On the stereochemistry of tethered intermediates in p-methoxybenzyl- assisted β-mannosylation

Article abstract of DOI:10.1002/(SICI)1099-0690(199906)1999:6<1367::AID-EJOC1367>3.0.CO;2-N

We have previously developed a novel method for the stereocontrolled synthesis of β-manno-glycoside. Starting from 2-O-PMB (p-methoxybenzyl)- protected mannosyl donor 1, conversion into the mixed acetal 3 under oxidative conditions followed by the activation of the anomeric position affords β-manno-glycoside as a single stereoisomer. Although the utility of this method has been further demonstrated in the synthesis of the core structure of Asn-linked glycan chains, there remained uncertainty with respect to the stereochemistry of the mixed acetal. In order to make a stereochemical assignment of this intermediate, diastereomeric acetals 14a, 15a and 14b, 15b were prepared from 9 + 10/7 and 11 + 12/13, respectively. Investigations by means of NMR and a computational approach using DADAS 90 for quantifying steric hindrance, resulted in the conclusion that 14a/15a derived from 2-O-PMB-protected 9 has an (S) configuration and 14b/15b derived from 2-O-unprotected 11 has an (R) configuration. Based on the characteristic ¹H-NMR patterns inherent to the (S) isomers 4,6-O-benzylidene-protected 30- 35, derived from thiomannosides 5, 23, 24, 26, 27, were also revealed to have the (S) configuration.

Full text of DOI:10.1002/(SICI)1099-0690(199906)1999:6<1367::AID-EJOC1367>3.0.CO;2-N

FULL PAPER
On the Stereochemistry of Tethered Intermediates in
p-Methoxybenzyl-Assisted β-Mannosylation
Matthias Lergenmüller,[a,b] Tomoo Nukada,[a,d] Koji Kuramochi,[a,c] Akihito Dan,[a,e]
Tomoya Ogawa,*[a] and Yukishige Ito*[a]
Keywords: Carbohydrates / Glycoproteins / Mannose / Glycosylation / Mixed acetals / Intramulecular aglycon delivery
We have previously developed a novel method for the
stereocontrolled synthesis of β-manno-glycoside. Starting
from 2-O-PMB (p-methoxybenzyl)-protected mannosyl donor
1, conversion into the mixed acetal 3 under oxidative
conditions followed by the activation of the anomeric position
diastereomeric acetals 14a, 15a and 14b, 15b were prepared
from 9 + 10/7 and 11 + 12/13, respectively. Investigations by
means of NMR and a computational approach using DADAS
90 for quantifying steric hindrance, resulted in the conclusion
that 14a/15a derived from 2-O-PMB-protected 9 has an (S)
affords β-manno-glycoside as
a
single stereoisomer. configuration and 14b/15b derived from 2-O-unprotected 11
Although the utility of this method has been further
demonstrated in the synthesis of the core structure of Asn-
linked glycan chains, there remained uncertainty with
respect to the stereochemistry of the mixed acetal. In order
to make a stereochemical assignment of this intermediate,
has an (R) configuration. Based on the characteristic 1H-NMR
patterns inherent to the (S) isomers, 4,6-O-benzylidene-
protected 30–35, derived from thiomannosides 5, 23, 24, 26,
27, were also revealed to have the (S) configuration.
Introduction
Stereoselective formation of β-manno-glycoside, which
constitutes the core structure of asparagine (Asn)-linked
glycoprotein oligosaccharides, has been the most challeng-
ing task in synthetic carbohydrate chemistry.[1] The diffi-
culty arises from its unique stereochemical array of C-1/
C-2 positions. Namely, 1,2-cis relative stereochemistry pre-
cludes the use of neighboring group participation and the
equatorial orientation of the glycosidic linkage is also dis-
favored by virtue of an anomeric effect.[2]
Recently, we reported a novel method for the stereocon-
trolled synthesis of β-manno-glycoside[3] as an extension of
the concept called intramolecular aglycon delivery
(IAD).[4][5] In our approach, the p-methoxybenzyl (PMB)[6]
group was utilized as a scaffold for making the tethered
intermediate required in the IAD process. Namely, starting
from 2-O-PMB-protected mannosyl donor 1, treatment
with DDQ in the presence of an aglycon afforded, presum-
ably via a quinonemethide-like species 2, the mixed acetal
3.[7] Subsequent activation of the mannose anomeric posi-
tion triggers the IAD process to afford 1,2-cis(β)-glycoside
(Scheme 1).
Scheme 1. Structures of diastereomeric mixed acetals
Of particular note in this strategy are its compatibility
with a variety of protecting groups (acetyl, benzyl, cyclic
acetal, silyl, phthalimide, p-methoxyphenyl) and its applica-
bility to oligosaccharide fragment coupling. The latter fea-
ture clearly distinguishes our strategy from others and al-
lowed us to apply it to the synthesis of the core pentasac-
charide structure of the asparagine-(Asn-)linked glyco-
[a]
The Institute of Physical and Chemical Research (RIKEN)
2Ϫ1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan
Fax: (internat.) ϩ 81-48/462-4680
E-mail: yukito@postman.riken.go.jp
[b]
Recipient of STA fellowship award (1995Ϫ1997).
Current address: ROVI GmbH,
Breitwiesenstraße 1, D-36381 Schluechtern, Germany
[c]
Current address: Faculty of Pharmaceutical Sciences, Science
protein oligosaccharide in
a
convergent and fully
University of Tokyo,
stereocontrolled manner.[3b,3c] Selectively protected mono-,
di- and trimannosyl thioglycosides 4,[3b] 5,[3b] and 6[3c] pro-
ved to be quite suitable for this purpose (Scheme 2). The
yields of β-manno-glycosides obtained to date are as fol-
Shinjuku-ku, Tokyo, 162Ϫ0826 Japan
[d]
Author for correspondence regarding computational studies;
E-mail: tnuka@postman.riken.go.jp
[e]
Current address: Sumitomo Pharmaceuticals Research Center,
Konohana-ku, Osaka, 554Ϫ0022 Japan
Eur. J. Org. Chem. 1999, 1367Ϫ1376
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0606Ϫ1367 $ 17.50ϩ.50/0
1367

M. Lergenmüller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito
FULL PAPER
lows: 74% (1Ǟ6-linked disaccharide from 9)[3a], 60% (1Ǟ4- fore, the questions to be asked are: (1) Is this transform-
linked di- and trisaccharide from 4),[3b] 53% (1Ǟ4-linked ation stereoselective at all? (2) If it is stereoselective, which
trisaccharide from 5)[3b] and 41% (pentasaccharide from diastereomer is formed preferentially? (3) If the process is
6)[3c] (Table 1).
not stereoselective, do both isomers give IAD products with
equal efficiency?
Synthesis of Diastereomeric Mixed Acetals
Due to its acyclic nature, as well as the lack of a vicinal
hydrogen atom, stereochemical assignment of the mixed
acetal 3 was thought to be rather problematic. In the search
for a clue to solve this problem, we planned to prepare the
mannosyl fluoride based mixed acetal 14 by an alternative
route (Route 2). This compound was made from C-2-un-
protected mannosyl fluoride 11[17] and C-4-PMB-protected
12. The aim was to compare this product with that obtained
previously by Route 1, which was made from C-2-PMB-
protected mannosyl fluoride 9 and C-4-unprotected 10[18]
(Scheme 3). Reactions were performed under conditions
˚
identical with those reported for Route 1 (DDQ, 4 A molec-
ular sieves/CH2Cl2, room temperature).
Scheme 2. Mannosyl donors and acceptors used for synthetic stu-
dies on Asn-linked glycans
Table 1. Results of PMB-assisted β-mannosylation
Donor/aglycon[a]
Yield of β-manno-glycoside [%][b]
Ref.
[3b]
[3b]
[3b]
[3b]
[3c]
[3a]
[3a]
[3a]
4/7
4/8
5/7
5/8
6/8
9/10
9/7
9/18
60
60
53
49
41
52
40
74
[b]
[a]Donor/aglycon ratios are from ca. 1.3 to ca. 1.5. Ϫ Yields are
calculated as overall from aglycon.
The success of our strategy mainly stems from the
smooth formation of the mixed acetal 3 under essentially
neutral conditions (DDQ, room temperature). This can be
compared favorably with previously reported methods for
mixed acetal formation[4,8Ϫ16] in terms of mildness of the
reaction conditions, as well as operational simplicity. Ad-
ditionally, by virtue of having a p-methoxyphenyl substitu-
ent on an acetal carbon atom, a high degree of charge de-
localization can be expected during the course of the IAD
process.
Scheme 3. Formation of diastereomeric mixed acetals
1H-NMR analysis revealed that mixed acetals (14a,b),
prepared as described above, are diastereomeric with each
Although the utility of this method is quite clear, there other and that both processes are substantially stereoselec-
remained uncertainty with respect to the stereochemistry of tive to give each isomer with Ն 95% diastereomeric purity.
the mixed acetal. Namely, the acetalic carbon atom of 3 is There are several characteristic features that clearly dis-
stereogenic and the formation of two diastereomers is pos- tinguish 14a from 14b. Firstly, chemical shifts of the 1-H
sible at this stage. Nucleophilic attack of an alcohol from and 2-H protons of the mannose differ by as much as ca.
the re and the si face of the presumed intermediate 2 should 1.2 and ca. 0.7 ppm, respectively (Table 2). Compared to
afford 3 as an (S) and (R) diastereomer, respectively. There- the starting materials [δ1-H ϭ 5.55 (9), 5.64 (11)], chemical
Man
1368
Eur. J. Org. Chem. 1999, 1367Ϫ1376

Tethered Intermediates in I-Methoxybenzyl-Assisted β-Mannosylation
FULL PAPER
shift deviations of 14b are relatively small and opposite configuration to 20a predominating. Conversion
quite a large low-field shift was observed for 14a derived of 20a and 20b into β-mannoside 21 proceeded in 65%[3a,19]
from Route 1. In addition, the signal of one of the methyl- and 74% yield, respectively, providing additional proof that
ene protons of the benzyl protecting group in 14a was the acetal configuration is not a critical factor in the IAD
shifted downfield to as low as δ ϭ 5.22. Similar trends were process.
observed for a pair of acetals bearing a 2-phthalimide unit:
15a [δH ϭ 6.41 (1-HMan), 5.40 (benzyl CH2), 4.32 (2-HMan)]
Stereochemical Assignments of Mixed Acetals
and 15b [δH ϭ 5.21 (1-HMan), 3.75 (2-HMan)].
