of 20 as a colorless syrup; [h]D −11.3 (c 0.30,
CHCl3); 1H NMR l (200 MHz, CDCl3) 7.91–7.21
(12H, m, aromatic), 4.90 (2H, d, J=12.0, CH2a,
CH2a‘), 4.75 (1H, d, J1,2=1.5, H-1), 4.73 (1H, d,
CH2b), 4.65 (1H, d, CH2b‘), 3.94 (1H, m, H-3), 3.78
(1H, dd, J2,3=4.0, H-2), 3.66 (1H, m, H-5), 3.35 (1H, t,
J
J
3,4=9.0, H-4), 3.31 (3H, s, OCH3), 2.35 (1H, d,
3H,OH=9.0, 3-OH), 1.35 (3H, d, J=6.0, CH3-6); 13C
NMR l (50 MHz, CDCl3) 138.4–125.7 (C aromatic),
97.9 (C-1), 82.2, 78.4 (C-2, C-4), 74.9 (CH2-NAP), 73.1
(CH2Ph), 71.6 (C-3), 66.9 (C-5), 54.7 (OCH3), 18.0
(C-6). Anal. Calcd for C25H28O5: C 73.51; H 6.91.
Found: C 73.62; H 6.98.
Methyl
4-O-tert-butyldimethylsilyl-3-O-(2-naph-
-rhamnopyranoside (18).—Compound
thyl)methyl-h-
L
Ethyl 3-O-(2-naphthyl)methyl-1-thio-h-L-rhamnopy-
5exo (215 mg, 0.5 mmol) was converted to 18 following
the general method A. The crude product was purified
by column chromatography (8:2 hexane–EtOAc) yield-
ing 200 mg (93%) of 18. Compound 18 crystallized
ranoside (21).—Compound 7exo (240 mg, 0.7 mmol)
was converted to 21 following the general method A.
The crude product was purified by column chromatog-
raphy (3:2 hexane–EtOAc) yielding 220 mg (92%) of 21
1
from EtOH: mp 74–76 °C (colorless crystals); [h]D
−
as a colorless syrup; [h]D −112.1 (c 0.69, CHCl3); H
53.8 (c 0.40, CHCl3); (Compound 5exo was also con-
verted to 18 following the general method B, with a
yield of 89%). 1H NMR d (500 MHz, CDCl3) 7.85–7.44
(7H, m, aromatic), 4.78 (1H, d, J=11.7, CH2a), 4.72
(1H, d, J=11.7, CH2b), 4.68 (1H, br.s, H-1), 3.98 (1H,
br.s, H-2), 3.67-3.56 (3H, m, H-3, H-4, H-5), 3.34 (3H,
s, OCH3), 2.47 (1H, br.s, OH-2), 1.30 (3H, d, J=6.0,
CH3-6), 0.91 (9H, s, But), 0.18 (2x3H, s, s, Si-CH3); 13C
NMR d (125 MHz, CDCl3) 135.4, 133.2, 133.0 (Cq,
aromatic), 128.3, 127.9, 127.7, 126.6, 126.2, 126.0, 125.7
(CH, aromatic), 100.1 (C-1), 80.4, 72.7, 6.84 (C-2, C-3,
C-4), 71.8 (CH2), 68.1 (C-5), 54.7 (OCH3), 25.9 (But),
18.3 (CH3-6), 18.1 (But-Cq), -3.8, −4.5 (Si-CH3). Anal.
Calcd for C24H36O5Si: C 66.63; H 8.39. Found: C 66.48;
H 8.30.
NMR l (500 MHz, CDCl3) 7.98–7.79 (4H, m, aro-
matic), 7.55–7.45 (3H, m, aromatic), 5.31 (1H, s, H-1),
4.78 (1H, d, J=12.0, CH2a),4.65 (1H, d, CH2b), 4.19
(1H, d, J2,3=4.0, H-2), 4.09 (1H, m, H-5), 3.67 (2H, m,
H-3, H-4), 3.11 (2H, s, 2-OH, 4-OH), 2.48 (2H, m,
SCH2CH3),), 1.25 (3H, d, J=6.0, CH3-6), 1.15 (3H, t,
J=7.0, SCH2CH3); 13C NMR l (125 MHz, CDCl3)
134.5-125.6 (C aromatic), 83.2 (C-1), 79.8 (C-2), 71.6
(CH2), 75.1 (C-4), 69.2 (C-2), 68.1 (C-5), 24.9
(SCH2CH3), 17.5 (C-6), 14.7 (SCH2CH3). Anal. Calcd
for C19H24O4S: C 65.49; H 6.94; S 9.20. Found: C
65.57; H 6.95; S 9.31.
