Glycosylation using hemiacetal sugar derivatives: Synthesis of O-α-D-rhamnosyl-(1 → 3)-O-α-D-rhamnosyl-(1 → 2) -D-rhamnose and O-α-D-tyvelosyl-(1 → 3)-O-α-D-mannosyl-(1 → 4)-L-rhamnose

Article abstract of DOI:10.1246/bcsj.76.1409

O-α-D-Rhamnopyranosyl-(1 → 3)-O-α-D-rhamnopyranosyl-(1 → 2)-D-rhamnopyranose, a repeating trisaccharide of the O-specific polysaccharides (OPSs) of Pseudomonades, and O-α-D-tyvelopyranosyl-(1 → 3)-O-α-D-mannopyranosyl-(1 → 4)-L-rhamnopyranose, a trisaccha

Full text of DOI:10.1246/bcsj.76.1409

ꢀ 2003 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 76, 1409–1421 (2003) 1409
Glycosylation Using Hemiacetal Sugar Derivatives: Synthesis of O-ꢀ-D-
Rhamnosyl-(1 ! 3)-O-ꢀ-D-rhamnosyl-(1 ! 2)-D-rhamnose and O-ꢀ-D-
Tyvelosyl-(1 ! 3)-O-ꢀ-D-mannosyl-(1 ! 4)-L-rhamnose
ꢀ
Ayano Takabatake, Aya Taniguchi, Yoshika Shinoda, and Aya Morinaga
ꢀ
Motoko Hirooka, Asako Yoshimura, Izumi Saito, Fumio Ikawa, Yoko Uemoto, Shinkiti Koto,
School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641
(Received November 19, 2002)
O-ꢀ-D-Rhamnopyranosyl-(1 ! 3)-O-ꢀ-D-rhamnopyranosyl-(1 ! 2)-D-rhamnopyranose, a repeating trisaccharide
of the O-specific polysaccharides (OPSs) of Pseudomonades, and O-ꢀ-D-tyvelopyranosyl-(1 ! 3)-O-ꢀ-D-mannopyran-
osyl-(1 ! 4)-L-rhamnopyranose, a trisaccharide composing the OPSs of Salmonella typhi, were synthesized by in-situ
activating glycosylation reactions using hemiacetal sugar derivatives. Allyl 2,4-di-O-benzyl-ꢀ-D-rhamnopyranoside was
prepared via the direct ditritylation of allyl ꢀ-D-mannopyranoside. 3-O-Acetyl-2,4-di-O-benzyl-D-rhamnopyranose was
used as a precursor for the moiety of D-tyvelose (3,6-dideoxy-D-arabino-hexose, 3,6-dideoxy-D-mannopyranose, 3-
deoxy-D-rhamnose) of the salmonella trisaccharide.
Glycosylation is the fundamental reaction for assembling
sugar units artificially. Modern currently developed methods
for glycosylation have been effectively used to synthesize var-
ious oligosaccharidal substances.1 In-situ-activation methods
using hemiacetal sugar derivatives (lactols) as donors (DOH in
Eq. 1) simplify the glycosylation of a given acceptor (AOH),
(OPSs) of Pseudomonades, which are opportunistic path-
ogens8c,f,h and phytopathogens.8d,h,j,k A recent paper8i in-
formed that the OPSs of phytopathogenic Xanthomonades also
contain 1 as a repeating unit of the branched-chain stem
polysaccharide. Although a polymer of 19a and 1-bovin serum
albumin conjugate9b were synthesized, 1 itself has never been
synthesized or characterized. On the other hand, 2 is a com-
mon trisaccharide composing repeating tetrasaccharide units of
the OPSs of Salmonella typhi,10 causing an acute enteric in-
fectious disease, typhus,10a and has not been synthesized. As
described below, we will show that the D-rhamnose donor 6
was useful as a precursor of the immunodominant ꢀ-D-tyvelo-
syl moiety11 at the non-reducing end of 2, avoiding any diffi-
culties due to the instability of tyvelosyl halides11b{d and, espe-
cially, the uncontrollable selectivity in glycosylation with the
benzyl-protected tyvelosyl chloride.11e
DOH þ AOH þ Reagent(s) ! DOA
ð1Þ
because they are free from the preparation of any activated
intermediates.2;3 Recently, using such methods,2;4 we carried
out ꢀ-selective syntheses of D-mannooligosaccharides2 and L-
rhamnooligosaccharides.5c This article presents new applica-
tions of our methods for ꢀ-selective syntheses of a trisaccha-
ride 1 (Fig. 1) consisting of the rare sugar D-rhamnose (6-
deoxy-D-mannose) and a trisaccharide 2 containing tyvelose
(3-deoxy-D-rhamnose), as described below.
Several years ago, we published the syntheses of ditrityl
derivatives6 of hexopyranosides (B in Fig. 2) and dihydroxy
derivatives (C) therefrom.6a Later, we reported that C in gluco-
form was useful as a precursor for partially protected 6-deoxy-
D-glucose (D-quinovose) (D).5b,7 This paper now shows that
ditrityl D-mannosides are good starting materials for preparing
monohydroxy derivatives of D-rhamnose,8a,b as shown in
Fig. 2; i.e., a D-mannoside A was converted into an acceptor
form D of D-rhamnose by successive reactions of ditritylation,
benzylation, detritylation, monotosylation, and reduction. Fur-
thermore, the selective removal of a protecting group (R) from
D, of which the OH group was pre-masked with a protecting
group (Q), gave a donor form E of D-rhamnose.
As described above, we planned to synthesize 1 and 2 start-
ing from the D-mannoside 3,5a as summarized in Fig. 1, to
show the utility of B in the manno-form. From 3, we prepared
four synthons: three D-rhamnose derivatives (4, 5, and 6) and
one D-mannosyl donor 8. The saccharide 1 is the common
repeating linear trisaccharide of the O-specific polysaccharides
The synthesis of 1 began with the preparation of 4 (Fig. 3).
Compound 35a was converted into the 6-OH derivative 10,12a,b
via conventional monotritylation,12c benzylation, and de-
tritylation. This compound was monotosylated and reduced
5b,7
with LiAlH4
yield from 3. The deallylation of 11 with PdCl2 gave 4 in
54% yield.
to afford the D-rhamnose derivative 11 in 37%
13
Direct tritylation without the tin-mediation14a of 3, readily
prepared from D-mannose,5a with trityl chloride (2.3 mol.
amt.)6a in pyridine at 55 ꢁC, afforded the 3,6-disubstituted
1214a in 67% yield. In contrast, a similar tritylation was con-
ducted, but at 100 ꢁC gave the 2,6-disubstituted 13 in 27%
yield as a major ditritylated derivative, as previously observed
in the cases of methyl and benzyl ꢀ-D-mannnosides.6a Benzy-
lation followed by detritylation of 12 gave the diol 1414a in
56% yield. This was tosylated selectively5b,7 and reduced with
LiAlH4 to afford 5 in 34% yield. To our knowledge,9 this is
the shortest route to a versatile 3-OH derivative of D-rhamnose
from D-mannose. Acetylation of 5, followed by removal of the
Published on the web July 15, 2003; DOI 10.1246/bcsj.76.1409

1410 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Glycosylation Using 1-OH Sugar Derivatives
Fig. 1. Synthetic scheme for ꢀ-D-Rhap-(1 ! 3)-ꢀ-D-Rhap-(1 ! 2)-D-Rhap-OH (1) and ꢀ-D-Tyvp-(1 ! 3)-ꢀ-D-Manp-(1 ! 4)-
L-Rhap-OH (2). A code with square shade is a donor, whereas that with round shade is an acceptor.
Fig. 2. A route to partially benzylated 6-deoxyhexoses.
allyl group, furnished 6. Through a similar sequence of reac-
tions, 13 was converted into the diol 15,14b,c and then into the
D-rhamnose derivative 16. The diol 17, prepared before by
bromide (Me3SiBr), CoBr2, tetrabutylammonium bromide (n-
Bu4NBr), and molecular sieves 4A (MS4A), in 1,2-di-
chloroethane.5b The desired disaccharide derivative 21 was
produced in 57% yield. The ꢁ-linked by-product was isolated
in 23% yield. The 1H and 13C NMR spectra of the filtrate of a
reaction mixture of 4 and the TCTM system in CD2Cl2 showed
a quantitative conversion of 4 into a (Fig. 3),4b indicating that
glycosylation proceeds via a.
ꢁ
means of a ditritylation reaction at 100 C,6a was readily con-
verted into the acceptor 7 in 35% yield, through monotosyla-
tion and subsequent reduction.
We have previously observed that a solvent-free ben-
zylation15a of methyl ꢀ-D-mannopyranoside in benzyl chloride
in the presence of 4.5 mol. amt. of KOH at 140 ꢁC15b afforded
mainly the 3-OH derivative.15c A similar reaction was applied
to 3 to give the desired 3-OH compound 18 in 31% yield;
minor products were the 4-OH derivative 195a (19%) and the
diol 2014d (17%). Compound 18, thus obtained only in two
steps from D-mannose, was then transformed into the donor 8
via acetylation and deallylation. Through a known meth-
od,16a,b the acceptor 9 (Fig. 1) was prepared from benzyl ꢀ-
L-rhamnopyranoside.5c,16c
13
Mild deallylation using PdCl2 converted 21 into 22 in
63% yield. This donor was condensed with 7 in the presence
of the TCTM system to selectively produce the protected tri-
saccharide 23 in 42% yield. In its NMR spectra observed in
CDCl3, the values of one-bond-coupling of the anomeric cen-
ters of the interglycosidic linkages17 indicated the ꢀ-linked
structure; the JC1,H1 values were 168.9 Hz for the C1b-H1b
bond and 169.3 Hz for the C1c-H1c bond. The linkage posi-
tions were analyzed by NOE experiments: the irradiation on
H1b at 5.08 ppm enhanced the signal of H2a at 4.07 ppm,
whereas that of H1c at 5.18 ppm did the signal of H3b at
ꢀ-Selective condensations of 4 and 5 (Fig. 4) were per-
formed with the TCTM system,4c,5b composed of trimethylsilyl

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 76, No. 7 (2003) 1411
Fig. 3. Synthesis of partially benzylated D-rhamnose derivatives: a. (i) TsCl + pyridine (Py), ꢂ10 ꢁC ! room temperature (rt), (ii)
LiAlH4/Et2O, 0 ꢁC ! reflux; b. PdCl2 + NaOAc/aq AcOH (95%), rt; c. TrCl (2.3 eq) + Py, 55 ꢁC; d. BnBr + NaH/DMF, 0 ꢁC
ꢁ
ꢁ
! rt; e. CF3CO2H + MeOH/CHCl3, rt; f. Ac2O + Py, rt; g. TrCl (3.0 eq) + Py, 100 C; h. BnCl + KOH, 140 C.
Fig. 4. Synthesis of ꢀ-D-Rhap-(1 ! 3)-ꢀ-D-Rhap-(1 ! 2)-D-Rhap-OH (1) (TCTM = Me3SiBr + CoBr2 + n-Bu4NBr + MS4A):
a. PdCl2 + NaOAc/aq AcOH (95%), rt; b. H2, Pd-C(10%)/MeOH, rt.

1412 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Glycosylation Using 1-OH Sugar Derivatives
Fig. 5. Synthesis of ꢀ-D-Tyvp-(1 ! 3)-ꢀ-D-Manp-(1 ! 4)-L-Rhap-OH (2) (NST = NsCl + AgOTf + Et3N): a. dil NaOMe, rt; b.
ꢁ
ꢁ
(i) TsCl + Py, ꢂ10 C ! rt, (ii) LiAlH4/Et2O, 0 C ! reflux; c. (i) NaH/THF, rt, (ii) CS2/THF, rt, (iii) MeI/THF, rt; d. n-
Bu3SnH + AIBN(cat.)/PhMe, N2, 110 ꢁC; e. (i) Tf2O + Py/CH2Cl2, ꢂ30 ꢁC ! 20 ꢁC, (ii) n-Bu4NBH4/PhMe, 50 ꢁC; f. H2, Pd-
C(10%)/MeOH, rt.
4.14 ppm. Total debenzylation gave 1. Its 13C NMR deter-
mined in D2O agreed well with those reported for the L-
form.18 The observed specific rotation of 1, being the D-form,
was +54ꢁ in H2O; the absolute value agreed with the reported
value of the L-form of 1, ꢂ52ꢁ,18 within the experimental
errors.
The synthesis of 2 started from condensations of 8 and 9
using an NST system,4a,5a composed of p-nitrobenzenesulfo-
nyl chloride (NsCl), silver trifluoromethanesulfonate (AgOTf),
and triethylamine (Et3N) (Fig. 5). The ꢀ-linked disaccharide
24 was selectively formed in 92% yield. Deacetylation of 24
with methanolic NaOMe gave the acceptor 25. The final ꢀ-
selective rhamnosylation of 25 with 6 was conducted in the
presence of the TCTM system to afford the trisaccharide 26
selectively only in 25% yield. It appears that the presence of
OAc group at C-3 in 6 makes it disarmed to give such a low
yield. It was, however, found that the NST system4a per-
formed this condensation to selectively form 26 in 90%
C1c-H1c bond, indicating their ꢀ-glycosidic structure. The
NOE experiments proved the C1b-to-O4a linkage and the C1c-
to-O3b linkage.
Deacetylation of 26 afforded 27. Before deoxygenating the
D-rhamnosyl moiety of 27 into the antigenic D-tyvelosyl
one,10a,19 we tried to convert a model D-rhamnoside derivative
29, obtained from a diol 28,6a into a tyvelose derivative 31.