1
Table 2. Key H-NMR signal of mixed acetals[a]
Having the diastereomeric acetals 14a/b and 15a/b in
hand, these materials were further studied by 1H-NMR
NOE experiments, which gave a clear indication that the
spatial arrangements of substituents on the acetalic carbon
atoms are markedly different in both cases. In acetals de-
rived from Route 1 (a series), strong NOEs were observed
between the acetal proton and 1-HMan, 2-HMan, and 4-HGlc
as well as aromatic protons of the p-methoxybenzyl sub-
stituent. For the other isomers (b series), NOE could be
observed only between the 2-HMan and the acetal proton.
Based on this information, computational studies were
performed using the program DADAS (Distance Analysis
in Dihedral Angle Space) 90[20] to make stereochemical as-
signments of mixed acetals. In order to quantify steric re-
pulsion under the condition that the observed NOEs should
be fulfilled, calculations were performed for a pair of dia-
stereomeric acetals 15a/b, which were calculated as both (S)
and (R) isomers. The following equation was applied to 100
initial structures for every distinct molecule (r ϭ distance
between two non-bonded atoms, Rs ϭ a sum of van der
Waals radii, Ru and Rl ϭ upper and lower limitation of
distance, Au and Al ϭ upper and lower limitation of di-
hedral angle) (Equation 1).
Mixed acetal
1Man
2Man
Acetal CH 1Glc/GlcN
(fluoride/aglycon) δH
14a (9/10)
14b (11/12)
15a (9/7)
6.37
5.19
6.41
5.21
4.52
3.8
4.32
3.75
5.94
5.91
6.01
5.94
4.6
ND[b]
6.03
6.17
15b (11/13)
[a]
[b]
Measured at 270 MHz in C6D6. Ϫ Not determined.
Acetal 14b was subjected to IAD (AgOTf, SnCl2, 2,6-di-
tert-butyl-4-methylpyridine, 4-A molecular sieves/CH2Cl2)
˚
to afford β-manno-glycoside 16 in 47% yield, which is a
nearly identical yield to that obtained previously by Route
1 (52%[3a]). This result demonstrates that the efficiency of
IAD is rather insensitive to the stereochemistry of the
mixed acetal as far as being effected by AgOTf/SnCl2 is
concerned.
A similar set of experiments was performed with the pri-
mary alcohol 18[18] and corresponding PMB ether 19. Thus,
18 and 19 were converted into 20 by treating with 9 (Route
1
1) and 11 (Route 2), respectively. H-NMR analysis of the
acetal 20a, derived from Route 1, again revealed its stereo-
chemical homogeneity and a characteristic downfield shift
was observed for a signal assigned as 1-HMan. On the other
hand, acetal 20b, derived from Route 2, proved to be a 3:2
mixture of diastereomers, with the compound having the
2
2
Tp ϭ Tr ϩ Tn ϩ Tt ϭ [Wr(Rs Ϫ r2)2] ϩ [Wn(Ru Ϫ r2)2 ϩ
ϩ Wn(R1 Ϫ r2)2] ϩ [Wt(Au Ϫ a2)2 ϩ Wt(Al2 Ϫ a2)2] (1)
2
2
soft repulsion term ϩ NOE term ϩ dihedral angle restriction
The soft repulsion term Tr is active when r < Rs, Rs being
the sum of van der Waals radii of the two atoms. The NOE
term Tn represents the observed effects under the condition
Table 3. Results of DADAS 90 calculations
15 (R)/(S) NOE restriction (Ha Ǟ)
φ
θ
Tp(min) Tp(max)
a
a
(R)
(S)
2-Hman
Ϫ70°Ϫ1351°36
15000
5855
1-Hman, 2-Hman, 4-Hag, ar 100° Ϫ50°27
b
b
(R)
(S)
2-Hman 32° 78°
0
34800
21800
1-Hman, 2-Hman, 4-Hag, ar Ϫ15°125° 221
Scheme 4. Formation of β-1Ǟ6-linked disaccharide
Eur. J. Org. Chem. 1999, 1367Ϫ1376
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M. Lergenmüller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito
FULL PAPER
˚
that R1 < r < Ru, where the lower limit R1 is 2 A and the 15a. In contrast, in another diastereomer 15b a reversal of
˚
upper limit Ru is 3 A for 15a (4 NOEs); for 15b (1 NOE) relative magnitudes of Tp is observed. In this case, all con-
˚
the lower limit Rl was set to be 3 A. The dihedral angle ditions avoiding steric congestion were fulfilled as an (R)
restriction term Tt deals mostly with the acetal bond, isomer (Tp ϭ 0) in comparison to that of (S) isomer (i.e.
whereas protecting groups were allowed to rotate freely. An 136).
anomeric effect was considered for the newly formed acetal These calculations led us to the conclusion that mixed ace-
bonds and was set the lower limit Al and the upper limit Au tals formed by Route 1 and having 4 positive NOEs are (S)
of angles ␾ and θ between Ϫ90° and 90°. Tp (pseudo en- diasteromers, whilst those obtained by Route 2 and having
ergy) should therefore reach a minimum provided that the only 1 NOE are (R) diastereomers (Figures 1 and 2). Since
1
sterically less hindered conformation is reached under the the H-NMR patterns of (S) and (R) isomers are clearly
condition that 4 NOEs for 15a and 1 NOE for 15b are exhi- distinct, the assignment of acetal stereochemistry is here-
bited. Table 3 shows the results of the calculations. As after possible simply by routine 1H-NMR measurement
clearly seen by comparison of the Tp values, (S)-15a is the (vide infra).
sterically less hindered diastereomer in comparison to (R)-
4,6-O-Benzylidene-protected thiomannosides 4 and 5
proved to be highly useful in the stereoselective synthesis of
Asn-linked glycans[3b] and the stereochemistry of corre-
sponding mixed acetals is of particular interest. For this
reason, detailed NMR studies were performed with mixed
acetals 30Ϫ33 (Table 4), obtained from 5, 23, 24, 26, which
were in turn prepared from 22 as a key intermediate
(Scheme 5). In the cases of 30Ϫ33, mixed acetals were puri-
fied to give spectroscopically homogeneous compounds and
isolated in 65Ϫ88% yield.[21] As summarized in Table 4,
uniformly strong downfield shifts were observed for 1-HMan
and one benzyl methylene proton, and this fact allowed us
to conclude that all of these mixed acetals have an (S) con-
Figure 1. Stereochemistry of mixed acetals 14a,b and 15a,b; pro-
tons having NOEs to Ha (bold typeface) are marked by dotted circ-
les
Figure 2. Computer-generated view of pseudo-energy minimum
conformers of 15a (top) and 15b (bottom); protons Ha, 4-HGlcN, 1-
HMan, 2-HMan, and Ar-HPMB (for 15a), and Ha and 2-HMan (for
15b) are depicted as spheres
Scheme 5. Precursors of mixed acetals 30Ϫ35
Eur. J. Org. Chem. 1999, 1367Ϫ1376
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Tethered Intermediates in I-Methoxybenzyl-Assisted β-Mannosylation
FULL PAPER
1
Table 4. Key H-NMR chemical sifts of thioglycoside-derived mi-
xed acetals[a]
Scheme 6. Stereocontrolled synthesis of tetrasaccharide
cyclohexylidene-protected thioglycoside 37 (Scheme 7). Re-
action with glucosamine-derived acceptor 4 afforded disac-
charide 39, via acetal 38, in 83% yield.[23] Inspection of the
1H-NMR spectrum [δH ϭ 5.59 (1-HMan)] revealed that the
stereochemistry of the acetalic carbon atom is again (S).
[b]
Mixed acetal
δH
(Thioglycoside/ 1-HMan 2-HMan Acetal PhCH 1-HGlcN Ref.
aglycon)
CH
30 (23/28)
31 (24/28)
32 (26/29)
33 (5/8)
5.73
5.78
5.69
5.73
5.63
5.68
3.92
4.11
3.78
3.81
3.29
ND
5.47
5.49
5.64
5.65
5.35
5.46
5.03
5.09
5.09
4.83
4.80
ND
5.59
5.58
5.34
5.36
5.87
ND
Ϫ
Ϫ
Ϫ
[3b]
[3e]
[3e]
34 (27/8)
35 (27/10)
Scheme 7. Use of cyclohexylidene-protected mannosyl donor
[a]
[b]
Measured at 270 MHz in CDCl3. Ϫ
Assignments for 30 and
32 were confirmed by H-H and C-H COSY experiments and those
for other compounds were made by analogy.