Ethyl 2-O-(2-naphthyl)methyl-1-thio-h-L-rhamnopy-
ranoside (22).—Compound 7endo (130 mg, 0.32 mmol)
was converted to 22 following the general method A.
The crude product was purified by column chromatog-
raphy (3:2 hexane–EtOAc) yielding 120 mg (92%) of
22. Compound 22 crystallized from EtOAc-nhexane:
Methyl
2-O-(2-naphthyl)methyl-h-L-rhamnopyran-
oside (19).—Compound 2endo (220 mg, 0.7 mmol) was
converted to 19 following the general method A. The

1950
A. Borba´s et al. / Carbohydrate Research 337 (2002) 1941–1951
mp 75–76 °C (white needles); [h]D −67.5 (c 0.49,
CHCl3); H NMR l (500 MHz, CDCl3) 7.98–7.76 (4H,
acetone, hexane–EtOAc), but no changes could be
detected. After 2 h the mixture was quenched with 0.1
mL of triethylamine, filtered, the filtrate was diluted
with dichloromethane, washed with water (3×10 mL),
1
m, aromatic), 7.85–7.43 (3H, m, aromatic), 5.57 (1H, s,
H-1), 4.81 (1H, d, J=12.0, CH2a),4.62 (1H, d, CH2b),
3.98 (1H, m, H-5), 3.82 (1H, d, J2,3=3.7, H-2), 3.72
(1H, dd, J3,4=9.5, H-3), 3.51 (1H, t, H-4), 3.43 (2H, s,
3-OH, 4-OH), 2.49 (2H, m, SCH2CH3), 1.30 (3H, d,
J=6.0, CH3-6), 1.19 (3H, t, J=7.0, SCH2CH3); 13C
NMR l (125 MHz, CDCl3) 134.7-125.6 (C aromatic),
80.8 (C-1), 79.5 (C-2), 73.9 (C-4), 72.3 (CH2), 71.8
(C-3), 68.1 (C-5), 24.9 (SCH2CH3), 17.5 (C-6), 14.7
(SCH2CH3). Anal. Calcd for C19H24O4S: C 65.49; H
6.94; S 9.20. Found: C 65.38 H 6.88; S 9.32.
1
dried and concentrated. The H NMR spectrum of the
residue showed an isomeric mixture of 11exo and endo
in a ratio of 1:2.36; l 1H NMR (200 MHz, CDCl3) 6.40
(H acetalic exo), 5.93 (H acetalic endo).
Isomerisation of the 1,6-anhydro-4-O-benzyl-2,3-O-
endo-(2-naphthyl)methylene-i-
D
-mannopyranose
with
AlCl3 (15endo-exo).—Compound 15endo (104 mg, 0.27
mmol) was isomerised in a similar manner as described
1
for compound 11endo. The H NMR spectrum of the
1,6-Anhydro-2-O-benzyl-3-O-(2-naphthyl)methyl-i-
-galactopyranose (23).—Compound 11endo (100 mg,
residue showed an isomeric mixture of 15exo and endo
in a ratio of 1:1.20; l 1H NMR (200 MHz, CDCl3) 6.45
(H acetalic exo), 5.93 (H acetalic endo).
Hydrogenolysis of the isomeric mixture of 1,6-anhy-
dro - 2 - O - benzyl - 3,4 - O - (2 - naphthyl)methylene - i - D-
galactopyranose with LiAlH4-AlCl3.—Isomeric mixture
of compound 11endo-exo (100 mg, 0.26 mmol) was
hydrogenolyzed following the general method A. The
reaction was monitored by TLC, the reaction was
completed after 7 h, formation of one product could be
detected. The crude product was purified by column
chromatography (7:3 hexane-EtOAc) yielding 83 mg
(83%) of 23 as a colorless syrup.
