Synthesis of methyl O-α-D-mannosyl-(1→4)-[(3-O-methyl-α-D-mannosyl) -(1→4)-]n3-O-methyl-α-D-mannosides (n = 0, 1, and 2) via dehydrative glycosylation

Article abstract of DOI:10.1246/bcsj.75.1301

Methyl O-α-D-mannopyranosyl-(1→4)-[(3-O-methyl-α-D-mannopyranosyl -(1→4)-]_n3-O-methyl-α-D-mannopyra-nosides (n = 0, 1, and 2), the lowest homologs related to the 3-O-methylmannose polysaccharides (MMP) from Mycobacterium smegmatis, were synthesized via dehydrative glycosylation reactions. The reagent systems, composed of p-nitrobenzenesulfonyl chloride, silver trifluoromethanesulfonate, and triethylamine, of p-nitrobenzenesulfonyl chloride, silver trifluoromethanesulfonate, and 1, 8-diazabicyclo[5.4.0]undec-7-ene, and of trimethylsilyl trifuloromethanesulfonate and pyridine were useful.

Full text of DOI:10.1246/bcsj.75.1301

c. Jpn.
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 1301–1309 (2002) 1301
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
α
α
Synthesis of Methyl O- -D-Mannosyl-(1→4)-[(3-O-methyl- -D-
α
mannosyl)-(1→4)-]n3-O-methyl- -D-mannosides (n = 0, 1, and 2) via
Dehydrative Glycosylation
Synthesis of Methyl O-α-d-Mannosyl-(1→4)-
M. Hirooka et al.
02
01
Motoko Hirooka,* Megumi Terayama, Emi Mitani, Shinkiti Koto,* Asako Miura, Kayo Chiba,
Ayano Takabatake, and Takako Tashiro
09
SJA8
09-2673
346
School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641
(Received September 26, 2001)
01
02
Methyl O-α-D-mannopyranosyl-(1→4)-[(3-O-methyl-α-D-mannopyranosyl-(1→4)-]n3-O-methyl-α-D-mannopyra-
nosides (n = 0, 1, and 2), the lowest homologs related to the 3-O-methylmannose polysaccharides (MMP) from Myco-
bacterium smegmatis, were synthesized via dehydrative glycosylation reactions. The reagent systems, composed of p-ni-
trobenzenesulfonyl chloride, silver trifluoromethanesulfonate, and triethylamine, of p-nitrobenzenesulfonyl chloride, sil-
ver trifluoromethanesulfonate, and 1, 8-diazabicyclo[5.4.0]undec-7-ene, and of trimethylsilyl trifuloromethanesulfonate
and pyridine were useful.
.5
4
The last quarter of the foregoing century was a time when
various improvements of the glycosylation method made it
possible to synthesize many kinds of oligosaccharides.1 Ef-
forts to improve the procedure for glycosylation have been car-
ried out from time to time.2 One such approach was the direct
use of a 1-OH sugar derivative (DOH) as a glycosyl donor, as
has recently been shown.3 This kind of method is free from the
preparation of any derivative carrying a leaving group at the
anomeric center.3,4 We have proposed several reagent systems
for one-stage dehydrative glycosylations.5 The one-stage
method allows one to add the activating reagent(s) directly into
a mixture of DOH and an acceptor (AOH) as Eq. 1. Oligosac-
charide syntheses via such one-stage dehydrative glycosylation
For synthesizing the disaccharide 1, the known acetal 49 was
transformed into an acceptor 5 via tin-mediated 3-O-methyla-
tion,10 benzylation, and convenient regioselective reduction of
the benzylidene group with triethylsilane in the presence of tri-
fluoroacetic acid.11 This was glycosylated with donors 612 and
7
13 in the presence of the NST reagent system5b for dehydrative
glycosylation to selectively afford the corresponding α-linked
disaccharides, 8 (62%, Run 1, Table 1) and 9 (83%, Run 2), re-
spectively. The by-products were the sulfonate 10 (8% and
7%, respectively) and self-condensates, 1114 (12%) and 1215
(5%). The TP system,5g composed of trimethylsilyl trifluo-
romethanesulfonate (Me3SiOTf) and pyridine (Py), a homoge-
neous system free from the use of heavy metal,4b was also use-
ful for the α-mannosylation of 5 with 7 (56%, Run 3). The tri-
methylsilyl derivatives, 13 (13%) and 14 (22%), were isolated.
Self-condensation16 did not proceed concurrently. The catalyt-
ic hydrogenolysis of the protecting groups of 8 and 9 furnished
1.
The synthesis of the trisaccharide 2 was started from the
known acetal 156d (Fig. 2). This was transformed into the alco-
hol 16 via 3-O-methylation, as in the above-described derivati-
zation of 4 into 5. This alcohol was transformed into a donor
17 having an acetyl group as a temporary masking group8a by
way of acetylation and deallylation.17 The above-described 5
was derived into another donor 18 with an allyl group as a tem-
porary protecting group via allylation and hydrolysis. The ac-
ceptor 5 was then glycosylated with 17 and 18 in the presence
of the NST system (Runs 4 and 5) to furnish intermediary dis-
accharide derivatives 19 and 20, respectively. The NSD sys-
tem,5f composed of NsCl, AgOTf, and diazabicyclo[5.4.0]un-
dec-7-ene (DBU), reported by us in a previous paper, slightly
improved the yields of the glycosides (Runs 6 and 7). The TP
system was useful (Runs 8 and 9). The acceptor 16 was also
glycosylated with 17 (Run 10) to furnish a known intermediate
21.8a Compounds 19 and 20 were deprotected into a known
(DOH + AOH) + Reagent(s) → DOA
(1)
remains to be explored.3,4b,4d,6 Recently, it has been found that
the NST reagent system,5b composed of p-nitrobenzenesulfo-
nyl chloride (NsCl), silver trifluoromethanesulfonate (AgOTf),
and triethylamine (Et3N), performs α-selective mannosyla-
tion.6d This dehydrative glycosylation is considered to proceed
via 1-O-p-nitrobenzenesulfonates of DOH.5e We now wish to
report on the utility of the two dehydrative glycosylation
systems5b,5f in the synthesis of a mannooligosaccharide series:
1, 2, and 3 (Fig. 1, n = 0, 1, and 2). These are the lowest ho-
mologs of the α(1→4)-linked linear 3-O-methylmannose
polysaccharides (MMP)-related oligosaccharides (Fig. 1, n ꢀ
3) in Mycobacterium smegmatis.7 The lower series of such oli-
gosaccharides of 3-O-methyl-D-mannopyranose, terminated at
the non-reducing end with D-mannopyranose and the reducing
end with simple methyl aglycon, are considered to be biosyn-
thetic precursors for higher MMP.7 Syntheses of the oligosac-
charides of the repeating part, composed of a 3-O-methyl-D-
mannopyranose unit,8a and the synthesis of the octamer in an
acceptor form have been accomplished.8b

1302 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Synthesis of Methyl O-α-D-Mannosyl-(1→4)-
condensation of 29 with 22 was performed in the presence of
the NSD system to furnish the desired 30 (67%, Run 18). The
TP system was also of use to connect 29 with 22 to give 30
(48%, Run 19). The catalytic deprotection of 30 yielded the
targeted tetrasaccharide 3.
The NMR spectra of the synthesized oligosaccharide series
(1, 2, and 3), observed in deuterium oxide, were consistent
with their structures. Table 2 summarizes the sets of assign-
ment of their 13C NMR spectra. The differential NOE spec-
Ⅱ
Ⅰ
trum of 2 showed the proximity between H1 and H4 in the
Ⅱ
Ⅰ
Ⅲ
Ⅱ
Ⅲ
C1 to C4 junction and that between H1 and H4 in the C1
Ⅱ
1
to C4 junction. The signals of the methyl groups of the H
NMR spectrum were assigned by observing its deifferential
NOE and GHMQC spectra.
In conclusion, the titled α-linked oligomannosides were
synthesized using the dehydrative glycosylation method. As a
temporary protecting group for the non-reducing end, the allyl
group was useful as an acetyl group.8a
Experimental3,6g
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 deprotection 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 Yana-
co Micro Melting Point Apparatus (Yanagimoto). The optical ro-
tations were measured on a JASCO DIP-180 Digital Polarimeter
at room temp. The 1H and 13C NMR spectra were recorded with a
Varian VXR300 spectrometer or a Varian XL-400 spectrometer,
along with measurements of the H,H-COSY, C,H-COSY, and
DEPT spectra. For assigning of the anomeric configuration of the
mannosides, their JC1,H1 values15 were determined by gated decou-
pling with the NOE experiment. The assignments of the spectra
of 2, 3, 23, 24, and 30 were made by auxiliary measurements of
HOHAHA, HMQC, HMBC, GHMQC, and differential NOE
spectra. The elemental analyses were carried out with a Yanaco
CHN Corder MT-5. The LRMS and the HRMS were recorded
with a JEOL JMS-AX505H spectrometer and a JEOL JMS-
AX505HA spectrometer as well as a JEOL JMS-700 spectrometer
(operated generously at JEOL System Technology Co., Ltd), re-
spectively. The abbreviations used here for the assigned substitu-
ents are All (allyl), Bd (benzylidene), Bn (benzyl), Ns (p-nitro-
phenylsulfonyl), and Tf (trifluoromethanesulfonyl).
Fig. 1. Synthesis of α-D-Manp-(1→4)-3-O-Me-α-D-Manp-
O-Me (1): a. (i) n-Bu2SnO/MeOH, ∆; (ii) MeI/DMF, ∆; b.
BnBr, NaH/DMF, 0 °C → room temperature (rt); c.