Discussion
Isopropylidene mixed acetals and mixed silaketals were
figuration. The assignment was also supported by NOE introduced by Baressi and Hindsgaul[4] and Stork and co-
studies for compound 30Ϫ32. Namely, strong NOEs were workers[5] as intermediates for IAD in β--mannosylation.
observed between the acetal proton and 1- and 2-H of man- These compounds were formed by bridging two alcohols
nose and 4-H of glucosamine. In addition, in the case of under the action of dichlorodimethylsilane, or by addition
polymer-supported thioglycoside 27,[3e] the corresponding of an alcohol to a vinyl ether protected carbohydrate. An
acetals 34 and 35 consist of a single stereoisomer and their n-pentenyl glycoside derived silaketal[24] and a glucose-de-
configurations were assigned as (S).
rived mixed acetal[25] were used for similar purposes. Com-
Among the compounds listed in Table 4, mixed acetals pared to the previously reported preparations of mixed ace-
32 and 33 were transformed into tetrasaccharides 36a and tals, the DDQ-mediated process described here seems to be
36b, respectively,[3b] by the action of methyl trifluorome- operationally simpler and has applicability to a wider range
thanesulfonate (MeOTf)/DBMP (Scheme 6). Compound of oligosaccharide structures.[26]
36, having a 4,5-dichlorophthaloyl group as an amine-pro-
tecting group,[22] was designed to be an advanced inter- 3 is concerned, it is now clear that the mixed acetal forma-
mediate for the synthesis of complex oligosaccharides. tion from the 2-O-PMB mannosyl donor proceeds with a
As far as the issue of the stereochemistry of mixed acetals
More recently it was discovered that the efficiency of β- uniformly high degree of diastereofacial selectivity, with at-
mannoside formation can be further improved by using 4,6- tack at the re face of the cationic intermediate 2. On the
Eur. J. Org. Chem. 1999, 1367Ϫ1376
1371

M. Lergenmüller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito
FULL PAPER
1
(c ϭ 1.9, CHCl3). Ϫ H NMR (CDCl3): δ ϭ 3.72 (s, 3 H, MeO),
other hand, 2-O-unprotected fluoride 11 gave the (R) iso-
mer 14/15b when treated with 4-O-PMB-protected Glc/
GlcN derivatives (12/13). Although the origins of these sel-
ectivities are obscure for the moment, these results strongly
suggest that the stereochemical outcomes are the result of
kinetic control. Additionally, it was demonstrated that IAD
processes proceed with nearly equal efficiency for both dia-
stereomers, as far as relatively reactive aglycon-derived acet-
als (14, 20) are concerned. That the IAD process is effective
for both stereoisomers, which are available by separate
routes (i.e. Route 1 and Route 2 in Scheme 3), may well
further broaden the flexibility of PMB-assisted β-manno-
sylation.
3.80 (s, 3 H, MeO), 5.63 (d, 1 H, 1-H), 6.6Ϫ7.4 (m, 18 H, Ar),
7.5Ϫ7.9 (br., 4 H, Phth); J1,2 ϭ 8.3 Hz. Ϫ 13C NMR (CDCl3) δ ϭ
55.26, 55.53, 55.80, 68.59, 73.48, 74.70, 74.84, 75.24, 77.22, 79.16,
79.18, 97.56 (C-1). Ϫ C43H41N1O9 (715.8): calcd. C 72.15, H 5.77,
N 1.96; found C 71.65, H 5.76, N 1.91.
Benzyl 2,3,4-Tri-O-benzyl-6-O-p-methoxybenzyl-β-D-glucopyrano-
side (19): Compound 18 (545 mg, 1.01 mmol) was treated with
NaH (60%, 60 mg, 1.5 mmol) and p-methoxybenzyl chloride (180
µL, 1.3 mmol) in DMF (3 mL) in the same manner as described
for 12. Purification by silica gel column chromatography (hexane/
AcOEt, 5:1) afforded 629 mg (94%) of 19, m.p. 57Ϫ58°C. Ϫ [α]D ϭ
6.3 (c ϭ 0.8, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 3.77 (s,
3 H, MeO), 6.85 (d, 2 H, PMB), 7.1Ϫ7.45 (m, 22 H, Ar); JPMB
ϭ
8.6 Hz. Ϫ 13C NMR (67.8 MHz, CDCl3): δ ϭ 55.2 (MeO), 68.5,
71.1, 73.1, 74.9, 74.9, 75.7, 76.2, 77.2, 77.9, 82.3, 84.7, 102.6 (C-1).
Ϫ C42H44O7 (660.8): calcd. C 76.34, H 6.71; found C 76.16, H 6.67.
Experimental Section
General Methods: Melting points were determined with a Yanagim-
oto micro-melting point apparatus and are not corrected. Ϫ Op-
tical rotations were measured with a JASCO DIP 370 Polarimeter
at ambient temperature (20±3°C). Ϫ NMR spectra were recorded
with a JEOL EX-270 spectrometer using Me4Si as internal stand-
ard for CDCl3 and C6D6 solutions. Ϫ TLC on silica gel 60 F254
(Merck, Darmstadt) was used to monitor the reactions and to
ascertain the purity of the products. Silica gel column chromatogra-
phy was performed with Merck silica gel 60 (63Ϫ200 µm) or Cica
silica gel 60 N (spherical, 40Ϫ100 or 100Ϫ210 µm). Ϫ Silver tri-
fluoromethanesulfonate (AgOTf) was recrystallized from hot tolu-
ene/n-hexane. All other reagents were used as received. Dichloro-
methane was distilled from CaH2. All other solvents were dried
Benzyl O-(3,4,6-Tri-O-benzyl-β-D-mannopyranosyl)-(1Ǟ4)-2,3,6-tri-
O-benzyl-β-
D
-glucopyranoside (16). ؊ From 11 and 12: To a stirred
˚
mixture of DDQ (26 mg, 0.11 mmol) and 4-A molecular sieves
(0.26 g) in CH2Cl2 (2 mL) were added compounds 11 (33.2 mg,
0.073 mmol) and 12 (60.3 mg, 0.091 mmol) as a solution in CH2Cl2
(3 mL) at 0°C. The mixture was stirred at 0°C for 10 min and at
room temperature for 60 min. The resulting mixture was quenched
with a solution of ascorbic acid (0.7%)/citric acid (1.3%)/NaOH
(0.9%) in water (3 mL), diluted with AcOEt, and filtered through
Celite. The filtrate was successively washed with water, aq.
NaHCO3 and brine, and then dried with Na2SO4. The solvent was
evaporated, coevaporated with toluene in vacuo and the material
exposed to high vacuum (ca. 1 h) to afford crude 14b. To a flask
˚
and stored over freshly activated molecular sieves (3 or 4 A). Mo-
lecular sieves were activated by heating to 180°C in vacuo for 24 h
˚
containing 4-A molecular sieves (0.3 g) and 2,6-di-tert-butyl-4-
methylpyridine (DBMP, 25 mg, 0.12 mmol) was added AgOTf
(30 mg, 0.12 mmol) and SnCl2 (22 mg, 0.12 mmol) followed by
CH2Cl2 (1 mL) and the mixture was cooled to ice/water tempera-
ture. 14b was then added as a solution in CH2Cl2 (4 mL) and the
mixture was stirred at ambient temperature for 18 h. The reaction
mixture was quenched with aq. NaHCO3/ice, diluted with AcOEt,
and filtered through Celite. The filtrate was successively washed
with water and brine, dried with MgSO4, and the solvent evapo-
rated in vacuo. The residual syrup was purified by silica gel column
chromatography (hexane/AcOEt, 5:1 Ǟ 2:3) to afford 33.7 mg
(47%) of 16, m.p. 94Ϫ96°C. Ϫ [α]D ϭ ϩ3.0 (c ϭ 0.8, CHCl3). Ϫ
1H NMR (270 MHz, CDCl3): δ ϭ 2.65 (br., 1 H, OH), 3.50 (dd, 1
H, 2-H), 3.98 (br. s, 1 H, 2Ј-H), 4.51 (d, 1 H, 1-H), 4.64 (s, 1 H, 1Ј-
H), 7.1Ϫ7.5 (m, 35 H, Ar); J1,2 ϭ 7.9, J2,3 ϭ 8.9 Hz. Ϫ 13C NMR
(67.8 MHz, CDCl3): δ ϭ 67.7, 69.0, 71.0, 71.1, 73.3, 73.4, 73.9,
prior to use. All reactions were performed under N2 or Ar.
Benzyl 2,3,6-Tri-O-benzyl-4-O-p-methoxybenzyl-β-D-glucopyrano-
side (12): To an ice/water-cold solution of compound 10 (1.47 g,
2.72 mmol) in DMF (15 mL) was added NaH (60%, 160 mg,
40 mmol) under a positive pressure of N2 and the mixture was
stirred for 10 min. p-Methoxybenzyl chloride (0.48 mL, 3.5 mmol)
was added dropwise and the mixture was gradually warmed to am-
bient temperature. After being stirred for 18 h, the reaction was
quenched with MeOH (ca. 0.5 mL) at 0°C, diluted with diethyl
ether, washed successively with water and brine, dried with MgSO4
and the solvent evaporated in vacuo. The residue was crystallized
from cold hexane to afford 1.66 g (93%) of 12, m.p. 98Ϫ99°C. Ϫ
1
[α]D ϭ Ϫ16.7 (c ϭ 0.72, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 3.78 (s, 3 H, OMe), 4.51 (d, 1 H, 1-H), 6.80 (d, 2 H, PMB),
74.4, 74.9, 75.1, 75.3, 75.5, 75.7, 81.5, 82.0, 83.1, 99.8 (1JCH
ϭ
7.07 (d, 2 H, PMB), 7.2Ϫ7.45 (m, 20 H, Ar), J1,2 ϭ 7.6, JPMB
ϭ
159 Hz), 102.6 (1JCH ϭ 159 Hz). Ϫ C61H64O11 (973.2): calcd. C
75.29, H 6.62; found C 75.34, H 6.62. Ϫ In a separate experiment,
14b was prepared from 37.1 mg (0.08 mmol) of 11 and 64.9 mg
(0.098 mmol) of 12 and purified by size exclusion chromatography
on Bio-Beads S-X4 (toluene); yield 85.0 mg (93%). Ϫ From 9 and
10: Compounds 9 (87.0 mg, 0.15 mmol) and 10 (56.3 mg) were
treated with DDQ (36 mg, 0.16 mmol) in CH2Cl2 (3 mL), as de-
scribed above, to afford crude 14a. This material was treated with
AgOTf (53 mg, 0.21 mmol)/SnCl2(39 mg, 0.21 mmol)/DBMP
(50 mg, 0.24 mmol) in 8 mL of CH2Cl2 (room temp., 5 h) and sub-
sequent purification by silica gel column chromatography afforded
52.5 mg (52%) of 16.