The reduction of a dithiocarbonate of 30 with n-Bu3SnH in
toluene with an initiator20a{d gave 31 in 48% yield; the starting
29 was obtained in 45% yield.20e Deoxygenation via triflate of
21a{c
29 and its reduction with n-Bu4NBH4
also gave 31 (43%);
the parent alcohol 29 was concurrently formed in 25%
yield.21d Ultrasonication21a,b did not give 31, but afforded only
29 quantitatively.
The trisaccharide derivative 27 was then converted into the
dithiocarbonate 32. The reduction of 32 with n-Bu3SnH in
boiling toluene containing an initiator afforded the desired
product 33 in 29% yield; the starting 27 was yielded in 38%.
The NMR spectra of 33 in CDCl3 clearly showed deoxygena-
tion at the C-3c position giving a methylene group; the ꢂ-value
of C-3c was 29.5 and those of H-3c were 1.80 and 2.23.
Deoxygenation of 32 via a triflate only gave a complex mix-
ture of many products. The total debenzylation of 33 afforded
2. The 1H and 13C NMR spectra determined in D2O was con-
sistent with its structure: (1) the ꢂ-value of C-3c was 35.8 and
those of H-3c were 1.85 and 2.02, (2) the JC1,H1 value17 of C1b
was 169.5 Hz and that of C1c was 170.0 Hz, and (3) GHMBC
experiments showed closs-couplings, indicating the C1b-to-
O4a linkage and the C1c-to-O3b linkage.
yield.
We considered that the in-situ generated 1-O-
sulfonates4d of 6 is reactive enough despite the presence of
the disarming 3-OAc group.4e It is known that the 1-OH group
is transformed into the 1-Cl group upon a reaction with sulfo-
nyl chloride and a base.4f{j We observed that 4 disappeared in
the presence of a 1.3 mol. amt. of NsCl and Et3N in CD2Cl2 in
a NMR-tube at room temperature to generate the chloride b
(Fig. 3). It is conceivable that the reactive intermediate of the
NST system might have been the 1-OTf derivative generated
from the 1-chloride, such as b and AgOTf.4e However, the
possibility of the intervention of 1-ONs as a reactive inter-
mediate giving glycosides directly could not be omitted. In
the NMR spectra of 26 observed in CDCl3, the JC1,H1 values17
were 167.8 Hz for the C1b-H1b bond and 170.0 Hz for the
In summary, the ditritylated D-mannopyranosides are of use
as starting materials for preparing monohydroxy derivatives, 5
and 7, of D-rhamnose. The donor 6 is useful as a precursor of

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 76, No. 7 (2003) 1413
J5,6a ¼ J5,6b ¼ 4:0 Hz, H5), 3.79 (dd, J5,6a ¼ 4:0 Hz, J6a,6b ¼ 11:5
Hz, H2), 3.83 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 3.85 (dd,
J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3), 3.98 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz,
H4), 4.86 (d, J1;2 ¼ 2:0 Hz, H1), 5.84 (m, All); 13C NMR (CDCl3,
75 MHz) ꢂ 62.4 (C6), 67.9 (All), 72.3 (C5), 74.9 (C3), 75.0 (C2),
80.2 (C4), 97.5 (C1, JC1,H1 ¼ 167:5 Hz), 117.3, 133.6 (All).
Found: C, 73.24; H, 7.01%. Calcd for C30H34O6: C, 73.45; H,
6.79%.
Allyl 2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopyranoside (11). To a
stirred solution of 10 (0.510 g, 1.04 mmol) in pyridine (2.5 mL, 31
mmol) at ꢂ15 ꢁC (bath temperature), TsCl (247.2 mg, 1.3 mmol)
was added. The bath temperature was allowed to rise up to 25 ꢁC.
The mixture was kept standing overnight and evaporated to
dryness. Chromatography using the TK system (100:1!10:1)
gave a syrupy tosylate (0.536 g, 80%); 1H NMR (CDCl3, 300
MHz) ꢂ 2.41 (s, Ts), 3.77 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz,
tyvelosyl residue in the glycoside 2. All of the condensations
of the building blocks in this study were performed by one-pot-
one-stage in-situ activation glycosylation using sugar deriva-
tives in the hemiacetal form.
Experimental2
The solvent systems for column chromatography on silica gel
(Kanto Chemical, No. 37047; gradient elusion) and thin-layer
chromatography (TLC)(Merck, DC-Plastikfolien Kieselgel 60 F
254, Art. 5735) were AcOEt–MeOH (EM), hexane–AcOEt
(HE), and PhMe–2-butanone (TK). Hydrogenolytic debenzylation
was carried out using a Parr-3911 hydrogenation apparatus under
340 kPa of H2 at room temperature. Evaporation was carried out
under reduced pressure. The melting points were determined on a
Yanaco Micro Melting Point Apparatus (Yanagimoto). The op-
tical rotations were measured on a JASCO DIP-180 Digital Po-
larimeter at room temperature. The 1H and 13C NMR spectra were
recorded with a Varian VXR300 spectrometer or a Varian XL-400
spectrometer, along with the measurements of the H,H-COSY,
C,H-COSY, and DEPT spectra. The JC1,H1 values17 were deter-
mined by gated decoupling with the NOE experiment. The as-
signments of the spectra of 1, 2, 23, 26, and 33 were made by
auxiliary measurements of HOHAHA, HMQC, HMBC, GHMQC,
and differential NOE spectra. The elemental analyses were car-
ried out with a Yanaco CHN Corder MT-5. The LRMS and the
HRMS were recorded with a JEOL JMS-AX505H spectrometer, a
JEOL JMS-AX505HA spectrometer, and a JEOL JMS-700,
respectively. The abbreviations used here for the assigned sub-
stituents are: All (allyl), Bn (benzyl), Ns (p-nitrobenzenesulfo-
nyl), Tf (trifluoromethanesulfonyl), Tr (triphenylmethyl), and Ts
(p-toluenesulfonyl).
Commercial NsCl (Wako) was passed through a silica-gel col-
umn eluted with benzene, evaporated to dryness, and stored in a
dry box in a refrigerator. Syrupy donor and acceptors were puri-
fied by chromatography using the HE system and stored in a
refrigerator. Commercial AgOTf (Aldrich), Me3SiBr (Tokyo
Kasei), CoBr2 (Wako), n-Bu4NBr (Wako), TsCl (Wako), LiAlH4
(Wako), and anhydrous pyridine (Tokyo Kasei) were used without
purification. Acceptor 9 was prepared by a known method16a,b
from benzyl ꢀ-L-rhamnopyranoside.5c,16c
The preparation of an acetate for the determination of the NMR
spectra was carried out as follows: a sample (ca. 20 mg) was
treated with Ac2O (0.2 mL) and pyridine (0.2 mL) at room tem-
perature overnight, quenched with MeOH (0.2 mL), evaporated to
dryness, and chromatographed using the HE system to give a
chromatographically pure acetate.
H2), 3.83 (ꢃt, J3;4 ¼ 8:5 Hz, J4;5 ¼ 9:0 Hz, H4), 3.88 (dd, J2;3
¼
3:0 Hz, J3:4 ¼ 8:5 Hz, H3), 4.23 (dd, J5,6a ¼ 5:0 Hz, J6a,6b ¼ 10:5
Hz, H6a), 4.28 (dd, J5,6b ¼ 2:5 Hz, J6a,6b ¼ 10:5 Hz, H6b), 4.80
(d, J1;2 ¼ 2:0 Hz, H1), 5.80 (m, All); 13C NMR (CDCl3, 75 MHz)
ꢂ 21.6 (Ts), 67.0 (All), 69.3 (C6), 70.2 (C5), 74.2 (C4), 74.7 (C2),
80.1 (C3), 97.0 (C1, JC1,H1 ¼ 168:7 Hz), 144.5 (Ts), 117.4, 133.5
(All). This (0.518 g, 0.80 mmol) was dissolved in dry Et2O (13
ꢁ
mL). To a stirred solution at 0 C, LiAlH4 (Wako, 1.447 g, 38
mmol) was added in three portions. The mixture was stirred at 0
ꢁC for 0.5 h under anhydrous conditions and then under reflux for
0.5 h. After a careful addition of EtOAc (15.3 mL), the mixture
was evaporated to dryness. Chromatography using TK system
23
(100:1!20:1) afforded 11 (294.7 mg, 62 %); [ꢀ]D +12ꢁ (c
0.3, CH2Cl2) (Ref. 22, L-form, [ꢀ]D ꢂ15:1ꢁ (c 2.01, CH2Cl2));
1H NMR (CDCl3, 300 MHz) ꢂ 1.34 (q, J5;6 ¼ 6:0 Hz, H6), 3.63 (t,
J3;4 ¼ J4;5 ¼ 9:0 Hz, H4), 3.72 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz,
H5), 3.81 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 3.89 (dd, J2;3 ¼
3:0 Hz, J3;4 ¼ 9:0 Hz, H3), 4.81 (d, J1;2 ¼ 2:0 Hz, H1), 5.84 (m,
All); 13C NMR (CDCl3, 75 MHz) ꢂ 18.0 (C6), 67.7 (All), 68.1
(C5), 75.1 (C2), 80.2 (C3), 80.6 (C4), 97.2 (C1, JC1,H1 ¼ 166:6
Hz), 117.1, 133.9 (All). HRMS (FAB) Found: m=z 497.2323.
Calcd for C30H34NaO5 [M + Na]þ: 497.2304.
2,3,4-Tri-O-benzyl-D-rhamnopyranose (4). A mixture of 11
(600.0 mg, 1.27 mmol), PdCl2 (Wako, 311.7 mg, 1.8 mmol),
NaOAc (573.5 mg, 7.0 mmol), and aq AcOH (95%, 47.2 mL)
was stirred at room temperature overnight. After the addition of
ꢁ
allyl alcohol (0.95 mL) at 0 C, the mixture was stirred at room
temperature for 0.5 h and evaporated to dryness. Chromatography
using TK system (100:1!2:1) afforded 4 (298.3 mg, 54%), mp
ꢁ
23
92–93 C, [ꢀ]D +14ꢁ (c 1.0, H2O) (Ref. 22, L-form, mp 88–89
ꢁC; Ref. 23a, L-form, mp 90–92 ꢁC, [ꢀ]D ꢂ15:4ꢁ (CHCl3);
Allyl 2,3,4-Tri-O-benzyl-ꢀ-D-mannopyranoside (10). To a
stirred solution of allyl 6-O-trityl-ꢀ-D-mannopyranoside (5.0 g, 11
mmol), prepared from 35a by a known method,12c in N,N-di-
methylformamide (DMF, 37.5 mL) containing BnBr (14.2 mL,
119 mmol), NaH (ca. 60% dispersion in oil, 2.235 g, 56 mmol)
was added at 0 ꢁC. After the resulting mixture was stirred for 20
Ref. 23b, L-form, mp 90 ꢁC, [ꢀ]D ꢂ15:0ꢁ (c 1.0, CHCl3);
20
Ref. 23c, L-form, mp 94–95 ꢁC, [ꢀ]D ꢂ12ꢁ (c 0.5, CHCl3));
20
1H NMR (CDCl3, 300 MHz) (60% ꢀ) ꢂ 1.33 (q, J5;6 ¼ 6:0 Hz,
H6ꢀ), 1.35 (q, J5;6 ¼ 6:0 Hz, H6ꢁ), 3.37 (dq, J4;5 ¼ 9:0 Hz, J5;6
6:0 Hz, H5ꢁ), 3.57 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4ꢁ), 3.64 (t, J3;4
¼
¼
J4;5 ¼ 9:0 Hz, H4ꢀ), 3.82 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2ꢀ),
3.85 (dd, J1;2 ¼ 1:0 Hz, J2;3 ¼ 2:0 Hz, H2ꢁ), 3.93 (dd, J2;3 ¼ 3:0
Hz, J3;4 ¼ 9:0 Hz, H3ꢀ), 3.93 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz,
H6ꢀ), 4.62 (d, J1;2 ¼ 1:0 Hz, H1ꢁ), 5.18 (d, J1;2 ¼ 2:0 Hz, H1ꢀ);
13C NMR (CDCl3, 75 MHz) ꢂ 18.0 (C6ꢁ), 18.1 (C6ꢀ), 68.3
(C5ꢀ), 71.6 (C5ꢁ), 75.3 (C2ꢀ), 76.7 (C2ꢁ), 79.8 (C3ꢀ), 80.0
(C4ꢁ), 80.1 (C4ꢀ), 83.1 (C3ꢁ), 93.1 (C1ꢀ, JC1,H1 ¼ 168:1 Hz),
93.4 (C1ꢁ, JC1,H1 ¼ 160:0 Hz). Found: C, 74.28; H, 6.96%. Calcd
for C27H30O5: C, 74.63; H, 6.96%.
