N-benzyl-2,3-trans-carbamate-bearing glycosyl donors for 1,2-cis-selective glycosylation reactions

Article abstract of DOI:10.1002/ejoc.201001278

Glycosyl donors for the preparation of 1,2-cis glycosides of amino sugars have been developed. The 2,3-trans-cyclic-carbamate-carrying glycosyl donors were readily prepared from the corresponding known trichloroethyl carbamate protected amino sugars under

Full text of DOI:10.1002/ejoc.201001278

FULL PAPER
DOI: 10.1002/ejoc.201001278
N-Benzyl-2,3-trans-Carbamate-Bearing Glycosyl Donors for 1,2-cis-Selective
Glycosylation Reactions
Shino Manabe,*[a,b] Kazuyuki Ishii,[a,b] and Yukishige Ito*[a,c]
Keywords: Carbohydrates / Glycosylation / Diastereoselectivity / Solid-phase synthesis / Carbamates
Glycosyl donors for the preparation of 1,2-cis glycosides of
towards secondary hydroxy group substrates. In the case of
amino sugars have been developed. The 2,3-trans-cyclic-car- primary hydroxy acceptors, high stereoselectivities were
bamate-carrying glycosyl donors were readily prepared from
the corresponding known trichloroethyl carbamate protected
amino sugars under standard hydroxy group benzylation
conditions. The donors exhibit high 1,2-cis stereoselectivity
achieved with the aid of the dioxane effect. After glycosyla-
tion, the carbamate was removed under alkaline conditions.
Importantly, these glycosyl donors can be used in polymer-
supported and solid-phase synthesis.
desired 1,2-cis glycosides. Secondly, the preparation of
azido sugars is not feasible. Attempts to generate these
compounds from glycal by an azido nitration reaction re-
sulted in the formation of many byproducts that required
purification by column chromatography and ultimately pro-
vided unsatisfactory yields.[7a] An alternative method for
the preparation of azido sugars from the corresponding 2-
amino precursors requires the use of potentially explosive
triflic azide.[8] The synthesis of 2-azido donors from man-
nose is possible by the transformation of the 2-hydroxy
group with inversion of configuration, but this method re-
quires a multistep reaction sequence.[9]
Introduction
The increased awareness of the biological importance of
oligosaccharides has stimulated the development of efficient
methods for the synthesis of glycoconjugates.[1] The 1,2-cis-
linked 2-deoxy-2-amino sugar structure is found in various
biologically interesting oligosaccharides such as amino gly-
coside antibiotics,[2] the GPI anchor,[3] and heparin/heparan
sulfate.[4] In addition, multiple 1,2-cis-aminoglycoside-con-
taining N-linked oligosaccharides have been found as pro-
tein modifications in Campylobacter jejuni.[5] Because oligo-
saccharides and glycoconjugates are usually found in low
concentrations and/or in microheterogeneous forms, a
major obstacle in the investigation of biologically important
carbohydrates is the limited availability of pure and struc-
turally well-defined sugar materials. Synthetic chemistry
represents the main access route to oligosaccharides and
glycoconjugates with rigorously defined chemical composi-
tions.
Although there has been much progress in carbohydrate
chemistry in the past two decades, 1,2-cis-selective glycosy-
lation is still a challenge.[6] For the synthesis of 2-amino-2-
deoxy sugars, 2-azidoglycosyl donors 1, which were devel-
oped about 30 years ago, are still employed (Figure 1).[7]
There are, however, some disadvantages of using these rea-
gents. First, the glycosylation reaction is generally only
moderately stereoselective. Typically, 1,2-trans aminoglyco-
sides are obtained in significant amounts together with the
Figure 1. 1,2-cis-selective aminoglycosyl donors.
Progress in resolving these issues was made with the de-
velopment of 2,3-trans-carbamate-carrying glycosyl donors
2, which exhibit extremely high 1,2-cis selectivities in glyco-
sylation reactions.[10,11] Although the 1,2-cis selectivity in
the glycosylation reaction is high, several disadvantages of
these glycosyl donors have also been reported, such as
1) significant side-reactions, including the sulfenylation and
glycosylation of the nitrogen atom and 2) the requirement
of at least 2 equiv. of the activator phenylsulfenyl
triflate.[10b–10d] To address these disadvantages, Kerns and
Oscarson and their co-workers independently reported the
use of the acetylated carbamate 3, a modified version of
the carbamate glycosyl donor.[10,12] Ye and co-workers also
reported the use of N-acetylated 2,3-trans carbamate do-
nors with various acceptors for 1,2-cis aminoglycoside for-
[a] RIKEN, Advanced Science Institute,
Hirosawa, Wako, Saitama 351-0198, Japan
Fax: +81-48-462-4680
E-mail: smanabe@riken.jp
[b] PRESTO, Japan Science and Technology Agency (JST),
Honcho, Kawaguchi, Saitama 332-0012, Japan
[c] ERATO, Japan Science and Technology Agency (JST),
Hirosawa, Wako, Saitama 351-0198, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001278.
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mation.[13] In reactions with acetylated oxazolidinone-car- ditions. Compound 6 is crystalline and can be purified on
rying donor 3, however, 1,2-cis selectivities were reduced a scale greater than 50 g by simple recrystallization from
significantly. In fact, β-selectivity was observed in some EtOAc/hexane. Reductive opening of the benzylidene group
cases.[10c] In addition, selective removal of the cyclic using Et3SiH/BF3·OEt2 afforded the C-4 hydroxy group 7 in
carbamate of the imide was rather difficult.[10d]
72% yield. Interestingly, the configuration of the anomeric
We recently reported the novel N-benzyl-2,3-trans-oxazo- carbon of 6 was labile under acidic conditions and the α-
lidinone-carrying glycosyl donor 4 for 1,2-cis-selective gly- thioglycoside 8 was obtained in 11% yield, as described by
cosylation.[14] This type of donor shows extremely high 1,2- Crich and Oscarson and their co-workers.[10e,12b] This ano-
cis selectivity in glycosylation reactions and side-reactions merization was caused by an endocyclic cleavage/recycliza-
at the carbamate nitrogen atom are negligible. We also re- tion process.[16] By using similar conditions to those de-
cently reported the first highly efficient synthesis of an anti- scribed above, dimethyl(ethyl)silane/Cu(OTf)2 in CH3CN[17]
Helicobacter pylori oligosaccharide using our novel glycosyl at room temperature gave a significant amount of anomer-
donor.[15] Herein we describe the scope of reactivity of our ized product 8 in 38% yield together with dimethylethylsi-
glycosyl donor with various substrates including polymer- lylated compound 9 in 52% yield. After chloroacetylation
supported and resin-bound acceptors.
of the hydroxy group, the thioglycosides 10 and 11 were
used as glycosyl donors. The relatively stable bromide 13
was prepared from thioglycoside 11 by Br2 treatment in
91% yield after purification by silica gel column
chromatography. Fluoride donor 12 was also directly pre-
pared from thioglycoside 11 in 83% yield using N-bromo-
Results and Discussion
Several donors were easily prepared from protected glu-
cosamine 5 (Scheme 1).[14] Cyclic carbamate 6 was prepared
in 96% yield under typical hydroxy group benzylation con-
succinimide
(NBS)/(diethylamino)sulfur
trifluoride
Scheme 1. Preparation of various 2,3-trans-carbamate donors.
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1,2-cis-Selective Glycosylation Reactions
(DAST).[18] Interestingly, the bromide 13 was also obtained
as a minor product in 14% in this reaction. From 6, the
corresponding sulfoxide 14 was prepared by m-chloroper-
benzoic acid (m-CPBA) oxidation. The major compound
14a possessed the R configuration at the sulfur atom and
was obtained in 66% yield, whereas the minor isomer 14b
with the S configuration was obtained in 13% yield.[19] Af-
ter separation of these two isomers by silica gel column
chromatography, the stereochemistry at the sulfur was de-
termined by X-ray crystallographic analysis of the ethyl
acetate adduct of the minor isomer (see the Supporting In-
formation).
Scheme 2. Glycosylation reaction with 4,6-benzylidene thioglyco-
side donor 6.
The galactosamine-type donor 16 was prepared from 4-
OH glucosamine derivative 7 by inversion of the configura- (Scheme 3). Interestingly, the amount of Tf2O affected the
tion at the 4-position. The hydroxy group at the 4-position stereoselectivity. When 0.6 equiv. of Tf2O were used as acti-
of 7 was changed to the corresponding triflate by using vator, the ratio of 21a and 21b was 87:13, whereas when
Tf2O/pyridine and then the triflate was converted into the 1.1 equiv. were used the 1,2-cis selectivity decreased to
acetate by using NaOAc in DMF. The anomerized α-thiog- 57:43. The difference in stereoselectivity probably depends
lycoside 16a was also obtained in 13% yield together with on the different intermediates involved in the glycosylation
β-thioglycoside 16b (73%). Diacetylated donor 15 was pre- reaction.[24]
pared from 6 in two steps. Removal of the benzylidene ace-
The glycosyl donor 11 lacking the cyclic benzylidene
tal in aqueous AcOH at 100 °C was followed by acetylation group was activated by using typical glycosylation condi-
to afford compound 15 in 95% yield. During removal of tions for thioglycoside activation (Table 1). Activating
the benzylidene group under acidic conditions, no anomer- agents NIS/TMSOTf (entries 1 and 2), N-(phenylthio)-ε-ca-
ization was observed. In summary, the glycosyl donors 10– prolactam/Tf2O (entry 3), dimethyl(methylthio)sulfonium
16 were each readily prepared from thioglycoside 6 or 7.
triflate (DMTST; entry 4),[25] AgOTf/PhSCl (entries 5, 6, 8,
Unfortunately, it was not possible to prepare the corre- and 9), and 1-(phenylsulfinyl)piperidine (BSP)/Tf2O[26] (en-
sponding trichloroacetimidate donor 17 because hemiacetal try 10) were effective with thioglycoside 11. The selectivity
18, a precursor of the trichloroacetimidate compound 17, for the highly reactive primary alcohol in glycosyl acceptor
could not be synthesized from thioglycoside 11, presumably 20 was low and essentially equimolar amounts of both α
due to the strained pyranose ring. Instead, the ring-opened and β compounds were obtained in CH2Cl2 regardless of
aldehyde 19 was obtained after treatment of thioglycoside the activation method and reaction temperature (entries 1–
11 by NBS treatment in acetone/water.
6). The reactivities of the anomeric stereoisomer thioglycos-
With various donors in hand we turned our attention ides 10 and 11 were almost the same, although the α an-
to the 1,2-cis-selective glycosylation reaction using reactive omer 10 gave slightly higher β selectivity (entry 7). When
primary alcohol 20 as an acceptor. The benzylidene-pro- the reaction was carried out in dioxane/toluene (3:1),[27] the
tected glycosyl thioglycoside 6 was not activated by NIS/ desired α selectivity dramatically increased in a favorable
TfOH,[20] AgOTf/PhSCl,[21] nor N-(phenylthio)-ε-caprolac- manner (entries 8–10). When thioglycoside 11 was activated
tam/Tf2O[22] even at room temperature (Scheme 2) and was with AgOTf/PhSCl in toluene/dioxane at room tempera-
recovered unchanged under these reaction conditions.
ture, α-disaccharide 22a was obtained in 73% yield together
To enhance the reactivity of donor 6, the sulfoxide group with 10% of β-disaccharide 22b (entry 8). Oscarson and co-
was used as a leaving group at the anomeric position.[23] workers reported the isomerization of the β-glycoside to the
Sulfoxide 14a was activated by Tf2O at –40 °C in the pres- α-glycoside under glycosylation reaction conditions em-
ence of acceptor 20. Although the yield and stereoselecti- ploying N-acetyloxazolidinone-carrying glycoside do-
vity were low, the disaccharides 21a and 21b were obtained nors,[10e,12b] but we did not observe any isomerization under
Scheme 3. Glycosylation reaction with 4,6-benzylidene sulfoxide donor 14a.