Et3SiH, CF3CO2H/CH2Cl2, 0 °C → rt; d. H2, Pd–C(10%)/
AcOH, rt. A code with square shade is a donor, whereas
that with round shade is an acceptor.
disaccharide acceptor 22.8a The donor 6 was condensed with
the acceptor 22 in the presence of the NST system to give the
protected trisaccharide 23 (72%, Run 11). The NSD system
condensed 7 with 22 (66%, Run 12) to give the condensate 24.
This was also obtained via glycosylation of 22 with 7 with the
TP system (68%, Run 13). In the case of Run 12, the sulfonate
25 was isolated (21%). Hydrogenolytic deprotection of 23 or
24 afforded the desired 2.
Finally, the synthesis of tetrasaccharide 3 was carried out
(Fig. 3). The acceptor 16 was glycosylated with 6 and 7 in the
presence of the NST system to give intermediates 26 and 27
(Runs 14 and 15), respectively. The NSD system gave a better
yield (64%, Run 16); the sulfonate 28 was isolated (15%). The
TP system was also useful (60%, Run 17). The deallylation of
27 smoothly afforded the disaccharide donor 29. The final
Commercial p-nitrobenzenesulfonyl chloride (NsCl) was
passed through a silica-gel column eluted with benzene, evaporat-
ed to dryness, and stored in a dry box in a refrigerator.5b Silver tri-
fluoromethansulfonate (AgOTf, Aldrich), triethylamine (Et3N,
Tokyo Kasei), diazabicyclo[5.4.0]undec-7-ene (DBU, Tokyo
Kasei), trimethylsilyl trifluoromethanesulfonate (Me3SiOTf,
Tokyo Kasei), and anhydrous pyridine (Py, Tokyo Kasei) were
used without purification.
α
Methyl 2,6-Di-O-benzyl-3-O-methyl- -D-mannopyranoside
(5). A mixture of 48 (19.2 g, 68 mmol), n-Bu2SnO (Tokyo Kasei,
17 g, 68 mmol), and MeOH (140 mL) was refluxed for 7 h. The
mixture was evaporated to dryness. The residue was stirred in dry
N, N-dimethylformamide (DMF, Tokyo Kasei, 150 mL) contain-
ing MeI (Tokyo Kasei, 8.5 mL, 136 mmol) and molecular sieves

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1303
Fig. 2. Synthesis of α-D-Manp-(1→4)-3-O-Me-α-D-Manp-(1→4)-3-O-Me-α-D-Manp-O-Me (2): a. (i) n-Bu2SnO/MeOH, ∆; (ii)
MeI/DMF, ∆; b. BnBr, NaH/DMF, 0 °C → rt; c. Et3SiH, CF3CO2H/CH2Cl2, 0 °C → rt; d. Ac2O, Py/rt; e. PdCl2, NaOAc/aq
AcOH, ∆; f. AllBr, NaH/∆; g. aq H2SO4/aq AcOH, ∆; h. NaOMe/MeOH, rt; i. H2, Pd–C(10%)/AcOH, rt. A code with square
shade is a donor, whereas that with round shade is an acceptor.
Fig. 3. Synthesis of α-D-Manp-(1→4)-[3-O-Me-α-D-Manp-(1→4)-]23-O-Me-α-D-Manp-O-Me (3): a. PdCl2, NaOAc/aq AcOH, ∆;
b. H2, Pd–C(10%)/AcOH, rt. A code with square shade is a donor, whereas that with round shade is an acceptor.

1304 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Synthesis of Methyl O-α-D-Mannosyl-(1→4)-
Table 1. Results of Glycosylation (DOH + AOH → DOA)a)
Run
Donor (DOH)
Acceptor (AOH)
Reagents
Glycosides (DOA)/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
6
7
7
5
5
5
5
5
5
5
5
5
16
22
22
22
16
16
16
16
22
22
NST
NST
TP
NST
NST
NSD
NSD
TP
8,
9,
9,
62b)
83c)
56d)
37
17
18
17
18
17
18
17
6
7
7
6
7
19,
20,
19,
20,
19,
20,
21,
23,
24,
24,
26,
27,
27,
27,
30,
30,
43
58
53
53
46
64
TP
NST
NST
NSD
TP
NST
NST
NSD
TP
72
66e)
68
36
41
7
7
29
29
64f)
60
NSD
TP
67
48
a) NST: acceptor (0.042 – 0.174 mmol), donor (1.3 equiv), NsCl (2.5 equiv), AgOTf
(2.5 equiv), Et3N (2.5 equiv), and CH2Cl2 (8 mL/mmol of acceptor); NSD: acceptor
(0.032 – 0.180 mmol), donor (1.3 equiv), NsCl (2.5 equiv), AgOTf (2.5 equiv), DBU
(2.5 equiv), and CH2Cl2 (8 mL/mmol of acceptor); TP: acceptor (0.023 – 0.065 mmol),
donor (1.3 equiv), Me3SiOTf (4.8 equiv), Py (2.8 equiv), and CH2Cl2 (5 mL/mmol of
acceptor). b) 10 (8%) and 11 (12%) were isolated. c) 10 (7%) and 12 (5%) were iso-
lated. d) 13 (18%) and 14 (22%) were isolated. e) 12 (23%) and 25 (21%) were iso-
lated. f) 12 (9%) and 28 (15%) were isolated.
4A powder (13 g) at 75 °C for 24 h. The mixture was evaporated
with CF3CO2H (1.2 mL, 16.2 mmol) in CH2Cl2 (13.5 mL) con-
taining Et3SiH (2.5 mL, 15.7 mmol), to furnish 16 (810 mg, 54%);
[α]D26 +6° (c 0.4, CHCl3)(lit.,8a [α]D +7° (c 1.3, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ 3.50 (dd, J2,3 = 3.5 Hz, J3,4 = 9.5 Hz, H-3),
to dryness and chromatographed with a TK system (10:1) to give
a syrup (13.6 g). This was dissolved in DMF (85 mL) containing
PhCH2Br (Wako, 7.0 mL, 59 mmol). After the addition of NaH
(ca. 60% in oil, Wako, 2.4 g, 60 mmol) at 0 °C (bath temperature),
the mixture was stirred at this temperature for 30 min and then at
room temperature for 2 h. After MeOH (6 mL) was added drop-
wise under cooling, the mixture was evaporated to dryness. The
residue was chromatographed with the HE system (3:1) to afford a
homogeneous syrup (11.8 g) of the benzyl ether. This syrup (10.5
g) was treated with CF3CO2H (Wako, 10 mL, 135 mmol) in
CH2Cl2 (Wako, 120 mL) containing Et3SiH (Tokyo Kasei, 21 mL,
131 mmol) at 0 °C for 30 min. After evaporation, the obtained
syrup was chromatographed with the TK system (10:1) to furnish
5 (7.535 g, 32%); [α]D20 −10° (c 0.6, CHCl3)(lit.,8a [α]D −5.3° (c
3.80 (t, J3,4 = J4,5 = 9.5 Hz, H-4), 3.83 (dd, J1,2 = 1.5 Hz, J2,3
=
3.5 Hz, H-2), 4.96 (d, J1,2 = 1.5 Hz, H-1), 2.66 (s, OH-4), 3.36 (s,
Me-3), 3.37 (s, Me-1), 5.89 (m, All); 13C NMR (CDCl3, 75 MHz)
δ 67.8 (C-4), 70.4 (C-6), 71.5 (C-5), 72.8 (C-2), 81.1 (C-3), 97.1
(C-1), 57.1 (Me-3).
α
4-O-Acetyl-2,6-di-O-benzyl-3-O-methyl- -D-mannopyran-
ose (17). A mixture of 16 (884.0 mg, 2.1 mmol), pyridine (5.0
mL), and Ac2O (5.0 mL, 53 mmol) was kept standing overnight.
Evaporation and chromatography with the HE system (4:1) af-
forded a homogeneous syrup (860.0 mg). This was dissolved in
aq AcOH (90%, 4.0 mL). After the addition of NaOAc (270.0 mg,
3.3 mmol) and PdCl2 (270.0 mg, 1.5 mmol), the mixture was
stirred overnight at room temperature for. Evaporation and chro-
matography with the HE system (2:1) gave 17 (498.4 mg, 56%),
1
2.6, CHCl3); H NMR (CDCl3, 300 MHz) δ 3.42 (dd, J2,3 = 3.0
Hz, J3,4 = 9.5 Hz, H-3), 3.47 (dd, J1,2 = 1.5 Hz, J2,3 = 3.0 Hz, H-
2), 3.94 (t, J3,4 = J4,5 = 9.5 Hz, H-4), 4.77 (d, J1,2 = 1.5 Hz, H-1),
2.73 (s, OH-4), 3.32 (s, Me-3), 3.34 (s, Me-1); 13C NMR (CDCl3,
75 MHz) δ 67.6 (C-4), 70.4 (C-6), 71.3 (C-5), 72.7 (C-2), 81.1 (C-
3), 99.0 (C-1), 54.0 (Me-1), 57.0 (Me-3).
[α]D23 +1° (c 1.1, CHCl3)(lit.,8a [α]D +3.2° (c 1.2, CHCl3); H
1
NMR (CDCl3, 300 MHz) (85% α) δ 3.47 (dd, J5,6a = 2.5 Hz, J6a,6b
= 10.5 Hz, H-6aα), 3.62 (dd, J2,3 = 3.0 Hz, J3,4 = 10.0 Hz, H-
3α), 3.80 (dd, J1,2 = 2.5 Hz, J2,3 = 3.0 Hz, H-2α), 4.08 (ddd, J4,5
= 10.0 Hz, J5,6a = 2.5 Hz, J5,6b = 7.5 Hz, H-5α), 5.20 (t, J3,4 = J4,5
= 10.0 Hz, H-4α), 5.24 (t, J1,2 = J1,OH = 2.5 Hz, H-1α), 3.60 (d,
J1,OH = 2.5 Hz, OH-1α), 2.00 (s, Ac), 3.34 (s, Me); 13C NMR
(CDCl3, 75 MHz) δ 68.7 (C-4β), 69.1 (C-4α), 69.8 (C-6β), 70.05
(C-6α), 70.11 (C-5α), 73.7 (C-2α, C-5β), 74.5 (C-2β), 78.7 (C-
3α), 82.5 (C-3β), 92.8 (C-1α), 93.6 (C-1β), 57.8 (Me-α), 58.4
(Me-β), 20.9, 170.1 (Ac).