ꢁ
min, it was stirred at 20 C for 1 h. After the addition of MeOH
(3.0 mL) at 0 ꢁC and stirring at room temperature, the mixture was
evaporated on a boiling water bath. Chromatography with TK
system (20:1) afforded a syrup (5.156 g). This (1.019 g, 1.4
mmol) was treated with aq AcOH (80%, 7.9 mL) at 95 ꢁC for
0.5 h. Evaporation and chromatography with TK system (10:1)
25
gave 10 (627.7 mg, 60%); [ꢀ]D +38ꢁ (c 0.6, CHCl3) (Ref. 12a,
[ꢀ]D +37ꢁ (c 0.45, CHCl3); Ref. 12b, [ꢀ]D +31.2ꢁ (c 1.03,
1
CHCl3)); H NMR (CDCl3, 300 MHz) ꢂ 3.68 (dt, J4;5 ¼ 9:0 Hz,
Allyl 3,6- and 2,6-Di-O-trityl-ꢀ-D-mannopyranosides (12

1414 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Glycosylation Using 1-OH Sugar Derivatives
and 13). A mixture of 3 (8.804 g, 40 mmol), TrCl (25 g, 90
mmol), and pyridine (44 mL, 54 mmol) was stirred at 55 ꢁC
overnight. After the addition of Et3N (44 mL), the mixture was
evaporated to dryness and chromatographed with the TK system
tion to dryness and chromatography with the TK system
24
(100:1!10:1) yielded 14 (2.656 g, 56%), [ꢀ]D +35ꢁ (c 0.5,
CHCl3) (Ref. 14a, [ꢀ]D +28ꢁ (c 1.25, CHCl3)); 1H NMR
25
(CDCl3, 300 MHz) ꢂ 2.27 (br s, 2H, OH), 3.64 (ddd, J4:5 ¼ 8:5
Hz, J5,6a ¼ 4:0 Hz, J5,6b ¼ 3:0 Hz, H5), 3.67 (t, J3;4 ¼ J4;5 ¼ 8:5
Hz, H4), 3.76 (dd, J1;2 ¼ 2:0 H, J2;3 ¼ 3:5 Hz, H2), 3.79 (dd,
J5,6a ¼ 4:0 Hz, J6a,6b ¼ 11:5 Hz, H6a), 3.86 (dd, J5,6b ¼ 3:0 Hz,
J6a,6b ¼ 11:5 Hz, H6b), 4.03 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 8:5 Hz,
H3), 4.91 (d, J1;2 ¼ 2:0 Hz, H1), 5.85 (m, All); 13C NMR (CDCl3,
75 MHz) ꢂ 62.3 (C6), 68.0 (All), 71.5 (C5), 71.7 (C3), 76.6 (C4),
78.5 (C5), 96.3 (C1), 117.5, 133.5 (All). Found: C, 68.68; H,
6.91%. Calcd for C23H28O6: C, 68.98; H, 7.05%.
23
(100:1!3:1) to give 12 (18.84 g, 67 %), [ꢀ]D +32ꢁ (c 1.3,
25
1
CHCl3) (Ref. 14a, [ꢀ]D +33ꢁ (c 1, CHCl3)); H NMR (CDCl3,
300 MHz) ꢂ 1.73 (br s, OH), 2.07 (br s, OH), 2.78 (dd, J1;2 ¼ 2:0
Hz, J2;3 ¼ 3:0 Hz, H2), 3.34 (dd, J5,6a ¼ 5:5 Hz, J5a,5b ¼ 10:0 Hz,
H6a), 3.37 (dd, J5,6b ¼ 4:0 Hz, J6a,6b ¼ 10:0 Hz, H6b), 3.63 (m,
J4;5 ¼ 8:5 Hz, J5,6a ¼ 5:5 Hz, J5,6b ¼ 4:9 Hz, H5), 3.89 (dd, J2;3
¼
3:0 Hz, J3;4 ¼ 8:5 Hz, H3), 3.96 (t, J3;4 ¼ J4;5 ¼ 8:5 Hz, H4), 4.63
(d, J1;2 ¼ 2:0 Hz, H1), 5.80 (m, All); 13C NMR (CDCl3, 75 MHz)
ꢂ 64.6 (C6), 67.4 (All), 68.0 (C4), 69.1 (C2), 71.4 (C5), 74.8 (C3),
86.8, 87.3 (Tr), 99.4 (C1, JC1,H1 ¼ 167:0 Hz), 116.3, 133.8 (All).
Found: C, 79.83; H, 6.39%. Calcd for C47H44O6: C, 80.09; H,
6.29%.
The NMR data of the acetate of 14: 1H NMR (CDCl3, 300
MHz) ꢂ 1.99 (s, Ac), 2.08 (s, Ac), 3.90 (dd, J1;2 ¼ 2:0 Hz, J2;3
3:5 Hz, H2), 3.92 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4), 3.95 (ddd, J4;5
¼
¼
9:0 Hz, J5,6a ¼ 5:0 Hz, J5,6b ¼ 2:5 Hz, H5), 4.30 (dd, J5,6a ¼ 5:0
Hz, J6a,6b ¼ 12:5 Hz, H6a), 4.35 (dd, J5,6b ¼ 2:5 Hz, J6a,6b ¼ 12:5
Hz, H6b), 4.89 (d, J1;2 ¼ 2:0 Hz, H1), 5.28 (dd, J2;3 ¼ 3:5 Hz,
J3;4 ¼ 9:0 Hz, H3), 5.87 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ
20.8, 21.0 (Ac), 63.4 (C6), 68.1 (All), 69.8 (C5), 72.9 (Bn), 73.4
(C4), 73.8 (C3), 74.7 (Bn), 75.9 (C2), 96.7 (C1), 117.6, 133.5
(All), 170.0, 170.7 (Ac).
25
Further elution afforded 13 (3.73 g, 13%), [ꢀ]D 0ꢁ (c 1.3,
CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ 2.21 (s, OH), 2.41 (s,
OH), 3.43 (dd, J5,6a ¼ 4:0 Hz, J61,6b ¼ 10:0 Hz, H6a), 3.55 (dd,
J5,6b ¼ 4:0 Hz, J5,6a ¼ 10:0 Hz, H6b), 3.55 (dd, J2;3 ¼ 3:0 Hz,
J3;4 ¼ 9:0 Hz, H3), 3.56 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2),
3.65 (ꢃdt, J4;5 ¼ 9:0 Hz, J5,6a ¼ 4:0 Hz, J5,6b ¼ 3:0 Hz, H5), 4.35
(t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4), 4.46 (d, J1;2 ¼ 2:0 Hz, H1), 5.67 (m,
All); 13C NMR (CDCl3, 75 MHz) ꢂ 63.3 (C6), 67.6 (All), 69.6
(C3), 71.2 (C5), 71.3 (C2), 73.5 (C3), 86.6, 88.4 (Tr), 96.8 (C1),
117.0, 133.7 (All). Found: C, 79.37; H, 6.50%. Calcd for
C47H44O6 H2O: C, 79.08; H, 6.35%.
Allyl 3,4-Di-O-benzyl-ꢀ-D-mannopyranoside (15). In a sim-
ilar manner as that for the transformation of 12 into 14, 13 (1.49 g,
22
2.1 mmol) was derived into 15 (0.606 g, 72%), [ꢀ]D +45ꢁ (c
23
0.3, CHCl3) (Ref. 14b, [ꢀ]D +56ꢁ (c 0.45, CHCl3). Ref. 14c,
[ꢀ]D20 +109.5ꢁ (c 1.16, CHCl3). A large difference in the specific
ꢄ
After a mixture of 3 (2.87 g, 13 mmol), TrCl (10.9ꢁg, 39 mmol),
and pyridine (15 mL, 185 mmol) was stirred at 100 C overnight,
followed by addition of Et3N (15 mL), evaporation and chroma-
tography afforded 12 (<1 g, <11%) and then 13 (2.50 g, 27%).
The NMR data of the acetate of 12: 1H NMR (CDCl3, 300
MHz) ꢂ 1.54 (s, Ac), 2.23 (s, Ac), 2.99 (dd, J5,5a ¼ 2:5 Hz,
J6a,6b ¼ 10:5 Hz, H6a), 3.14 (dd, J5,6b ¼ 6:0 Hz, J6a,6b ¼ 10:5
Hz, H6b), 3.58 (ddd, J4;5 ¼ 10:0 Hz, J5,6a ¼ 2:5 Hz, J5,6b ¼ 6:0
Hz, H5), 3.91 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 10:0 Hz, H3), 4.26 (dd,
J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 4.74 (d, J1;2 ¼ 2:0 Hz, H1),
5.39 (t, J3;4 ¼ J4;5 ¼ 10:0 Hz, H4), 5.80 (m, All); 13C NMR
(CDCl3, 75 MHz) ꢂ 20.9, 21.3 (Ac), 63.2 (C6), 67.7 (All), 67.8
(C4), 69.9 (C3), 70.9 (C5), 71.9 (C2), 86.5, 87.4 (Tr), 95.8 (C1,
JC1,H1 ¼ 170:0 Hz), 169.7, 170.3 (Ac), 116.3, 133.5 (All).
The NMR data of the acetate of 13: 1H NMR (CDCl3, 300
MHz) ꢂ 1.76 (s, Ac), 1.87 (s, Ac), 3.14 (dd, J5,5a ¼ 4:5 Hz,
J6a,6b ¼ 10:5 Hz, H6a), 3.30 (dd, J5,6b ¼ 2:0 Hz, J6a,6b ¼ 10:5
Hz, H6b), 3.84 (ddd, J4;5 ¼ 10:0 Hz, J5,6a ¼ 4:5 Hz, J5,6b ¼ 2:0
Hz, H5), 3.86 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 10:0 Hz, H2), 4.12 (d,
J1;2 ¼ 2:0 Hz, H1), 5.14 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 10:0 Hz, H3),
5.96 (t, J3;4 ¼ J4;5 ¼ 10: Hz, H4), 5.67 (m, All); 13C NMR
(CDCl3, 75 MHz) ꢂ 20.5, 21.0 (Ac), 62.5 (C6), 67.0 (C4), 68.0
(All), 70.2 (C5), 71.3 (C3), 71.8 (C2), 86.8, 88.0 (Tr), 97.1 (C1),
117.2, 133.7 (All), 169.2, 170.1 (Ac).
rotation was not clarified, but our 1H NMR data shown below
1
agree well with those in Ref. 14c); H NMR (CDCl3, 300 MHz)
ꢂ 3.68 (dt, J4;5 ¼ 9:0 Hz, J5,6a ¼ J5,6b ¼ 3:0 Hz, H5), 3.80 (dd,
J5,6a ¼ 3:0 Hz, J6a,6b ¼ 12:0 Hz, H6a), 3.85 (dd, J5,6b ¼ 3:0 Hz,
J6a,6b ¼ 12:0 Hz, H6b), 3.91 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4), 3.92
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3), 4.05 (dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:0 Hz, H2), 4.92 (d, J1;2 ¼ 2:0 Hz, H1), 5.87 (m, All);
13C NMR (CDCl3, 75 MHz) ꢂ 61.9 (C6), 68.1 (All), 68.5 (C2),
71.7 (C5), 74.0 (C4), 80.0 (C3), 98.4 (C1), 117.5, 133.6 (All).
HRMS (FAB) Found: m=z 423.1815. Calcd for C23H28NaO6
[M + Na]þ: 423.1784.
1
NMR data of the acetate of 15: H NMR (CDCl3, 300 MHz) ꢂ
2.07 (s, Ac), 2.15 (s, Ac), 3.74 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4), 3.88
(ddd, J4;5 ¼ 9:5 Hz, J5,6a ¼ 2:0 Hz, J5,6b ¼ 4:5 Hz, H5), 4.03 (dd,
J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:5 Hz, H3), 4.31 (dd, J5,6a ¼ 2:0 Hz,
J6a,6b ¼ 12:0 Hz, H6a), 4.36 (dd, J5,6b ¼ 4:5 Hz, J6a,6b ¼ 12:0
Hz, H6b), 4.86 (d, J1;2 ¼ 2:0 Hz, H1), 5.39 (dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:5 Hz, H2), 5.87 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ
20.9, 21.0 (Ac), 63.4 (C6), 68.3 (All), 68.6 (C2), 69.7 (C5), 74.1
(C4), 78.1 (C3), 96.9 (C1, JC1,H1 ¼ 168:5 Hz), 118.0, 133.2 (All),
170.3, 170.8 (Ac).
Allyl 2,4-Di-O-benzyl-ꢀ-D-rhamnopyranoside (5). To a stir-
red mixture of 14 (2.429 g, 6.1 mmol) and dry pyridine (15.2 mL,
188 mmol) at ꢂ15 ꢁC (bath temperature), TsCl (2.267 g, 1.2
mmol) was added, and the bath temperature was allowed to rise
up to 25 ꢁC. After being kept stanꢁding overnight, MeOH (2.0 mL)
was added into the mixture at 0 C under stirring. The mixture
was evaporated to dryness, followed by chromatography using the
TK system (100:1!10:1) to give a syrup (1.978 g); 1H NMR
(CDCl3, 300 MHz) ꢂ 2.36 (d, J3,OH ¼ 9:5 Hz, OH), 2.41 (s, Ts),
3.54 (ꢃt, J3;4 ¼ 9:5 Hz, J4;5 ¼ 10:0 Hz, H4), 3.72 (dd, J1;2 ¼ 2:0
Hz, J2;3 ¼ 3:5 Hz, H2), 3.74 (ddd, J4;5 ¼ 10:0 Hz, J5,6a ¼ 4:0 Hz,
J5,6b ¼ 3:0 Hz, H5), 3.98 (dt, J2;3 ¼ 3:5 Hz, J3;4 ¼ J3,OH ¼ 9:5
Hz, H3), 4.22 (dd, J5,6a ¼ 4:0 Hz, J6a,6b ¼ 10:5 Hz, H6a), 4.28
(dd, J5,6b ¼ 3:0 Hz, J6a,6b ¼ 10:5 Hz, H6b), 4.87 (d, J1;2 ¼ 2:0 Hz,
Allyl 2,4-Di-O-benzyl-ꢀ-D-mannopyranoside (14). To a stir-
red mixture of 12 (8.686 g, 12.3 mmol), BnBr (4.4 mL, 37 mmol),
and DMF (43.3 mL) at 0 ꢁC, NaH (ca. 60% dispersion in oil, 1.472
g, 37 mmol) was added. The resulting mixture was stirred at 0 ꢁC
for 0.5 h, and then at room temperature for 2 h. After a careful
addition of MeOH (5.2 mL) at 0 ꢁC, the mixture was evaporated to
dryness at 95 ꢁC and chromatographed using the TK system
(100:1!20:1) to give a syrup (9.05 g). This (8.78 g, 9.9 mmol)
was dissolved in CHCl3 (125 mL) containing MeOH (37.6 mL).