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Table 1. The selectivity of the glycosylation reaction with primary alcohol 20 under various conditions.[a]
[a] DTBMP = 2,6-di-tert-butyl-4-methylpyridine; TTBP = 2,4,6-tri-tert-butylpyrimidine.
our glycosylation conditions. When the β-glycoside 22b was selectivities were observed for both glucuronic and idoronic
submitted to the same reaction conditions used in entry 6, acid derivatives 29[32] and 31[32] following activation using
it was recovered unchanged in 89% yield.[16,28]
N-(phenylthio)-ε-caprolactam/Tf2O (entries 4 and 5). In the
Unfortunately, fluoridated glycoside 12 was not activated case of glucuronic acid derivative 29, almost complete α
under Suzuki conditions even at 40 °C in CH2Cl2 (en- selectivity was achieved in dioxane/toluene with 75% yield
try 11).[29] Bromide donor 13 was not activated by the weak (entry 5). In addition to these carbohydrate-derivative ac-
activators Ag2O (entry 12) or Ag2CO3 (entry 13), but was ceptors, chorestanol 33 also gave moderate selectivity (en-
activated by AgOTf. Selectivity was low in CH2Cl2 (en- try 6). Galactosamine-type thioglycoside 16 gave high cis
try 14) but high 1,2-cis selectivity was observed in dioxane/ stereoselectivity with the primary hydroxy group in 20 when
toluene (3:1; entry 15).
the reaction was carried out in dioxane/toluene (entry 7).
Next we explored the scope of the reaction with respect Comparing the above results, azido donor 36,[14] which has
to the activity of different acceptors. High 1,2-cis selectivi- a similar protecting group pattern to 11, gave a lower yield
ties were obtained with these donors when less reactive gly- and selectivity with acceptor 23 (Scheme 4). From this re-
cosyl donors were used as acceptors in CH2Cl2 (Table 2). sult, the superiority of the N-benzyl-2,3-trans-carbamate-
For example, glycosylation of 11 with the hydroxy group at carrying glycosyl donors for 1,2-cis glycoside formation is
the 4-position of glucosamine 23 gave extremely high 1,2- clear.
cis selectivity (entry 1). Furthermore, although the hydroxy
The different protecting group pattern of 6-acetate glyco-
group at the 4-position of glucosamine is known to be unre- syl donor 15 gave similar results to donors 11 and 16
active as an acceptor,[30] disaccharide 24 was obtained in (Table 3). When the primary alcohol 20 was used as an ac-
54% yield. After the usual work-up and gel filtration of the ceptor (entry 1), no selectivity was observed. When glycosyl
crude mixture, the corresponding β-disaccharide was not acceptors 22 and 40 with secondary alcohols were used,
1
observed within the detection limits of 400-MHz H NMR however, complete cis stereoselectivity was once again
analysis. In the case of the 4-position of glucose derivative achieved (entries 2 and 3).
25 as an acceptor (entry 2), almost complete 1,2-cis selectiv-
Our next concern was the application of our donor to
ity was observed in 52% yield. Furanose-type derivative 27 polymer-supported or solid-phase oligosaccharide synthe-
was also found to be a good acceptor for 1,2-cis glycosyla- sis.[33] Because our reaction system does not require very
tion (entry 3). Synthetic studies of glycosaminoglycan have low temperatures for 1,2-cis selectivity, these donors are ex-
recently increased as a result of its potential biological im- pected to be suitable for automated oligosaccharide synthe-
portance.[31] Thus, uronic acids such as iduronic and glucu- sis.[34] To demonstrate the utility of our donors under these
ronic acids are interesting structures as acceptors of the 1,2- conditions, their use in low-molecular-weight poly(ethylene
cis glycosylation reaction of aminoglycosides. High 1,2-cis glycol) methyl ether (MPEG, average molecular weight 750)
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1,2-cis-Selective Glycosylation Reactions
Table 2. Scope of acceptors in the glycosylation reaction.[a]
[a] Conditions A: N-(phenylthio)-ε-caprolactam, Tf2O, CH2Cl2, room temp. Conditions B: AgOTf, PhSCl, DTBMP, 1,4-dioxane/toluene
(3:1). [b] 1.6 equiv. of donor was used.
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1H NMR integrations of the anomeric position and the 4-
position without cleavage from MPEG after separation of
the reagents and byproducts from MPEG-bound compo-
nents. For the hydroxy group at the 4-position of glucosa-
mine 48, almost complete cis stereoselectivity was again ob-
served in CH2Cl2. In the case of primary alcohol acceptor
49, the α/β selectivity was 83:17 when using a mixture of
dioxane/toluene as solvent.
To apply our donor to solid-phase oligosaccharide syn-
thesis, a resin-bound acceptor precursor 55 (Scheme 6) was
prepared from the known pentenyl glycoside 52[37] in seven
steps. After removal of the acetyl group of 52, the primary
hydroxy group was protected as the TBDPS ether. After
protecting other hydroxy groups as benzyl ethers under
standard conditions, the TBDPS ether was removed
and the resulting alcohol was protected as a chloroacetyl
group.
Scheme 4. Glycosylation reaction with 2-azide carrying donor 36.
supported oligosaccharide synthesis was investigated.[35]
First, a stable Lewis acid linker was attached to MPEG
in two steps.[36] After Mitsunobu reaction of MPEG and
commercially available phenol 42, subsequent reduction of
The direct oxidation of the terminal alkene of 54 to a
the aldehyde by NaBH4 in MeOH gave alcohol 43 in quan- carboxylic acid was possible by using a combination of
titative yield (Scheme 5). Glucosaminyl imidate derivatives RuO2·nH2O/NaIO4, but the prolonged reaction time caused
44 and 45 were glycosylated to the MPEG linker in the undesired oxidation of the benzyl ethers to benzoyl esters so
presence of 0.5 equiv. of BF3·OEt2. As we previously re- that the reaction was difficult to reproduce.[38] The terminal
ported,[35] owing to the high polarity of MPEG, separation alkene was instead transformed into the corresponding al-
of the MPEG compound from any byproducts was easily dehyde, which was oxidized by Jones’ reagent to afford car-
achieved by chromatography by passage through a short boxylic acid 55. The p-nitrophenyl carbonate modified
silica gel column. The chloroacetyl group was removed un- Tentagel resin 56 (0.23 mmol/g)[39] was used as the solid-
der weakly basic conditions to afford acceptors 48 and 49 phase (Scheme 7).[40] Resin 56 was treated with 2-aminoe-
in 98% yields, respectively. The glycosylation reaction was thanol to afford alcohol 57. The progress of the reaction
carried out using glycosyl donor 11 and MPEG-supported was monitored by following the production of yellow p-ni-
acceptors 48 and 49. The α/β ratios were determined by trophenolate released from the resin. The carboxylic acid
Table 3. Scope of glycosyl acceptors with 4,6-diacetate donor 15.
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1,2-cis-Selective Glycosylation Reactions
Scheme 5. Glycosylation of N-benzyl-2,3-trans-carbamate thioglycoside 11 with polymer-supported acceptors. MPEG = poly(ethylene
glycol) methyl ether, average molecular weight 750.
Scheme 6. Preparation of resin-bound acceptor precursor 55.
55 was then immobilized on resin 57 using MSNT [1-(me- gave a red color. Although the Disperse Red color test
sitylene-2-sulfonyl)-3-nitro-1H-1,2,4-triazole] and 1-methyl- showed the absence of a hydroxy group, the capping reac-
imidazole.[41] Unlike solution-phase synthesis, a lack of tion with benzoyl isocyanate was carried out to cap the re-
methodology for monitoring the progress of solid-phase re- maining hydroxy group.[43] After removal of the chloroace-
actions hampers the setting-up of reaction conditions.[42] To tyl group of the resin-bound compound 58 by HDTC (hyd-
overcome this difficulty, we have previously developed a razinedithiocarbonate),[44] the two color tests gave the op-
color test for monitoring the glycosylation and deprotection posite results. Then 59 was glycosylated using donor 11.
reactions.[35c] The nucleophilic amino groups and hydroxy After glycosylation, the p-nitrobenzylpyridine test for the
groups are detected with Disperse Red/cyanuric chloride chloroacetyl group showed the existence of a chloroacetyl
conjugate 62, whereas chloroacetyl groups are detected with group, whereas the Disperse Red color test revealed the ab-
p-nitrobenzylpyridine (63). After immobilization of acid 55 sence of the hydroxy group. Disaccharides 61a/61b were ob-
to the resin, the Disperse Red/cyanuric chloride test pro- tained after cleavage from the resin in 58% yield in five
vided negative results, but the p-nitrobenzylpyridine test steps in a 68:32 ratio in favor of the 1,2-cis product.
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Scheme 7. Application of N-benzyl-2,3-trans-carbamate donor to solid-phase synthesis with the color test.
Scheme 8. Deprotection procedure for N-benzyl-2,3-trans-carbamates.
Deprotection of the glycosidation products prepared genolysis of both the N- and O-benzyl groups (Scheme 8).
with our new donors proceeded under typical conditions. The fully deprotected disaccharide was then acetylated for
For example, the carbamate group of disaccharide 22a was easy handling. Disaccharide 64 was obtained in 94% overall
cleaved under basic conditions [Ba(OH)2 in EtOH/THF/ yield for the three steps. The carbamate 6 was recovered
H2O or aqueous NaOH in dioxane] followed by hydro- without rupture of the carbamate group after stirring over-
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1,2-cis-Selective Glycosylation Reactions
Micro Scope Inf-550, from Moritex) and Image Pro Plus[52] were
used to analyze the color of the resins on a computer.
night with a catalytic amount of NaOMe in MeOH, 10%
ethylenediamine in BuOH at 90 °C, hydrazine monohydrate
in DMF at 90 °C, or 10 equiv. of NaBH4 in MeOH.
Phenyl 2-Amino-N-benzyl-4,6-O-benzylidene-2-N,3-O-carbonyl-2-
deoxy-1-thio-α-D-glucopyranoside (6): NaH (0.2 g, 8.22 mmol) was
added to an ice-cold mixture of trichloroethyl carbamate 5 (2.20 g,
4.11 mmol) and benzyl bromide (0.98 mL, 8.22 mmol) in DMF
(40 mL). After stirring the mixture for 30 min in an ice–water bath,
the reaction mixture was warmed up to room temperature and
stirred for 30 min. The excess benzyl bromide was quenched by the
addition of Et3N (1.5 mL) and the mixture was diluted with
EtOAc, poured into saturated aqueous NH4Cl, and extracted with
EtOAc. The combined organic extracts were washed with water
and brine, dried with Na2SO4, filtered, and concentrated. The crys-
talline residue was crystallized from EtOAc/hexane to give 6
(1.88 g, 96%) as a colorless crystal; m.p. 216–217 °C. [α]2D4 = 72 (c
Conclusions
In this paper we have described the preparation of N-
benzyl-2,3-trans-carbamate-carrying glycosyl donors and
discussed the scope of the glycosylation reaction using these
novel reagents.[45] We believe that our donors are excellent
for 1,2-cis glycosidic bond formation with respect to their
preparation, glycosylation selectivity, and deprotection pro-
cedures, as demonstrated by their reactivity with a variety
of substrates including their use in polymer-supported and
solid-phase oligosaccharide synthesis. Application of such
donors to automated oligosaccharide synthesis is possible
because no severe low temperature is required for 1,2-cis
selectivity.[33,34]
1
= 1.0, CHCl3). H NMR (500 MHz, CDCl3): δ = 7.47–7.26 (m, 15
3
H, aromatic H), 5.59 (s, 1 H, acetal-PhCH), 4.85 (d, JH,H
=
10.0 Hz, 1 H, 1-H), 4.83 (d, 3JH,H = 15.5 Hz, 1 H, N-CH2Ph), 4.78
3
3
(d, JH,H = 15.5 Hz, 1 H, N-CH2Ph), 4.32 (t, JH,H = 10.5 Hz, 1
H, 3-H), 4.32 (dd, 3JH,H = 10.5, 5.0 Hz, 1 H, 6a-H), 4.04 (dd, 3JH,H
3
= 10.0, 8.5 Hz, 1 H, 4-H), 3.90 (t, JH,H = 10.0 Hz, 1 H, 6b-H),
The origin of the high 1,2-cis selectivity of the trans-car-
bamate-carrying donor in the glycosylation reaction is pres-
ently unclear. One example of a β-triflate of pyranoside has
been reported[46] and thus the possibility of SN2 displace-
ment of an in situ generated β-triflate cannot be eliminated.