α
2,6-Di-O-benzyl-3-O-methyl- -D-mannopyranoside
Allyl
(16). Similarly to the case of the derivatization of 4 into 5, se-
quential reactions were carried out. The reaction of 156d (1.20 g,
3.9 mmol), n-Bu2SnO (1.59 g, 6.4 mmol), and MeOH (20 mL),
followed by evaporation and a reaction with MeI (0.73 mL, 11.7
mmol) in DMF (14 mL) containing molecular sieves 4A (1.2 g),
afforded the 3-O-methyl ether (1.088 g). This (1.008 g) was ben-
zylated with PhCH2Br (0.58 mL, 4.9 mmol) and NaH (ca. 60%,
188.2 mg, 4.7 mmol) in DMF (6.7 mL), followed by a treatment
α
4-O-Allyl-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranose

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1305
Table 2. 13C NMR Chemical Shifts of Methyl O-α-D-Mannosyl-(1→4)-[3-O-methyl-O-α-D-man-
nosyl-(1→4)-]n3-O-methyl-α-D-mannosides (n = 0, 1, and 2)a)
C
1 (n = 0)
2 (n = 1)
3 (n = 2)
Ⅰ
1
103.3 (JC,H = 171.8 Hz) 103.3 (JC,H = 170.1 Hz) 103.3 (JC,H = 172.1 Hz)
Ⅰ
2
68.3
83.6
75.3
73.6
63.63
57.4
58.8
68.3
83.6
75.4
73.6
63.64
57.5
58.8
68.3
83.6
75.3
73.6
63.63
57.5
58.8
Ⅰ
3
4
5
Ⅰ
Ⅰ
Ⅰ
6
Ⅰ
Ⅰ
Me-1
Me-3
Ⅱ
1
2
104.1 (JC,H = 171.9 Hz) 103.9 (JC,H = 170.6 Hz) 103.85d) (JC,H = 170.0 Hz)
Ⅱ
73.0
73.0
69.2
76.4
63.55
68.8
83.4
75.0
74.9
63.55
58.8
68.8
83.4e)
75.1
74.8
63.56
58.8
Ⅱ
3
Ⅱ
4
Ⅱ
5
Ⅱ
6
(Me-3 )b)
Ⅱ
Ⅲ
1
104.1 (JC,H = 171.9 Hz) 103.88d) (JC,H = 171.3 Hz)
72.98
73.01
69.2
76.4
63.55
Ⅲ
2
68.8
Ⅲ
3
4
5
6
83.3e)
Ⅲ
75.0
74.9
63.56
58.8
Ⅲ
Ⅲ
(Me-3 )c)
Ⅲ
Ⅳ
1
2
3
4
5
6
104.1 (JC,H = 170.6 Hz)
Ⅳ
72.99
73.01
69.2
76.4
63.56
Ⅳ
Ⅳ
Ⅳ
Ⅳ
a) Determined at 400.0 MHz for 1H NMR spectra and at 100.6 MHz for 13C NMR spectra in
D2O (see Experimental). b) In the case of 1, methyl group was absent. c) In the case of 2,
methyl group was absent. d) Exchageable. e) Exchangeable.
(18). A mixture of 5 (7.535 mg, 19.4 mmol), allyl bromide (60
mL, 694 mmol), and NaH (ca. 60%, 2.3 g, 57.5 mmol) was stirred
at 80 °C for 2 h. After evaporation, the residue was chromato-
graphed using the TK system (20:1) to give a homogeneous syrup
(7.939 g). To this, AcOH (150 mL) and aq H2SO4 (30%, 20 mL)
were added and the mixture was stirred at 100 °C for 60 min. The
cooled mixture was diluted with PhMe (200 mL) and H2O (100
mL) under stirring. The organic layer was washed with aq
NaHCO3 (5%, 50 mL, four times). Evaporation and chromatogra-
phy with the TK system (6:1) afforded 18 (5.144 g, 64%), [α]D26
+14° (c 1.2, CHCl3); 1H NMR (CDCl3, 300 MHz) (80% α) δ 3.36
(dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3β), 3.64 (t, J3,4 = J4,5 = 9.5
Hz, H-4α), 3.78 (dd, J1,2 = 2.0 Hz, J2,3 = 3.5 Hz, H-2α), 3.82 (dd,
J1,2 = 1.5 Hz, J2,3 = 3.0 Hz, H-2β), 5.23 (dd, J1,2 = 2.0 Hz, J1,OH
= 3.5 Hz, H-1α), 3.34 (dd, J1,OH = 3.5 Hz, OH-1α), 3.40 (s, Me-
3α), 3.49 (s, Me-3β), 5.84 (allyl); 13C NMR (CDCl3, 75 MHz) δ
69.2 (C-6β), 69.9 (C-6α), 71.5 (C-α), 74.3 (C-2α), 74.4 (C-5β),
75.2 (C-4α, C-2β, C-5β), 81.3 (C-3α), 81.3 (C-3α), 85.4 (C-3β),
92.6 (C-1α), 93.7 (C-1β); 57.7 (Me-3α), 58.4 (Me-3β), 116.4,
135.1 (All-β), 116.6, 134.9 (All-α); HRMS (FAB) Found: m/z
437.1940. Calcd for C24H30NaO6 [M + Na]+: 437.19400.
equiv) or DBU (2.5 equiv) was added. The reaction temperature
was allowed to rise up to 0 °C during ca. 5 h. The mixture was
stirred for 16 h at this temperature under anhydrous conditions.
To the mixture, PhMe (3 mL/mL of CH2Cl2) and powderized
NaHCO3 (10 equiv) were added; the mixture was stirred for 15
min and transferred onto a silica-gel column, which was then elut-
ed with the TK system (gradient) to give a crude condensate. This
was further purified with the TK system, or occasionally with the
HE system. The results were summarized in Table 1.
Glycosylation Using the TP System. To a stirred mixture of
an acceptor (0.030 – 0.065 mmol), a donor (1.3 equiv), Py (2.8
equiv), and CH2Cl2 (5 mL/mmol of acceptor), Me3SiOTf (4.8
equiv) was added at −50 °C (bath temperature). The reaction
temperature was increased to 0 °C during ca. 4 h. The mixture
was then stirred at this temperature for 4.5 h. After the addition of
Et3N (4.8 equiv) and PhMe (3 mL/mL of CH2Cl2), the mixture
was transferred onto a silica-gel column, which was then eluted
with the TK system (gradient) to give crude glycoside. This was
further purified with the TK system, or occasionally with the HE
system. The results are summarized in Table 1.
α
Methyl O-(2,3,4,6-Tetra-O-benzyl- -D-mannopyranosyl)-
α
Glycosylation Using the NST System or the NSD System.
To a stirred mixture of an acceptor (0.030 – 0.120 mmol), a donor
(1.3 equiv), NsCl (2.5 equiv), AgOTf (2.5 equiv), and CH2Cl2 (8
mL/mmol of acceptor) at −60 °C (bath temperature), Et3N (2.5
(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranoside(8).
(Run 1). After elusion of 10 and 11 , there appeared 8, [α]D22
+16° (c 0.8, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 3.39 (dd, J2,3
Ⅰ
= 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.55 (dd, J5,6 = 10.5 Hz, J6a,6b
=

1306 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Synthesis of Methyl O-α-D-Mannosyl-(1→4)-
Ⅱ
Ⅰ
1.5 Hz, H-6a ), 3.76 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.80
mannopyranoside (13). (Run 3). [α]D +16° (c 0.6, CHCl3);
1H NMR (CDCl3, 300 MHz) δ 3.35 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0
Hz, H-3), 3.80 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2), 3.93 (dd,
J3,4 = J4,5 = 9.0 Hz, H-4), 4.77 (d, J1,2 = 2.0 Hz, H-1); 3.32 (Me-
3), 3.35 (Me-1), 0.07 (MeSi); 13C NMR (CDCl3, 75 MHz) δ 68.1
(C-4), 69.7 (C-6), 72.9 (C-5), 73.4 (C-2), 81.9 (C-3), 99.2 (C-1);
54.6 (Me-1), 57.1 (Me-3), 0.4 (MeSi); HRMS (FAB) Found: m/z
483.2179. Calcd for C25H36NaO6Si [M + Na]+: 483.21786.
Ⅱ
(dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.84 (dd, J2,3 = 3.0 Hz,
J3,4 = 9.0 Hz, H-3 ), 3.93 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 4.02 (t,
Ⅱ
Ⅰ
Ⅱ
Ⅰ
J3,4 =J4,5 = 9.0 Hz, H-4 ), 4.78 (d, J1,2 = 2.0 Hz, H-1 ), 5.30 (d,
J1,2 = 2.0 Hz, H1 ), 3.14 (Me-3 ), 3.36 (Me-1 ); 13C NMR (CDCl3,
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
75 MHz): δ 69.4 (C-6 ), 70.2 (C-6 ), 71.3 (C-5 ), 72.97 (C-5 ),
73.02 (C-2 ), 74.7 (C-4 ), 75.0 (C-4 ), 75.4 (C-2 ), 80.0 (C-3 ),
81.9 (C-3 ), 98.8 (C-1 , JC1,H1 = 169.0 Hz), 99.9 (C-1 , JC1,H1
171.0 Hz); 54.9 (Me-1 ), 56.7 (Me-3 ). Found: C, 73.77; H,
6.99%. Calcd for C56H62O11: C, 73.82; H, 6.86%.