After the addition of CF3CO2H (12.5 mL) under stirring, the so-
lution was kept standing at room temperature for 0.5 h. Evapora-

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 76, No. 7 (2003) 1415
H1), 5.81 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ 21.6 (Ts), 68.0
(All), 69.2 (C6), 69.3 (C5), 71.8 (C3), 76.0 (C4), 78.3 (C2), 95.8
(C1), 117.5, 133.4 (All), 144.6 (Ts). This (544.4 mg, 0.98 mmol)
was dissolved in dry Et2O (14 mL) and cooled at 0 ꢁC (bath
temperature). Then, LiAlH4 (232.3 mg, 6.1 mmol) was added
in two portionsꢁto the stirring solution. The mixture was efficient-
J3;4 ¼ 9:0 Hz, H3), 4.21 (dd, J5,6a ¼ 2:5 Hz, J6a,6b ¼ 10:5 Hz,
H6a), 4.25 (dd, J5,6a ¼ 4:0 Hz, J6a,6b ¼ 10:5 Hz, H6b), 4.30 (dd,
J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2), 4.87 (d, J1;2 ¼ 2:0 Hz, H1);
13C NMR (CDCl3, 75 MHz) ꢂ 21.6 (Ts), 68.2 (C2), 69.0 (C6),
69.6 (C5), 73.6 (C4), 80.1 (C3), 98.3 (C1), 144.7 (Ts). This (85.0
mg, 0.14 mmol) was then subjected to reduction with LiAlH4
(23.7 mg, 0.62 mmol) in Et2O (2.5 mL) to give 7 (26.3 mg,
ꢁ
ꢁ
ly stirred at 0 C for 10 min, at 20 C for 10 min, and at 40 C
under reflux for 30 min. After a careful addition of EtOAc (3 mL)
under cooling, the mixture was evaporated to dryness and chro-
matographed using the TK system (100:1!10:1) to give 5 (220.3
25
35%), [ꢀ]D +52ꢁ (c 0.9, CHCl3) (Ref. 16a, L-form, [ꢀ]D
ꢂ58ꢁ (c 0.6, CHCl3); Ref. 18b, [ꢀ]D ꢂ49ꢁ (c 1, CHCl3));
1H NMR (CDCl3, 300 MHz) ꢂ 1.33 (q, J5;6 ¼ 6:0 Hz, H6), 3.48
(t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4), 3.82 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0
Hz, H5), 3.90 (dd, J2;3 ¼ 3:5 Hz, H3), J3;4 ¼ 9:5 Hz, H3), 4.08
(dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2), 4.91 (d, J1;2 ¼ 2:0 Hz, H1);
13C NMR (CDCl3, 75 MHz) ꢂ 17.9 (C6), 67.6 (C5), 68.7 (C2),
80.0 (C4), 80.2 (C3), 99.3 (C1). Found: C, 73.54; H, 6.89%.
24
22
mg, 34%), [ꢀ]D +5ꢁ (c 1.2, CH2Cl2) (Ref. 5h, L-form, [ꢀ]D
ꢂ2ꢁ (c 0.5, CH2Cl2). Ref. 24a, L-form, [ꢀ]D +0.5ꢁ (c 0.5,
25
1
CH2Cl2)); H NMR (CDCl3, 300 MHz) ꢂ 1.34 (q, J5;6 ¼ 6:0 Hz,
H6), 2.33 (d, J3,OH ¼ 9:5 Hz, OH), 3.34 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz,
H4), 3.71 (dq, J4;5 ¼ 9:5 Hz, J4;5 ¼ 6:0 Hz, H5), 3.76 (dd, J2;3
4:0 Hz, J3;4 ¼ 9:5 Hz, H2), 3.98 (dt, J2;3 ¼ 4:0 Hz, J3;4 ¼ J3,OH
¼
¼
Calcd for C27H30O5 0.5H2O: C, 73.11; H, 7.05%.
3-O-Acetyl-2,4-di-O-benzyl-ꢀ-D-rhamnopyranose (6).
ꢄ
9:5 Hz, H3), 4.87 (d, J1;2 ¼ 2:0 Hz, H1), 5.86 (m, All); 13C NMR
(CDCl3, 75 MHz) ꢂ 18.0 (C6), 67.3 (C5), 67.8 (All), 71.7 (C3),
78.7 (C2), 82.3 (C4), 96.1 (C1), 117.2, 133.7 (All). Found: C,
71.65; H, 7.26%. Calcd for C23H28O5: C, 71.85; H, 7.34%.
A
mixture of 5 (0.335 g, 0.87 mmol), pyridine (0.5 mL, 6.2 mmol),
and Ac2O (0.5 mL, 5.3 mmol) was kept standing overnight. After
the addition of MeOH (1.6 mL) under cooling, the mixture was
evaporated to dryness and chromatographed with the TK system
(100:1!20:1) to give a syrup (369 mg); 1H NMR (CDCl3, 300
Allyl 3,4-Di-O-benzyl-ꢀ-D-rhamnopyranoside (16).
This
was synthesized via an essentially same procedure as that used
in the conversion of diol 14 into 5. A treatment of 15 (0.510 g, 1.3
mmol) with TsCl (0.480 g, 2.5 mmol) and pyridine (3.2 mL, 40
MHz) ꢂ 1.34 (q, J5;6 ¼ 6:0 Hz, H6), 1.97 (s, Ac), 3.64 (t, J3;4
¼
J4;5 ¼ 9:5 Hz, H4), 3.81 (dq, J4;5 ¼ 9:5 Hz, J4;5 ¼ 6:0 Hz, H5),
3.88 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:5 Hz, H2), 4.81 (d, J1;2 ¼ 2:0 Hz,
H1), 5.24 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:5 Hz, H3), 5.86 (m, All);
13C NMR (CDCl3, 75 MHz) ꢂ 18.0 (C6), 21.0 (Ac), 67.8 (C5),
67.9 (All), 73.8 (C3), 76.3 (C2), 79.2 (C4), 96.8 (C1), 117.3, 133.7
(All), 170.1 (Ac). This (0.121 g, 0.28 mmol) was treated with
PdCl2 (70 mg, 0.40 mmol) and NaOAc (257.6 mg, 3.1 mmol) in
aq AcOH (95%, 21.2 mL) at room temperature overnight. After
the addition of allyl alcohol (42 mL) under cooling, evaporation to
dryness and chromatography with the TK system (100:1!10:1)
1
mmol) afforded a syrup (314.5 mg); H NMR (CDCl3, 300 MHz)
ꢂ 2.42 (s, Ts), 3.69 (dd, J3;4 ¼ 9:0 Hz, J4;5 ¼ 10:0 Hz, H4), 3.81
(ꢃdt, J4;5 ¼ 10:0 Hz, J5,6a ¼ 4:0 Hz, J5,6b ¼ 3:0 Hz, H5), 3.88
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3), 4.02 (dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:0 Hz, H2), 4.21 (dd, J5,6a ¼ 4:0 Hz, J6a,6b ¼ 12:0 Hz,
H6a), 4.25 (dd, J5.6b ¼ 4:0 Hz, J6a,6b ¼ 12:0 Hz, H6b), 4.84 (d,
J1;2 ¼ 2:0 Hz, H1), 5.83 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ
21.6 (Ts), 68.05 (All), 68.10 (C2), 69.0 (C6), 69.4 (C5), 73.4 (C4),
80.1 (C3), 98.1 (C1, JC1,H1 ¼ 169:5 Hz), 144.7 (Ts), 117.7, 133.3
(All). This (227.5 mg, 0.41 mmol) was reduced with LiAlH4 (60
mg, 1.6 mmol) in Et2O (5.6 mL) to give 16 (87.9 mg, 25%),
25
gave 6 (55.0 mg, 50%), [ꢀ]D ꢂ23ꢁ (c 3.1, CHCl3) (Ref. 23c, L-
form, [ꢀ]D +20ꢁ (c 1.0, CHCl3)); 1H NMR (CDCl3, 300 MHz)
(70% ꢀ), ꢂ 1.33 (q, J5;6 ¼ 6:0 Hz, H6ꢀ), 1.37 (q, J5;6 ¼ 6:0 Hz,
23
20
[ꢀ]D +51ꢁ (c 0.3, CHCl3) (Ref. 24b, L-form, [ꢀ]D ꢂ35ꢁ (c
1, CHCl3); Ref. 24c, L-form, [ꢀ]D ꢂ47:2ꢁ (c 1.4, CHCl3);
H6ꢁ), 1.97 (s, Acꢀ), 1.99 (s, Acꢁ), 3.43 (br, OHꢀ), 3.45 (q, J4;5
¼
20
Ref. 24d, L-form, [ꢀ]D ꢂ43:6ꢁ (c 1, CHCl3)); 1H NMR(CDCl3,
300 MHz) ꢂ 1.32 (q, J5;6 ¼ 6:0 Hz, H6), 3.47 (t, J3;4 ¼ J4;5 ¼ 9:5
Hz, H4), 3.73 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5), 3.89 (dd,
9:5 Hz, J5;6 ¼ 6:0 Hz, H5ꢁ), 3.61 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4ꢁ),
3.65 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4ꢀ), 3.77 (br d, J1,OH ¼ 10:0 Hz,
OHꢁ), 3.89 (dd, J1;2 ¼ 2:0 Hz, J5;6 ¼ 3:5 Hz, H2ꢀ), 3.95 (dd,
J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3), 4.07 (dd, J1;2 ¼ 2:0 Hz, J2;3
¼
J1;2 ¼ 1:5 Hz, J2;3 ¼ 3:0 Hz, H2ꢁ), 4.03 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼
3:0 Hz, H2), 4.87 (d, J1;2 ¼ 2:0 Hz, H1), 5.86 (m, All); 13C NMR
(CDCl3, 75 MHz) ꢂ 17.9 (C6), 67.4 (C5), 67.9 (All), 68.6 (C2),
80.1 (C3), 80.6 (C4), 98.2 (C1, JC1,H1 ¼ 168:4 Hz), 117.3, 133.8
6:0 Hz, H5ꢀ), 4.77 (br d, J1;2 ¼ 1:5 Hz, J1,OH ¼ 10:0 Hz, H1ꢁ),
4.96 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3ꢁ), 5.15 (d, J1;2 ¼ 2:0
Hz, H1ꢀ), 5.28 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:5 Hz, H3ꢀ); 13C NMR
(CDCl3, 75 MHz) ꢂ 17.9 (C6ꢁ), 18.0 (C6ꢀ), 20.9 (Acꢁ), 21.0
(Acꢀ), 67.8 (C5ꢀ), 71.5 (C5ꢁ), 73.3 (C3ꢀ), 76.1 (C3ꢁ), 76.5
(C2ꢀ), 77.5 (C2ꢁ), 78.3 (C4ꢁ), 79.1 (C4ꢀ), 92.5 (C1ꢀ), 93.3
(C1ꢁ), 170.2 (Ac). Found: C, 68.20; H, 6.80%. Calcd for
C22H26O6: C, 68.38; H, 6.78%.
(All).
HRMS (FAB) Found: m=z 407.1827.
Calcd for
C23H28NaO5 [M + Na]þ: 407.1834.
1
NMR data of the acetate of 16: H NMR (CDCl3, 300 MHz) ꢂ
1.34 (q, J5;6 ¼ 6:0 Hz, H6), 2.16 (s, Ac), 3.45 (t, J3;4 ¼ J4;5 ¼ 10:0
Hz, H4), 3.74 (dq, J4;5 ¼ 10:0 Hz, J5;6 ¼ 6:0 Hz, H5), 3.97 (dd,
J2;3 ¼ 3:5 Hz, J3;4 ¼ 10:0 Hz, H3), 4.78 (d, J1;2 ¼ 2:0 Hz, H1),
5.40 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2), 5.86 (m, All);
13C NMR (CDCl3, 75 MHz) ꢂ 17.9 (C6), 21.1 (Ac), 67.8 (C5),
Allyl 2,4,6-Tri-O-benzyl-ꢀ-D-mannopyranoside (18).
mixture of 3 (0.978 g, 4.4 mmol), powdered KOH (0.996 g,
A
17.8 mmol), and BnCl (19.6 mL, 170 mmol) was strongly stirred
ꢁ
68.0 (All), 69.1 (C2), 78.1 (C3), 80.1 (C4), 96.8 (C1, JC1,H1
168:0 Hz), 117.5, 133.5 (All), 170.3 (Ac).
¼
at 140 C for 4.5 h. The mixture was evaporated at 95 ꢁC and
chromatographed with the TK system (100:1!10:1) to give 18
(682.3 mg, 31%), followed by the elution of allyl 2,3,6-tri-O-ben-
zyl-ꢀ-D-mannopyranoside 19 (408.4 mg, 19%), which was iden-
tified with a sample prepared previously.5a Further elution with
the TK system (1:1) afforded allyl 2,6-di-O-benzyl-ꢀ-D-manno-
pyranoside 20 (296.1 mg, 17%).