8.6 Hz. Ϫ 13C NMR (67.8 MHz, CDCl3): δ ϭ 55.3(MeO), 68.9,
71.1, 73.5, 74.6, 74.9, 74.9, 75.7, 77.6, 82.3, 84.8, 102.6 (C-1). Ϫ
C42H44O7 (660.8): calcd. C 76.34, H 6.71; found C 76.18, H 6.70.
p-Methoxyphenyl 3,6-Di-O-benzyl-2-deoxy-4-O-p-methyloxy-
benzyl-2-phthalimido-β-D-glucopyranoside (13): To an ice/water-cold
solution of compound 7 (176 mg, 0.29 mmol) in DMF (3 mL) was
added NaH (60%, 16 mg, 0.44 mmol) under a positive flush of N2
and the mixture was stirred for 10 min. p-Methoxybenzyl chloride
(60 µL, 0.44 mmol) was added dropwise and the mixture was
gradually warmed to ambient temperature over 1 h. After being
stirred for additional 2 h, the reaction was quenched with MeOH
(ca. 0.1 mL) at 0°C, diluted with diethyl ether, successively washed
with water and brine, dried with MgSO4, and concentrated in va-
cuo. The residue was purified by silica gel column chromatography
(hexane/AcOEt, 2:1) to afford 124 mg (59%) of 13, [α]D ϭ ϩ62.1
Benzyl O-(3,4,6-Tri-O-benzyl-β-D-mannopyranosyl)-(1Ǟ6)-2,3,4-tri-
O-benzyl-β- -glucopyranoside (21). ؊ From 11 and 19: Compounds
D
11 (32.4 mg, 0.072 mmol) and 19 (57.8 mg, 0.087 mmol) were trans-
1372
Eur. J. Org. Chem. 1999, 1367Ϫ1376

Tethered Intermediates in I-Methoxybenzyl-Assisted β-Mannosylation
FULL PAPER
formed into 20b in the same manner as described for 14b in the column chromatography with toluene/AcOEt (10:1) afforded
preparation of 16. In short, treatment of 11 and 19 with DDQ 295 mg (89%) of 23 as a colorless foam, [α]D ϭ ϩ59.6 (c ϭ 1.0,
1
(25 mg, 0.087 mmol) in CH2Cl2 (5 mL) at room temperature for CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 2.01, 2.13 (2 s, each
1
70 min afforded crude 20b (93 mg). Ϫ H NMR (270 MHz, C6D6) 3 H, CH3S, CH3CO), 3.81 (s, 3 H, CH3OC6H4CH2), 3.89 (m, 1 H,
δ ϭ 4.3 [m, 2Ј-H, (R) isomer], 4.6 [m, 2Ј-H, (S) isomer], 5.88 [3/5
H, s, acetal CH, (R) isomer], 6.03 [dd, 3/5 H, J ϭ 50 and < 1 Hz,
6-Ha), 4.05 (dd, 1 H, 2-H), 4.18 (dd, 1 H, 4-H), 4.21Ϫ4.31 (m, 2
H, 5-H, 6-Hb), 4.48, 4.63 (2 d, 1 H each, CH3OC6H4CH2), 5.20 (d,
1Ј-H, (R) isomer], 6.04 [2/5 H, s, acetal CH, (S) isomer], 6.25 [d, 2/ 1 H, 1-H), 5.21 (dd, 1 H, 3-H), 5.56 (s, 1 H, C6H5CH), 6.89, 7.28
5 H, J ϭ 50 Hz, 1Ј-H, (S)isomer]. Ϫ Subsequent transformation (2 d, 2 H each, CH3OC6H4CH2), 7.32Ϫ7.48 (m, 5 H, C6H5CH);
into 21 was performed using AgOTf (30 mg, 0.12 mmol), SnCl2 J1,2 ϭ 1.3, J2,3 ϭ 3.6, J3,4 ϭ 9.7, J4,5 ϭ 9.6, JCH2 ϭ 11.9 Hz. Ϫ
˚
(22 mg, 0.12 mmol), DBMP (25 mg, 0.12 mmol) and 4-A molecular C24H28O7S (460.5): calcd. C 62.59, H 6.13; found C 62.73, H 6.13.
sieves (0.3 g) in 5 mL of CH2Cl2 (0°C, 10 min, room temp.,
75 min). Purification by silica gel column chromatography afforded
Methyl
methylbenzoyl-␣-
4,6-O-Benzylidene-2-O-p-methoxybenzyl-1-thio-3-O-p-
-mannopyranoside (24): To a solution of 22
D
52.0 mg (75%) of compound 21, m.p. 115Ϫ117°C. Ϫ [α]D ϭ Ϫ3.0
(548 mg, 1.31 mmol) in anhydrous CH2Cl2 (10 mL) and pyridine
(10 mL) were added at 0°C p-toluoyl chloride (208 µL, 1.57 mmol)
and 4-dimethylaminopyridine (DMAP, 8 mg, 0.07 mmol) and the
solution stirred for 20 h at room temperature. The reaction was
quenched with MeOH (1 mL), stirred for 1 h and concentrated to
dryness. The residue (940 mg) was purified by elution from silica
gel with toluene/AcOEt, 1:0 Ǟ 10:1 to afford 475 mg (68%) of 24
as a colorless foam, [α]D ϭ ϩ9.2 (c ϭ 1.0, CHCl3). Ϫ 1H NMR
(270 MHz, CDCl3): δ ϭ 2.15 (s, 3 H, CH3S), 2.41 (s, 3 H,
CH3OC6H4CO), 3.73 (s, 3 H, CH3OC6H4CH2), 3.94 (m, 1 H, 6-
Ha), 4.18 (dd, 1 H, 2-H), 4.24Ϫ4.40 (m, 3 H, 4-H, 5-H, 6-Hb), 4.48
and 4.60 (2 d, 1 H each, CH3OC6H4CH2), 5.24 (d, 1 H, 1-H), 5.46
1
(c ϭ 1.1, CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 3.88 (t, 1
H, J ϭ 9.2 Hz), 4.03 (d, 1 H, 2Ј-H), 4.22 (1 H, d, J ϭ 9.9 Hz), 4.31
(s, 1 H, 1Ј-H), 4.50 (d, 1 H, 1-H), 7.1Ϫ7.5 (m, 35 H, Ar); J1,2
ϭ
7.6, J
ϭ 2.6 Hz. Ϫ 13C NMR (67.8 MHz, CDCl3): δ ϭ 68.2,
2Ј,3Ј
68.7, 69.1, 71.2, 71.4, 73.5, 74.1, 74.4, 74.79, 74.83, 75.1, 75.2, 75.7,
78.0, 81.3, 82.2, 84.7, 100.3 (1JCH ϭ 159 Hz), 102.4 (1JCH
ϭ
160 Hz). Ϫ C61H64O11 (973.2): calcd. C 75.29, H 6.62; found C
75.26, H 6.58. Ϫ From 9 and 18: Compounds 9 (122.3 mg,
0.21 mmol) and 18 (80.2 mg, 0.15 mmol) were treated with DDQ
(50 mg, 0.23 mmol) in 4 mL of CH2Cl2 to afford 20a. This material
was converted into 21 with AgOTf (74 mg, 0.29 mmol)/SnCl2
(55 mg, 0.29 mmol)/DBMP (60 mg, 0.29 mmol) in 8 mL of CH2Cl2.
Yield 94.0 mg (65%).
(dd,
CH3OC6H4CH2), 7.16Ϫ7.46 (m, 9 H, C6H5CH, CH3OC6H4CH2,
CH3OC6H4CO), 7.93 (d, 2 H, CH3OC6H4CO); J1,2 ϭ 1.2, J2,3
1 H, 3-H), 5.62 (s, 1 H, C6H5CH), 6.70 (m, 2 H,
Mixed Acetals 14a/b and 15a/b for NOE Studies: These compounds
were prepared from anomerically pure α-fluorides 9 and 11. A typi-
cal experimental procedure is given for the preparation of 14a: To
ϭ
3.5, J3,4 ϭ 9.7, J6a,b ϭ 9.9, JCH2 ϭ 11.7 Hz. Ϫ C30H32O7S (536.6):
calcd. C 67.15, H 6.01, S 5.97; found C 67.00, H 6.02, S 5.96.