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
=
Ⅰ
Ⅰ
α
Trimethylsilyl 2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-man-
nopyranoside (14). (Run 3). [α]D +18° (c 0.6, CHCl3); 1H
NMR (CDCl3, 300 MHz) δ 3.60 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz,
H-2), 3.62 (dd, J5,6a = 2.0 Hz, J6a,6b = 10.0 Hz, H-6a), 3.76 (dd,
J5,6b = 4.0 Hz, J5a,5b = 10.0 Hz, H-6b), 3.82 (ddd, J4,5 = 9.0 Hz,
α
Methyl O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopy-
α
ranosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyra-
noside (9). (Run 2). After elusion of 10 and 12 , there appeared
9, [α]D23 +14° (c 1.6, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 3.43
J5,6a = 2.0 Hz, J5,6b = 4.0 Hz, H-5), 3.92 (dd, J2,3 = 3.0 Hz, J3,4
=
Ⅱ
(dd, J5,6 = 10.5 Hz, J6a,6b = 1.5 Hz, H-6a ), 3.43 (dd, J2,3 = 3.0
Hz, J3,4 = 9.5 Hz, H-3 ), 3.62 (dd, J5,6 = 10.5 Hz, J6a,6b = 4.0 Hz,
H-6b ), 3.74 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.79 (dd, J1,2
= 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.96 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ),
9.0 Hz, H-3), 3.99 (t, J3,4 = J4,5 = 9.0 Hz, H-4), 5.18 (d, J1,2 = 2.0
Ⅰ
Hz, H-1), 0.11 (MeSi); 13C NMR (CDCl3, 75 MHz) δ 69.2 (C-6),
Ⅱ
Ⅱ
71.7 (C-5), 75.0 (C-4), 76.7 (C-2), 79.8 (C-3), 92.8 (C1, JC1,H1 =
Ⅰ
Ⅰ
166.5 Hz), −2.0 (MeSi); HRMS (FAB) Found: m/z 771.1246.
Ⅱ
Ⅰ
3.97 (t, J3,4 =J4,5 = 9.5 Hz, H-4 ), 4.80 (d, J1,2 = 2.0 Hz, H-1 ),
Calcd for C37H40Cl4NaO6Si [M + Na]+: 771.12457.
5.30 (d, J1,2 = 2.0 Hz, H-1 ), 3.18 (Me-3 ), 3.37 (Me-1 ); 13C
Methyl
O-(4-O-Acetyl-2,6-di-O-benzyl-3-O-methyl- -D-
Ⅱ
Ⅰ
Ⅰ
α
Ⅱ
Ⅰ
Ⅰ
α
NMR (CDCl3, 75 MHz) δ 69.1 (C-6 ), 70.1 (C-6 ), 71.2 (C-5 ),
72.7 (C-5 ), 72.8 (C-2 ), 74.5 (C-4 ), 74.7 (C-4 ), 75.5 (C-2 ), 79.9
(C-3 ), 81.8 (C-3 ), 98.6 (C-1 , JC1,H1 = 168.3 Hz), 99.6 (C-1 ,
JC1,H1 = 170.9 Hz); 55.0 (Me-1 ), 56.5 (Me-3 ). Found: C, 63.88;
H, 5.65%. Calcd for C56H58Cl4O11: C, 64.13; H, 5.57%.
mannopyranosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-
mannopyranoside (19). [α]D24 +23° (c 0.9, CHCl3)(lit.,8a [α]D
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
1
+20.2° (c 1.3, CHCl3); H NMR (CDCl3, 300 MHz) δ 3.52 (dd,
J2,3 = 3.0 Hz, J3,4 = 10.0 Hz, H-3 ), 3.78 (dd, J1,2 = 2.0 Hz, J2,3
3.0 Hz, H-2 ), 3.94 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ), 4.79 (d, J1,2
2.0 Hz, H-1 ), 5.30 (dd, J1,2 = 2.0 Hz, H-1 ), 5.30 (t, J3,4 = J4,5
Ⅰ
Ⅰ
Ⅱ
=
=
=
Ⅰ
Ⅰ
Ⅰ
Ⅱ
Methyl 2,6-Di-O-benzyl-3-O-methyl-4-O-(p-nitrophenylsul-
fonyl)- -D-mannopyranoside (10). [α]D25 −15° (c 0.6, CHCl3);
10.0 Hz, H-4 ); 3.19 (Me-3 ), 3.33 (Me-3 ), 3.77 (Me-1 ), 2.08 (s.
Ⅱ
Ⅰ
Ⅱ
Ⅰ
α
1H NMR (CDCl3, 300 MHz) δ 3.45 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5
Hz, H-3), 3.75 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2), 4.76 (d, J1,2
= 2.0 Hz, H-1), 5.04 (t, J3,4 = J4,5 = 9.5 Hz, H-4), 2.78 (Me-3),
3.34 (Me-1); 13C NMR (CDCl3, 75 MHz) δ 69.0 (C-6), 70.1 (C-5),
73.4 (C-2), 78.6 (C-4), 78.7 (C-3), 98.8 (C-1), 55.1 (Me-1), 56.3
(Me-3); 143.2, 150.0 (Ns); HRMS (FAB) Found: m/z 596.1566.
Calcd for C28H31NaO10S [M + Na]+: 596.15662.
Ac); 13C NMR (CDCl3, 75 MHz) δ 69.1 (C-4 ), 70.1 (C-6 ), 70.4
Ⅱ
Ⅱ
Ⅰ Ⅱ Ⅰ Ⅰ Ⅱ
(C-6 ), 71.3 (C-5 ), 71.4 (C-5 ), 72.8 (C-2 ), 74.0 (C-2 ), 74.1 (C-
4 ), 78.8 (C-3 ), 81.3 (C-3 ), 98.7 (C-1 , JC1,H1 = 169.2 Hz), 99.5
(C-1 , JC1,H1 = 172.0 Hz); 54.9 (Me-1 ), 56.6 (Me-3 ), 57.6 (Me-
3 ); 21.0, 169.9 (Ac). Found: C, 68.48; H, 6.86%. Calcd for
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
C45H54O12: C, 68.68; H, 6.92%.
α
Methyl O-(4-O-Allyl-2,6-di-O-benzyl-3-O-methyl- -D-man-
α
α
O-(2,3,4,6-Tetra-O-benzyl- -D-mannopyranosyl)-(1→1)-
nopyranosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-manno-
2,3,4,6-tetra-O-benzyl- -D-mannopyranoside (11). [α]D24
pyranoside (20). [α]D21 +19° (c 0.6, CHCl3); H NMR (CDCl3,
1
α
+32° (c 0.4, CHCl3) (lit.,16 [α]D20 +40° (c 0.85, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ 3.55 (ddd, J4,5 = 9.5 Hz, J5,6a = 2.0 Hz, J5,6b
= 5.0 Hz, H5), 3.61 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2), 3.63
(dd, J5,6a = 2.0 Hz, J5a,5b = 11.0 Hz, H-6a), 3.72 (dd, J2,3 = 3.0
Hz, J3,4 = 9.5 Hz, H-3), 3.76 (dd, J5,6b = 5.0 Hz, J6a,6b = 11.0 Hz,
H-6b), 3.98 (t, J3,4 = J4,5 = 9.5 Hz, H-4), 5.20 (d, J1,2 = 2.0 Hz,
H-1); 13C NMR(CDCl3, 75 MHz) δ 69.1 (C-6), 72.8 (C-5), 74.2
(C-2), 74.3 (C-4), 79.5 (C-3), 93.4 (C1, JC1,H1 = 168.0 Hz);
HRMS (FAB) Found: m/z 1085.4816. Calcd for C68H70NaO11 [M
+ Na]+: 1085.4815.
300 MHz) δ 3.44 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3 ), 3.45 (dd,
J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.70 (t, J3,4 = J4,5 = 9.5 Hz, H-
4 ), 3.77 (dd, J1,2 = 2.0 Hz, J2,3 = 9.5 Hz, H-2 ), 3.82 (dd, J1,2
2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.94 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ),
Ⅰ
Ⅱ
Ⅱ
Ⅰ
=
Ⅱ
Ⅱ
Ⅰ
Ⅱ
4.79 (d, J1,2 = 2.0 Hz, H-1 ), 5.31 (dd, J1,2 = 2.0 Hz, H-1 ); 3.20
(Me-3 ), 3.36 (Me-1 ), 3.41 (Me-3 ), 5.85 (m, All); 13C NMR
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
(CDCl3, 75 MHz) δ 69.3 (C6 ), 70.2 (C-6 ), 71.3 (C-5 ), 72.9 (C-
Ⅱ
Ⅰ
Ⅱ
Ⅰ
Ⅱ
Ⅱ
5 ), 73.0 (C-2 ), 74.5 (C-2 ), 74.6 (C-4 ), 74.8 (C-4 ), 81.4 (C-3 ),
Ⅰ
Ⅰ
Ⅱ
81.8 (C-3 ), 98.7 (C-1 , JC1,H1 = 167.8 Hz), 99.7 (C-1 , JC1,H1
=
Ⅰ
Ⅰ
Ⅱ
169.0 Hz); 54.9 (Me-1 ), 56.7 (Me-3 ), 57.6 (Me-3 ); 116.2, 135.3
(All). Found: C, 70.25; H, 7.32%. Calcd for C46H56O11: C, 70.39;
H, 7.19%.
α
O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopyranosyl-
α
(1→1)-2,3,4,6-tetra-O-(p-chlorobenzyl)- -D-mannopyranoside
[α]D23 +25° (c 1.4, CHCl3)(lit.,17 [α]D20 +21° (c 1,
Allyl O-(4-O-Acetyl-2,6-di-O-benzyl-3-O-methyl- -D-man-
α
(12).