Benzyl 3,4-Di-O-benzyl-ꢀ-D-rhamnopyranoside (7). In a
similar manner as that described for 5 derived from diol 14, this
was synthesized via essentially the same procedure as in the case
of 5. The tosylation of diol 176a (129.1 mg, 0.29 mmol) with TsCl
(107 mg, 0.56 mmol) and pyridine (0.72 mL, 8.9 mmol) afforded a
syrup (139.8 mg); 1H NMR (CDCl3, 300 MHz) ꢂ 2.42 (s, Ts), 3.84
(ddd, J4;5 ¼ 10:0 Hz, J5,6a ¼ 2:5 Hz, J5,6b ¼ 4:0 Hz, H5), 3.71
(dd, J3;4 ¼ 9:0 Hz, J4;5 ¼ 10:0 Hz, H4), 3.85 (dd, J2;3 ¼ 3:5 Hz,
25
18: [ꢀ]D +22ꢁ (c 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ
4.03 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 8:5 Hz, H3), 5.00 (d, J1;2 ¼ 2:0 Hz,
H1), 5.88 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ 67.9 (All), 69.2

1416 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Glycosylation Using 1-OH Sugar Derivatives
(C6), 71.1 (C5), 71.8 (C3), 76.7 (C4), 78.5 (C5), 96.1 (C1,
JC1,H1 ¼ 167:0 Hz), 117.3, 133.7 (All). Found: C, 73.22; H,
6.81%. Calcd for C30H34O6: C, 73.45; H, 6.99%.
20: [ꢀ]D +11ꢁ (c 1.4, CHCl3) (Ref. 14d, [ꢀ]D +7.2ꢁ (c 2.1,
CHCl3)); 1H NMR (CDCl3, 300 MHz) ꢂ 4.96 (d, J1;2 ¼ 2:0 Hz,
H1), 5.88 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ 67.9 (All), 69.8
(C4), 70.3 (C6), 70.8 (C5), 71.5 (C3), 73.0, 73.5 (Bn), 77.9 (C2),
96.2 (C1), 117.3, 133.6 (All), 137.6, 138.1 (Bn). Found: C, 68.38;
temperature overnight under anhydrous conditions. After the ad-
dition of PhMe (3 mL) and powdered NaHCO3 (0.2 mg), the
mixture was stirred for 15 min and then transferred onto the top
of a silica-gel column, which was eluted with the TK system
(100:1!10:1) to give 21 (69.4 mg, 57%) and the ꢁ-linked isomer
(28.0 mg, 23%).
24
23
26
21: [ꢀ]D +30ꢁ (c 0.7, CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ
a
1.28 (d, J5;6 ¼ 6:0 Hz, H6 ), 1.31 (d, J5;6 ¼ 6:0 Hz, H6b), 3.58 (t,
H, 7.06%. Calcd for C23H28O6 0.25H2O: C, 68.21; H, 7.09%.
1
J3;4 ¼ J4;5 ¼ 9:0 Hz, H4a), 3.64 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4b),
3.73 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5a), 3.76 (dd, J1;2 ¼ 2:0
Hz, J2;3 ¼ 3:0 Hz, H2a), 3.79 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz,
ꢄ
NMR data of the acetate of 18: H NMR (CDCl3, 300 MHz) ꢂ
1.96 (s, Ac), 3.71 (dd, J5,6a ¼ 1:5 Hz, J6a,6b ¼ 10:5 Hz, H6a), 3.80
(dd, J5,6b ¼ 4:0 Hz, J6a,6b ¼ 10:5 Hz, H6b), 3.85 (ddd, J4;5 ¼ 9:5
Hz, J5,6a ¼ 1:5 Hz, J5,6b ¼ 4:0 Hz, H5), 3.89 (dd, J1;2 ¼ 2:0 H,
J2;3 ¼ 3:0 Hz, H2), 4.06 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4), 4.93 (d,
J1;2 ¼ 2:0 Hz, H1), 5.27 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3,
5.87 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ 21.0 (Ac), 68.0 (All),
69.0 (C6), 71.5 (C5), 73.6 (C4), 73.9 (C3), 76.1 (C2), 96.9 (C1),
117.4, 133.7 (All), 170.1 (Ac).
H2b), 3.85 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5b), 4.13 (dd, J2;3
¼
3:0 Hz, J3;4 ¼ 9:0 Hz, H3a), 4.81 (d, J1;2 ¼ 2:0 Hz, H1a), 5.18 (d,
J1;2 ¼ 2:0 Hz, H1b), 5.87 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ
17.9 (C6b), 18.1 (C6a), 67.8 (All), 68.2 (C5a), 68.7 (C5b), 75.8
(C2b), 77.9 (C3a), 78.0 (C2a), 79.9 (C3b), 80.5 (C4b), 80.9 (C4a),
96.8 (C1a, JC1,H1 ¼ 166:5 Hz), 99.8 (C1b, JC1,H1 ¼ 170:0 Hz),
116.9, 133.9 (All). Found: C, 74.74; H, 7.05%. Calcd for
C50H56O9: C, 74.98; H, 7.05%.
1
NMR data of the acetate of 20: H NMR (CDCl3, 300 MHz) ꢂ
25
1.91 (s, Ac), 2.00 (s, Ac), 3.55 (dd, J5,6a ¼ 3:5 Hz, J6a,6b ¼ 11:0
Hz, H6a), 3.61 (dd, J5,6b ¼ 5:0 Hz, J6a,6b ¼ 11:0 Hz, H6b), 3.84
(dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 3.93 (ddd, J4;5 ¼ 10:0 Hz,
J5,6a ¼ 3:5 Hz, J5,6b ¼ 5:0 Hz, H5), 4.90 (d, J1;2 ¼ 2:0 Hz, H1),
The ꢁ-linked isomer: [ꢀ]D +2ꢁ (c 2.3, CHCl3); 1H NMR
(CDCl3, 300 MHz) ꢂ 1.35 (d, J5;6 ¼ 6:0 Hz, H6b), 1.36 (d, J5;6
¼
6:0 Hz, H6a), 3.26 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5b), 3.38
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3b), 3.60 (dd, J3;4 ¼ 8:0 Hz,
J4;5 ¼ 9:0 Hz, H4a), 3.63 (dd, J3;4 ¼ 9:5 Hz, J4;5 ¼ 9:0 Hz, H4b),
3.75 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2a), 3.76 (dq, J4;5 ¼ 9:0
5.26 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 10:0 Hz, H3), 5.41 (t, J3;4 ¼ J4;5
¼
10:0 Hz, H4), 5.88 (m, All); 13C NMR (CDCl3, 75 MHz) ꢂ 20.7,
20.8 (Ac), 67.6 (C4), 68.1 (All), 69.5 (C6), 70.0 (C5), 71.5 (C3),
73.1, 73.5 (Bn), 75.6 (C2), 96.9 (C1), 117.6, 133.5 (All), 138.0,
137.8 (Bn), 170.1 (Ac).
a
Hz, J5;6 ¼ 6:0 Hz, H5 ), 3.78 (d, J1;2 ¼ 90 Hz, J2;3 ¼ 3:0 Hz,
H2b), 4.18 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 8:0 Hz, H3a), 4.36 (s, J1;2
¼
0 Hz, H1b), 4.89 (d, J1;2 ¼ 2:0 Hz, H1a), 5.89 (m, All); 13C NMR
(CDCl3, 75 MHz) ꢂ 18.0 (C6b), 18.2 (C6a), 67.8 (All), 67.9 (C5a),
72.1 (C5b), 75.0 (C2b), 75.2 (C2a), 77.0 (C3a), 80.2 (2C, C4a and
C4b), 82.3 (C3b), 96.9 (C1a, JC1,H1 ¼ 166:7 Hz), 98.9 (C1b,
JC1,H1 ¼ 152:3 Hz); 117.4, 133.9 (All). Found: C, 74.93; H,
7.07%. Calcd for C50H56O9: C, 74.98; H, 7.05%.
3-O-Acetyl-2,4,6-tri-O-benzyl-D-mannopyranose (8).
A
mixture of 18 (453.1 mg, 0.92 mmol), pyridine (2.0 mL, 25
mmol), and Ac2O (2.0 mL, 21 mmol) was kept standing overnight
at room temperature. After the addition of MeOH (2 mL) under
cooling, evaporation and chromatography using the TK system
(100:1!10:1) yielded the acetate (438.3 mg). This (373.4 mg,
0.70 mmol) was dissolved in aq AcOH (95%, 32 mL) containing
NaOAc (384 mg, 4.7 mmol) and PdCl2 (209 mg, 1.2 mmol) was
added. The mixture was stirred at 60 ꢁC for 2 h. Evaporation and
chromatography using the TK system (100:1!10:1) gave 8
NMR Study Detecting 2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopy-
ranosyl Bromide (a).
To a stirred mixture of 4 (15.5 mg,
0.036 mmol), CoBr2 (9.4 mg, 0.043 mmol), n-Bu4NBr (13.8
mg, 0.043 mmol), MS4A (41 mg), and CD2Cl2 containing TMS
(1%) (Aldrich, 1.0 mL), Me3SiBr (5.6 mL, 0.043 mmol) was
added at room temperature. After 1 h, the mixture was filtered
23
(313.4 mg, 81%), [ꢀ]D ꢂ8ꢁ (c 1.5, CHCl3) (Ref. 23c. [ꢀ]D
ꢂ8ꢁ (c 1.0, CHCl3); 1H NMR (CDCl3, 300 MHz) (75% ꢀ) ꢂ
through a pad of Celite and the H NMR spectrum of the filtrate
was determined at 300 MHz.
1
1.95 (s, Acꢁ), 1.96 (s, Acꢀ), 3.42 (br s, OHꢀ), 3.49 (ddd, J4;5
10:0 Hz, J5,6a ¼ 2:0 Hz, J5,6b ¼ 4:0 Hz, H5ꢁ), 3.68 (dd, J5,6a
3:0 Hz, J6a,6b ¼ 10:5 Hz, H6aꢀ), 3.71 (dd, J5,6b ¼ 4:0 Hz, J6a,6b
¼
¼
¼
Separately, the bromide a was generated as follows: a mixture
of 4 (15.5 mg, 0.036 mmol), AcBr25 (4.5 mL, 0.056 mmol), and
CD2Cl2 containing TMS (1%) (1 mL) was kept standing at room
temperature. The 1H NMR spectrum of the solution was deter-
mined after 1 h. The spectrum showed that 4 was completely
exhausted and a was the sole product. 1H NMR (CD2Cl2, 300
MHz) ꢂ 1.33 (d, J5;6 ¼ 6:5 Hz, H6), 3.62 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz,
H4), 3.86 (ddq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:5 Hz, J1;5 ¼ 1:0 Hz, H5),
4.01 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 4.25 (dd, J2;3 ¼ 3:0
Hz, J4;5 ¼ 9:5 Hz, H3), 6.45 (dd, J1;2 ¼ 2:0 Hz, J1;5 ¼ 1:0 Hz,
H1); 13C NMR (CD2Cl2, 75 MHz) ꢂ 17.5 (C6), 73.1 (C5), 78.5
(C3), 79.4 (C2), 79.7 (C4), 88.9 (C1, JC1,H1 ¼ 181:5 Hz).
The 1H NMR spectrum of the above-described filtrate was iden-
tical with that of a at ꢂ 3.8–7.5, indicating a quantitative conver-
sion of 4 into a.
10:5 Hz, H6bꢀ), 3.73 (dd, J5,6a ¼ 2:0 Hz, J6a,6b ¼ 11:0 Hz,
H6aꢁ), 3.77 (dd, J5,6b ¼ 4:0 Hz, J6a,6b ¼ 11:0 Hz, H6bꢁ), 3.88
(dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2ꢀ), 3.92 (dd, J1;2 ¼ 1:5 Hz,
J2;3 ¼ 3:0 Hz, H2ꢁ), 3.95 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4ꢀ), 4.01 (t,
J3;4 ¼ J4;5 ¼ 10:0 Hz, H4ꢁ), 4.10 (ddd, J4;5 ¼ 9:5 Hz, J5,6a ¼ 3:0
Hz, J5,6b ¼ 4:0 Hz, H5ꢀ), 4.77 (br d, J1;2 ¼ 1:5 Hz, J1,OH ¼ 9:0
Hz, H1ꢁ), 4.97 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 10:0 Hz, H3ꢁ), 5.25 (d,
J1;2 ¼ 2:0 Hz, H1ꢀ), 5.31 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3ꢀ);
13C NMR (CDCl3, 75 MHz) ꢂ 20.9 (Acꢁ), 21.0 (Acꢀ), 68.8
(C6ꢁ), 69.3 (C6ꢀ), 71.3 (C5ꢀ), 72.8 (C4ꢁ), 73.4 (C3ꢀ), 73.8
(C4ꢀ), 75.2 (C5ꢁ), 76.3 (C2ꢀ and C3ꢁ), 77.3 (C2ꢁ), 92.5
(C1ꢀ), 93.6 (C1ꢁ), 170.1 (Ac). Found: C, 70.58; H, 6.45%. Calcd
for C29H32O7: C, 70.71; H, 6.55%.
Allyl
3)-2,4-di-O-benzyl-D-rhamnopyranosides (21).
mixture of 4 (86.5 mg, 0.20 mmol), 5 (58.9 mg, 0.15 mmol),
CoBr2 (43.6 mg, 0.20 mmol), n-Bu4NBr (64.3 mg, 0.20 mmol),
molecular sieve 4A (215 mg), and (CH2Cl)2 (0.61 mL), Me3SiBr
(25.9 mL, 0.20 mmol) was added. The mixture was stirred at room
O-(2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopyranosyl)-(1 !