˚
a flask containing DDQ (16 mg, 0.070 mmol) and 4-A molecular
Methyl
O-(2-O-Acetyl-3,4,6-tri-O-benzyl-␣-D-mannopyranosyl)-
sieves (0.1 g) in CH2Cl2 was added a mixture of compounds 9
(30.2 mg, 0.0527 mmol) and 12 (34.1 mg, 0.063 mmol) as a solution
in CH2Cl2 (1.5 mL) under ice/water cooling. The mixture was
stirred at 0°C for 10 min and at room temperature for 130 min,
and then quenched with a mixture of ascorbic acid (0.7%)/citric
acid (1.3%)/NaOH (0.9%) in water (3 mL). The lemon-yellow sus-
pension was diluted with AcOEt, filtered through Celite and the
filtrate was successively washed with aq. NaHCO3, water, and
brine, dried with Na2SO4, and the solvent evaporated in vacuo. The
residue was subjected to size exclusion chromatography on a col-
umn of Bio-Beads S-X3 (Bio-Rad) to afford 14a (44.5 mg, 76%).
(1Ǟ3)-4,6-O-benzylidene-2-O-p-methoxybenzyl-1-thio-␣-
D-manno-
pyranoside (5): Methyl thiomannopyranoside 22 (1.15 g,
2.75 mmol) and 2,6-di-tert-butyl-4-methylpyridine (DBMP, 1.02 g,
4.95 mmol) were dissolved in anhydrous CH2Cl2 (25 mL) and
stirred for 30 min under Ar and exclusion of light with AgOTf
˚
(1.27 g, 4.95 mmol) over freshly activated 4-A molecular sieves
(5.0 g). After cooling to Ϫ15°C, 2-O-acetyl-3,4,6-tri-O-benzyl-α--
mannopyranosyl chloride (25,[27] 1.97 g, 3.85 mmol) was added as
a solution in CH2Cl2 (15 mL). The mixture was gradually warmed
up to room temperature, stirred for 90 min and diluted with
CH2Cl2 (100 mL). The suspension was filtered through Celite and
the filtrate was washed with satd. NaHCO3 solution (30 mL), 10%
Na2S2O3 solution (30 mL), and dried (Na2SO4). Removal of the
solvent in vacuo gave a colorless foam (3.79 g), which was purified
by elution from silica gel with toluene/AcOEt (10:1) to afford 2.10 g
(86%) of 5 as a colorless foam, [α]D ϭ ϩ57.0 (c ϭ 1.1, CHCl3). Ϫ
1H NMR (270 MHz, CDCl3): δ ϭ 2.07, 2.09 (2 s, 3 H each, CH3S
and CH3CO), 3.63 (s, 3 H, CH3OC6H4CH2), 3.64Ϫ3.79 and
4.10Ϫ4.26 (2 m, 3 H and 4 H, 3-H, 5-H, 6-H2, 5Ј-H, 6Ј-H2), 3.84
(dd, 1 H, 4Ј-H), 3.86 (dd, 1 H, 2-H), 3.88 (dd, 1 H, 4-H), 3.97 (dd,
1 H, 3Ј-H), 4.47 (d, 3 H, C6H5CH2 and CH3OC6H4CH2), 4.60 (s,
2 H, C6H5CH2), 4.66, 4.70, 4.87 (3 d, 1 H each, C6H5CH2 and
CH3OC6H4CH2), 5.15 (br. s, 1 H, 1-H), 5.30 (d, 1 H, 1Ј-H), 5.60
1
Ϫ H-NMR data (270 MHz, C6D6): 14a: δ ϭ 3.25 (s, 3 H, OMe),
3.9 (t, 1 H, 4-H), 4.52 (d, 1 H, 2Ј-H), 5.96 (s, 1 H, acetal CH), 6.38
1
(d, 1 H, 1Ј-H); J3,4 ϭ J4,5 ϭ 9, J2Ј3Ј ϭ 2, JCH2 ϭ 12.5 Hz, J1Ј,F
ϭ
51.1 Hz. Ϫ 14b: δ ϭ 3.24 (s, 3 H, MeO), 3.75 (dd, 1 H, 2Ј-H), 5.19
(dd, 1 H, 1Ј-H), 5.22 (s, 1 H, benzyl CH2), 5.91 (1 H, s, acetal CH);
J1Ј2Ј < 1, J2Ј,3Ј ϭ 2, J1Ј,F ϭ 50 Hz. Ϫ 15a: δ ϭ 3.19 and 3.32 (2 s,
each 3 H, OMe), 4.32 (d, 1 H, 2Ј-H), 4.5 (4-H), 5.05 (dd, 1 H, 2-
H), 5.40 and 4.90 (ABq, each 1 H, benzylic CH2), 6.00 (d, 1 H, 1-
H), 6.02 (s, 1 H, acetal CH), 6.40 (1 H, d, 1Ј-H); J1,2 ϭ 8.6, J2,3
ϭ
10.6, J1,F ϭ 50.9, J2,3ЈЈ ϭ 2, JCH2 ϭ 12.5 Hz. Ϫ 15b: δ ϭ 3.17 and
3.26 (2 s, each 3 H, OMe), 3.78 (d, 1 H, 2Ј-H), 4.4 (4-H), 5.21 (d,
1 H, 1Ј-H), 5.94 (s, 1 H, acetal CH), 6.17 (d, 1 H, 1-H); J1,2 ϭ 8.6,
J1Ј,F ϭ 50.8, J2Ј,3Ј ϭ 2 Hz.
(dd,
CH3OC6H4CH2), 7.03Ϫ7.47 (m, 22 H, C6H5CH2, C6H5CH, and
CH3OC6H4CH2); J1,2 < 0.5, J3,4 ϭ J4,5 ϭ 9.7, J1Ј,2Ј ϭ 1.8, J2Ј,3Ј
1 H, 2Ј-H), 5.61 (s, 1 H, C6H5CH), 6.77 (m, 2 H,
Methyl 3-O-Acetyl-4,6-O-benzylidene-2-O-p-methoxybenzyl-1-thio-
␣-D-mannopyranoside (23): Acetic anhydride (2.5 mL) was added at
0°C to a solution of 22 (300 mg, 0.72 mmol) in CH2Cl2 (5 mL) and
pyridine (2.5 mL) and stirred for 3 d at room temperature. The
solution was poured into ice/water (50 mL), stirred for 30 min and
diluted with CH2Cl2 (100 mL). The organic phase was washed with
ϭ
3.3, J3Ј,4Ј ϭ 8.9 Hz. Ϫ C51H56O12S (893.1): calcd. C 68.59, H 6.32;
found C 68.63, H 6.36.
Methyl O-(3,4,6-Tri-O-benzyl-2-O-levulinoyl-1-thio-␣-D-mannopy-
2  HCl (20 mL), satd. NaHCO3 solution (20 mL), water (20 mL) ranosyl)-(1Ǟ3)-4,6-O-benzylidene-2-O-p-methoxybenzyl-1-thio-␣-
and dried (Na2SO4). Removal of volatile mateials in vacuo gave
323 mg of crude product as a clear syrup. Purification by silica gel
D-mannopyranoside (26): A solution of dimannoside 5 (1.03 g,
1.16 mmol) in anhydrous CH2Cl2/methanol (1:1, 50 mL) was
1373
Eur. J. Org. Chem. 1999, 1367Ϫ1376

M. Lergenmüller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito
FULL PAPER
treated at 0°C with 28% NaOMe solution in methanol (20 µL,
0.1 mmol), gradually warmed to room temperature and stirred for
30 h. Concentration to dryness and coevaporation with CH2Cl2
(10 mL) left a brownish foam, which was levulinoylated by dissolv-
4Ј, C-5Ј), 82.5 (C-1Ј), 97.8 (C-1), 101.4 (CH3OC6H4CH, C6H5CH),
113.9, 114.4, 118.8 (CH3OC6H4, CH3OC6H4CH), 125.4Ϫ138.6
(C6H5CH, C6H5CH2), 150.7, 155.5, 160.4 (DCPhth, CH3OC6H4),
169.8 (CH3CO). Ϫ C59H57Cl2NO15S (1123.1): calcd. C 63.10, H
ing the intermediate in pyridine (10 mL), adding a 1  levulinic 5.12, N 1.25; found C 63.21, H 5.11, N 1.27.