D
0.26 mmol) was converted to 23 following the general
method A. The crude product was purified by column
chromatography (7:3 hexane–EtOAc) yielding 87 mg
(87%) of 23 as a colorless syrup; [h]D −43.4 (c 0.42,
CHCl3); 1H NMR l (500 MHz, CDCl3) 7.94–7.20
(12H, m, aromatic), 5.40 (1H, s, H-1), 4.68 (1H, d,
J=11.5, CH2a-Bn), 4.53 (1H, d, J=12.0, CH2a-NAP),
4.46 (2H, d, CH2b-Bn, CH2b-NAP), 4.41 (1H, t, J=
4.5, H-5), 4.19 (1H, d, J=7.2, H-6a), 4.09 (1H, t, H-4),
3.79 (1H, d, H-3), 3.62 (1H, dd, H-6b), 3.58 (1H, s,
H-2), 2.95 (H, br. s, 4-OH); 13C NMR l (125 MHz,
CDCl3) 1347.1-125.5 (C aromatic), 99.8 (C-1), 75.6
(C-3), 74.2 (C-5), 74.1 (C-2), 72.7 (CH2-Bn), 72.1 (CH2-
NAP), 64.5 (C-4), 63.3 (C-6). Anal. Calcd for
C24H24O5: C 73.45; H 6.16. Found: C 73.53; H 6.21.
1,6-Anhydro-4-O-benzyl-3-O-(2-naphthyl)methyl-i-
Hydrogenolysis of the isomeric mixture of the 1,6-an-
hydro-4-O-benzyl-2,3-O-endo-(2-naphthyl)methylene-i-
D
-mannopyranose with LiAlH4–AlCl3.—Isomeric mix-
ture of compound 15endo-exo (80 mg, 0.23 mmol) was
hydrogenolyzed following the general method A. The
reaction was monitored by TLC, after 18 h the conver-
sion was ꢀ90%, and formation of one product could
be detected. After the work-up procedure the crude
product was purified by column chromatography (7:3
hexane–EtOAc) yielding 53 mg (66%) of 24.
D
-mannopyranose (24).—Compound 15 endo (130 mg,
0.32 mmol) was converted to 24 following the general
method A, the rection was completed after 3 h. The
crude product was purified by column chromatography
(7:3 hexane–EtOAc) yielding 120 mg (92%) of 24 as a
1
colorless syrup; [h]D −35.2 (c 0.48, CHCl3); H NMR
l (500 MHz, CDCl3) 7.95–7.12 (12H, m, aromatic),
5.39 (1H, s, H-1), 4.70 (1H, d, J=12.4, CH2a-Bn), 4.62
(1H, d, CH2b-Bn), 4.39 (1H, d, J=12.5, CH2a-NAP),
(1H, d, J=12.5, CH2a-NAP), 4.10 (1H, d, J=7.2,
H-6a), 4.19 (1H, d, J=7.2, H-6a), 4.09 (1H, t, H-4),
3.79 (1H, d, H-3), 3.62 (1H, dd, H-6b), 3.58 (1H, s,
H-2), 2.95 (H, br. s, 4-OH); 13C NMR l (125 MHz,
CDCl3) 1347.1–125.5 (C aromatic), 99.8 (C-1), 75.6
(C-3), 74.2 (C-5), 74.1 (C-2), 72.7 (CH2-Bn), 72.1 (CH2-
NAP), 64.5 (C-4), 63.3 (C-6). Anal. Calcd for
C24H24O5: C 73.45; H 6.16. Found: C 73.37; H 6.11.
Isomerisation of the 1,6-anhydro-2-O-benzyl-3,4-O-
Acknowledgements
This work was supported by grants from the Min-
istry of Education (FKFP T035128), the Hungarian
Academy of Sciences (AKP 2000-162 2,4) and the
Hungarian Scientific Research Fund (OTKA T25244,
OTKA T34515). A. B. acknowledges the Bolyai fellow-
ship of the Hungarian Academy of Sciences.
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