Although only α-triflates derived from N-acetyl-2,3-trans-
carbamate-carrying pyranosides have been observed,[10c] the
higher-energy β-triflates may exist in minor amounts. The
reaction, however, probably proceeds in an SN1 manner via
a very reactive oxacarbonium ion.[47] The trans-fused cyclic
protecting group would severely decrease the flexibility of
the attached oxacarbonium ion ring in the SN1 reaction,
which allows the alcohol to approach from only one side
resulting in the high selectivity.[48] Recently, 1,2-cis selective
glycosylation reactions using glycosyl donors bearing trans-
cyclic protecting groups such as glucoside,[49] sialic acid,[50]
and 2-keto-deoxy-d-glycero-d-galacto-nonulosonic acid
(KDN) have been reported.[51] Investigations to further elu-
cidate the mechanism behind the high 1,2-cis selectivity of
these glycosylation reactions are underway.
3.57 (m, 1 H, 5-H), 3.52 (dd, 3JH,H = 10.5, 10.0 Hz, 1 H, 2-H) ppm.
13C NMR (125 MHz, CDCl3): δ = 158.8 (C=O), 136.4, 136.3,
132.6, 131.7, 129.3, 129.2, 128.7, 128.3, 128.0, 127.6, 126.1, 101.4
(acetal-CHPh), 87.7 (C-1), 78.9 (C-3), 78.4 (C-4), 72.8 (C-5), 68.2
(C-6), 61.5 (C-2), 47.7 (N-CH2Ph) ppm. C27H25NO5S (475.56):
calcd. C 68.19, H 5.30, N 2.95; found C 68.15, H 5.17, N 2.88.
Phenyl
thio-α- (7) and -β-
6-O-Benzyl-2-benzylamino-2-N,3-O-carbonyl-2-deoxy-1-
-glucopyranoside (8): BF3·OEt2 (3.9 mL,
D
30.8 mmol) was added slowly to an ice-cold mixture of 6 (7.3 g,
15.4 mmol) and triethylsilane (30 mL, 184.8 mmol) in CH2Cl2
(200 mL). After stirring the mixture for 80 min at the ice-cold tem-
perature, the mixture was poured into saturated aqueous NaHCO3
and extracted with CHCl3. The combined organic extracts were
washed with water, dried with Na2SO4, filtered, and concentrated.
Purification of the residue by flash column chromatography on sil-
ica gel (CHCl3/EtOAc, 3:1–2:1–1:9) and subsequent crystallization
from EtOAc/hexane gave β-glycoside 7 (5.3 g, 72%) and α-glyco-
side 8 (0.78 g, 11%). Compounds 7 and 8 were crystallized from
EtOAc and hexane, respectively.
β-Glycoside 7: M.p. 125–126 °C. [α]2D2 = –77 (c = 1.0, CHCl3). H
1
NMR (500 MHz, CDCl3): δ = 7.40–7.22 (m, 15 H, aromatic H),
3
4.77 (d, JH,H = 9.0 Hz, 1 H, 1-H), 4.74 (s, 2 H, N-CH2Ph), 4.58
(d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph) 4.55 (d, 3JH,H = 11.5 Hz, 1 H,
3
Experimental Section
O-CH2Ph), 4.07 (t, JH,H = 10.5 Hz, 1 H, 3-H), 4.01 (m, 1 H, 4-
3
3
H), 3.79 (dd, JH,H = 10.0, 5.0 Hz, 1 H, 6a-H), 3.76 (dd, JH,H
=
General Procedures: 1H NMR spectra were with a JEOL EX-400
spectrometer as solutions in CDCl3 unless otherwise stated. Chemi-
cal shifts are reported in ppm downfield from the signal for Me4Si.
13C NMR spectra were recorded in CDCl3 unless otherwise stated
and CDCl3 (δ = 77.0 ppm) was used as the internal standard. Op-
tical rotations were measured with a JASCO DIP3-10 instrument
in CHCl3 at ambient temperature. All chemicals were reagent grade
and were used as supplied unless otherwise noted. Technical grade
or reagent grade solvents for extraction and chromatography were
used without further purification. Molecular sieves (4-Å) were acti-
vated by heating at 170 °C in vacuo just before use. Merrifield and
Tentegel resins were purchased from NOVA Biochem. Bio-beads
was purchased from BIO-RAD and used for gel filtration column
chromatography. A cute mixer CM-1000 (EYELA) was used as a
shaker for solid-phase reactions. Polypropylene tubes equipped
with a filter (RT5-M100 and RT20-M50; EYELA) were used as a
reaction vessel for solid-phase synthesis. A microscope (CCD
8.0, 5.0 Hz, 1 H, 6b-H), 3.56 (m, 1 H, 5-H), 3.41 (dd, 3JH,H = 10.5,
9.0 Hz, 1 H, 2-H), 2.97 (d, JH,H = 2.5 Hz, 1 H, 4-OH) ppm. 13C
3
NMR (125 MHz, CDCl3): δ = 159.3 (C=O), 137.5, 136.22, 132.4,
132.3, 129.1, 128.6, 128.5, 128.4, 128.2, 127.9, 127.7, 127.6, 86.7
(C-1), 82.4 (C-3), 79.6 (C-5), 73.7 (O-CH2Ph), 69.7 (C-6), 69.1 (C-
4), 60.1 (C-2), 47.6 (N-CH2Ph) ppm. C27H27NO5S (477.57): calcd.
C 67.90, H 5.70, N 2.93; found C 67.89, H 5.56, N 2.84.
1
β-Glycoside 8: M.p. 118–119 °C. [α]2D2 = +210 (c = 1.0, CHCl3). H
NMR (400 MHz, CDCl3, 22 °C): δ = 7.50–7.24 (m, 15 H, aromatic
3
3
H), 5.37 (d, JH,H = 4.5 Hz, 1 H, 1-H), 4.79 (d, JH,H = 15.0 Hz, 1
3
H, N-CH2Ph), 4.60 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.50 (d,
3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.36 (dd, 3JH,H = 12.0, 9.5 Hz, 1
3
H, 3-H), 4.17 (d, JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.14 (m, 1 H,
5-H), 4.02 (m, 1 H, 4-H), 3.78 (dd, JH,H = 10.5, 4.5 Hz, 1 H, 6a-
H), 3.70 (dd, JH,H = 10.5, 4.0 Hz, 1 H, 6b-H), 3.50 (dd, JH,H
12.0, 4.5 Hz, 1 H, 2-H), 2.71 (d, JH,H = 3.0 Hz, 1 H, 4-OH) ppm.
3
3
3
=
3
Eur. J. Org. Chem. 2011, 497–516
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
505

S. Manabe, K. Ishii, Y. Ito
FULL PAPER
13C NMR (100 MHz, CDCl3, 21 °C): δ = 158.6 (C=O), 137.5,
134.4, 132.9, 131.9, 129.1, 129.0, 128.9, 128.5, 128.4, 127.9, 127.7,
84.9 (C-1), 78.4 (C-3), 73.6 (O-CH2Ph), 73.0 (C-5), 69.4 (C-4), 68.7
(C-6), 59.6 (C-2), 47.8 (N-CH2Ph) ppm. C27H27NO5S (477.57): H), 5.42 (dd, JH,H = 2.0, JH,F = 57.2 Hz, 1 H, 1-H), 4.60 (d,
calcd. C 67.90, H 5.70, N 2.93; found C 67.96, H 5.64, N 2.85.
3:3:1) to give 70 mg (83%) of fluoride 12 as a colorless oil. [α]2D4
=
–3.9 (c = 1.1, CHCl3). 1H NMR (400 MHz, CDCl3, 22 °C): δ =
3
7.36–7.16 (m, 10 H, aromatic H), 5.49 (t, JH,H = 10.4 Hz, 1 H, 4-
3
2
3
3JH,H = 15.2 Hz, 1 H, N-CH2Ph), 4.54 (d, JH,H = 12.0 Hz, 1 H,
O-CH2Ph), 4.53 (t, 3JH,H = 10.8 Hz, 1 H), 4.39 (d, 3JH,H = 12.0 Hz,
Phenyl 6-O-Benzyl-2-benzylamino-2-N,3-O-carbonyl-4-O-chloro-
3
1 H, O-CH2Ph), 4.32 (d, JH,H = 15.2 Hz, 1 H, N-CH2Ph), 3.97
acetyl-2-deoxy-1-thio-α- -glucopyranoside (10): Chloroacetic anhy-
D
3
(m, 1 H, 5-H), 3.95 (d, JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.86 (d,
dride (42 mg, 0.245 mmol) was added to a solution of alcohol 8
(78 mg, 0.163 mmol) in pyridine (26 μL, 0.326 mmol) and CH2Cl2
(3 mL) at 4 °C. After 1 h, the solution was diluted with CHCl3 and
washed with 1 m HCl. The aqueous layer was extracted with CHCl3
and the whole extract was washed with brine. The organic layer
was washed with brine and filtered. After concentration, the crude
was purified by silica gel column chromatography (hexane/toluene/
EtOAc, 2:1:1) to give the product 10 (90 mg, 99%). [α]2D4 = +220 (c
3
3JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.55 (dd, JH,H = 11.2, 2.4 Hz,
3
3
1 H), 3.47 (dd, JH,H = 10.8, 3.2 Hz, 1 H, 6a-H), 3.38 (dd, JH,H
=
3
12.0, 1.6 Hz, 1 H, 6b-H), 3.32 (dd, JH,H = 12.0, 1.6 Hz, 1 H, 2-
H) ppm. 13C NMR (100 MHz, CDCl3, 23 °C): δ = 165.3, 157.5,
136.8, 134.0, 129.0, 128.6, 128.4, 128.1, 128.0, 127.9, 103.3, 101.0,
73.7, 73.6, 72.8, 69.3, 66.6, 60.5, 60.2, 48.6, 40.3 ppm. HRMS:
calcd. for C23H23ClFNO6 + Na [M + Na]+ 486.1090; found
486.1093.
1
= 1.0, CHCl3). H NMR (500 MHz, CDCl3): δ = 7.44–7.24 (m, 15
6-O-Benzyl-2-benzylamino-2-N,3-O-carbonyl-4-O-chloroacetyl-2-de-
oxy-α-D-glucopyranosyl Bromide (13): A solution of 1 m Br2 in
3
3
H, aromatic H), 5.41 (d, JH,H = 5.0 Hz, 1 H, 1-H), 5.40 (t, JH,H
3
= 10.5 Hz, 1 H, 4-H), 4.81 (d, JH,H = 14.5 Hz, 1 H, N-CH2Ph),
4.57 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.44 (dd, JH,H = 12.0,
CH2Cl2 was added to a stirring ice-cold solution of 11 (360 mg,
0.65 mmol) in CH2Cl2. After stirring the mixture for 30 min, the
mixture was poured into ice-cold 10% aqueous Na2S2O3 and ex-
tracted with CHCl3. The combined organic extracts were washed
with brine, dried with Na2SO4, filtered, and concentrated. Purifica-
tion by flash column chromatography on silica gel (toluene/hexane/
3
3
3
10.5 Hz, 1 H, 3-H), 4.30 (m, 1 H, 5-H), 4.19 (d, JH,H = 11.5 Hz,
1 H, O-CH2Ph), 4.17 (d, 3JH,H = 14.5 Hz, 1 H, N-CH2Ph), 3.89 (d,
3JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.97 (d, JH,H = 15.0 Hz, 1 H,
3
3
COCH2Cl), 3.64 (dd, JH,H = 12.0, 5.0 Hz, 1 H, 2-H), 3.58 (dd,
3JH,H = 11.0, 2.5 Hz, 1 H, 6a-H), 3.56 (dd, JH,H = 11.0, 4.0 Hz, 1
3
EtOAc, 3:3:1) gave 13 as a colorless foam (310 mg, 91%). [α]2D6
=
H, 6b-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 165.6 (oxazolid-
inone C=O), 157.8, 137.1, 134.1, 132.3, 131.9, 129.3, 129.1, 128.9,
128.6, 128.4, 128.2, 128.1, 128.0, 84.8 (C-1), 75.8 (C-3), 73.6 (O-
CH2Ph), 71.2 (C-5), 69.9 (C-4), 67.2 (C-6), 59.6 (C-2), 47.9 (N-
CH2Ph), 40.3 (COCH2Cl) ppm. C29H28ClNO6S (554.05): calcd. C
62.87, H 5.09, N 2.53; found C 62.65, H 5.05, N 2.42.