anhydride solution in CH2Cl2 (5.5 mL, 5.5 mmol) and stirring the
(S)-p-Methoxybenzaldehyde [p-Methoxyphenyl 3,6-di-O-benzyl-2,4-
dideoxy-2-(4,5-dichlorophthalimido)-β- -glucopyranosid-4-yl] (Methyl
4,6-O-benzylidene-2-deoxy-1-thio-3-O-toluyl-␣- -mannopyranosid-
mixture for 4 d at room temperature. The solution was poured into
ice/water (100 mL), stirred for 30 min and extracted with CH2Cl2
(250 mL). The organic layer was washed with 2  HCl (2 ϫ 50 mL),
satd. NaHCO3 solution (50 mL), dried (Na2SO4), and concentrated
to give a brown syrup (1.4 g). Elution from silica gel with toluene/
D
D
2-yl) Acetal (31): This compound was prepared by treatment of
compounds 28 (150 mg, 0.23 mmol) and 24 (170 mg, 0.32 mmol)
with DDQ (123 mg, 0.54 mmol) in anhydrous CH2Cl2 (2.3 mL) in
an analogous manner as described for 30. Purification by size ex-
clusion chromatography (Bio-Beads S-X2) with toluene afforded
184 mg (66%) of 31 as a colorless foam, [α]D ϭ ϩ17.4 (c ϭ 1.1,
CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 2.11 (s, 3 H, CH3S),
2.38 (s, 3 H, CH3C6H4CO), ca. 3.60 (m, 1 H, 5-H), 3.62 (s, 3 H,
CH3OC6H4), 3.70 (dd, 1 H, 6-Ha), 3.72 (s, 3 H, CH3OC6H4), 3.81
(dd, 1 H, 6-Hb), 3.98 (dd, 1 H, 6Ј-Ha), 4.11 (d, 1 H, 2Ј-H),
4.31Ϫ4.39 (m, 4 H, 3-H, 4-H, 5Ј-H, 6Ј-Hb), 4.42 (dd, 1 H, 4Ј-H),
4.46 (dd, 1 H, 2-H), 4.55, 4.59, 4.81 (3 d, 1 H each, C6H5CH2),
5.09 (s, 1 H, C6H5CH), 5.36 (d, 1 H, C6H5CH2), 5.40 (dd, 1 H, 3Ј-
H), 5.49 (s, 1 H, CH3OC6H4CH), 5.58 (d, 1 H, 1-H), 5.78 (br. s, 1
H, 1Ј-H), 6.40 (d, 1 H, CH3C6H4CH), 6.72, 6.83 (2 m, 2 H each,
AcOEt (5:1) afforded 905 mg (82%) 26 as a colorless foam, [α]D
ϭ
ϩ50.4 (c ϭ 1.0, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 2.07
(s, 3 H, CH3S), 2.10 (s, 3 H, CH3Lev), 2.64 (m, 4 H, CH2Lev), 3.63
(s, 3 H, CH3OC6H4CH2), 3.66Ϫ3.91 and 4.10Ϫ4.27 (2 m, 6 H and
4 H, 2-H, 3-H, 4-H, 5-H, 6-H2, 4Ј-H, 5Ј-H, 6Ј-H2), 3.96 (3Ј-H),
4.45, 4.48 (3 d, 1 H each, C6H5CH2 and CH3OC6H4CH2), 4.59 (s,
2 H, C6H5CH2), 4.64, 4.67, 4.87 (3 d, 1 H each, C6H5CH2 and
CH3OC6H4CH2), 5.15 (d, 1 H, 1-H), 5.27 (d, 1 H, 1Ј-H), 5.56 (dd,
1 H, 2Ј-H), 5.61 (s, 1 H, C6H5CH), 6.77 (m, 2 H, CH3OC6H4CH2),
7.16Ϫ7.47 (m, 22 H, C6H5CH2, C6H5CH, and CH3OC6H4CH2);
J1,2 ϭ 1.0, J1Ј,2Ј ϭ 1.8, J2Ј,3Ј ϭ 3.2, J3Ј,4Ј ϭ 8.4 Hz. Ϫ 13C NMR
(67.80 MHz, CDCl3): δ ϭ 13.7 (CH3S), 28.1 (CH2Lev), 29.7
(CH3Lev), 38.0 (CH2Lev), 55.0 (CH3OC6H4CH2), 68.3 (C-2Ј), 68.5,
68.8 (C-6, C-6Ј), 71.3, 72.5, 73.3, 75.1 (C6H5CH2, CH3OC6H4CH2),
77.7 (C-3Ј), 84.7 (C-1), 98.7 (C-1Ј), 101.2 (C6H5CH), 113.9
CH3OC6H4), 6.89Ϫ7.02 (2 d,
2
H
each, CH3C6H4CO,
CH3OC6H4CH), 7.11Ϫ7.39 (m, 15 H, 2 C6H5CH2, C6H5CH), 7.74
(d, 2 H, CH3C6H4CO), 7.75, 7.90 (2 br. s, 1 H each, DCPhth);
(CH3OC6H4CH2),
126.0Ϫ138.4
(C6H5CH2,C6H5CH,
J1,2 ϭ 8.3, J2,3 ϭ 9.4, J1Ј,2Ј < 0.5, J2Ј,3Ј ϭ 3.1, J3Ј,4Ј ϭ 9.9, J4Ј,5Ј
ϭ
CH3OC6H4CH2), 159.3 (CH3OC6H4CH2), 171.6 (CH2COO), 206.0
(CH3CO), 64.4, 72.0, 73.3, 74.3, 78.3, 79.0 (C-2, C-3, C-4, C-5, C-
4Ј, C-5Ј). Ϫ C54H60O13S (949.1): calcd. C 68.34, H 6.37; found C
67.93, H 6.28.
10.2, J6Јa,b ϭ 11.6, JCH2 ϭ 12.2 Hz. Ϫ C65H61Cl2NO15S (1199.2):
calcd. C 65.10, H 5.13, N 1.17; found C 65.15, H 5.08, N 1.46.
(S)-p-Methoxybenzaldehyde {p-Methoxyphenyl O-[3,6-di-O-benzyl-
2,4-dideoxy-2-(4,5-dichlorophthalimido)-β-
(1Ǟ4)-3,6-di-O-benzyl-2-deoxy-2-(4,5-dichlorophthalimido)-β-
glucopyranosid-4-yl} [Methyl O-(3,4,6-tri-O-benzyl-2-O-levulinoyl-
1-thio-α- -mannopyranosyl)-(1Ǟ3)-4,6-O-benzylidene-2-deoxy-1-
pyranosid-2-yl) Acetal (30): A solution of compounds 28 (100 mg, thio-␣- -mannopyranosid-2-yl] Acetal (32): Prepared from com-
D-glucopyranos-4-yl]-
(S)-p-Methoxybenzaldehyde [p-Methoxyphenyl 3,6-di-O-benzyl-
D-
2,4-dideoxy-2-(4,5-dichlorophthalimido)-β-
(Methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-1-thio-␣-
D
-glucopyranosid-4-yl]
-manno-
D
D
D
0.15 mmol) and 23 (83 mg, 0.18 mmol) in anhydrous CH2Cl2
(1.5 mL) was stirred in the presence of freshly activated 4-A molec-
pounds 29 (560 mg, 0.46 mmol) and 26 (620 mg, 0.65 mmol) by
treatment with DDQ (253 mg, 1.12 mmol) in CH2Cl2 (5 mL) in an
˚
ular sieves for 30 min under exclusion of light at 0°C. DDQ (68 mg, analogous manner to that described for 30. Purification by size
0.30 mmol) was then added and the deep green mixture was al-
lowed to warm up to room temperature. After stirring for 2 h, the
reaction was quenched by addition of a solution of ascorbic acid
exclusion chromatography (Bio-Beads S-X1) with toluene afforded
790 mg (80%) of 32 as a yellowish foam, [α]D ϭ ϩ26.4 (c ϭ 1.6,
CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 1.84 (s, 3 H, CH3S),
(0.7%)/citric acid (1.3%)/NaOH (0.9%) in water (7 mL), stirred un- 2.07 (s, 3 H, CH3Lev), 2.59 (s, 4 H, CH2Lev), 3.26 (s, 3 H,
til the color turned to bright yellow (10 min) and diluted with
CH2Cl2 (50 mL). The organic phase was washed with satd.
NaHCO3 solution (10 mL), dried (Na2SO4), and the volatiles were
removed in vacuo to give 150 mg (89%) of crude product. Purifi-
cation by size exclusion chromatography (Bio-Beads S-X2) with
CH3OC6H4CH), 3.32 and 3.41Ϫ3.63 (ddd and m, 1 H and 6 H,
ring protons), 3.67 (s, 3 H, CH3OC6H4), 3.69Ϫ3.76 (m, 3 H, ring
protons, 3ЈЈЈ-H), 3.78 (br. dd, 1 H, 2ЈЈ-H), 3.95, 4.07 (dd and d, 1
H each, ring protons) 4.12Ϫ4.49 (m, 16 H, ring protons, 2-H, 2Ј-
H), 4.54 (d, 2 H, C6H5CH2), 4.63 (br. s, 2 H, C6H5CH2), 4.81, 4.89
(2 d, 1 H each, C6H5CH2), 5.09 (s, 1 H, C6H5CH), 5.21 (d, 1 H,
toluene afforded 109 mg (65%) of 30 as a colorless foam, [α]D
ϭ
ϩ44.2 (c ϭ 0.65, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 1ЈЈЈ-H), 5.34 (d, 1 H, 1Ј-H), 5.36 (d, 1 H, C6H5CH2), 5.43 (d, 1 H,
1.83 (s, 3 H, CH3CO), 2.09 (s, 3 H, CH3S), 3.64 (m, 1 H, 5-H), 1-H), 5.50 (br. dd, 1 H, 2ЈЈЈ-H), 5.64 (s, 1 H, CH3OC6H4CH), 5.69
3.72 (s, 3 H, CH3OC6H4), 3.74 (dd, 1 H, 6-Ha), 3.80 (s, 3 H, (s, 1 H, 1ЈЈ-H), 6.61Ϫ6.79 (m, 6 H, CH3OC6H4, CH3OC6H4CH),
CH3OC6H4), 3.82 (dd, 1 H, 6-Hb), 3.92 (m, 2 H, 2Ј-H, 6Ј-Ha), 6.85Ϫ7.42 (m, 42 H, C6H5CH, C6H5CH2), 7.68, 7.81 (2 s, 2 H each,
4.24Ϫ4.36 (m, 5 H, 3-H, 4-H, 4Ј-H, 5Ј-H, 6Ј-Hb), 4.47 (dd, 1 H, 2-
H), 4.54, 4.60, 4.83 (3 d, 1 H each, C6H5CH2), 5.03 (s, 1 H, J1ЈЈЈ,2ЈЈЈ
C6H5CH), 5.18 (dd, 1 H, 3Ј-H), 5.31 (d, 1 H, C6H5CH2), 5.47 (s, (67.80 MHz, CDCl3): δ ϭ 13.4 (CH3S), 28.1 (CH2Lev), 29.6
1 H, CH3OC6H4CH), 5.59 (d, 1 H, 1-H), 5.73 (br. s, 1 H, 1Ј-H), (CH3Lev), 38.0 (CH2Lev), 54.8 (CH3OC6H4CH), 55.5 (CH3OC6H4),
6.70Ϫ6.96, 7.08Ϫ7.16 (2 m, 9 H and 4 H, CH3OC6H4, C6H5CH), 56.0 (C-2), 57.4 (C-2Ј), 67.0 (C-2ЈЈЈ), 64.7, 69.0Ϫ78.4 (other ring
DCPhth); J1,2 ϭ 8.3, J1Ј,2Ј ϭ 7.6, J1ЈЈ,2ЈЈ < 0.5, J2ЈЈ,3ЈЈ ϭ 3.0,
ϭ
1.7, JCH2 10.9, 11.6, 12.9 Hz.