1
α
CHCl3); H NMR (CDCl3, 300 MHz) δ 3.49 (ddd, J4,5 = 9.5 Hz,
J5,6a = 2.0 Hz, J5,6b = 5.0 Hz, H5), 3.53 (dd, J1,2 = 2.0 Hz, J2,3
nopyranosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-manno-
=
pyranoside (21).
[α]D22 +24° (c 1.3, CHCl3) (lit.,8a [α]D
1
3.0 Hz, H-2), 3.57 (dd, J5,6a = 2.0 Hz, J5a,5b = 10.5 Hz, H-6a),
3.65 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3), 3.68 (dd, J5,6b = 5.0
Hz, J6a,6b = 10.5 Hz, H-6b), 3.91 (t, J3,4 = J4,5 = 9.5 Hz, H-4),
5.11 (d, J1,2 = 2.0 Hz, H-1); 13C NMR (CDCl3, 75 MHz) δ 69.1
(C-6), 72.8 (C-5), 74.5 (C-2), 74.6 (C-4), 79.5 (C-3), 93.5 (C1,
JC1,H1 = 170.5 Hz). Found: C, 61.17; H, 4.81%. Calcd for
C68H62Cl8O11: C, 61.00; H, 4.67%.
+28.7° (c 2.8, CHCl3)); H NMR (CDCl3, 300 MHz) δ 3.43 (dd,
Ⅱ
J5,6a = 3.0 Hz, J6a,6b = 11.0 Hz, H-6a ), 3.80 (dd, J1,2 = 2.0 Hz,
Ⅰ
Ⅰ
J2,3 = 3.0 Hz, H-2 ), 3.96 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 4.94 (d,
Ⅰ
Ⅱ
J1,2 = 2.0 Hz, H-1 ), 5.30 (t, J3,4 = J4,5 = 10.0 Hz, H-4 ), 5.32 (dd,
Ⅱ
Ⅰ
Ⅱ
J1,2 = 2.0 Hz, H-1 ); 3.20 (s, Me-3 ), 3.33 (s, Me-3 ), 5.90 (m,
All), 1.98 (s. Ac); 13C NMR (CDCl3, 75 MHz) δ 69.1 (C-4 ), 70.1
Ⅱ
Ⅱ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
(C-6 ), 70.4 (C-6 ), 71.2 (C-5 ), 71.5 (C-5 ), 72.8 (C-2 ), 73.9 (C-
2 ), 74.7 (C-4 ), 78.8 (C-3 ), 81.8 (C-3 ), 98.7 (C-1 , JC1,H1 =
169.0 Hz), 99.9 (C-1 , JC1,H1 = 172.1 Hz); 56.6 (Me-3 ), 57.6
(Me-3 ); 68.1, 117.5, 133.8 (All), 21.0, 169.9 (Ac). Found: C,
Ⅱ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
In the case of Run 3 using TP system, the order of elution of the
products was 14, 13, and then 9.
Ⅱ
Ⅰ
Ⅱ
α
Methyl 2,6-Di-O-benzyl-3-O-methyl-4-O-trimethylsilyl- -D-

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1307
Ⅰ
69.29; H, 6.93%. Calcd for C47H56O12: C, 69.44; H, 6.94%.
2.0 Hz, J5,6b = 7.0 Hz, H-5 ), 3.72 (dd, J5,6a = 2.0 Hz, J6a,6b = 12.0
Ⅰ
Ⅲ
α
Methyl O-(2,6-Di-O-Benzyl-3-O-methyl- -D-mannopyrano-
Hz, H-6a ), 3.73 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.79 (dd,
J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.80 (dd, J2.3 = 3.0 Hz, J3,4 =
9.5 Hz, H-3 ), 3.82 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.88
(ddd, J5,6b = 7.0 Hz, J6a,6b = 12.0 Hz, H-6b ), 3.92 (t, J3,4 = J4,5
9.5 Hz, H-4 ), 3.98 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ), 3.99 (t, J3,4
J4,5 = 9.5 Hz, H-4 ), 4.79 (d, J1,2 = 2.0 Hz, H-1 ), 5.30 (d, J1,2
Ⅰ
α
syl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranoside
Ⅲ
Ⅱ
(22).
A mixture of 20 (76.1 mg, 0.097 mmol) and dil
Ⅲ
NaOMe (0.2%, 8.2 mL) was kept standing overnight. Evaporation
and chromatography using the TK system (10:1) furnished 22
(58.6 mg, 81%), [α]D23 +7° (c 1.2, CHCl3) (lit.,8a [α]D +7.4° (c
=
=
=
Ⅰ
Ⅲ
Ⅱ
Ⅰ
1
Ⅱ
Ⅲ
Ⅰ
1.4, CHCl3)); H NMR (CDCl3, 300 MHz) δ 3.40 (dd, J2,3 = 3.0
2.0 Hz, H-1 ), 5.30 (d, J1,2 = 2.0 Hz, H-1 ); 3.16 (s, Me-3 ), 3.21
Ⅱ
Ⅱ
Ⅰ
Hz, J3,4= 9.5 Hz, H-3 ), 3.49 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-
(s, Me-3 ), 3.37 (s, Me-1 ); 13C NMR (CDCl3, 100 MHz) δ 69.0
Ⅰ
Ⅰ
Ⅲ Ⅱ Ⅰ Ⅰ Ⅱ
3 ), 3.79 (dd, J1,2 = 2.0 Hz, J3,4 = 9.0 Hz, H-2 ), 3.81 (dd, J5,6b
=
(C-6 ), 70.2 (C-6 ), 70.5 (C-6 ), 71.4 (C-5 ), 72.3 (C-5 ), 72.7 (C-
Ⅰ
Ⅰ
Ⅱ
Ⅲ
Ⅱ
Ⅲ
Ⅰ
1.5 Hz, J6a,6b = 10.5 Hz, H-6b ), 3.85 (dd, J2,3 = 2.0 Hz, J3,4 = 3.0
Hz, H-2 ), 3.99 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 4.00 (t, J3,4 = J4,5
9.5 Hz, H-4 ), 4.80 (d, J1,2 = 2.0 Hz, H-1 ), 5.35 (d, J1,2 = 2.0 Hz,
2 ), 72.8 (C-2 ), 73.1 (C-5 ), 74.1 (C-4 ), 74.3 (C-4 ), 75.0 (C-4 ),
Ⅱ
Ⅰ
Ⅲ
Ⅲ
Ⅱ
Ⅰ
Ⅰ
=
75.5 (C-2 ), 79.5 (C-3 ), 81.5 (C-3 ), 81.8 (C-3 ), 98.7 (C-1 ,
JC1,H1 = 168.7 Hz), 99.4 (C-1 , JC1,H1 = 170.0 Hz), 99.6 (C-1 ,
JC1,H1 = 170.0 Hz); 54.9 (Me-1 ), 56.3 (Me-3 ). 56.6 (Me-3 );
HRMS (FAB) Found: m/z 1425.4253. Calcd for C77H82Cl4NaO16
[M + Na]+: 1425.4255.
Ⅱ
Ⅰ
Ⅱ
Ⅲ
Ⅱ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅰ
Ⅱ
H-1 ); 3.24 (s, Me-3 ), 3.35 (s, Me-3 ), 3.37 (s, Me-1 ), 2.27 (s,
OH-4 ); 13C NMR (CDCl3, 75 MHz) δ 67.9 (C-4 ), 70.2 (C-6 ),
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅰ
Ⅱ
Ⅰ
Ⅱ
70.6 (C-6 ), 71.3 (C-5 ), 72.4 (C-5 ), 72.9 (C-2 ), 73.3 (C-2 ), 74.4
(C-4 ), 80.7 (C-3 ), 81.9 (C-3 ), 98.7 (C-1 ), 99.8 (C-1 ); 54.9
(Me-1 ), 56.6 (Me-3 ). 57.0 (Me-3 ).
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Methyl O-(2,6-Di-O-benzyl-3-O-methyl-4-O-(p-nitrophenyl-
Ⅰ
Ⅰ
Ⅱ
α
sulfonyl)- -D-mannopyranosyl)-(1→4)-2,6-di-O-benzyl-3-O-
methyl- -D-mannopyranoside (25). [α]D23 +9° (c 0.7, CHCl3);
α
This was obtained via deallylation of 20: a mixture of 20 (48.1
mg, 0.061 mmol), NaOAc (55.6 mg, 0.68 equiv), PdCl2 (30.2 mg,
0.17 equiv), and aq AcOH (95%, 2.26 mL) was stirred at 60 °C for
60 min. Evaporation and chromatography as above gave 22 (22.2
mg, 49%).