+118 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.40–
3
7.24 (m, 10 H, aromatic H), 6.25 (d, JH,H = 3.5 Hz, 1 H, 1-H),
5.52 (dd, 3JH,H = 10.5, 9.5 Hz, 1 H, 4-H), 4.82 (d, 3JH,H = 15.0 Hz,
3
1 H, N-CH2Ph), 4.66 (dd, JH,H = 11.5, 10.5 Hz, 1 H, 3-H), 4.45
3
3
(d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.39 (d, JH,H = 11.5 Hz, 1
3
H, O-CH2Ph), 3.96 (d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 4.05 (d,
3JH,H = 15.0 Hz, 1 H, N-CH2Ph), 3.95 (m, 1 H, 5-H), 3.87 (d, 3JH,H
Phenyl
acetyl-2-deoxy-1-thio-β-
5.44 mmol) was added to an ice-cold mixture of
6-O-Benzyl-2-benzylamino-2-N,3-O-carbonyl-4-O-chloro-
-glucopyranoside (11): Pyridine (0.59 mL,
(2.6 g,
3
D
= 15.0 Hz, 1 H, COCH2Cl), 3.56 (dd, JH,H = 11.0, 3.0 Hz, 1 H,
3
3
7
6a-H), 3.51 (dd, JH,H = 11.0, 3.5 Hz, 1 H, 6b-H), 3.37 (dd, JH,H
= 11.5, 3.5 Hz, 1 H, 2-H) ppm. 13C NMR (125 MHz, CDCl3): δ =
165.4 (COCH2Cl), 157.4 (oxazolidinone C=O), 136.8, 133.6, 129.3,
128.9, 128.8, 128.5, 128.2, 128.1, 83.4 (C-1), 75.3 (C-3), 74.7 (C-5),
73.6 (O-CH2Ph), 68.5 (C-4), 66.2 (C-6), 60.7 (C-2), 47.6 (N-
CH2Ph), 40.2 (COCH2Cl) ppm. C23H23BrClNO6 (524.79): calcd. C
52.64, H 4.42, N 2.67; found C 52.36, H 4.45, N 2.57.
3.64 mmol) and chloroacetic anhydride (0.94 g, 5.47 mmol) in
CH2Cl2 was added. After stirring the mixture for 30 min, the mix-
ture was poured into 0.1 m aqueous HCl and extracted with CHCl3.
The combined organic extracts were washed with water, dried with
Na2SO4, filtered, and concentrated. Purification by column
chromatography on silica gel (toluene/hexane/EtOAc, 2:1:1) gave 4-
O-ClAc 11 (2.02 g, 99%) as a colorless syrup. [α]2D5 = –59 (c = 1.0,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.40–7.14 (m, 15 H,
Sulfoxides 14a and 14b: m-CPBA (0.20 g, 1.16 mmol) was added to
a solution of thioglycoside 6 (0.5 g, 1.05 mmol) in CH2Cl2 and 10%
aq. NaHCO3 at 0 °C. After stirring the mixture at 0 °C for 1 h, the
mixture was warmed to room temperature and stirred for 1 h. The
mixture was diluted with CHCl3 and washed with 10% NaHCO3.
After extracting the aqueous layer, the organic phase was washed
with10% Na2S2O3 and brine. The extract was dried with Na2SO4,
filtered, and concentrated. The residue was purified by silica gel
column chromatography (CHCl3/EOAc, 3:1) to give 14a (342 mg,
66%) and 14b (68 mg, 13%) as products. Sulfoxide 14a: m.p.
160 °C. [α]2D4 = –137.5 (c = 0.59, CHCl3). 1H NMR (400 MHz,
CDCl3, 23 °C): δ = 7.47–7.32 (m, 14 H, aromatic H), 7.14 (d, 3JH,H
= 8.0 Hz, 1 H, aromatic H), 5.55 (s, 1 H, acetal PhCH), 5.14 (d,
3
aromatic H), 5.37 (dd, JH,H = 10.5, 8.5 Hz, 1 H, 4-H), 4.80 (d,
3
3JH,H = 9.5 Hz, 1 H, 1-H), 4.74 (s, 2 H, N-CH2Ph), 4.55 (d, JH,H
3
= 11.5 Hz, 1 H, O-CH2Ph), 4.47 (d, JH,H = 11.5 Hz, 1 H, O-
3
3
CH2Ph), 4.18 (t, JH,H = 11.0 Hz, 1 H, 3-H), 3.99 (d, JH,H
=
3
15.0 Hz, 1 H, COCH2Cl), 3.91 (d, JH,H = 15.0 Hz, 1 H,
COCH2Cl), 3.74 (m, 1 H, 5-H), 3.57 (dd, 3JH,H = 11.0, 9.5 Hz, 1 H,
2-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 165.8 (oxazolidinone
C=O), 158.4, 137.4, 135.9, 132.5, 132.0, 129.1, 128.7, 128.5, 128.4,
128.2, 127.9, 127.9, 127.8, 86.8 (C-1), 79.5 (C-3), 78.3 (C-5), 73.6
(O-CH2Ph), 69.6 (C-4), 68.6 (C-6), 60.1 (C-2), 47.6 (N-CH2Ph),
40.4 (COCH2Cl) ppm. C29H28ClNO6S (554.05): calcd. C 62.87, H
5.09, N 2.53; found C 62.71, H 5.04, N 2.47.
3
3JH,H = 16.8 Hz, 1 H, N-CH2Ph), 4.53 (d, JH,H = 16.8 Hz, 1 H,
3
3
N-CH2Ph), 4.39 (t, JH,H = 10.0 Hz, 1 H), 4.12 (t, JH,H = 8.4 Hz,
6-O-Benzyl-2-benzylamino-2-N,3-O-carbonyl-4-O-chloroacetyl-2-de-
oxy-α-D-glucopyranosyl Fluoride (12): NBS (49 mg, 0.273 mmol)
3
1 H), 4.04–3.94 (m, 3 H), 3.90 (t, JH,H = 10.4 Hz, 1 H), 3.42 (m,
1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3, 23 °C): δ = 158.3
(oxazolidinone C=O), 137.8, 136.8, 136.0, 131.6, 129.2, 128.9,
128.7, 128.2, 127.7, 127.1, 125.9, 124.8, 101.4 (acetal PhCH), 90.8
(C-1), 78.1, 77.8, 73.6, 67.6, 59.2, 48.9 ppm. HRMS for
C27H25NO6S + Na [M + Na]+ 514.1295; found 514.1289.
and DAST (48 μL, 0.364 mmol) were added to a solution of thiog-
lycoside 11 (101 mg, 0.182 mmol) in CH2Cl2 (4 mL) at –10 °C. Af-
ter stirring the mixture at 0 °C for 2 h, satd. NaHCO3 was added.
The aqueous layer was extracted with EtOAc. The combined layers
were washed with satd. NaHCO3 and brine. After drying the ex-
tract over Na2SO4, the solvent was removed. The residue was puri-
fied by silica gel column chromatography (hexane/toluene/EtOAc,
Sulfoxide 14b: M.p. 168 °C. [α]2D4 = –30.9 (c = 0.95, CHCl3). 1H
NMR (400 MHz, CDCl3, 23 °C): δ = 7.53–7.31 (m, 15 H, aromatic
506
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 497–516

1,2-cis-Selective Glycosylation Reactions
3
H), 5.47 (s, 1 H, acetal PhCH), 5.11 (d, JH,H = 15.6 Hz, 1 H, N- C=O), 137.5, 134.5, 132.3, 129.1, 129.0, 128.9, 128.4, 128.3, 128.1,
3
3
CH2Ph), 4.87 (d, JH,H = 15.6 Hz, 1 H, N-CH2Ph), 4.30 (t, JH,H
127.8, 127.7, 85.8 (C-1), 74.2 (C-3), 73.5 (O-CH2Ph), 70.0 (C-5),
= 10.4 Hz, 1 H, 1-H), 4.26 (d, 3JH,H = 9.2 Hz, 1 H), 3.99 (dd, 3JH,H 68.3 (C-6), 66.1 (C-4), 56.1 (C-2), 48.2 (N-CH2Ph), 20.6
= 10.0, 4.4 Hz, 1 H), 3.87 (t, JH,H = 8.8 Hz, 1 H), 3.62 (t, JH,H
3
3
=
(COCH3) ppm. C29H29NO6S (519.61): calcd. C 67.03, H 5.63, N
3
10.4 Hz, 1 H), 3.56 (t, JH,H = 10.4 Hz, 1 H), 3.40 (m, 1 H, 5- 2.70; found C 66.78, H 5.41, N 2.64.
H) ppm. 13C NMR (100 MHz, CDCl3, 23 °C): δ = 158.8 (oxazolidi-
β-Galactoside 16b: M.p. 119–120 °C. [α]2D5 = –95 (c = 1.0, CHCl3).
none C=O), 139.2, 135.9, 134.9, 132.1, 129.2, 128.9, 128.8, 128.7,
128.2, 128.0, 125.9, 125.9, 101.4 (acetal PhCH), 95.0 (C-1), 78.2,
77.8, 77.2, 73.5, 67.5, 60.8, 48.5 ppm. C27H25NO6S (491.56): calcd.
C 65.97, H 5.13, N 2.85; found C 65.87, H 5.17, N 2.57.
1H NMR (500 MHz, CDCl3): δ = 7.40–7.20 (m, 15 H, aromatic
H), 5.67 (br. s, 1 H, 4-H), 4.78 (d, 3JH,H = 15.5 Hz, 1 H, N-CH2Ph),
3
3
4.76 (d, JH,H = 9.5 Hz, 1 H, 1-H), 4.70 (d, JH,H = 15.5 Hz, 1 H,
N-CH2Ph), 4.52 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.42 (d, 3JH,H
= 12.0 Hz, 1 H, O-CH2Ph), 4.21 (dd, 3JH,H = 11.5, 2.0 Hz, 1 H, 3-
Phenyl 4,6-Di-O-acetyl-2-benzylamino-2-N,3-O-carbonyl-2-deoxy-1-
thio-α-D-glucopyranoside (15): A mixture of benzylidene acetal 6
3
H), 3.93 (br. t, 1 H, 5-H), 3.84 (dd, JH,H = 11.5, 9.5 Hz, 1 H, 2-
H), 3.57 (d, JH,H = 6.0 Hz, 2 H, 6a-H, 6b-H), 2.04 (s, 3 H,
3
(2.14 g, 4.51 mmol) in AcOH (40 mL) and water (10 mL) was
stirred at 100 °C for 1 h. After concentration, the mixture was
washed with diethyl ether/hexane to remove benzaldehyde. After
drying the mixture in vacuo, the crude was dissolved in pyridine
(20 mL) and Ac2O (20 mL) was added. After stirring overnight, the
mixture was evaporated. The residue was diluted with AcOEt and
1 m HCl. The aqueous layer was extracted with EtOAc. The com-
bined layers were washed with brine. After drying the extract over
Na2SO4, the solvent was removed. The residue was purified by sil-
ica gel column chromatography (hexane/EtOAc, 7:3–1:1) to give
COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 169.2 (C=O),
153.6 (oxazolidinone C=O), 137.5, 136.4, 132.4, 132.2, 129.1, 128.6,
128.4, 128.4, 128.0, 127.8, 127.5, 88.0 (C-1), 78.9 (C-3), 77.2 (C-5),
73.6 (O-CH2Ph), 68.1 (C-6), 65.1 (C-4), 57.1 (C-2), 48.1 (N-
CH2Ph), 20.6 (COCH3) ppm. C29H29NO6S (519.61): C 67.03, H
5.63, N 2.70; found C 66.95, H 5.36, N 2.59.