ϭ
Ϫ
13C NMR
7.32Ϫ7.42 (m, 10 H, C6H5CH2), 7.70 and 7.88 (2 bs, 1 H each,
DCPhth); J1,2 ϭ 8.4, J2,3 ϭ 8.6, J2Ј,3Ј ϭ 3.3, J3Ј,4Ј ϭ 9.9, JCH2
C, C6H5CH2), 82.2 (C-1ЈЈ), 97.0 (C-1Ј), 97.4 (C-1), 99.1 (C-1ЈЈЈ),
100.3 (CH3OC6H4CH), 100.8 (C6H5CH), 114.2, 114.3, 118.5
ϭ
12.2, 12.4 Hz. Ϫ 13C NMR (67.80 MHz, CDCl3): δ ϭ 13.6 (CH3S), (CH3OC6H4, CH3OC6H4CH), 125.2Ϫ138.7 (C6H5CH2,C6H5CH),
20.8 (CH3CO), 55.3, 55.6 (2 CH3OC6H4), 56.2 (C-2), 64.6 (C-4Ј),
150.6, 155.3, 160.2, 165.6 (DCPhth, CH3OC6H4), 171.2
67.3 (C-6), 68.7 (C-6Ј), 70.1 (C-3Ј), 74.1 (C6H5CH2), 74.3 (C-2Ј), (CH2COO), 206.0 (CH3CO). Ϫ C117H112Cl4N2O27S (2152.1): C
75.0 (C-5), 75.4 (C6H5CH2), 75.6, 75.9, 77.2, 78.2 (C-3, C-4, C-
65.30, H 5.25, N 1.30; found C 64.83, H 5.28, N 1.23.
Eur. J. Org. Chem. 1999, 1367Ϫ1376
1374

Tethered Intermediates in I-Methoxybenzyl-Assisted β-Mannosylation
FULL PAPER
(S)-[Methyl O-(3,4,6-tri-O-benzyl-2-O-acetyl-1-thio-␣-
ranosyl)-(1Ǟ3)-4,6-O-benzylidene-2-deoxy-1-thio-␣-
ranosid-2-yl][p-methoxyphenyl O-[3,6-di-O-benzyl-2,4-dideoxy-2-phthal-
imido-β- -glucopyranos-4-yl]-(1Ǟ4)-3,6-di-O-benzyl-2-
deoxy-2-phthalimido-β- -glucopyranosid]-p-methoxybenzylidene
Acetal (33): Prepared from compounds 5 (165 mg, 0.18 mmol) and
8 (152 mg, 0.14 mmol) by treatment with DDQ (42 mg, 0.18 mmol) C108H102Cl4N2O26 (1985.8): calcd. C 65.32, H 5.18, N 1.41; found
D
-mannopy-
101.4 (C6H5CH), 114.3, 118.5 (CH3OC6H4), 125.3, 126.0
(DCPhth), 127.0Ϫ139.0 (C6H5CH2,C6H5CH), 150.6, 155.3, 160.2,
165.6 (CH3OC6H4, DCPhth), 171.7 (CH2COO), 206.1 (CH3CO);
1JC1-H ϭ 163.6 (C-1), 161.4 (C-1Ј), 159.7 (C-1ЈЈ), 173.4 (C-1ЈЈЈ) Hz.
Ϫ FAB MS (positive); m/z: 2006.9, 2007.9, 2008.8, 2009.7 [M ϩ
D
-mannopy-
D
D
Na]ϩ; (negative); m/z: 2083.6, 2084.6 [M
Ϫ
H]Ϫ.
Ϫ
in CH2Cl2 (1.2 mL) in an analogous manner to that described for
30. Purification by size exclusion chromatography (Bio-Beads S-
X3) with toluene afforded 246 mg (88%) of 33 as yellowish foam.
C 65.44, H 5.15, N 1.43.
p-Methoxyphenyl O-(3,4,6-Tri-O-benzyl-2-O-acetyl-␣-D-mannopyran-
osyl)-(1Ǟ3)-O-(4,6-O-benzylidene-β-
(1Ǟ4)-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-
glucopyranosyl]-(1Ǟ4)-3,6-di-O-benzyl-2-deoxy-2-phthal-imido-β-
glucopyranoside (36b): To a mixture of compound 33 (30 mg,
0.015 mmol), DBMP (9.4 mg, 0.046 mmol) and 4-A molecular si-
D-mannopyranosyl)-
1
Ϫ H NMR (270 MHz, CDCl3): δ ϭ 1.82 and 2.06 (2 s, 3 H each,
D
-
-
SMe and Ac), 3.25 and 3.66 (2 s, 3 H each, OMe), 5.24 (d, 1 H,
1ЈЈЈ-H), 5.35 (s, 1 H, benzylidene CH), 5.38 (d, 1 H, 1Ј-H), 5.49 (d,
1 H, 1-H), 5.61 (dd, 1 H, 2ЈЈЈ-H), 5.65 (s, 1 H, acetal CH), 5.73 (s,
1 H, 1ЈЈ-H), 6.6Ϫ7.8 (m, 56 H, aromatic); J1,2 ϭ 8.3, J1Ј,2Ј ϭ 8,
J1ЈЈЈ,2ЈЈЈ ϭ 2.0, J2ЈЈЈ,3ЈЈЈ ϭ 2.8 Hz). Ϫ 13C NMR (67.80 MHz,
CDCl3): δ ϭ 82.2 (C-1ЈЈ), 97.2, 97.6, 99.3 (C-1, -1Ј, -1ЈЈЈ), 100.3
and 100.5 (acetal CH).
D
˚
eves (0.2 g) in 1,2-dichloroethane (1 mL) was added MeOTf (1 
in CCl4, 46 µL, 0.046 mmol) and the mixture was stirred at 40°C.
Additional portions of MeOTf (0.015 mmol) and DBMP
(0.015 mmol) were added at 24 h intervals, while the stirring was
continued for 4 d. The mixture was worked up as described for 32a
and the crude material was purified by size exclusion chromatogra-
phy (Bio-Beads S-X4) with toluene, followed by preparative TLC
(toluene/AcOEt, 5:1) to afford 15.2 mg (55%, 49% from 8) as well
as recovered 8 (3.7 mg). ϪCompound 36b; [α]D ϭ ϩ22.2 (c ϭ 0.6,
CHCl3). Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 2.11 (s, 3 H, Ac),
2.79 (br. s, 1 H, OH), 3.65 (s, 3 H, OMe), 4.55 (s, 1 H, 1ЈЈ-H), 5.12
(d, 1 H, 1ЈЈЈ-H), 5.28 (d, 1 H, 1Ј-H), 5.44 (d, 1 H, 1-H), 5.45 (s, 1
H, benzylidene CH), 5.49 (dd, 1 H, 2ЈЈЈ-H), 6.6Ϫ7.9 (m, 52 H,
aromatic); J1,2 ϭ 8.8, J1Ј,2Ј ϭ 8.3, J1ЈЈЈ,2ЈЈЈ ϭ 1.5 Hz. Ϫ 13C NMR
(100.40 MHz, CDCl3): δ ϭ 66.8, 67.7, 68.0, 68.4, 68.6, 69.3, 70.7,
71.8, 71.9, 72.7, 73.2, 73.6, 74.4, 74.5, 74.6, 75.1, 75.8, 76.8, 77.2,
77.9, 78.9, 79.1, 97.1 (C-1Ј), 97.5 (C-1), 98.8 (C-1ЈЈЈ), 100.6 (C-1ЈЈ),
101.4 (benzylidene CH). Ϫ C105H102N2O25 (1792.0): calcd. C 70.38,
H 5.74, N 1.56; found C 70.14, H 5.84, N 1.41.
p-Methoxyphenyl O-(3,4,6-Tri-O-benzyl-2-O-levulinoyl-␣-
nopyranosyl)-(1Ǟ3)-(4,6-O-benzylidene-β- -mannopyranosyl)-
(1Ǟ4)-[3,6-di-O-benzyl-2-deoxy-2-(4,5-dichlorophthalimido)-β-
glucopyranosyl]-(1Ǟ4)-3,6-di-O-benzyl-2-deoxy-2-(4,5-dichloro-
phthalimido)-β- -glucopyranoside (36a): Mixed acetal 32 (654 mg,
D-man-
D
D
-
D
0.30 mmol) and 2,6-di-tert-butyl-4-methylpyridine (DBMP,
218 mg, 1.06 mmol) were stirred in 1,2-dichloroethane (60 mL)
˚
with freshly activated 4-A molecular sieves (1.5 g) under argon for
30 min. A solution of MeOTf in 1,2-dichloroethane (1 , 1.37 mL,
1.37 mmol) was injected and the mixture stirred for 44 h at 40 °C.