1H NMR (CDCl3, 300 MHz) δ 3.39 (dd, J2,3 = 3.0 Hz, J3,4 = 10.0
Ⅱ
Ⅰ
Hz, H-3 ), 3.43 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.56 (dd,
J5,6a = 4.5 Hz, J6a,6b = 11.0 Hz, H-6a ), 3.82 (ddd, J4,5 = 10.0 Hz,
J5,6a = 4.5 Hz, J5,6b = 2.5 Hz, H-5 ), 3.94 (t, J3,4 = J4,5 = 9.5 Hz,
H-4 ), 4.78 (d, J1,2 = 1.5 Hz, H-1 ), 5.05 (t, J3,4 = J4,5 = 10.0 Hz,
Ⅱ
Ⅱ
Ⅰ
Ⅱ
α
Methyl O-(2,3,4,6-Tetra-O-benzyl- -D-mannopyranosyl)-
Ⅱ
Ⅱ
Ⅱ
α
(1→4)-O-(2,6-di-O-benzyl-3-O-methyl- -D-mannopyranosyl)-
H-4 ), 5.32 (d, J1,2 = 1.5 Hz, H-1 ); 2.78 (s, Me-3 ), 3.16 (s, Me-
Ⅰ
Ⅰ
Ⅱ
α
(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranoside
3 ), 3.35 (s, Me-1 ); 13C NMR (CDCl3, 75 MHz) δ 68.8 (C-6 ),
(23). [α]D21 +23° (c 1.6, CHCl3); 1H NMR (CDCl3, 400 MHz) δ
70.1 (C-6 ), 71.1 (C-5 ), 71.2 (C-5 ), 72.6 (C-2 ), 73.6 (C-2 ), 74.7
Ⅰ Ⅱ Ⅰ Ⅰ Ⅱ
Ⅱ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
3.37 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.44 (dd, J2,3 = 3.0
Hz, J3,4 = 9.5 Hz, H-3 ), 3.56 (dd, J5,6a = 1.5 Hz, J6a,6b = 10.5 Hz,
(C-4 ), 78.4 (C-3 ), 78.6 (C-4 ), 81.7 (C-3 ), 98.7 (C-1 , JC1,H1 =
166.6 Hz), 99.4 (C-1 , JC1,H1 = 171.7 Hz); 54.9 (Me-1 ), 56.1
Ⅰ
Ⅱ
Ⅰ
Ⅲ
Ⅱ
Ⅱ
Ⅰ
H-6a ), 3.62 (dd, J5,6a = 6.0 Hz, J6a,6b = 11.0 Hz, H-6a ), 3.69
(Me-3 ); 56.5 (Me-3 ); 143.4, 150.4 (Ns); HRMS (FAB) Found:
Ⅲ
(dd, J5,6b = 4.0 Hz, J6a,6b = 10.5 Hz, H-6b ), 3.69 (dd, J5,6a = 2.0
m/z 952.3190. Calcd for C49H55NaO15 [M + Na]+: 952.31897.
Ⅰ
α
Hz, J6a,6b = 10.0 Hz, H-6a ), 3.69 (dd, J5,6b = 2.0 Hz, J6a,6b = 11.0
Hz, H-6b ), 3.71 (ddd, J4,5 = 9.5 Hz, J5,6a = 2.0 Hz, J5,6b = 6.0
Hz, H-5 ), 3.72 (dd, J5,6a = 2.0 Hz, J6a,6a = 12.0 Hz, H-6a ), 3.73
(dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.77 (ddd, J5,6a = 1.5 Hz,
Allyl
O-(2,3,4,6-Tetra-O-benzyl- -D-mannopyranosyl)-
Ⅱ
α
(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranoside
(26). [a]D23 +16° (c 1.5, CHCl3); 1H NMR (CDCl3, 300 MHz) δ
Ⅱ
Ⅰ
Ⅲ
Ⅰ
3.43 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3 ), 3.56 (dd, J5,6a = 1.5
Hz, J6a,6b = 10.5 Hz, H-6a ), 3.78 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0
Hz, H-2 ), 3.80 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.94 (t, J3,4
= J4,5 = 9.0 Hz, H-4 ), 4.02 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ), 4.93 (d,
Ⅲ
Ⅱ
J5,6b = 4.0 Hz, J6a,6b = 9.5 Hz, H-5 ), 3.80 (dd, J1,2 = 2.0 Hz, J2,3
Ⅱ
Ⅲ
Ⅰ
Ⅱ
= 3.0 Hz, H-2 ), 3.83 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ),
Ⅲ
Ⅰ
Ⅱ
3.86 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.91 (t, J3,4 = J4,5
=
=
Ⅰ
Ⅱ
Ⅰ
Ⅱ
Ⅰ
9.5 Hz, H-4 ), 3.96 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ), 4.04 (dd, J3,4
9.5 Hz, J4,5 = 10.5 Hz, H-4 ), 4.77 (d, J1,2 = 2.0 Hz, H-1 ), 5.28
J1,2 = 2.0 Hz, H-1 ), 5.30 (d, J1,2 = 2.0 Hz, H-1 ); 3.14 (Me-3 ),
5.89 (m, All); 13C NMR (CDCl3, 75 MHz) δ 69.3 (C-6 ), 70.2 (C-
Ⅲ
Ⅰ
Ⅱ
Ⅱ
Ⅲ
Ⅰ
Ⅰ
Ⅰ
Ⅱ
Ⅰ
Ⅱ
(d, J1,2 = 2.0 Hz, H-1 ), 5.32 (d, J1,2 = 2.0 Hz, H-1 ); 3.16 (s, Me-
6 ), 71.4 (C-5 ), 73.0 (2C, C-2 and C-5 ), 74.7 (C-4 ), 74.9 (C-4 ),
75.3 (C-2 ), 79.9 (C-3 ), 81.8 (C-3 ), 96.8 (C-1 , JC1,H1 = 168.0
Hz), 99.9 (C-1 , JC1,H1 = 171.0 Hz); 56.7 (Me-1 ); 68.0, 117.5,
133.8 (All). Found: C, 74.35; H, 6.97%. Calcd for C58H64O11: C,
74.34; H, 6.88%.
3 ), 3.20 (s, Me-3 ), 3.36 (s, Me-1 ); 13C NMR (CDCl3, 100 MHz)
Ⅰ
Ⅱ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
Ⅲ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
δ 69.2 (C-6 ), 70.2 (C-6 ), 70.4 (C-6 ), 71.5 (C-5 ), 72.3 (C-5 ),
72.7 (C-2 ), 72.9 (C-2 ), 73.1 (C-5 ), 74.3 (C-4 ), 74.9 (C-4 ),
75.0 (C-4 ), 75.2 (C-2 ), 80.1 (C-3 ), 81.5 (C-3 ), 81.8 (C-3 ),
98.7 (C-1 , JC1,H1 = 170.4 Hz), 99.7 (C-1 , JC1,H1 = 171.5 Hz),
99.8 (C-1 , JC1,H1 = 171.5 Hz); 54.9 (Me-1 ), 56.4 (Me-3 ), 56.7
(Me-3 ); HRMS (FAB) Found: m/z 1289.5846. Calcd for
Ⅰ
Ⅱ
Ⅲ
Ⅱ
Ⅲ
Ⅰ
Ⅲ
Ⅲ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
α
Allyl O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopyra-
Ⅲ
Ⅰ
Ⅰ
α
nosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyrano-
Ⅱ
side (27). (Run16). After elution of 28 and 12, there appeared
C77H86NaO16 [M + Na]+: 1289.5814.
27, [α]D22 +18° (c 1.2, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 3.62
Ⅱ
α
Methyl O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopy-
(dd, J5,6b = 4.0 Hz, J6a,6b = 10.5 Hz, H-6b ), 3.74 (dd, J1,2 = 2.0
Hz, J2,3 = 2.3 Hz, H-2 ), 3.82 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-
2 ), 3.97 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 3.98 (t, J3,4 = J4,5 = 9.5
Ⅱ
α
ranosyl)-(1→4)-O-(2,6-di-O-benzyl-3-O-methyl- -D-mannopy-
Ⅰ
Ⅱ
α
ranosyl)-(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyra-
Ⅰ
Ⅰ
noside (24).
(Run 12). After the elution of 25 and 12, there
Hz, H-4 ), 4.96 (d, J1,2 = 2.0 Hz, H-1 ), 5.30 (d, J1,2 = 2.0 Hz, H-
appeared 24; [α]D22 +17° (c 0.8, CHCl3); H NMR (CDCl3, 400
1 ); 3.19 (Me-3 ), 5.90 (m, All); 13C NMR (CDCl3, 75 MHz) δ
1
Ⅱ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
Ⅰ
Ⅰ
Ⅱ
MHz) δ 3.39 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.46 (dd, J2,3
69.1 (C-6 ), 70.1 (C-6 ), 71.3 (C-5 ), 72.8 (2C, C-2 and C-5 ),
74.1 (C-4 ), 74.7 (C-4 ), 75.5 (C-2 ), 79.8 (C-3 ), 81.8 (C-3 ), 96.7
(C-1 , JC1,H1 = 168.7 Hz), 99.6 (C-1 , JC1,H1 = 170.9 Hz); 56.7
(Me-1 ); 68.1, 117.5, 133.8 (All). Found: C, 64.91; H, 5.62%.
Ⅰ
Ⅱ
Ⅰ
Ⅱ
Ⅱ
Ⅰ
= 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.46 (dd, J5,6a = 1.5 Hz, J6a,6b
=
Ⅲ
Ⅰ
Ⅱ
10.5 Hz, H-6a ), 3.63 (dd, J5,6b = 4.0 Hz, J6a,6b = 10.5 Hz, H-
6b ), 3.63 (dd, J5,6a = 6.0 Hz, J6a,6b = 11.0 Hz, H-6a ), 3.69 (dd,
J5,6b = 2.0 Hz, J6a,6b = 11.0 Hz, H-6b ), 3.71 (ddd, J4.5 = 9.5 Hz,
J5,6a = 1.5 Hz, J5,6b = 4.0 Hz, H-5 ), 3.71 (ddd, J4,5 = 9.5 Hz, J5,6b
Ⅲ
Ⅱ
Ⅰ
Ⅱ
Calcd for C58H60Cl4O11: C, 64.81; H, 5.63%.