Disaccharides 21a and 21b: Tf2O (10 μL, 0.06 mmol) was added
dropwise to a solution of acceptor (46 mg, 0.099 mmol), donor
(58 mg, 0.119 mmol), DTBMP (41 mg, 0.198 mmol), and 4-Å mo-
lecular sieves (200 mg) in CH2Cl2 (4 mL) at –40 °C. After stirring
the mixture at –40 °C for 12 h, Et3N and satd. NaHCO3 were
added. The aqueous layer was extracted with EtOAc and the com-
bined layers were washed with brine. After drying the mixture over
Na2SO4, the solvent was evaporated. The residue was purified by
preparative TLC (hexane/EtOAc, 7:3) to give 21a (21 mg, 26%) and
21b (3.2 mg, 3%).
the diacetate 15 (2.02 g, 95%). [α]2D4 = –74 (c = 0.85, CHCl3). H
NMR (400 MHz, CDCl3, 22 °C): δ = 7.38–7.26 (m, 10 H, aromatic
H), 5.23 (t, JH,H = 9.2 Hz, 1 H, 4-H), 4.75 (d, JH,H = 9.6 Hz, 1
H, 1-H), 4.74 (s, 2 H, N-CH2Ph), 4.21–4.11 (m, 3 H, 6-H, 3-H),
3.71 (m, 1 H, 5-H), 3.51 (t, JH,H = 9.6 Hz, 1 H, 2-H), 2.09 (s, 3
1
3
3
3
H, COCH3), 2.04 (s, 3 H, COCH3) ppm. 13C NMR (500 MHz,
CDCl3, 22 °C): δ = 170.2 (COCH3), 167.0 (oxazolidinone C=O),
158.3, 135.7, 132.8, 129.0, 128.6, 128.1, 127.7, 86.7 (C-1), 79.8,
77.2, 67.4, 62.3, 60.3, 47.7, 20.9 (COCH3), 20.8 (COCH3) ppm.
C24H25NO7S (471.52): calcd. C 61.13, H 5.34, N 2.97; found C
61.10, H 5.25, N 2.86.
Disaccharide 21a: [α]2D4 = 21.7 (c = 0.95, CHCl3). 1H NMR
(400 MHz, CDCl3, 23 °C): δ = 7.48–7.14 (m, 25 H, aromatic H),
3
5.50 (s, 1 H, acetal PhCH), 5.00 (d, JH,H = 10.8 Hz, 1 H, O-
3
3
CH2Ph), 4.90 (d, JH,H = 11.2 Hz, 1 H, O-CH2Ph), 4.83 (d, JH,H
Phenyl 4-O-Acetyl-2-benzylamino-6-O-benzyl-2-N,3-O-carbonyl-2-
deoxy-1-thio-α- and β-D-galactopyranoside (16): Trifluoromethane-
3
= 11.2 Hz, 1 H, O-CH2Ph), 4.83 (d, JH,H = 3.2 Hz, 1 H, 1-H),
4.79 (d, 3JH,H = 12.4 Hz, 1 H, O-CH2Ph), 4.62 (d, 3JH,H = 12.0 Hz,
sulfonic anhydride (Tf2O, 1.8 mL, 10.5 mmol) was added to a mix-
ture of 7 (2.5 g, 5.23 mmol) and pyridine (1.7 mL, 21.0 mmol) in
CH2Cl2 (30 mL) at –40 °C and then the mixture was warmed to
–20 °C. After stirring the mixture for 3 h, the mixture was poured
into 0.1 m aqueous HCl and extracted with CHCl3. The combined
organic extracts were washed with satd. aqueous NaHCO3 and
water, dried (Na2SO4), filtered, and concentrated to dryness. The
crude triflate was used in the next step without further purification.
The triflate was treated with sodium acetate (4.3 g, 52.3 mmol) in
DMF (30 mL) at 60 °C for 2 d. The mixture was diluted with
EtOAc, poured into ice-cold water, and extracted with EtOAc. The
combined organic extracts were washed with water and brine, dried
(Na2SO4), filtered, and concentrated. The residue was purified by
flash column chromatography (CHCl3/EtOAc, 14:1). The first elu-
tion was α-galactoside 16a (0.34 g, 13%) and eluted next was β-
galactoside 16b (2.0 g, 73%). Galactosides 16a and 16b were crys-
tallized from EtOAc/hexane, respectively.
3
1 H, O-CH2Ph), 4.60–4.48 (m, 4 H), 4.13 (d, JH,H = 4.4 Hz, 1 H),
4.10–4.01 (m, 2 H), 3.88 (t, JH,H = 8.4 Hz, 1 H), 3.85–3.74 (m, 3
3
H), 3.73 (m, 1 H), 3.51–3.43 (m, 3 H), 3.42 (s, 3 H), 3.16 (dd,
3JH,H = 11.2, 2.4 Hz, 1 H, 2-H) ppm. 13C NMR (100 MHz, CDCl3,
22 °C): δ = 158.2 (oxazolidinone C=O), 138.4, 137.8, 137.6, 136.4,
134.7, 129.1, 128.8, 128.5, 128.4, 128.3, 128.2, 128.1, 128.1, 127.9,
127.5, 125.9, 101.3 (acetal PhCH), 98.3 (C-1), 96.6 (C-1), 82.0, 80.1,
79.5, 77.2, 75.8, 74.9, 73.5, 73.0, 70.1, 68.5, 66.7, 65.5, 60.9, 55.5,
47.7 ppm. HRMS: calcd. for C49H51NO11 + Na [M + Na]+
852.3354; found 852.3354.
Disaccharide 21b: [α]2D4 = 7.7 (c = 0.5, CHCl3). 1H NMR (400 MHz,
CDCl3, 22 °C): δ = 7.43–7.21 (m, 25 H, aromatic H), 5.47 (s, 1 H,
3
acetal PhCH), 4.98 (d, JH,H = 10.4 Hz, 1 H, O-CH2Ph), 4.87 (d,
3
3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.79 (d, JH,H = 10.8 Hz, 1 H,
O-CH2Ph), 4.78 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.60 (d, 3JH,H
3
= 12.4 Hz, 1 H, O-CH2Ph), 4.55–4.39 (m, 3 H), 4.40 (d, JH,H
=
3
α-Galactoside 16a: M.p. 148–149 °C. [α]2D5 = +186 (c = 1.0, CHCl3).
8.0 Hz, 1 H), 4.29 (d, JH,H = 14.8 Hz, 1 H, N-CH2Ph), 4.24 (dd,
1H NMR (500 MHz, CDCl3): δ = 7.40–7.21 (m, 15 H, aromatic 3JH,H = 10.4, 4.4 Hz, 1 H), 4.13 (t, JH,H = 10.4 Hz, 1 H), 4.00 (t,
3
H), 5.66 (br. s, 1 H, 4-H), 5.40 (d, JH,H = 4.5 Hz, 1 H, 1-H), 4.71 3JH,H = 9.2 Hz, 1 H), 3.94–3.79 (m, 4 H), 3.52 (dd, JH,H = 9.6,
3
3
3
(d, JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.56 (m, 1 H, 5-H), 4.49 (dd,
3.2 Hz, 1 H), 3.47–3.22 (m, 4 H), 3.33 (s, 3 H, OCH3) ppm. 13C
NMR (100 MHz, CDCl3, 22 °C): δ = 158.4 (oxazolidinone C=O),
138.3, 137.9, 137.8, 136.2, 135.1, 129.2, 129.1, 128.5, 128.4, 128.3,
128.2, 128.0, 128.0, 127.9, 127.9, 127.8, 127.6, 125.9, 102.7, 101.2,
98.2, 81.9, 79.7, 78.7, 77.8, 77.3, 76.1, 75.9, 74.8, 73.5, 69.7, 69.5,
3JH,H = 12.5, 2.5 Hz, 1 H, 3-H), 4.49 (d, JH,H = 12.0 Hz, 1 H, O-
3
3
3
CH2Ph), 4.43 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.28 (d, JH,H
= 15.0 Hz, 1 H, N-CH2Ph), 3.97 (dd, 3JH,H = 12.5, 4.5 Hz, 1 H, 2-
3
3
H), 3.56 (dd, JH,H = 10.0, 5.5 Hz, 1 H, 6a-H), 3.51 (dd, JH,H
=
10.0, 6.0 Hz, 1 H, 6b-H), 2.01 (s, 3 H, COCH3) ppm. 13C NMR 68.7, 68.3, 61.4, 55.6, 48.2 ppm. HRMS: calcd. for C49H51NO11
(125 MHz, CDCl3): δ = 169.3 (COCH3), 158.0 (oxazolidinone Na [M + Na]+ 852.3354; found 852.3360.
+
Eur. J. Org. Chem. 2011, 497–516
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
507

S. Manabe, K. Ishii, Y. Ito
FULL PAPER
General Glycosylation Procedure
CH2Ph), 70.8 (C-5II), 70.2 (C-4II), 70.0 (C-5I), 67.1 (C-6II), 66.6 (C-
6I), 59.9 (C-2II), 55.4 (OCH3), 47.8 (N-CH2Ph), 40.3
(COCH2Cl) ppm. C51H54ClNO12 (908.43): calcd. C 67.43, H 5.99,
N 1.54; found C 67.41, H 5.88, N 1.57.
Method A: Tf2O (1 equiv., based on the donor) was added to a
mixture of N-(phenylthio)-ε-caprolactam (1.1 equiv.), DTBMP
(2.0 equiv., based on the donor), an acceptor, and a donor in
CH2Cl2 containing activated molecular sieves (4 Å). After stirring
the mixture for 0.5–1.5 h, the reaction was quenched by the ad-
dition of saturated aqueous NaHCO3 and then filtered through
Celite. The filter cake was washed with CHCl3 and the filtrates
were extracted with CHCl3. The combined organic extracts were
washed with water, dried with Na2SO4, filtered, and concentrated.
The residue was purified by size-exclusion chromatography [Bio-
beads SX-3 (3.0ϫ58 cm, toluene)] and subsequent silica gel col-
umn chromatography or preparative TLC.
β-Linked Disaccharide 22b: [α]2D6 = +12 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.40–7.23 (m, 25 H, aromatic H), 5.22 (dd,
3
3JH,H = 10.5, 8.0 Hz, 1 H, 4II-H), 4.99 (d, JH,H = 11.0 Hz, 1 H,
O-CH2Ph), 4.87 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.80 (d, 3JH,H
3
= 11.5 Hz, 1 H, O-CH2Ph), 4.80 (d, JH,H = 11.0 Hz, 1 H, O-
3
3
CH2Ph), 4.62 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.56 (d, JH,H
= 15.0 Hz, 1 H, N-CH2Ph), 4.56 (d, JH,H = 3.0 Hz, 1 H, 1I-H),
3
4.52 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.49 (d, 3JH,H = 12.0 Hz,
1 H, O-CH2Ph), 4.41 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.40 (d,
3JH,H = 8.0 Hz, 1 H, 1II-H), 4.27 (d, JH,H = 15.0 Hz, 1 H, N-
3
Method B: PhSCl (1.2 equiv., based on the donor) was added to a
mixture of DTBMP (2.0 equiv., based on the donor), AgOTf
(1.5 equiv., based on the donor), an acceptor (1 equiv.), and a do-
nor (1.2 equiv.) in 1,4-dioxane/toluene (3:1, v/v) containing acti-
vated 4-Å molecular sieves at 0 °C. The reaction mixture, whilst
stirred, was warmed to room temperature and then stirred over-
night. The reaction was quenched by the addition of saturated
aqueous NaHCO3 and then filtered through Celite. The filter cake
was washed with EtOAc and the filtrates were extracted with
EtOAc. The combined organic extracts were washed with brine,
dried with Na2SO4, filtered, and concentrated. The residue was
purified in the same manner as described for Method A.
3
3
CH2Ph), 4.02 (t, JH,H = 10.0 Hz, 1 H), 4.01 (dd, JH,H = 12.5,
10.5 Hz, 1 H), 4.00 (dd, 3JH,H = 12.0, 10.5 Hz, 1 H, 3II-H), 3.93 (d,
3JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.85 (d, JH,H = 15.0 Hz, 1 H,
3
COCH2Cl), 3.84 (m, 1 H, 5II-H), 3.60 (m, 1 H, 5II-H), 3.54 (m, 2
H, 6IIa-H, 6IIb-H), 3.52 (dd, JH,H = 12.5, 5.5 Hz, 1 H, 6Ib-H),
3
3.47 (dd, 3JH,H = 9.5, 3.0 Hz, 1 H, 2I-H), 3.34 (s, 3 H, OCH3), 3.33
(t, JH,H = 10.0 Hz, 1 H, 4I-H), 3.30 (dd, JH,H = 12.0, 8.0 Hz, 1
3
3
H, 2II-H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 165.7
(COCH2Cl), 158.1 (oxazolidinone C=O), 138.5, 138.1, 137.9, 137.3,
135.1, 129.3–127.7, 102.0 (C-1I), 98.2 (C-1II), 81.9 (C-3I), 79.8 (C-
2I), 77.8 (C-4I), 76.7 (C-3II), 75.8 (O-CH2Ph), 75.3 (C-5II), 74.7 (O-
CH2Ph), 73.7 (O-CH2Ph), 73.4 (O-CH2Ph), 70.0 (C-4II), 69.8 (C-
5I), 68.6 (C-6II), 68.5 (C-6I), 60.1 (C-2II), 55.5 (OCH3), 48.0 (N-
CH2Ph), 40.3 (COCH2Cl) ppm. C51H54ClNO12 (908.43): calcd. C
67.43, H 5.99, N 1.54; found C 67.47, H 5.89, N, 1.49.