To a solution of 4 (15.5 mg, 0.036 mmol) in CD2Cl2 containing
TMS (1%) (1 mL), Me3SiBr (5.6 mL, 0.043 mmol) alone was
added. The mixture was kept standing for 1 h at room
temperature. The H NMR spectra of the obtained reaction mix-
ture showed that ca. 30% of 4 remained unreacted, based on the
integral value of H6 of a (ꢂ 1.33, d, J5;6 ¼ 6:5 Hz) and those of 4
To a stirred
1

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 76, No. 7 (2003) 1417
(ꢂ 1.27, d, J1;2 ¼ 6:0 Hz for the ꢀ-anomer and ꢂ 1.29, d, J1;2 ¼ 6:0
Hz for the ꢁ-anomer).
H6a), 3.44 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4a), 3.52 (t, J3;4 ¼ J4;5 ¼ 9:0
Hz, H4b), 3.62 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4c), 3.71 (dq, J4;5 ¼ 9:0
Hz, J5;6 ¼ 6:0 Hz, H5a), 3.74 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz,
H5b), 3.78 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2c), 3.78 (dq,
NMR Study Detecting 2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopy-
ranosyl Chloride (b). A solution of 4 (20.0 mg, 0.046 mmol)
in SOCl2 (1.0 mL, 13.2 mmol) was kept standing at room tem-
perature overnight.4k After evaporation to dryness at 25 ꢁC, the 1H
and 13C NMR spectra showed that 4 was completely transformed
into the 1-chloride b. 1H NMR (CD2Cl2, 300 MHz) ꢂ 1.34 (d,
J5;6 ¼ 6:5 Hz, H6), 3.63 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4), 3.96 (ddq,
J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5c), 3.81 (dd, J1;2 ¼ 2:0 Hz, J2;3
¼
3:0 Hz, H2b), 3.87 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3c), 3.90
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3a), 4.07 (dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:0 Hz, H2a), 4.14 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3b),
4.80 (d, J1;2 ¼ 2:0 Hz, H1a), 5.08 (d, J1;2 ¼ 2:0 Hz, H1b), 5.18 (d,
J1;2 ¼ 2:0 Hz, H1c); 13C NMR (CDCl3, 100 MHz) ꢂ 17.8 (C6a),
17.9 (C6b), 18.0 (C6c), 68.2 (C5a), 68.5 (C5c), 68.6 (C6b), 74.6
(C2a), 77.0 (C3b), 77.91 (C2b), 79.94 (2C, C3a and C2c), 80.4
(C4c), 80.5 (C4a), 80.8 (C4b), 98.1 (C1a, JC1,H1 ¼ 169:9 Hz),
99.0 (C1b, JC1,H1 ¼ 168:9 Hz), 99.5 (C1c, JC1,H1 ¼ 169:3 Hz).
Found: C, 75.37; H, 6.90%. Calcd for C74H80O13: C, 75.49; H,
6.85%.
J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:5 Hz, J1;5 ¼ 1:0 Hz, H5), 3.97 (dd, J1;2
¼
2:0 Hz, J2;3 ¼ 3:0 Hz, H2), 4.15 (dd, J2;3 ¼ 3:0 Hz, J4;5 ¼ 9:5 Hz,
H3), 6.09 (br d, J1;2 ¼ 2:0 Hz, J1;5 ¼ 1:0 Hz, H1); 13C NMR
(CD2Cl2, 75 MHz) ꢂ 17.6 (C6), 71.4 (C5), 78.5 (C3), 79.4 (C2),
79.7 (C4), 92.1 (C1, JC1,H1 ¼ 180:0 Hz).
To a solution of 4 (20.0 mg, 0.046 mmol) and NsCl (13.3 mg,
0.060 mmol) in CD2Cl2 (with TMS (1%), ca. 0.5 mL) in a NMR-
tube, Et3N (8.4 mL, 0.060 mmol) was added at room temperature.
After 0.5 h, the 1H NMR spectrum of the clear solution showed
that 4 disappeared completely and the diagnostic isolated signals
of H1 (ꢂ 6.09, br d, J1;2 ¼ 2:0 Hz, J1;5 ¼ 1:0 Hz) and H3 (ꢂ 4.15,
dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz) of b were clearly observed.
O-(2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopyranosyl)-(1 ! 3)-2,4-
di-O-benzyl-D-rhamnopyranose (22). A mixture of 21 (69.7
mg, 0.087 mmol), NaOAc (76.8 mg, 0.94 mmol), PdCl2 (42.4
mg, 0.24 mmol), and aq AcOH (95%, 3.3 mL) was stirred at room
temperature overnight. After the addition of allyl alcohol (32 mL)
under cooling, the mixture was evaporated to dryness and chro-
matographed using the TK system (100:1!10:1) to afford 22
O-ꢀ-D-Rhamnopyranosyl-(1!3)-O-ꢀ-D-rhamnopyranosyl-
(1!2)-D-rhamnopyranose (1). The hydrogenation of 23 (20.5
mg, 0.017 mmol) over Pd on C (10%, 34 mg) in MeOH (6 mL)
was carried out at room temperature overnight. Filtration of the
catalyst, evaporation, and chromatography with EM system
24
(100:1!2:1) gave 1 (7.0 mg, 88%), [ꢀ]D +54ꢁ (c 0.3, H2O)
(Ref. 18b, [ꢀ]D ꢂ52ꢁ (c 0.5, H2O)); 1H NMR (D2O, 400 MHz)
(ꢀ-anomer) ꢂ 1.24 (6H, d, J5;6 ¼ 6:5 Hz, H6a and H6b), 1.27 (3H,
d, J5;6 ¼ 6:5 Hz, H6c), 3.43 (dd, J3;4 ¼ 10:0 Hz, J4;5 ¼ 9:5 Hz,
H4c), 3.45 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4a), 3.50 (t, J3;4 ¼ J4;5 ¼ 9:5
Hz, H4b), 3.76 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:5 Hz, H5b), 3.81 (dd,
J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:5 Hz, H3b), 3.81 (dd, J2;3 ¼ 3:0 Hz, J3;4
¼
23
1
(41.8 mg, 63%), [ꢀ]D +16ꢁ (c 0.7, CHCl3); H NMR (CDCl3,
10:0 Hz, H3c), 3.82 (2H, dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:5 Hz, H5a and
300 MHz) (63% ꢀ) ꢂ 1.26 (d, J5;6 ¼ 6:0 Hz, H6aꢀ), 1.29 (d, J5;6
¼
H5c), 3.86 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz, H3a), 3.88 (dd, J1;2
¼
6:0 Hz, H6b), 1.33 (d, J5;6 ¼ 6:0 Hz, H6aꢁ), 3.36 (dq, J4;5 ¼ 9:0
Hz, J5;6 ¼ 6:0 Hz, H5aꢁ), 3.54 (ꢃt, J3;4 ¼ 9:5 Hz, J4;5 ¼ 9:0 Hz,
1:5 Hz, J2;3 ¼ 3:0 Hz, H2a), 4.03 (dd, J1;2 ¼ 1:5 Hz, J5;6 ¼ 3:0
Hz, H2c), 4.12 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2b), 4.92 (d,
H4bꢁ), 3.57 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4bꢀ), 3.62 (t, J3;4 ¼ J4;5
¼
J1;2 ¼ 2:0 Hz, H1b), 5.01 (d, J1;2 ¼ 2:0 Hz, H1c), 5.20 (d, J1;2
¼
9:5 Hz, H4 ꢀ), 3.65 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4aꢁ), 3.74 (dd,
a
1:5 Hz, H1a); 13C NMR (D2O, 100 MHz) ꢂ 19.1 (2C, C6b and
C6c), 19.3 (C6a), 71.1 (C5a), 71.8 (C5c), 71.9 (C5b), 72.4 (C3a),
72.5 (C2b), 72.8 (2C, C2c and C3c), 74.0 (C4b), 74.6 (C4c), 75.0
(C4a), 81.6 (C3a), 81.8 (C2a), 95.0 (C1a, JC1,H1 ¼ 169:0 Hz), 104.4
(C1b, JC1,H1 ¼ 170:0 Hz), 104.8 (C1c, JC1,H1 ¼ 170:0 Hz).
HRMS (FAB) Found: m=z 479.1778. Calcd for C18H32NaO13
[M + Na]þ: 479.1741.
J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2b), 3.76 (dd, J1;2 ¼ 2:0 Hz, J2;3
¼
3:0 Hz, H2aꢁ), 3.77 (dd, J1;2 ¼ 2:0 Hz, J5;6 ¼ 3:0 Hz, H2aꢀ), 3.79
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3aꢁ), 3.83 (dd, J2;3 ¼ 3:0 Hz,
J5;6 ¼ 9:0 Hz, H3bꢁ), 3.74 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz,
H4bꢀ), 3.86 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5bꢁ), 3.88 (dq,
J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5bꢀ), 3.93 (dq, J4;5 ¼ 9:5 Hz,
J5;6 ¼ 6:0 Hz, H5aꢀ), 4.15 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5 Hz,
H3aꢀ), 4.64 (d, J1;2 ¼ 2:0 Hz, H1aꢁ), 5.15 (d, J1;2 ¼ 2:0 Hz,
H1aꢀ), 5.17 (d, J1;2 ¼ 2:0 Hz, H1bꢀ), 5.22 (d, J1;2 ¼ 2:0 Hz,
H1bꢁ); 13C NMR (CDCl3, 75 MHz) ꢂ 17.8 (C6aꢁ), 18.0 (C6aꢀ),
18.07 (C6bꢀ), 18.12 (C6bꢁ), 68.4 (C5aꢀ), 68.8 (C5bꢀ), 69.3
(C5bꢁ), 71.7 (C5aꢁ), 75.75 (C2aꢁ), 75.82 (C2aꢀ), 77.1 (C3aꢀ),
78.1 (C3aꢁ), 79.0 (C2b), 79.5 (C3bꢁ), 79.8 (C3bꢀ), 80.3 (C4aꢁ),
80.5 (C4aꢀ), 80.6 (C4bꢀ), 80.9 (C4bꢁ), 92.0 (C1aꢁ), 93.3 (C1aꢀ),
99.7 (C1bꢁ), 99.8 (C1bꢀ). Found: C, 73.67; H, 6.82%. Calcd for
Benzyl O-(3-O-Acetyl-2,4,6-tri-O-benzyl-ꢀ-D-mannopyrano-
syl)-(1 ! 4)-2,3-di-O-benzyl-ꢀ-L-rhamnopyranoside (24). To
a stirred mixture of 8 (166.3 mg, 0.34 mmol), 9 (125.5 mg, 0.29
mmol), NsCl (160.1 mg, 0.72 mmol), AgOTf (185.8 mg, 0.72
mmol), and CH2Cl2 (2.2 mL), Et3N (100.8 mL, 0.72 mmol) was
ꢁ
added at ꢂ60 C (bath temperature), and the mixture was stirred.
ꢁ
ꢁ
The bath temperature was allowed to rise up to 0 C (ca. 0.3 C
per min) and the mixture was stirred for 16 h at room temperature.
After the addition of PhMe (5 mL) and powdered NaHCO3 (0.34
mg), the mixture was chromatographed with the TK system
C47H52O9 0.5H2O: C, 73.32; H, 6.94%.
ꢄ
24
Benzyl O-(2,3,4-Tri-O-benzyl-ꢀ-D-rhamnopyranosyl)-(1 !
3)-O-(2,4-di-O-benzyl-ꢀ-D-rhamnopyranosyl)-(1 ! 2)-3,4-di-
O-benzyl-ꢀ-D-rhamnopyranoside (23). To a stirred mixture of
7 (33.7 mg, 0.078 mmol), 22 (47 mg, 0.062 mmol), CoBr2 (21.6
mg, 0.099 mmol), n-Bu4NBr (32.0 mg, 0.099 mmol), molecular
sieve 4A (94 mg), and (CH2Cl)2 (0.55 mL), Me3SiBr (13.0 mL,
0.10 mmol) was added and the mixture was stirred for 16 h at
room temperature. After the addition of PhMe (2 mL) and pow-
dered NaHCO3 (0.1 g), the mixture was chromatographed with the
TK system (100:1!10:1) to give 23 (30.8 mg, 42%), [ꢀ]D24 +21ꢁ
(c 0.7, CHCl3); 1H NMR (CDCl3, 400 MHz) ꢂ 1.18 (d, J5;6 ¼ 6:0
Hz, H6b), 1.26 (d, J5;6 ¼ 6:0 Hz, H6c), 1.30 (d, J5;6 ¼ 6:0 Hz,
(100:1!10:1) to give 24 (240.9 mg, 92%), [ꢀ]D ꢂ2ꢁ (c 1.1,
CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ 1.15 (d, J5;6 ¼ 6:0 Hz,
H6a), 1.99 (s, Ac), 3.29 (br s, 2H, H6b), 3.70 (dq, J4;5 ¼ 9:0 Hz,
J5;6 ¼ 6:0 Hz, H5a), 3.78 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:0 Hz, H3a),
3.80 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4a), 3.83 (2H, dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:5 Hz, H2a and H2b), 4.08 (br s, H5b), 4.10 (ꢃt, J3;4 ¼ 9:0
Hz, J5;6 ¼ 9:5 Hz, H4b), 4.85 (d, J1;2 ¼ 2:0 Hz, H1a), 5.21 (dd,
J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:0 Hz, H3b); 13C NMR (CDCl3, 75 MHz) ꢂ
18.1 (C6a), 21.1 (Ac), 68.4 (2C, C5a and C6b), 71.6 (C5b), 73.3
(C3a), 74.0 (C3b), 74.6 (C4b), 75.6 (C4a), 78.2 (C2b), 78.5 (C2b),
97.3 (C1a, JC1,H1 ¼ 166:0 Hz), 98.6 (C1b, JC1,H1 ¼ 168:0 Hz),
170.0 (Ac). Found: C, 73.91; H, 6.69%. Calcd for C56H60O11:

1418 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Glycosylation Using 1-OH Sugar Derivatives
C, 73.99; H, 6.65%.