Ⅲ
Allyl 2,6-Di-O-benzyl-3-O-methyl-4-O-(p-nitrophenylsulfo-
Ⅱ
= 2.0 Hz, J6a,6b = 6.0 Hz, H-5 ), 3.71 (ddd, J4,5 = 9.5 Hz, J5,6a
=
nyl)- -D-mannopyranoside (28). [α]D25 −21° (c 0.5, CHCl3);
α

1308 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Synthesis of Methyl O-α-D-Mannosyl-(1→4)-
1H NMR (CDCl3, 300 MHz) δ 3.49 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5
Hz, H-3), 3.76 (dd, J1,2 = 1.5 Hz, J2,3 = 3.0 Hz, H-2), 4.63 (d, J1,2
= 1.5 Hz, H-1), 5.06 (t, J3,4 = J4,5 = 9.5 Hz, H-4), 2.80 (Me-3),
5.84 (m, All); 13C NMR (CDCl3, 75 MHz) δ 68.9 (C-6), 70.2 (C-
5), 73.4 (C-2), 78.7 (2C, C-3 and C-4), 96.8 (C-1), 56.3 (Me-3),
68.3, 117.9, 133.3 (All); 143.2, 150.0 (Ns). HRMS (FAB) Found:
m/z 622.1723. Calcd for C30H33NaO10 [M + Na]+: 622.17227.
Methyl
O- -D-Mannopyranosyl-(1→4)-3-O-methyl- -D-
α
α
mannopyranoside (1). A mixture of 8 (22.4 mg, 0.021 mmol),
Pd on C (Kawaken Fine Chemical Co., 10%, 25 mg), and AcOH
(6 mL) was shaken at room temperature overnight under H2. Fil-
tration, evaporation, and chromatography with the EM system
(2:1) afforded 1 (7.1 mg, 78%), glass, [α]D22 +82° (c 0.3, H2O); 1H
NMR (D2O, 400 MHz) δ 3.56 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-
3 ), 3.62 (ddd, J4,5 = 9.0 Hz, J5,6a = 5.5 Hz, J5,6b = 1.5 Hz, H-5 ),
3.63 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 3.67 (ddd, J4,5 = 9.0 Hz, J5,6a
= 6.0 Hz, J5,6b = 2.0 Hz, H-5 ), 3.72 (dd, J5,6a = 5.5 Hz, J6a,6b
12.0 Hz, H-6a ), 3.75 (dd, J5,6a = 6.0 Hz, J6a,6b = 12.0 Hz, H-6a ),
3.75 (dd, J2,3 = 3.0 Hz, J4,5 = 9.0 Hz, H-3 ), 3.78 (t, J3,4 = J4,5
9.0 Hz, H-4 ), 3.84 (dd, J5,6b = 1.5 Hz, J5a,5b = 12.0 Hz, H-6b ),
3.85 (dd, J5,6b = 2.0 Hz, J6a,6b = 12.0 Hz, H-6b ), 3.96 (dd, J1,2
2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 4.12 (dd, J1,2 = 1.5 Hz, J2,3 = 3.0 Hz,
H-2 ), 4.77 (d, J1,2 = 1.5 Hz, H-1 ), 5.13 (d, J1,2 = 2.0 Hz, H-1 );
3.35 (Me-1 ), 3.40 (Me-3 ). Found: C, 43.59; H, 7.05%. Calcd for
C14H26O11•H2O: C, 43.30; H, 7.27%.
A similar hydrogenolysis of 9 (31.5 mg, 0.024 mmol) over Pd
on C (35 mg) in AcOH (6 mL), followed by chromatography, af-
forded 1 (7.0 mg, 63%).
Ⅰ
Ⅱ
α
O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopyranosyl)-
Ⅱ
α
(1→4)-2,6-di-O-benzyl-3-O-methyl- -D-mannopyranose (29).
Ⅰ
A mixture of 27 (41.2 mg, 0.038 mmol), NaOAc (25.7 mg, 0.31
mmol), PdCl2 (14.3 mg, 0.081 mmol), and aq AcOH (95%, 1.5
mL) was stirred at 60 °C for 60 min. Additional portions of
NaOAc (25.7 mg, 0.31 mmol) and PdCl2 (14.3 mg, 0.081 mmol)
were added to the mixture, which was further stirred at 60 °C for
another 60 min. Evaporation and chromatography with the TK
=
Ⅱ
Ⅰ
Ⅱ
=
Ⅰ
Ⅱ
Ⅰ
=
Ⅱ
system (10:1) afforded 29 (32.0 mg, 81%), [α]D23 +6° (c 1.2,
Ⅰ
Ⅰ
Ⅱ
1
Ⅰ
Ⅰ
CHCl3); H NMR (CDCl3, 300 MHz) (80% α) δ 3.13 (dd, J2,3
=
Ⅰ
Ⅱ
2.5 Hz, J3,4 = 9.0 Hz, H-3β ), 3.42 (dd, J5,6a = 1.5 Hz, H-6aα ),
Ⅰ
3.48 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H 3α ), 3.58 (dd, J5,6b = 4.0
Ⅱ
Hz, J6a,6b = 10.5 Hz, H-6bα ), 3.72 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0
Ⅰ
Ⅰ
Hz, H-2α ), 3.78 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2α ), 3.98 (t,
Ⅱ
Ⅱ
α
α
J3,4 = J4,5 = 9.5 Hz, H-4α ), 5.25 (d, J1,2 = 2.0 Hz, H-1α ), 5.27
Methyl O- -D-Mannopyranosyl-(1→4)-O-(3-O-methyl- -D-
Ⅰ
Ⅰ
Ⅰ
α
(d, J1,2 = 2.0 Hz, H-1α ); 1.63 (s, OH-1α ), 3.17 (Me-3α ), 3.25
mannopyranosyl)-(1→4)-3-O-methyl- -D-mannopyranoside
(Me-3β ); 13C NMR (CDCl3, 75 MHz) δ 69.0 (C-6α ), 70.5 (C-
(2). Hydrogenolysis of 23 (23.2 mg, 0.018 mmol) over Pd on C
(10%, 25 mg) in AcOH (6 mL) and chromatography with EM sys-
tem (2:1) furnished 2 (5.4 mg, 54%), glass, [α]D23 +97° (c 0.4,
Ⅰ
Ⅱ
Ⅰ
Ⅰ
Ⅱ
Ⅰ
Ⅰ
6α ), 71.1 (C-5α ), 72.9 (C-5α ), 73.0 (C-2α ), 74.8 (C-4α ), 75.0
Ⅱ
Ⅱ
Ⅰ
Ⅱ
Ⅰ
(C-4α ), 75.6 (C-2α ), 79.8 (C-3β ), 79.9 (C-2α ), 81.3 (C-3α ),
Ⅰ
Ⅰ
Ⅰ
Ⅱ
85.5 (C-3β ), 92.4 (C-1α ), 93.7 (C-1β ), 99.6 (C-1β ), 99.8 (C-
H2O); 1H NMR (D2O, 400 MHz) δ 3.59 (dd, J2,3 = 3.0 Hz, J3,4
=
Ⅰ Ⅱ
Ⅱ
Ⅰ
Ⅰ
1α ); 56.6 (Me-3α ), 57.2 (Me-3β ); HRMS (FAB) Found: m/z
9.0 Hz, H-3 ), 3.61 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3 ), 3.64
1055.2489. Calcd for C55H56Cl4NaO11 [M + Na]+: 1055.2474.
(ddd, J4,5 = 9.5 Hz, J5,6a = 5.5 Hz, J5,6b = 2.0 Hz, H-5 ), 3.65 (~t,
J3,4 = 9.0 Hz, J4,5 = 9.5 Hz, H-4 ), 3.67 (ddd, J4,5 = 9.5 Hz, J5,6a
= 5.5 Hz, J5,6b = 2.0 Hz, H-5 ), 3.73 (ddd, J4,5 = 9.5 Hz, J5,6a
5.5 Hz, J5,6b = 2.0 Hz, H-5 ), 3.76 (dd, J5,6a = 5.5 Hz, J6a,6b
12.0 Hz, H-6a , H-6a , H-6a ), 3.77 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0
Hz, H-3 ), 3.81 (~t, J3,4 = 9.0 Hz, J4,5 = 9.5 Hz, H-4 ), 3.82 (~t,
Ⅲ
Ⅲ
α
Methyl O-(2,3,4,6-Tetra-O-(p-chlorobenzyl)- -D-mannopy-
Ⅰ
α
ranosyl-(1→4)-[O-(2,6-di-O-benzyl-3-O-methyl- -D-mannopy-
=
=
Ⅱ
α
ranosyl-(1→4)-]22,6-di-O-benzyl-3-O-methyl- -D-mannopyra-
[α]D23 +14° (c 1.4, CHCl3); 1H NMR (CDCl3,
Ⅰ
Ⅱ
Ⅲ
noside (30).
Ⅰ
Ⅲ
Ⅰ
400 MHz) δ 3.44 (dd, J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3 ), 3.42 (dd,
J2,3 = 3.0 Hz, J3,4 = 9.0 Hz, H-3 ), 3.46 (dd, J2,3 = 3.0 Hz, J3,4
9.0 Hz, H-3 ), 3.46 (dd, J5,6a = 2.0 Hz, J6a,6b = 11.0 Hz, H-6a ),
3.63 (dd, J5,6b = 4.0 Hz, J6a,6b = 11.0 Hz, H-6b ), 3.64 (dd, J5,6a
6.0 Hz, J6a,6b = 10.0 Hz, H-6a ), 3.68 (dd, J5,6a = 2.0 Hz, J6a,6b
10.0 Hz, H-6a ), 3.70 (ddd, J4,5 = 9.0 Hz, J5,6a = 2.0 Hz, J5,6b
5.5 Hz, H-5 ), 3.72 (dd, J5,6a = 2.0 Hz, J6a,6b = 10.0 Hz, H-6a ),
3.74 (ddd, J4,5 = 9.0 Hz, J5,6a = 2.0 Hz, J5,6b = 6.0 Hz, H-5 ),
Ⅱ
Ⅱ
=
J3,4 = 9.0 Hz, J4,5 = 9.5 Hz, H-4 ), 3.85 (dd, J5,6a = 2.0 Hz, J6a,6b
Ⅲ
Ⅳ
Ⅰ
Ⅱ
Ⅲ
= 12.0 Hz, H-6b , H-6b , H-6b ), 3.98 (dd, J1,2 = 2.0 Hz, J2,3 =
Ⅳ
Ⅲ
Ⅰ
=
=
3.0 Hz, H-2 ), 4.14 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 4.16
(dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 4.78 (d, J1,2 = 2.0 Hz, H-
1 ), 5.15 (d, J1,2 = 2.0 Hz, H-1 ), 5.18 (d, J1,2 = 2.0 Hz, H-1 );
3.39 (Me-1 ), 3.42 (Me-3 ), 3.43 (Me-3 ). Found: C, 44.58; H,
7.10%. Calcd for C21H38O16•H2O: C, 44.68; H, 7.14%.