The reaction was quenched with triethylamine (2 mL), stirred for
15 min (color changed from yellow to brownish), diluted with
CH2Cl2 (100 mL), and filtered through Celite. The organic phase
was washed with water (2 ϫ 30 mL), dried (Na2SO4), and after
evaporation of the solvent the residue was subjected to size ex-
clusion chromatography (Bio-Beads S-X1) with toluene to give
390 mg of crude 36a and 87 mg (24%) recovered disaccharide ac-
ceptor 29. Crude 36a was further purified by silica gel chromatog-
raphy with toluene/AcOEt, 10:1 Ǟ 5:1, to furnish another 43 mg
(12%) acceptor 29 and 234 mg tetrasaccharide 36a (39%, 43%
based on consumed 29 over 2 steps) as a beige foam, [α]20D ϭ ϩ7.5
DADAS 90 Experiment: For the calculation studies 100 initial con-
formers for every sample (S)-15a, (R)-15a, (S)-15b, and (R)-15b
were generated by using randomly generated torsion angles in
DADAS 90. Bond lengths and angles of pyranose rings were based
on X-ray data.[28] Anomeric fluorine was substituted by hydrogen.
Minimization of pseudo energy values (Tp) was performed under
the distance restrictions for NOE and soft repulsion and angle re-
striction for the acetal moiety by using the conjugate gradient
method. Tp values for (S)-15a, (R)-15a, (S)-15b, and (R)-15b be-
tween 0 and 34800 were observed and the smallest for each individ-
ual diastereomer selected for the determination of the absolute con-
figuration at the acetalic position. Ϫ All calculations were carried
out with an IRIS Indy computer. Molgraph (DAIKIN Co. Ltd.)
and Molskop (JEOL Co. Ltd.) were used as graphical editors.
1
(c ϭ 1.5, CHCl3). Ϫ H NMR (400 MHz, CDCl3): δ ϭ 2.12 (s, 3
H, CH3Lev), 2.66 (m, 4 H, 2 CH2Lev), 2.84 (d, 1 H, 2ЈЈ-OH), 3.12
(ddd, 1 H, 5ЈЈ-H), 3.25 (d, 1 H, 5Ј-H), 3.34Ϫ3.42 (m, 2 H, 5-H, 6-
Ha), 3.52Ϫ3.56 (m, 3 H, 6-Hb, 6Ј-Ha, 6ЈЈ-Ha), 3.64 (dd, 1 H, 3ЈЈ-
H), 3.66 (s, 3 H, CH3OC6H4), 3.67Ϫ3.82 (m, 4 H, 6Ј-Hb, 4ЈЈЈ-H,
6ЈЈЈ-H2), 3.91 (dd, 1 H, 4ЈЈ-H), 4.02 (dd, 1 H, 3ЈЈЈ-H), 4.07 (m, 1
H, 2ЈЈ-H), 4.09Ϫ4.13 (m, 3 H, 4Ј-H, 6ЈЈ-Hb, 5ЈЈЈ-H), 4.14 (2 dd, 1
H each, 3-H, 2Ј-H), 4.23 (dd, 1 H, 4-H), 4.25 (dd, 1 H, 3Ј-H),
4.30 (dd, 1 H, 2-H), 4.38 (d, 1 H, C6H5CH2), 4.43Ϫ4.67 (m, 10 H,
C6H5CH2), 4.60 (br. s 1 H, 1ЈЈ-H), 4.81 (d, 1 H, C6H5CH2),
4.84 and 4.87 (2 d, 1 H each, C6H5CH2), 5.08 (d, 1 H, 1ЈЈЈ-H), 5.24
(d, 1 H, 1Ј-H), 5.39 (d, 1 H, 1-H), 5.45 (s and dd, 1 H each,
C6H5CH and 2ЈЈЈ-H), 6.60Ϫ6.70 (m, 4 H, CH3OC6H4), 6.82Ϫ7.44
(m, 40 H, C6H5CH2), 7.45Ϫ7.88 (2 s and 2 br. s, 1 H each,
DCPhth); J1,2 ϭ 8.7, J2,3 ϭ 10.5, J3,4 ϭ J4,5 ϭ 9.0, J1Ј,2Ј ϭ 8.3,
J4Ј,5Ј ϭ 9.8, J1ЈЈ,2ЈЈ < 0.5, J2ЈЈ,3ЈЈ ϭ 3.4, J2ЈЈ,OH ϭ 2.9, J3ЈЈ,4ЈЈ ϭ 10.0,
Acknowledgments
Part of this work was financially supported by a Grant-in-
Aid for Scientific Research from The Ministry of Edu-
cation, Science, Culture, and Sports and also by the Special
Coordination Fund from the Science and Technology Ag-
ency of the Japanese Government. M. L. thanks the Science
and Technology Agency of the Japanese Government for
an STA fellowship award and the Alexander-von-Hum-
boldt Foundation, Bonn, Germany for a supporting
J4ЈЈ,5ЈЈ ϭ 9.4, J5ЈЈ,6ЈЈa ϭ 9.5, J5ЈЈ,6ЈЈb ϭ 4.9, J1ЈЈЈ,2ЈЈЈ ϭ 1.5, J2ЈЈЈ,3ЈЈЈ
ϭ
3.2, J3ЈЈЈ,4ЈЈЈ ϭ 9.0 Hz. Ϫ 13C NMR (100.40 MHz, CDCl3): δ ϭ 28.1
(CH2Lev), 29.8 (CH3Lev), 38.0 (CH2Lev), 55.5 (CH3OC6H4), 56.0 (C-
2), 56.9 (C-2Ј), 66.8 (C-5ЈЈ), 67.6 (C-6Ј), 68.0 (C-6), 68.4 (C-6ЈЈ),
68.7 (C-2ЈЈЈ), 69.4 (C-6ЈЈЈ), 70.6 (C-2ЈЈ), 71.6, 71.8, 72.9, 73.2, 73.6,
74.4, 74.7, 74.8, 75.1, 78.7 (C-5, C-4Ј, C-5Ј, C-4ЈЈЈ, C-5ЈЈЈ,
C6H5CH2), 75.8 (C-4), 76.9 (C-3), 77.2 (C-3Ј, C-4ЈЈ), 77.4 (C-3ЈЈ),
77.8 (C-3ЈЈЈ), 96.9 (C-1Ј), 97.3 (C-1), 98.6 (C-1ЈЈЈ), 100.6 (C-1ЈЈ), Feodor-Lynen fellowship.
Eur. J. Org. Chem. 1999, 1367Ϫ1376
1375

M. Lergenmüller, T. Nukada, K. Kuramochi, A. Dan, T. Ogawa, Y. Ito
FULL PAPER
[1]
[13]
F. Barresi, O. Hindsgaul in Modern Methods in Carbohydrate
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[14]
K. J. Schönauer, P. Walter, C. R. Noe, Monatsh. Chem. 1986,
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H. Hashimoto, T. Endo, Y. Kajihara, J. Org. Chem. 1997, 62,
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[17]
Compound 11 was prepered from an anomeric mixture (α/β ϭ
7:1) of 2-O-acetyl-3,4,6-tri-O-benzyl--mannopyranosyl fluor-
ide (DIBAL/THF) and was further transformed into 9 (p-meth-
oxybenzyl chloride, NaH/DMF) as reported previously.[3a] For
the use of 11 as a glycosyl acceptor in polymer support oligos-
accharide synthesis, see: Y. Ito, O. Kanie, T. Ogawa, Angew.
Chem. 1996, 108, 2691Ϫ2693; Angew. Chem. Int. Ed. Engl.
1996, 35, 2510Ϫ2512. For IAD experiments, anomeric mixtures
of 9 and 11 were used, while stereochemical homogeneities on
the acetalic carbon atoms of 14a,b and 15a,b were confirmed
[2]
For general discussion, see: H. Paulsen, Angew. Chem. 1982, 94,
184Ϫ201; Angew. Chem. Int. Ed. Engl. 1982, 21, 155Ϫ173.
[3] [3a]
Y. Ito, T. Ogawa, Angew. Chem. Int. Ed. Engl. 1994, 35,
[3b]
2510Ϫ2512. Ϫ
1995, 60, 4680Ϫ4681. Ϫ
hedron Lett. 1995, 36, 7487Ϫ7490. Ϫ
A. Dan, Y. Ito, T. Ogawa, J. Org. Chem.
[3c]
A. Dan, Y. Ito, T. Ogawa, Tetra-
[3d]
A. Dan, Y. Ito, T.
in separate experiments, by preparation from anomerically pure
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[3e]
Ogawa, Carbohydr. Lett. 1996, 1, 469Ϫ474. Ϫ
Y. Ito, T.
[18]
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bohydr. Res. 1980, 82, 130Ϫ134. Compound 7: T. Nakano, Y.
Ito, T. Ogawa, Tetrahedron Lett. 1990, 31, 1597Ϫ1600.
In this particular case, a better result (74% yield) was obtained
when IAD was performed in diethyl ether.[3a]
Ver. 5.1, JEOL Co. Ltd., Akishima, Tokyo Japan. This program
was created based upon the algorithm developed by Braun and
Go: W. Braun, N. Go, J. Mol. Biol. 1985, 186, 611Ϫ626.
Satisfactory combustion analysis data were obtained for 31Ϫ33.
For the use of the DCPhth group as an amino protection, see:
M. Lergenmüller, Y. Ito, T. Ogawa, Tetrahedron 1998, 54,
1381Ϫ1394.
[4]
[5]
[6]
[19]
[20]
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G. Stork, J. J. La Clair, J. Am. Chem. Soc. 1996, 118, 247Ϫ248.
The PMB group has been extensively used as a hydroxy-protect-
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[21]
[22]
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[23]
[24]
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Y. Ito, Y. Ohnishi, T. Ogawa, Y. Nakahara, Synlett 1998,
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[9]
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