1.18 (d, J5;6 ¼ 6:0 Hz, H6a), 1.32 (d, J5;6 ¼ 6:0 Hz, H6c), 2.02 (br
s, OH), 3.35 (dd, J5,6a ¼ 2:5 Hz, J6a,6b ¼ 9:0 Hz, H6ab), 3.36 (t,
J3;4 ¼ J4;5 ¼ 9:0 Hz, H4c), 3.38 (dd, J5,6b ¼ 2:5 Hz, J6a,6b ¼ 9:0
Hz, H6bb), 3.69 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5c), 3.72 (dd,
Benzyl O-(2,4,6-Tri-O-benzyl-ꢀ-D-mannopyranosyl)-(1 !
4)-2,3-di-O-benzyl-ꢀ-L-rhamnopyranoside (25). A mixture of
24 (230.0 mg, 0.25 mol), MeOH (10 mL), 1,4-dioxane (1.0 mL),
and dil NaOMe (7%, 0.3 mL) was stirred at room temperature
overnight. After the addition of AcOH (0.1 mL), evaporation and
chromatography with the TK system (100:1!10:1) furnished 25
J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2b), 3.76 (dd, J1;2 ¼ 1:5 Hz, J2;3
¼
3:5 Hz, H2c), 3.83 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5a), 3.85
(2H, dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3a and H3b), 3.88 (dd,
(196.3 mg, 89%), [ꢀ]D ꢂ8ꢁ (c 0.8, CHCl3); H NMR (CDCl3,
300 MHz) ꢂ 1.18 (d, J5;6 ¼ 6:0 Hz, H6a), 2.29 (d, J3,OH ¼ 9:0 Hz,
OH), 3.31 (dd, J5,6a ¼ 2:0 Hz, J6a,6b ¼ 11:0 Hz, H6ab), 3.36 (dd,
J5,6b ¼ 3:0 Hz, J5;6 ¼ 11:0 Hz, H6bb), 3.66 (dq, J4;5 ¼ 9:0 Hz,
J5;6 ¼ 6:0 Hz, H5a), 3.70 (dd, J1;2 ¼ 1:5 Hz, J5;6 ¼ 3:5 Hz,
H2b), 3.76 (dt, J2;3 ¼ 3:0 Hz, J3;4 ¼ J3,OH ¼ 9:0 Hz, H3a), 3.82
(dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2a), 3.84 (t, J3;4 ¼ J4;5 ¼ 9:0
Hz, H4a), 3.93 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 10:0 Hz, H3b), 3.99 (t,
J3;4 ¼ J4;5 ¼ 10:0 Hz, H4b), 4.85 (d, J1;2 ¼ 2:0 Hz, H1a), 5.11 (d,
J1;2 ¼ 1:5 Hz, H1b); 13C NMR (CDCl3, 75 MHz) ꢂ 18.3 (C6a),
68.4 (C5a), 68.6 (C6b), 71.3 (C5b), 71.8 (C3b), 74.6 (C4a), 76.4
(C4b), 78.1 (C2a), 78.2 (C2b), 78.5 (C3a), 97.4 (C1a,
JC1,H1 ¼ 167:5 Hz), 97.7 (C1b, JC1,H1 ¼ 167:5 Hz). Found: C,
74.84; H, 6.82%. Calcd for C54H58O10: C, 74.80; H, 6.74%.
Benzyl O-(3-O-Acetyl-2,4-di-O-benzyl-ꢀ-D-rhamnopyrano-
syl)-(1 ! 3)-(2,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl)-(1 ! 4)-
2,3-di-O-benzyl-ꢀ-L-rhamnopyranoside (26). To a stirred mix-
ture of 6 (34.4 mg, 0.089 mmol), 25 (58.0 mg, 0.067 mmol), NsCl
(40.1 mg, 0.18 mmol), AgOTf (46.5 mg, 0.18 mmol), and CH2Cl2
(0.40 mL), Et3N (25.2 mL, 0.18 mmol) was added and the mixture
was stirred for 16 h at room temperature. After the addition of
PhMe (3 mL) and powdered NaHCO3 (0.2 g), the mixture was
chromatographed with the TK system (100:1!10:1) to give 26
J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2a), 4.06 (dt, J4;5 ¼ 9:0 Hz, J5,6a
¼
24
1
J5,6b ¼ 2:5 Hz, H5b), 4.06 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:0 Hz, H3c),
4.10 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4b), 4.14 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz,
H4a), 4.90 (d, J1;2 ¼ 2:0 Hz, H1a), 5.10 (d, J1;2 ¼ 2:0 Hz, H1b),
5.27 (d, J1;2 ¼ 1:5 Hz, H1c); 13C NMR (CDCl3, 75 MHz) ꢂ 18.0
(C6c), 18.2 (C6a), 67.7 (C5c), 68.4 (C5a), 68.6 (C6b), 71.5 (C3c),
71.8 (C5b), 74.5 (C3b), 75.3 (C3b), 77.4 (C2b), 77.6 (C4a), 78.5
(C2a), 78.6 (C3a), 79.2 (C2c), 82.3 (C4c), 97.4 (C1a,
JC1,H1 ¼ 166:0 Hz), 98.7 (C1b, JC1,H1 ¼ 167:9 Hz), 98.8 (C1c,
JC1,H1 ¼ 167:2 Hz). Found: C, 74.18; H, 6.75%. Calcd for
C74H80O14: C, 74.47; H, 6.76%.
Methyl 2,4-Di-O-benzyl-ꢀ-D-rhamnopyranoside (29). This
was prepared as described for 5. The tosylation of methyl 2,4-di-
O-benzyl-ꢀ-D-mannopyranoside (28)6a (0.371 g, 0.99 mmol) with
TsCl (246 mg, 1.3 mmol) and pyridine (2.3 mL, 28 mmol), fol-
lowed by chromatography with the TK system, afforded a tosylate
(378 mg). This (314.3 mg, 0.60 mmol) was reduced with LiAlH4
(94.8 mg, 2.5 mmol) in Et2O (8.3 mL) for 30 min at reflux tem-
perature followed by chromatography with the TK system, to give
23
16
29 (129.7 mg, 44%); [ꢀ]D +14ꢁ (c 0.8, CHCl3) (Ref. 26, [ꢀ]D
1
+14.8ꢁ (c 1.9, CHCl3)); H NMR (CDCl3, 300 MHz) ꢂ 1.34 (d,
J5;6 ¼ 6:0 Hz, H6), 3.32 (t, J3;4 ¼ J4;5 ¼ 9:5 Hz, H4), 3.33 (s,
OMe), 3.66 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5), 3.72 (dd,
(74.2 mg, 90%), [ꢀ]D +11ꢁ (c 0.9, CHCl3); H NMR (CDCl3,
300 MHz) ꢂ 1.14 (d, J5;6 ¼ 6:0 Hz, H6a), 1.26 (d, J5;6 ¼ 6:0 Hz,
H6c), 1.94 (s, Ac), 3.29 (dd, J5,6a ¼ 2:0 Hz, J6a,6b ¼ 11:0 Hz,
H6b), 3.34 (dd, J5,6b ¼ 3:0 Hz, J6a,6b ¼ 11:0 Hz, H6bb), 3.61(t,
J3;4 ¼ J4;5 ¼ 9:5 Hz, H4c), 3.62 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0
Hz, H5a), 3.68 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2b), 3.80 (dd,
J1;2 ¼ 1:5 Hz, J2;3 ¼ 3:5 Hz, H2), 3.93 (dd, J2;3 ¼ 3:5 Hz, J3;4 ¼
22
1
9:5 Hz, H3), 4.71 (d, J1;2 ¼ 1:5 Hz, H1); 13C NMR (CDCl3, 75
MHz) ꢂ 18.0 (C6), 54.7 (Me), 67.0 (C5), 71.7 (C3), 78.7 (C2),
82.3 (C4), 98.0 (C1). Found: C, 70.31; H, 7.31%. Calcd for
C21H26O5: C, 70.03; H, 7.26%.
Methyl 2,4-Di-O-benzyl-ꢀ-D-tyvelopyranoside (31). A. A
mixture of 29 (37.0 mg, 0.10 mmol), imidazol (0.4 mg, 0.006
mmol), NaH (60% in oil, 10.7 mg, 0.27 mmol), and THF (0.51
mL) was stirred at room temperature for 1.5 h. To this, CS2 (32
mL, 0.53 mmol) was added and the mixture was further stirred at
room temperature for 3.5 h. After the addition of MeI (32 mL,
0.51 mmol), the mixture was stirred overnight at room
temperature. Neutralization with AcOH (10 mL), evaporation
and chromatography with the TK system afforded methyl 2,4-
di-O-benzyl-3-O-(methylthio)thiocarbonyl-ꢀ-D-rhamnopyrano-
J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3b), 3.81 (dd, J1;2 ¼ 2:0 Hz, J2;3
¼
3:0 Hz, H2a), 3.83 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:0 Hz, H5c), 3.84
(dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:0 Hz, H3a), 3.85 (dd, J1;2 ¼ 2:0 Hz,
J2;3 ¼ 3:0 Hz, H2c), 4.00 (ddd, J4;5 ¼ 9:0 Hz, J5,6a ¼ 2:0 Hz,
J5,6b ¼ 3:0 Hz, H5b), 4.09 (2H, J3;4 ¼ J4;5 ¼ 6:0 Hz, H4a and
H4b), 4.84 (d, J1;2 ¼ 2:0 Hz, H1a), 5.06 (d, J1;2 ¼ 2:0 Hz, H2b),
5.17 (d, J1;2 ¼ 2:0 Hz, H1c), 5.32 (dd, J2;3 ¼ 3:0 Hz, J3;4 ¼ 9:5
Hz, H3c); 13C NMR (CDCl3, 75 MHz) ꢂ 18.1 (C6c), 18.3 (C6a),
21.1 (Ac), 68.3 (C5c), 68.4 (C5a), 68.6 (C6b), 72.4 (C5b), 73.5
(C3c), 74.6 (C3b), 75.2 (C3a), 77.0 (C2c), 77.1 (C2b), 78.0 (C4b),
78.5 (C2a), 78.6 (C3a), 79.2 (C4c), 97.4 (C1a, JC1,H1 ¼ 169:0 Hz),
98.7 (C1b, JC1,H1 ¼ 167:8 Hz), 99.6 (C1c, JC1,H1 ¼ 170:0 Hz),
170.1 (Ac). HRMS (FAB) Found: m=z 1257.5548. Calcd for
C76H82O15Na [M + Na]þ: 1257.5551.
24
side (30) (45.4 mg, 98%); [ꢀ]D +10ꢁ (c 0.7, CHCl3) (Ref. 20c,
L-form, ½ꢀꢅD ꢂ 4:4ꢁ (CHCl3)); 1H NMR (CDCl3, 300 MHz) ꢂ
1.37 (d, J5;6 ¼ 6:0 Hz, H6), 2.54 (s, SMe), 3.34 (s, OMe), 3.79
(dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5), 3.85 (t, J3;4 ¼ J4;5 ¼ 9:0
Hz, H4), 4.14 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2), 4.66 (d,
J1;2 ¼ 2:0 Hz, H1), 6.02 (d, J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:0 Hz, H3);
13C NMR (CDCl3, 75 MHz) ꢂ 18.0 (C6), 19.2 (SMe), 54.7
(OMe), 67.6 (C5), 75.1 (C2), 78.8 (C4), 83.2 (C3), 99.2 (C1),
215.1 (C=S). Found: C, 61.11; H, 6.23%. Calcd for C23H28O5S2:
C, 61.58; H, 6.29%. This (24.5 mg, 0.055 mmol) was heated in
PhMe (1.5 mL), containing n-Bu3SnH (18.6 mL, 0.071 mmol) and
azobisisobutyronitrile (AIBN, 0.4 mg, 0.002 mmol), at 115 ꢁC
(bath temperature) under N2 for 3 h. Chromatography using the
The condensation of 6 (55.9 mg, 0.145 mmol) and 25 (94.7 mg,
0.109 mmol) in (CH2Cl)2 in the presence of Me3SiBr (18.5 mL,
0.143 mmol), CoBr2 (31.2 mg, 0.143 mmol), n-Bu4NBr (45.9 mg,
0.143 mmol), and MS4A (109.7 mg) afforded 26 (32.9 mg, 25%).
Benzyl O-(2,4-Di-O-benzyl-ꢀ-D-rhamnopyranosyl)-(1 ! 3)-
O-(2,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl)-(1 ! 4)-2,3-di-O-
benzyl-ꢀ-L-rhamnopyranoside (27). A mixture of 26 (230.2
mg, 0.19 mmol), MeOH (30 mL), 1,4-dioxane (2 mL), and dil
NaOMe (7%, 1 mL) was stirred at room temperature overnight.