Disaccharides 22a and 22b. Method A: Glycosylation of 11 (22 mg,
0.047 mmol) with 20 (31 mg, 0.056 mmol) in CH2Cl2 (3 mL) in the
presence of N-(phenylthio)-ε-caprolactam (14 mg, 0.062 mmol),
Tf2O (13 μL, 0.074 mmol), and 4-Å molecular sieves (0.3 g) at
room temperature for 1.5 h, subsequent work-up, and purification
by preparative TLC (toluene/hexane/EtOAc, 4:1:1) gave 22a
(15 mg, 35%) and 22b (20 mg, 47%).
Disaccharide 24. Method A: Glycosylation of 23 (27 mg,
0.045 mmol) with 11 (30 mg, 0.054 mmol) in CH2Cl2 (3 mL) in the
presence of N-(phenylthio)-ε-caprolactam (13 mg, 0.059 mmol),
Tf2O (11 μL, 0.065 mmol), and 4-Å molecular sieves (0.3 g) at
room temperature for 40 min, subsequent work-up, and purifica-
tion by preparative TLC (toluene/hexane/EtOAc, 4:1:1) gave 24
Method B: Glycosylation of 10 (100 mg, 0.215 mmol) with 20
(143 mg, 0.258 mmol) in 1,4-dioxane/toluene (3:1, 8 mL) in the
presence of DTBMP (106 mg, 0.516 mmol), AgOTf (99 mg,
0.387 mmol), PhSCl (36 μL, 0.310 mmol), and 4-Å molecular sieves
(0.8 g) at 0 °C to room temperature overnight, subsequent work-
up, and purification by size-exclusion chromatography (SX-3) and
flash column chromatography on silica gel (CHCl3/toluene/EtOAc,
10:4:1–10:1:1) gave 22a (156 mg, 80%) and 22b (15 mg, 8%).
1
(26 mg, 56%). [α]2D6 = +69 (c = 0.5, CHCl3). H NMR (500 MHz,
3
CDCl3): δ = 7.44–7.00 (m, 29 H, aromatic H), 5.60 (d, JH,H
=
8.5 Hz, 1 H, 1I-H), 5.49 (d, JH,H = 3.0 Hz, 1 H, 1II-H), 5.32 (t,
3
3JH,H = 10.0 Hz, 1 H, 4II-H), 4.73 (d, JH,H = 12.0 Hz, 1 H, O-
3
3
3
CH2Ph), 4.64 (d, JH,H = 14.5 Hz, 1 H, N-CH2Ph), 4.60 (d, JH,H
3
= 11.5 Hz, 1 H, O-CH2Ph), 4.59 (dd, JH,H = 12.0, 10.5 Hz, 1 H,
α-Linked Disaccharide 22a: [α]2D6 = +54 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.83–7.14 (m, 25 H, aromatic H), 5.38 (t,
3II-H), 4.58 (t, 3JH,H = 9.0 Hz, 1 H, 2I-H), 4.55 (d, 3JH,H = 11.5 Hz,
1 H, O-CH2Ph), 4.54 (t, JH,H = 9.0 Hz, 1 H, 3I-H), 4.50 (d, JH,H
3
3
3JH,H = 10.0 Hz, 1 H, 4II-H), 5.01 (d, JH,H = 11.0 Hz, 1 H, O-
3
3
= 11.5 Hz, 1 H, O-CH2Ph), 4.36 (d, JH,H = 12.0 Hz, 1 H, O-
3
3
CH2Ph), 4.92 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.84 (d, JH,H
3
3
CH2Ph), 4.36 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.26 (t, JH,H
3
= 3.0 Hz, 1 H, 1II-H), 4.80 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph),
= 9.0 Hz, 1 H, 4I-H), 4.05 (dd, JH,H = 11.5, 3.0 Hz, 1 H, 6Ia-H),
3
4.64 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.58 (d, 3JH,H = 11.5 Hz,
1 H, O-CH2Ph), 4.55 (d, 3JH,H = 14.5 Hz, 1 H, N-CH2Ph), 4.51 (d,
4.01 (m, 1 H, 5I-H), 4.00 (d, 3JH,H = 14.5 Hz, 1 H, N-CH2Ph), 3.96
3
3
(d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.88 (d, JH,H = 15.0 Hz, 1
3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.38 (d, JH,H = 11.0 Hz, 1 H,
3
H, COCH2Cl), 3.79 (dd, 3JH,H = 11.5, 1.5 Hz, 1 H, 6Ib-H), 3.71 (s,
O-CH2Ph), 4.35 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.50 (d, 3JH,H
3 H, PhOCH3), 3.41 (dd, JH,H = 11.0, 2.5 Hz, 1 H, 6IIa-H), 3.36
3
3
= 4.0 Hz, 1 H, 1I-H), 4.41 (dd, JH,H = 12.0, 10.5 Hz, 1 H, 3II-H),
(dd, 3JH,H = 11.0, 4.0 Hz, 1 H, 6IIb-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 165.6 (COCH2Cl), 157.9 (oxazolidinone C=O), 155.5,
150.7, 138.0, 137.2, 134.2, 134.2, 131.4, 129.1–127.4, 123.5, 118.9,
114.4, 97.8 (C-1I), 95.5 (C-1II), 79.1 (C-3I), 76.5 (C-4I), 74.9 (C-5I),
73.5 (O-CH2Ph), 73.5 (C-3II), 73.4 (O-CH2Ph), 73.2 (O-CH2Ph),
71.8 (C-5II), 70.4 (C-4II), 68.6 (C-6I), 67.6 (C-6II), 59.9 (C-2II), 55.6
(PhOCH3), 55.0 (C-2I), 47.7 (N-CH2Ph), 40.4 (COCH2Cl) ppm.
C58H55ClN2O14 (1039.52): calcd. C 67.01, H 5.33, N 2.69; found C
66.83, H 5.29, N, 2.63.
3
3
4.01 (t, JH,H = 9.5 Hz, 1 H, 3I-H), 4.00 (d, JH,H = 14.5 Hz, 1 H,
3
N-CH2Ph), 3.92 (d, JH,H = 14.5 Hz, 1 H, COCH2Cl), 3.85 (d,
3JH,H = 14.5 Hz, 1 H, COCH2Cl), 3.75 (dd, JH,H = 11.5, 4.0 Hz,
3
1 H, 6Ia-H), 3.68 (m, 1 H, 5II-H), 3.67 (m, 1 H, 5I-H), 3.50 (dd,
3JH,H = 11.5, 2.0 Hz, 1 H, 6Ib-H), 3.46 (dd, JH,H = 9.5, 4.0 Hz, 1
3
3
3
H, 2I-H), 3.44 (t, JH,H = 10.0 Hz, 1 H, 4I-H), 3.41 (dd, JH,H
=
=
11.0, 3.0 Hz, 1 H, 6IIa-H), 3.39 (s, 3 H, OCH3), 3.36 (dd, JH,H
3
11.0, 3.5 Hz, 1 H, 6IIb-H), 3.24 (dd, 3JH,H = 10.5, 3.0 Hz, 1 H, 2II-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 165.5 (COCH2Cl),
158.0 (oxazolidinone C=O), 138.5, 138.1, 137.8, 137.2, 134.6,
Disaccharide 26. Method A: Glycosylation of 25 (26 mg,
129.0–127.7, 98.3 (C-1I), 95.6 (C-1II), 82.0 (C-3I), 79.6 (C-2I), 77.0 0.051 mmol) with 11 (34 mg, 0.061 mmol) in CH2Cl2 (3 mL) in the
(C-4I), 75.8 (O-CH2Ph), 74.8 (O-CH2Ph), 73.6 (C-3II), 73.5 (O- presence of N-(phenylthio)-ε-caprolactam (15 mg, 0.067 mmol),
508
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 497–516

1,2-cis-Selective Glycosylation Reactions
Tf2O (12 μL, 0.073 mmol), and 4-Å molecular sieves (0.3 g) at
room temperature for 30 min, subsequent work-up, and purifica-
tion by preparative TLC (CHCl3/EtOAc, 19:1) gave 26 (25 mg,
52%). [α]2D6 = +132 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3):
δ = 8.11–7.01 (m, 25 H, aromatic H), 6.14 (dd, 3JH,H = 10.0, 9.0 Hz,
(3:1, 8 mL) at 0 °C to room temperature in the presence of DTBMP
(118 mg, 0.574 mmol), AgOTf (111 mg, 0.431 mmol), PhSCl
(40 μL, 0.344 mmol), and 4-Å molecular sieves (0.8 g), subsequent
work-up, and purification by size-exclusion chromatography (SX-
3) and flash column chromatography on silica gel (CHCl3/EtOAc,
14:1–12:1) gave 30a (135 mg, 71%) and 30b (7 mg, 4%).
3
3
1 H, 3I-H), 5.32 (d, JH,H = 3.5 Hz, 1 H, 1II-H), 5.26 (t, JH,H
=
3
10.0 Hz, 1 H, 4II-H), 5.26 (dd, JH,H = 10.0, 3.5 Hz, 1 H, 2I-H),
α-Linked Disaccharide 30a: [α]2D6 = +52 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.34–7.10 (m, 15 H, aromatic H), 5.79 (d,
5.15 (d, 3JH,H = 3.5 Hz, 1 H, 1I-H), 4.76 (dd, 3JH,H = 12.5, 2.0 Hz,
1 H, 6Ia-H), 4.60 (dd, JH,H = 12.5, 3.5 Hz, 1 H, 6Ib-H), 4.52 (dd,
3
3
3JH,H = 4.0 Hz, 1 H, 1I-H), 5.39 (t, JH,H = 10.0 Hz, 1 H, 4II-H),
3JH,H = 12.0, 10.5 Hz, 1 H, 3II-H), 4.50 (d, JH,H = 15.0 Hz, 1 H,
3
3
5.10 (d, 3JH,H = 3.0 Hz, 1 H, 1II-H), 4.64 (d, JH,H = 12.0 Hz, 1 H,
N-CH2Ph), 4.41 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.20 (d, 3JH,H
3
O-CH2Ph), 4.61 (d, JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.58 (dd,
= 12.0 Hz, 1 H, O-CH2Ph), 4.37 (t, JH,H = 9.5 Hz, 1 H, 4I-H),
3
3
3JH,H = 12.0, 10.0 Hz, 1 H, 3II-H), 4.57 (d, JH,H = 11.5 Hz, 1 H,
4.23 (m, 1 H, 5I-H), 3.92 (d, JH,H = 14.5 Hz, 1 H, COCH2Cl),
3
O-CH2Ph), 4.55 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.53 (d, 3JH,H
3.79 (d, 3JH,H = 14.5 Hz, 1 H, COCH2Cl), 3.64 (d, 3JH,H = 15.0 Hz,
3
= 5.5 Hz, 1 H, 5I-H), 4.38 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph),
3
1 H, N-CH2Ph), 3.47 (s, 3 H, OCH3), 3.30 (dd, JH,H = 11.0,
3
3
4.21 (t, JH,H = 4.0 Hz, 1 H, 2I-H), 4.16 (dd, JH,H = 5.5, 4.0 Hz,
2.0 Hz, 1 H, 6IIa-H), 3.20 (dd, JH,H = 11.0, 3.5 Hz, 1 H, 6IIb-H),
3
1 H, 4I-H), 4.02 (d, JH,H = 15.0 Hz, 1 H, N-CH2Ph), 3.92 (m, 1
3
3.13 (dd, JH,H = 12.0, 3.5 Hz, 1 H, 2II-H) ppm. 13C NMR
3
H, 5II-H), 3.91 (d, 3JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.84 (d, 3JH,H
= 15.0 Hz, 1 H, COCH2Cl), 3.82 (t, 1 H, 3I-H), 3.65 (s, 3 H,
(125 MHz, CDCl3): δ = 166.0 (COPh), 165.9 (COPh), 165.9
(COPh), 165.5 (COPh), 157.7, 136.9, 134.0, 133.8, 133.5, 129.9–
127.9, 96.8 (C-1I), 94.6 (C-1II), 73.5 (O-CH2Ph), 73.4 (C-4I), 73.0
(C-3II), 72.6 (C-3I), 72.3 (C-5II), 71.9 (C-2I), 69.8 (C-4II), 68.1 (C-
5I), 66.8 (C-6II), 59.0 (C-2I), 55.7 (OCH3), 47.1 (N-CH2Ph), 40.3
(COCH2Cl) ppm. C51H48ClNO15 (950.38): calcd. C 64.45, H 5.09,
N 1.47; found C 64.35, H 5.05, N 1.47.