A similar hydrogenolytic deprotection of 24 (25.5 mg, 0.018
mmol) over Pd on C (10%, 30 mg) in AcOH (6 mL) gave 2 (4.9
mg, 49%).
Ⅱ
Ⅱ
Ⅲ
Ⅰ
Ⅲ
Ⅱ
=
Ⅰ
Ⅰ
Ⅰ
Ⅰ
Ⅱ
Ⅲ
Ⅳ
3.74 (ddd, J4,5 = 9.5 Hz, J5,6a = 2.0 Hz, J5,6b = 4.0 Hz, H-5 ),
3.76 (dd, J5,6b = 6.0 Hz, J6a,6b = 10.0 Hz, H-6b ), 3.78 (dd, J1,2
Ⅲ
=
Ⅰ
2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.78 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz,
Ⅳ
Ⅳ
α
α
H-2 ), 3.80 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.83 (d, J1,2
Methyl O- -D-Mannopyranosyl-(1→4)-[O-(3-O-methyl- -
Ⅱ
α
= 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 3.84 (d, J1,2 = 2.0 Hz, J2,3 = 3.0
Hz, H-2 ), 3.90 (t, J3,4 = J4,5 = 9.0 Hz, H-4 ), 3.92 (dd, J5,6b = 5.5
Hz, J6a,6b = 10.0 Hz, H-6b ), 3.96 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ),
3.99 (t, J3,4 = J4,5 = 9.5 Hz, H-4 ), 4.03 (t, J3,4 = J4,5 = 9.0 Hz,
H-4 ), 4.79 (d, J1,2 = 2.0 Hz, H-1 ), 5.29 (d, J1,2 = 2.0 Hz, H-1 ),
5.32 (d, J1,2 = 2.0 Hz, H-1 ), 5.34 (d, J1,2 = 2.0 Hz, H-1 ), 3.20
D-mannopyranosyl)-(1→4)-]23-O-methyl- -D-mannopyrano-
Ⅲ
Ⅰ
side (3). The hydrogenolysis of 30 (36.8 mg, 0.021 mmol) was
performed over Pd on C (10%, 50 mg) in AcOH (6 mL) at room
temperature overnight. Filtration of the catalyst, evaporation, and
chromatography with EM system (3:2) afforded 3 (7.2 mg, 48%),
glass, [α]D24 +89° (c 0.4, H2O); 1H NMR (D2O, 400 MHz) δ 3.57
Ⅰ
Ⅱ
Ⅳ
Ⅱ
Ⅰ
Ⅱ
Ⅲ
Ⅳ
Ⅰ
Ⅱ
Ⅲ
Ⅰ
(s, 3H, Me-3 ), 3.21 (s, 6H, Me-3 and Me-3 ), 3.36 (s, 3H, Me-
(dd, J2,3 = 3.5 Hz, J3,4 = 9.0 Hz, H-3 ), 3.60 (dd, J2,3 = 3.0 Hz, J3,4
= 9.0 Hz, H-3 , H-3 ), 3.64 (~t, J3,4 = 9.5 Hz, J4,5 = 10.0 Hz, H-
4 ), 3.65 (ddd, J4,5 = 10.0 Hz, J5,6a = 5.0 Hz, J5,6b = 2.0 Hz, H-
5 ), 3.67 (ddd, J4,5 = 10.0 Hz, J5,6a = 5.0 Hz, J5,6b = 2.0 Hz, H-
5 ), 3.70 (ddd, J4,5 = 10.0 Hz, J5,6a = 5.0 Hz, J5,6b = 2.0 Hz, H-5 ,
H-5 ), 3.74 (dd, J5,6a = 5.0 Hz, J6a,6b = 12.0 Hz, H-6a , H-6a , H-
6a , H-6a ), 3.77 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, H-3 ), 3.80
(~t, J3,4 = 9.0 Hz, J4,5 = 10.0 Hz, H-4 , H-4 ), 3.82 (~t, J3,4 =
1 ); 13C NMR (CDCl3, 100 MHz) δ 69.0 (C-6 ), 70.1 (C-6 ), 70.5
Ⅰ
Ⅳ
Ⅲ
Ⅱ
Ⅲ
Ⅰ
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Ⅰ
Ⅱ
Ⅲ
Ⅳ
(2C, C-6 and C-6 ), 71.6 (C-5 ), 72.5 (C-5 ), 72.6 (C-5 ), 72.8
Ⅳ
Ⅱ
Ⅲ
Ⅲ
Ⅳ
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(C-5 ), 73.0 (C-2 ), 73.1 (C-2 ), 74.07 (C-4 ), 74.10 (C-4 ),
Ⅱ
Ⅰ
Ⅰ
Ⅳ
Ⅳ
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74.7 (C-4 ), 74.8 (C-4 ), 75.3 (C-2 ), 75.4 (C-2 ), 80.0 (C-3 ),
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Ⅱ
Ⅲ
Ⅰ
Ⅲ
Ⅰ
Ⅱ
81.4 (2C, C-3 and C-3 ), 81.7 (C-3 ), 98.6 (C-1 , JC1,H1 = 168.0
Hz), 99.4 (C-1 , JC1,H1 = 171.0 Hz), 99.5 (C-1 , JC1,H1 = 170.5
Hz), 99.7 (C-1 , JC1,H1 = 170.0 Hz); 54.9 (Me-1 ), 56.3 (Me-3 ).
Ⅳ
Ⅲ
Ⅲ
Ⅳ
Ⅳ
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Ⅰ
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56.4 (Me-3 ).
56.6 (Me-3 ); HRMS (FAB) Found: m/z
9.0 Hz, J4,5 = 9.5 Hz,H-4 ), 3.84 (dd, J5,6a = 2.0 Hz, J6a,6b = 12.0
1781.5878. Calcd for C98H106Cl4NaO21 [M + Na]+: 1781.5876.
Hz, H-6b , H-6b , H-6b , H-6b ), 3.96 (dd, J1,2 = 2.0 Hz, J2,3
=
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Ⅳ

M. Hirooka et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1309
Ⅳ
Ⅰ
3.0 Hz, H-2 ), 4.13 (dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 ), 4.16
6
a) S. Koto, N. Morishima, M. Uchino, M. Fukuda, M.
Ⅱ
Ⅲ
(dd, J1,2 = 2.0 Hz, J2,3 = 3.0 Hz, H-2 , H-2 ), 4.77 (d, J1,2 = 2.0
Hz, H-1 ), 5.14 (d, J1,2 = 2.0 Hz, H-1 ), 5.18 (d, J1,2 = 2.0 Hz, H-
Yamazaki, and S. Zen, Bull. Chem. Soc. Jpn., 61, 3943 (1988). b)
S. Koto, H. Haigoh, S. Shichi, M. Hirooka, T. Nakamura, C.
Maru, M. Fujita, A. Goto, T. Sato, M. Okada, S. Zen, K. Yago, and
F. Tomonaga, Bull. Chem. Soc. Jpn., 68, 2331 (1995). c) S. Koto,
T. Miura, M. Hirooka, A. Tomaru, M. Iida, M. Kanemitsu, K.
Takenaka, S. Miyaji, N. Kuroyanagi, M. Yagishita, S. Zen, K.
Yago, and F. Tomonaga, Bull. Chem. Soc. Jpn., 69, 3247 (1996).
d) S. Koto, K. Asami, M. Hirooka, K. Nagura, M. Takizawa, S.
Yamamoto, N. Okamoto, M. Sato, H. Tajima, T. Yoshida, N.
Nonaka, T. Sato, S. Zen, K. Yago, and F. Tomonaga, Bull. Chem.
Soc. Jpn., 72, 765 (1999). e) S. Koto, M. Hirooka, K. Yago, M.
Komiya, T. Shimizu, K. Kato, T. Takehara, A. Ikefuji, A. Iwasa, S.
Hagino, M. Sekiya, Y. Nakase, S. Zen, F. Tomonaga, and S.
Shimada, Bull. Chem. Soc. Jpn., 73, 173 (2000). f) S. Koto, A.
Kusunoki, and M. Hirooka, Bull. Chem. Soc. Jpn., 73, 967 (2000).
g) S. Koto, M. Hirooka, T. Yoshida, K. Takenaka, C. Asai, T.
Nagamitsu, H. Sakuma, M. Sakurai, S. Masuzawa, M. Komiya, T.
Sato, S. Zen, K. Yago, and F. Tomonaga, Bull. Chem. Soc. Jpn.,
73, 2521 (2000).
Ⅰ
Ⅳ
Ⅱ
Ⅲ
Ⅰ
Ⅰ
Ⅱ
Ⅱ
1 , H-1 ); 3.38 (Me-1 ), 3.41 (Me-3 ), 3.42 (Me-3 or Me-3 ),
Ⅲ
Ⅱ
3.43 (Me-3 or Me-3 ); HRMS (FAB) Found: m/z 721.2766.
Calcd for C28H49O21 [M − 1]−: 721.27662.
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