After the addition of AcOH (0.4 mL), evaporation and chromato-
graphy with the TK system (100:1!10:1) afforded 27 (211.0 mg,
95%), [ꢀ]D23+15ꢁ (c 1.7, CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ
22
HE system afforded 31 (9.0 mg, 47%); [ꢀ]D +66ꢁ (c 0.4,
CHCl3) (Ref. 20c, L-form, [ꢀ]D ꢂ58ꢁ (CHCl3)); 1H NMR (CDCl3,
300 MHz) ꢂ 1.31 (d, J5;6 ¼ 6:0 Hz, H6), 1.71 (ddd, J2,3a ¼ 3:0 Hz,
J3a,3e ¼ 13:0 Hz, J3a,4 ¼ 11:0 Hz, H3a), 2.22 (dddd, J1,3e ¼ 1:0

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 76, No. 7 (2003) 1419
Hz, J2,3e ¼ 3:0 Hz, J3a,3e ¼ 13:0 Hz, J3e,4 ¼ 4:0 Hz, H3e), 3.36 (s,
OMe), 3.45 (ddd, J3a,4 ¼ 11:0 Hz, J3e,4 ¼ 4:0 Hz, J4;5 ¼ 9:0 Hz,
H4), 3.58 (dt, J1;2 ¼ 1:5 Hz, J2.3a ¼ J2,3e ¼ 3:0 Hz, H2), 3.71 (dq,
J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5), 4.58 (br, H1); 13C NMR
(CDCl3, 75 MHz) ꢂ 18.1 (C6), 54.5 (Me), 68.0 (C5), 29.5 (C3),
75.0 (C2), 75.4 (C4), 98.2 (C1, JC1,H1 ¼ 165:0 Hz). HRMS (FAB)
Found: m=z 365.1700. Calcd for C21H26NaO4 [M + Na]þ:
365.1729.
the addition of AIBN (2.0 mg, 0.012 mmol), the mixture was
ꢁ
stirred at 110 C under N2 for 2 h. The mixture was evaporated
and chromatographed with the TK system (100:1!10:1) to give
33 (21.9 mg, 29%), [ꢀ]D +15ꢁ (c 1.5, CHCl3); 1H NMR
23
(CDCl3, 400 MHz) ꢂ 1.11 (d, J5;6 ¼ 6:0 Hz, H6a), 1.25 (d, J5;6
¼
6:0 Hz, H6c), 1.80 (ddd, J2,3ax ¼ 3:0 Hz, J3ax,4 ¼ 11:0 Hz,
J3ax,3eq ¼ 13:0 Hz, H3axc), 2.23 (dt, J2,3eq ¼ J3eq,4 ¼ 4:0 Hz,
J3ea,3eq ¼ 13:0 Hz, H3eqc), 3.27 (dd, J5,6a ¼ 2:0 Hz,
J6a,6b ¼ 11:0 Hz, H6ab), 3.30 (dd, J5,6b ¼ 3:0 Hz, J6a,6b ¼ 11:0
Hz, H6bb), 3.46 (ddd, J3eq,4 ¼ 4:0 Hz, J3ax,4 ¼ 11:0 Hz,
J4;5 ¼ 9:0 Hz, H4c), 3.62 (dd, J1;2 ¼ 0 Hz, J2,3ax ¼ 3:0 Hz,
J2,3eq ¼ 4:0 Hz, H2c), 3.64 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz,
The slower-moving starting material 29 (9.0 mg, 45%) was
recovered.
B. To a stirred mixture of 29 (24.1 mg, 0.067 mmol), ꢁpyridine
(134.9 mL, 1.67 mmol), and CH2Cl2 (1.14 mL) at ꢂ30 C (bath
temperature), Tf2O (Tokyo Kasei, 202.5 mL, 1.23 mꢁmol) was
added, and the temperature was gradually raised to 20 C during
40 min. After stirring was continued for 30 min at 20 ꢁC, hexane
(2 mL) and H2O (33.7 mL, 1.9 mmol) were added to the mixture at
ꢂ10 ꢁC. After being stirred for 15 min at 20 ꢁC, the mixture was
transferred onto a silica-gel column and developed with the TK
system (100:1!10:1) to give a triflate (22.0 mg). This was dis-
solved into PhMe (1.1 mL) containing n-Bu4NBH4 (Aldrich,
115.5 mg, 0.45 mmol), and the mixture was stirred overnight
for 50 ꢁC. Chromatography with the TK system (100:1!10:1)
gave 31 (9.9 mg, 43%) and 29 (6.0 mg, 25%).
H5a), 3.70 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2b), 3.76 (t, J3;4
¼
J4;5 ¼ 9:0 Hz, H4a), 3.79 (dd, J2;3 ¼ 2:0 Hz, J3;4 ¼ 9:0 Hz, H3a),
3.80 (t, J1;2 ¼ J2;3 ¼ 2:0 Hz, H2a), 3.85 (dq, J4;5 ¼ 9:0 Hz, J5;6
¼
6:0 Hz, H5c), 3.97 (ꢃt, J4;5 ¼ 9:5 Hz, J5,6a ¼ 2:0 Hz, J5,6b ¼ 3:0
Hz, H5b), 4.04 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4b), 4.15 (dd, J2;3 ¼ 2:0
Hz, J3;4 ¼ 9:5 Hz, H3b), 4.83 (d, J1;2 ¼ 2:0 Hz, H1a), 5.03 (d,
J1;2 ¼ 2:0 Hz, H1b), 5.10 (s, H1c); 13C NMR (CDCl3, 100
MHz) ꢂ 18.1 (C6c), 18.2 (C6a), 29.5 (C3c), 68.4 (C5a), 68.6
(C6b), 68.7 (C5c), 72.2 (C5b), 74.5 (C2a), 75.3 (C4b), 75.4
(C4c), 75.6 (C2c), 76.2 (C3b), 77.5 (C2b), 78.5 (C3a), 78.6
(C4a), 97.4 (C1a, JC1,H1 ¼ 167:5 Hz), 98.7 (C1c, JC1,H1 ¼ 166:7
Hz), 98.8 (C1b, JC1,H1 ¼ 166:7 Hz). HRMS (FAB) Found: m=z
1199.5491. Calcd for C74H80NaO13 [M + Na]þ: 1199.5497.
Further elution with TK system (10:1), 27 (28.7 mg, 38%) was
recovered.
When reduction was conducted under ultrasonical treatments,
31 did not form and 29 was quantitatively obtained.
Benzyl O-[2,4-Di-O-benzyl-3-O-(methylthio)thiocarbonyl-ꢀ-
D-rhamnopyranosyl]-(1 ! 3)-(2,4,6-tri-O-benzyl-ꢀ-D-manno-
pyranosyl)-(1 ! 4)-2,3-di-O-benzyl-ꢀ-L-rhamnopyranoside
(32). To a stirred mixture of 27 (185.3 mg, 0.16 mmol), imidazol
(1.8 mg, 0.03 mmol), and THF (1.56 mL), NaH (ca. 60% in oil
dispersion, 32.4 mg, 0.81 mmol) was added. The mixture was
stirred at room temperature for 1.5 h. To this mixture, CS2 (96.5
mL, 1.6 mmol) was added. The mixture was stirred at room
temperature for 3.5 h to give a yellow mixture. Then, MeI
(96.5 mL, 1.5 mmol) was added. The mixture was further stirred
at room temperature overnight. After the addition of AcOH (46.2
mL, 0.81 mmol) to the resulting heterogeneous mixture, the mix-
ture was evaporated and chromatographed with the TK system
O-ꢀ-D-Tyvelopyranosyl-(1 ! 3)-O-ꢀ-D-mannopyranosyl-
(1 ! 4)-L-rhamnopyranose (2). Hydrogenation of 29 (23.6 mg,
0.020 mmol) over Pd on C (10%, 69 mg) in MeOH (6 mL) was
carried out at room temperature overnight. Filtration of the cat-
alyst, evaporation, and chromatography with the EM system
25
(100:1!2:1) afforded 2 (7.2 mg, 79%), [ꢀ]D +86ꢁ (c 0.4,
H2O); 1H NMR (D2O, 400 MHz) (70%) ꢂ 1.22 (3H, d, J5;6
6:5 Hz, H6c), 1.27 (3H, d, J5;6 ¼ 6:5 Hz, H6a), 1.85 (ddd, J2,3ax
¼
¼
3:0 Hz, J3ax,4eq ¼ 13:0 Hz, J3ax,4 ¼ 11:0 Hz, H3axc), 2.02 (ꢃdt,
J2,3eq ¼ 3:0 Hz, J3ax,3eq ¼ 13:0 Hz, J3eq,4 ¼ 4:5 Hz, H3eqc), 3.42
(t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4aꢁ), 3.48 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:5
Hz, H5aꢁ), 3.49 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4aꢀ), 3.59 (ddd,
J3ax,4 ¼ 11:0 Hz, J3eq,4 ¼ 4:5 Hz, J4;5 ¼ 9:5 Hz, H4c), 3.68 (dd,
J2;3 ¼ 3:5 Hz, J3;4 ¼ 9:0 Hz, H3aꢁ), 3.75 (dd, J5,6a ¼ 5:0 Hz,
J6a,6b ¼ 12:0 Hz, H6ab), 3.76 (dq, J4;5 ¼ 9:5 Hz, J5;6 ¼ 6:5 Hz,
H5c), 3.78 (dt, J4;5 ¼ 9:0 Hz, J5,6a ¼ J5,6b ¼ 5:0 Hz, H5b), 3.82
(dd, J5,6b ¼ 5:0 Hz, J6a,6b ¼ 12:0 Hz, H6bb), 3.86 (dd, J2;3 ¼ 3:5
22
(100:1!10:1) to give 32 (186.3 mg, 93%), [ꢀ]D +6ꢁ (c 1.7,
CHCl3); 1H NMR (CDCl3, 300 MHz) ꢂ 1.14 (d, J5;6 ¼ 6:0 Hz,
H6c), 1.29 (d, J5;6 ¼ 6:0 Hz, H6a), 2.55 (s, SMe), 3.29 (dd, J5,6a
2:0 Hz, J6a,6b ¼ 11:0 Hz, H6ab), 3.39 (dd, J5,6b ¼ 3:0 Hz, J5;6
¼
¼
11:0 Hz, H6bb), 3.65 (dq, J4;5 ¼ 9:0 Hz, J5;6 ¼ 6:0 Hz, H5a), 3.70
(dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2b), 3.80 (2H, dd, J2;3 ¼ 3:0
Hz, J3;4 ¼ 9:0 Hz, H3 and H3b), 3.82 (dd, J1;2 ¼ 2:0 Hz, J2;3
a
¼
¼
Hz, J3;4 ¼ 9:0 Hz, H3aꢀ and H3b), 3.89 (dd, J1;2 ¼ 2:0 Hz, J2;3
3:5 Hz, H2aꢀ), 3.93 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4b), 3.94 (dq, J4;5
¼
¼
a
3:0 Hz, H2 ), 3.82 (t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4c), 3.88 (dq, J4;5
9:0 Hz, J5;6 ¼ 6:0 Hz, H5c), 4.00 (ddd, J4;5 ¼ 9:0 Hz, J5,6a ¼ 2:0
Hz, J5,6b ¼ 3:0 Hz, H5b), 4.10 (2H, t, J3;4 ¼ J4;5 ¼ 9:0 Hz, H4a
and H4b), 4.14 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0 Hz, H2c), 4.85 (d,
9:0 Hz, J5;6 ¼ 6:5 Hz, H5aꢀ), 4.03 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:0
Hz, H2c), 4.04 (dd, J1;2 ¼ 2:0 Hz, J2;3 ¼ 3:5 Hz, H2b), 4.84 (d,
J1;2 ¼ 2:0 Hz, H1c), 4.93 (d, J1;2 ¼ 2:0 Hz, H1b), 5.07 (d, J1;2
¼
J1;2 ¼ 2:0 Hz, H1a), 5.08 (d, J1;2 ¼ 2:0 Hz, H1b), 5.22 (d, J1;2
¼
2:0 H1aꢀ), 5.08 (d, J1;2 ¼ 1:5 Hz, H1aꢁ); 13C NMR (D2O, 100
MHz) ꢂ 19.2 (C6c), 19.5 (C6a), 35.8 (C3c), 63.1 (H6b), 68.3
(H5b), 69.3 (H4c), 69.7 (H5aꢀ), 69.9 (C2c), 71.4 (H3aꢀ), 72.6
(C5c), 72.7 (C2b), 73.5 (C2aꢀ and C5aꢁ), 74.0 (C2aꢁ), 74.1
(C3aꢁ), 75.8 (C4b), 80.4 (C3b), 83.8 (H4aꢁ), 84.2 (C4aꢀ), 96.0
(C1aꢁ, JC1,H1 ¼ 159:0 Hz), 96.2 (C1aꢀ, JC1,H1 ¼ 169:0 Hz), 103.7
(C1c, JC1,H1 ¼ 169:5 Hz), 103.8 (C1b, JC1,H1 ¼ 170:0 Hz).
HRMS (FAB) Found: m=z 479.1762. Calcd for C18H32NaO13
[M + Na]þ: 479.1741.
2:0 Hz, H1c); 13C NMR (CDCl3, 75 MHz) ꢂ 18.0 (C6a), 18.3
(C6c), 19.2 (SMe), 68.4 (2C, C5a and C5c), 68.6 (C6b), 72.4
(C5b), 74.6 (C3b), 75.2 (C4a), 76.6 (C2c), 77.4 (C2b), 77.9
(C4b), 78.4 (C3a), 78.6 (C4c), 78.8 (C2a), 82.9 (C3c), 96.8 (C1b,
JC1,H1 ¼ 167:0 Hz), 97.4 (C1a, JC1,H1 ¼ 166:5 Hz), 99.3 (C1c,
JC1,H1 ¼ 165:0 Hz), 215.0 (C=S). Found: C, 71.00; H, 6.39%.
Calcd for C76H82O14S2: C, 71.11; H, 6.44%.
Benzyl O-(2,4-Di-O-benzyl-ꢀ-D-tyvelopyranosyl)-(1 ! 3)-
O-(2,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl)-(1 ! 4)-2,3-di-O-
benzyl-ꢀ-L-rhamnopyranoside (33). A mixture of 32 (81.9 mg,
0.064 mmol), n-Bu3SnH (33.4 mL, 0.127 mmol), and PhMe (5.7
mL) was stirred at room temperature under N2 for 20 min. After
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