CO2CH3), 3.53 (dd, JH,H = 11.0, 2.5 Hz, 1 H, 6IIa-H), 3.46 (dd,
3
3JH,H = 11.0, 3.5 Hz, 1 H, 6IIb-H), 3.33 (dd, JH,H = 12.0, 3.0 Hz,
3
1 H, 2II-H), 1.58 [s, 3 H, C(CH3)2], 1.38 [s, 3 H, C(CH3)2] ppm. 13
C
NMR (125 MHz, CDCl3): δ = 169.8 (C-6I), 165.5 (COCH2Cl),
157.9 (oxazolidinone C=O), 137.1, 136.9, 134.6, 129.0, 128.6, 128.5,
128.3, 128.2, 128.1, 127.9, 127.5, 111.1 [C(CH3)2], 95.5 (C-1I), 94.2
(C-1II), 75.1 (C-2I), 74.5 (C-3I), 73.6 (C-3II), 73.5 (O-CH2Ph), 72.5
(C-4I), 71.9 (C-5I), 71.8 (O-CH2Ph), 71.6 (C-5II), 67.0 (C-4II), 66.9
(C-6II), 59.7 (C-2II), 52.4 (CO2CH3), 47.6 (N-CH2Ph), 40.3
(COCH2Cl), 27.3 [C(CH3)2], 25.8 [C(CH3)2] ppm. C40H45ClNO13
(783.24): calcd. C 61.34, H 5.79, N 1.79; found C 61.35, H 5.63, N
1.71.
Disaccharides 28a and 28b. Method B: Glycosylation of 27 (12 mg,
0.045 mmol) with 11 (30 mg, 0.054 mmol) in 1,4-dioxane/toluene
(3:1, 8 mL) in the presence of DTBMP (106 mg, 0.516 mmol), Ag-
OTf (99 mg, 0.387 mmol), PhSCl (36 μL, 0.310 mmol), and 4-Å
molecular sieves (0.8 g) at 0 °C to room temperature overnight,
subsequent work-up, and purification by size-exclusion chromatog-
raphy (SX-3) and preparative TLC (toluene/hexane/EtOAc, 4:1:1)
gave 28a (21 mg, 65%) and 28b (4.8 mg, 15%).
β-Linked Disaccharide 30b: 1H NMR (500 MHz, CDCl3): δ = 7.46–
3
7.20 (m, 5 H, aromatic H), 5.64 (d, JH,H = 4.5 Hz, 1 H, 1I-H),
α-Linked Disaccharide 28a: 1H NMR (500 MHz, CDCl3): δ = 7.39–
5.28 (dd, 3JH,H = 10.0, 9.0 Hz, 1 H, 4II-H), 5.37 (d, 3JH,H = 8.0 Hz,
3
7.24 (m, 10 H, aromatic H), 5.90 (d, JH,H = 3.7 Hz, 1 H, 1-H),
3
1 H, 1II-H), 4.72 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.64 (d,
3
3
5.29 (t, JH,H = 9.7 Hz, 1 H, 4II-H), 5.20 (d, JH,H = 2.8 Hz, 1 H,
3
3JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.55 (d, JH,H = 12.0 Hz, 1 H,
3
3
1-H), 4.85 (d, JH,H = 14.7 Hz, 1 H, N-CH2Ph), 4.65 (d, JH,H
=
O-CH2Ph), 4.42 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.39 (d, 3JH,H
3
3.7 Hz, 1 H), 4.53 (t, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.43 (d,
3
= 12.0 Hz, 1 H, O-CH2Ph), 4.36 (d, JH,H = 8.0 Hz, 1 H, 5I-H),
3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.28 (m, 1 H), 4.22–4.21 (m, 2
3
4.30 (br. d, 1 H, 4I-H), 4.27 (m, JH,H = 4.0, 1.0 Hz, 1 H, 2I-H),
3
H), 4.14–4.08 (m, 3 H), 3.97 (d, JH,H = 15.2 Hz, 1 H, COCH2Cl),
3
3
4.24 (d, JH,H = 4.0 Hz, 1 H, 3I-H), 4.24 (d, JH,H = 15.0 Hz, 1 H,
3.90 (d, 3JH,H = 15.2 Hz, 1 H, COCH2Cl), 3.82 (m, 1 H), 3.55 (dd,
N-CH2Ph), 4.11 (dd, JH,H = 11.5, 10.0 Hz, 1 H, 3II-H), 3.95 (d,
3
3JH,H = 10.6, 2.3 Hz, 1 H), 3.51 (dd, JH,H = 10.6, 5.1 Hz, 1 H),
3
3JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.87 (d, JH,H = 15.0 Hz, 1 H,
3
3
3.28 (dd, JH,H = 12.4, 3.3 Hz, 1 H), 1.50 [s, 3 H, C(CH3)2], 1.49
COCH2Cl), 3.79 (s, 3 H, CO2CH3), 3.75 (m, 1 H, 5II-H), 3.54 (dd,
[s,
3
H, C(CH3)2], 1.36 [s,
3
H, C(CH3)2], 1.22 [s,
3
H,
3JH,H = 11.0, 5.0 Hz, 1 H, 6IIa-H), 3.49 (dd, JH,H = 11.0, 3.0 Hz,
3
C(CH3)2] ppm. 13C NMR (125 MHz, CDCl3):
δ
=
165.6
1 H, 6IIb-H), 3.39 (dd, JH,H = 11.5, 8.0 Hz, 1 H, 2II-H), 1.55 [s, 3
3
(COCH2Cl), 157.8 (oxazolidinone C=O), 137.0, 134.4, 129.2, 128.5,
128.0, 112.2, 109.6, 105.2, 96.6, 83.3, 82.7, 80.8, 73.7, 73.3, 72.1,
72.0, 70.2, 67.5, 59.3, 47.1, 40.3, 27.3, 26.7, 26.1, 25.3 ppm.
C35H42ClNO12 (704.16): calcd. C 59.70, H 6.01, N 1.99; found C
59.78, H 6.00, N 1.97.
H, C(CH3)2], 1.35 [s, 3 H, C(CH3)2] ppm.
Disaccharides 32a and 32b. Method A: Glycosylation of 31 (24 mg,
0.071 mmol) with 11 (47 mg, 0.085 mmol) in CH2Cl2 (3 mL) in the
presence of DTBMP (35 mg, 0.170 mmol), N-(phenylthio)-ε-capro-
lactam (21 mg, 0.093 mmol), Tf2O (14 μL, 0.085 mmol), and 4-Å
molecular sieves (0.3 g) at room temperature for 30 min, subse-
quent work-up, and purification by size-exclusion chromatography
(SX-3) and flash column chromatography on silica gel (CHCl3/
EtOAc, 10:1) gave 32a (35 mg, 63%) and 32b (2 mg, 4%).
α-Linked Disaccharide 28b: 1H NMR (500 MHz, CDCl3): δ = 7.33–
3
7.26 (m, 10 H, aromatic H), 5.46 (d, JH,H = 4.2 Hz, 1 H, 1I-H),
5.41 (dd, 3JH,H = 10.0, 8.3 Hz, 1 H, 4II-H), 4.74 (d, 3JH,H = 7.8 Hz,
3
1 H, 1II-H), 4.60 (d, JH,H = 16.0 Hz, 1 H, N-CH2Ph), 4.54 (d,
3
3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.46 (d, JH,H = 12.0 Hz, 1 H,
3
O-CH2Ph), 4.35 (d, JH,H = 16.0 Hz, 1 H, N-CH2Ph), 4.28–4.19
Method B: Glycosylation of 31 (25 mg, 0.074 mmol) with 11
(65 mg, 0.118 mmol) in 1,4-dioxane/toluene (3:1, 3 mL) in the pres-
ence of DTBMP (48 mg, 0.236 mmol), AgOTf (45 mg,
0.177 mmol), PhSCl (16 μL, 0.142 mmol), and 4-Å molecular sieves
(0.3 g) at 0 °C to room temperature overnight, then work-up, and
purification by size-exclusion chromatography (SX-3) and flash
column chromatography on silica gel (CHCl3/EtOAc, 10:1) gave
32a (44 mg, 71%).
3
(m, 4 H), 4.00 (d, JH,H = 19.7 Hz, 1 H, COCH2Cl), 3.99 (s, 2 H),
3
3.93 (d, JH,H = 19.7 Hz, 1 H, COCH2Cl), 3.73 (m, 1 H), 3.69 (d,
3JH,H = 6.5 Hz, 1 H), 3.61 (m, 1 H), 3.41 (dd, 3JH,H = 12.0, 7.9 Hz,
1 H), 1.43 [s, 3 H, C(CH3)2], 1.38 [s, 3 H, C(CH3)2], 1.28 [s, 3 H,
C(CH3)2], 1.18 [s, 3 H, C(CH3)2] ppm.
Disaccharides 30a and 30b. Method B: Glycosylation of 29 (81 mg,
0.239 mmol) with 11 (159 mg, 0.287 mmol) in 1,4-dioxane/toluene
Eur. J. Org. Chem. 2011, 497–516
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
509

S. Manabe, K. Ishii, Y. Ito
FULL PAPER
α-Linked Disaccharide 32a: [α]2D6 = +8.0 (c = 1.0, CHCl3). 1H NMR
3
3
H), 4.52 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.50 (d, JH,H
=
(500 MHz, CDCl3): δ = 7.44–7.10 (m, 15 H, aromatic H), 5.39 (t, 15.2 Hz, 1 H, N-CH2Ph), 4.44 (d, 3JH,H = 15.2 Hz, 1 H, N-CH2Ph),
3JH,H = 10.0 Hz, 1 H, 4II-H), 5.37 (d, JH,H = 2.5 Hz, 1 H, 1I-H), 4.43 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.10 (t, JH,H = 11.6 Hz,
3
3
3
4.91 (d, 3JH,H = 3.0 Hz, 1 H, 1II-H), 4.75 (d, JH,H = 15.0 Hz, 1 H,
1 H, O-CH2Ph), 3.94 (d, JH,H = 15.2 Hz, 1 H, COCH2Cl), 3.86
3
3
N-CH2Ph), 4.70 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.67 (d, 3JH,H
(d, 3JH,H = 15.2 Hz, 1 H, COCH2Cl), 3.68 (m, 1 H), 3.58–3.56 (m,
3
3
= 12.0 Hz, 1 H, O-CH2Ph), 4.58 (d, JH,H = 11.5 Hz, 1 H, O- 3 H), 3.34 (dd, JH,H = 12.0, 7.6 Hz, 1 H), 1.96 (m, 1 H), 1.9–0.76
CH2Ph), 4.48 (dd, 3JH,H = 12.0, 10.0 Hz, 1 H, 3II-H), 4.48 (d, 3JH,H
(m, 45 H), 0.64 (s, 3 H, CH3), 0.57 (m, 1 H) ppm. 13C NMR
= 1.5 Hz, 1 H, 5I-H), 4.37 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), (100 MHz, CDCl3, 23 °C): δ = 165.4 (COCH2Cl), 134.9, 128.8,
3
3
3
4.10 (t, JH,H = 2.5 Hz, 1 H, 3I-H), 3.99 (d, JH,H = 15.0 Hz, 1 H,
128.4, 128.3, 128.2, 127.9, 127.8, 93.7, 78.5, 73.9, 73.6, 70.8, 60.8,
56.5, 56.3, 54.3, 40.4, 44.9, 42.7, 40.5, 40.1, 39.6, 36.8, 36.3, 35.9,
3
N-CH2Ph), 3.88 (d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.82 (d,
3JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.74 (s, 3 H, CO2CH3), 3.73 (m, 35.8, 35.6, 35.5, 32.1, 28.8, 28.4, 28.1, 27.8, 24.3, 24.0, 23.0, 22.7,
3
1 H, 5II-H), 3.54 (dd, JH,H = 11.0, 3.0 Hz, 1 H, 6IIa-H), 3.42 (dd,
21.4, 18.8, 12.5, 12.2 ppm. C51H73ClNO7 (847.58): calcd. C 72.27,
3JH,H = 11.0, 3.5 Hz, 1 H, 6IIb-H), 3.26 (dd, JH,H = 12.0, 3.0 Hz, H 8.68, N 1.65; found C 72.31, H 8.49, N, 1.58.
3
1 H, 2II-H), 1.57 [s, 3 H, C(CH3)2], 1.40 [s, 3 H, C(CH3)2] ppm. 13
C
Disaccharides 35a and 35b. Method B: Glycosylation of 16 (100 mg,
0.215 mmol) with 20 (134 mg, 0.258 mmol) in 1,4-dioxane/toluene
(3:1, 8 mL) in the presence of DTBMP (106 mg, 0.516 mmol), Ag-
OTf (99 mg, 0.387 mmol), PhSCl (36 μL, 0.310 mmol), and 4-Å
molecular sieves (0.8 g) at 0 °C to room temperature overnight,
subsequent work-up, and purification by size-exclusion chromatog-
raphy (SX-3) and flash column chromatography on silica gel
(CHCl3/toluene/EtOAc, 7:2:1–4:1:1) gave 35a (143 mg, 76%) and
35b (9 mg, 5%).
NMR (125 MHz, CDCl3): δ = 169.2, 165.4, 157.8, 137.1, 136.5,
134.6, 129.1, 128.8, 128.6, 128.5, 128.5, 128.4, 128.2, 128.0, 127.8,
112.4, 96.7, 93.2, 74.7, 73.6, 73.5, 72.4, 71.4, 71.1, 71.0, 71.0, 69.8,
66.5, 58.9, 52.6, 47.1, 40.3, 28.0, 26.2 ppm. C40H45ClNO13 (783.24):
calcd. C 61.34, H 5.79, N 1.79; found C 61.51, H 5.63, N 1.79.
β-Linked Disaccharide 32b: 1H NMR (500 MHz, CDCl3): δ = 7.41–
3
7.21 (m, 15 H, aromatic H), 5.30 (d, JH,H = 2.0 Hz, 1 H, 1I-H),
5.24 (dd, 3JH,H = 10.5, 9.0 Hz, 1 H, 4II-H), 4.84 (d, 3JH,H = 8.0 Hz,
3
1 H, 1II-H), 4.60 (d, JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.15 (d,
α-Linked Disaccharide 35a: [α]2D6 = +34 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.37–7.17 (m, 25 H, aromatic H), 5.54 (br.
3
3JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.57 (d, JH,H = 11.5 Hz, 1 H,
O-CH2Ph), 4.54 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.48 (d, 3JH,H
3
s, 1 H 4II-H), 5.01 (d, JH,H = 11.0 Hz, 1 H, O-CH2Ph), 4.90 (d,
3
= 12.0 Hz, 1 H, O-CH2Ph), 4.46 (m, 1 H, 5I-H), 4.44 (d, JH,H
=
3
3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.83 (d, JH,H = 11.0 Hz, 1 H,
12.0 Hz, 1 H, O-CH2Ph), 4.36 (t, JH,H = 2.0 Hz, 1 H, 1I-H), 4.18
3
O-CH2Ph), 4.79 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.75 (d, 3JH,H
(br. s, 1 H, 2I-H), 4.08 (dd, 3JH,H = 12.0, 10.5 Hz, 1 H, 3II-H), 3.98
3
= 3.0 Hz, 1 H, 1II-H), 4.63 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph),
(d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.94 (br. s, 1 H, 2I-H), 3.92
3
4.54 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.58 (d, 3JH,H = 12.0 Hz,
1 H, O-CH2Ph), 4.49 (d, 3JH,H = 3.5 Hz, 1 H, 1I-H), 4.47 (dd, 3JH,H
(d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.74 (m, 1 H, 5II-H), 3.70 (s,
3
3 H, CO2CH3), 3.58 (dd, JH,H = 10.5, 5.5 Hz, 1 H, 6IIa-H), 3.46
3
3
= 12.0, 3.0 Hz, 1 H, 3II-H), 4.45 (d, JH,H = 15.0 Hz, 1 H, N-
(dd, 3JH,H = 10.5, 2.5 Hz, 1 H, 6IIb-H), 1.44 [s, 3 H, C(CH3)2], 1.38
[s, 3 H, C(CH3)2] ppm.
3
3
CH2Ph), 4.35 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.17 (d, JH,H
= 15.0 Hz, 1 H, N-CH2Ph), 4.00 (t, JH,H = 9.5 Hz, 1 H, 3I-H),
3
Compounds 34a and 34b. Method B: Glycosylation of 33 (18 mg,
0.045 mmol) with 11 (30 mg, 0.054 mmol) in 1,4-dioxane/toluene
(3:1, 8 mL) in the presence of DTBMP (106 mg, 0.516 mmol), Ag-
OTf (99 mg, 0.387 mmol), PhSCl (36 μL, 0.310 mmol), and 4-Å
molecular sieves (0.8 g) at 0 °C to room temperature overnight,
subsequent work-up, and purification by size-exclusion chromatog-
raphy (SX-3) and preparative TLC (toluene/hexane/EtOAc, 4:1:1)
gave 34a (16.8 mg, 44%) and 34b (7.5 mg, 20%).
3.93 (br. t, 1 H, 5II-H), 3.67 (dd, 3JH,H = 10.5, 5.0 Hz, 1 H, 6Ia-H),
3.65 (m, 1 H, 5II-H), 3.59 (dd, JH,H = 12.0, 3.0 Hz, 1 H, 2II-H),
3
3.45 (dd, JH,H = 9.5, 3.5 Hz, 1 H, 2I-H), 3.41 (dd, JH,H = 10.5,
3
3
1.5 Hz, 1 H, 6Ib-H), 3.38 (d, JH,H = 5.5 Hz, 2 H, 6II-H), 3.38 (s,
3
3 H, OCH3), 3.38 (t, JH,H = 9.5 Hz, 1 H, 4I-H), 1.97 (s, 3 H,
3
COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 169.3 (COCH3),
158.2 (oxazolidinone C=O), 138.5, 138.1, 137.8, 137.4, 135.0,
128.8–127.6, 98.1, 96.4, 82.0, 79.6, 77.3, 75.8, 74.8, 73.5, 72.0, 69.8,
69.5, 67.9, 66.8, 66.3, 65.4, 55.3, 48.0, 20.6 ppm. C51H55NO12
(873.98): calcd. C 70.09, H 6.34, N 1.60; found C 70.14, H 6.15, N
1.55.
α-Linked Compound 34a: [α]2D6 = –13.4 (c = 0.73, CHCl3). 1H NMR
(400 MHz, CDCl3, 22 °C): δ = 7.33–7.23 (m, 10 H, aromatic H),
3
3
5.36 (t, JH,H = 9.6 Hz, 1 H, 4-H), 4.95 (d, JH,H = 2.8 Hz, 1 H, 1-
3
3
H), 4.60 (t, JH,H = 10.4 Hz, 1 H, 3-H), 4.57 (d, JH,H = 11.6 Hz,
1
β-Linked Disaccharide 35b: [α]2D6 = –12 (c = 0.5, CHCl3). H NMR
1 H, O-CH2Ph), 4.51 (d, 3JH,H = 14.8 Hz, 1 H, N-CH2Ph), 4.38 (d,
(500 MHz, CDCl3): δ = 7.40–7.21 (m, 25 H, aromatic H), 5.56 (br.
3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.23 (d, JH,H = 14.8 Hz, 1 H,
3
3
3
t, JH,H = 2.5 Hz, 1 H, 4II-H), 4.99 (d, JH,H = 11.0 Hz, 1 H, O-
3
N-CH2Ph), 3.93 (d, JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.84 (m, 1
H), 3.84 (d, JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.35 (dd, JH,H
3
3
CH2Ph), 4.83 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.79 (d, JH,H
= 11.0 Hz, 1 H, O-CH2Ph), 4.79 (d, JH,H = 12.5 Hz, 1 H, O-
3
3
=
3
16.0, 6.4 Hz, 1 H), 3.34 (m, 1 H), 3.25 (m, 1 H), 1.97 (m, 1 H),
3
3
CH2Ph), 4.62 (d, JH,H = 12.5 Hz, 1 H, O-CH2Ph), 4.55 (d, JH,H
1.85 (m, 1 H), 1.75–0.84 (m, 44 H), 0.63 (s, 3 H, CH3), 0.57 (m, 1
= 4.0 Hz, 1 H, 1I-H), 4.53 (d, JH,H = 15.0 Hz, 1 H, N-CH2Ph),
3
H) ppm. 13C NMR (100 MHz, CDCl3, 22 °C):
δ = 165.4
4.49 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.48 (d, 3JH,H = 11.5 Hz,
1 H, O-CH2Ph), 4.40 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.33 (d,
3JH,H = 15.0 Hz, 1 H, N-CH2Ph), 4.33 (d, 3JH,H = 8.0 Hz, 1 H, 1II-
(COCH2Cl), 158.1 (oxazolidinone C=O), 137.1, 134.9, 128.8, 128.4,
128.3, 128.2, 127.9, 127.8, 93.7 (C-1), 78.5, 77.3, 73.8, 73.6, 70.8,
70.5, 67.4, 60.8, 56.5, 56.4, 54.3, 48.4, 44.9, 42.7, 40.5, 40.5, 40.1,
39.6, 36.8, 36.3, 35.9, 35.8, 35.6, 35.6, 32.1, 28.8, 28.4, 28.1, 27.8,
24.3, 24.0, 23.0, 22.7, 21.4, 18.8, 12.5, 12.2 ppm. C51H73ClNO7
(847.58): calcd. C 72.27, H 8.68, N 1.65; found C 72.38, H 8.49, N
1.48.
H), 4.00 (t, JH,H = 9.5 Hz, 1 H, 3I-H), 4.00 (dd, JH,H = 12.0,
3
3
2.5 Hz, 1 H, 3II-H), 3.98 (dd, JH,H = 10.5, 2.0 Hz, 1 H, 6Ia-H),
3
3.83 (m, 1 H, 5I-H), 3.81 (m, 1 H, 5II-H), 3.58 (dd, JH,H = 12.0,
3
8.0 Hz, 1 H, 2II-H), 3.48 (m, 1 H, 6Ib-H), 3.48 (m, 2 H, 6II-H), 3.47
(m, 1 H, 2I-H), 3.33 (s, 3 H, OCH3), 3.32 (dd, J = 9.5, 10 Hz, 1 H,
4I-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 169.1 (COCH3),
1
β-Linked Compound 34b: [α]2D6 = 170.8 (c = 0.5, CHCl3). H NMR
(400 MHz, CDCl3, 22 °C): δ = 7.34–7.26 (m, 10 H, aromatic H), 158.3 (oxazolidinone C=O), 138.5, 138.1, 138.0, 137.4, 135.7, 129.0,
3
3
5.25 (t, JH,H = 8.8 Hz, 1 H, 4-H), 4.75 (d, JH,H = 8.0 Hz, 1 H, 1-
127.9, 102.8 (C-1II), 98.1 (C-1I), 81.9 (C-3I), 79.8 (C-2I), 77.9 (C-
510
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 497–516

1,2-cis-Selective Glycosylation Reactions
4I), 76.4 (C-3II), 75.8 (O-CH2Ph), 74.7 (O-CH2Ph), 74.3 (C-5II),
73.7 (O-CH2Ph), 73.4 (O-CH2Ph), 69.7 (C-5I), 68.4 (C-6I), 67.5 (C-
0.318 mmol), PhSCl (30 μL, 0.254 mmol), and 4-Å molecular sieves
(0.8 g) at 0 °C to room temperature overnight, subsequent work-
6II), 64.7 (C-4II), 57.5 (C-2II), 57.5 (C-2I), 55.5 (OCH3), 48.3 (N- up, and purification by size-exclusion chromatography (SX-3) and
CH2Ph), 20.5 (COCH3) ppm. C51H55NO12 (873.98): calcd. C 70.09,
flash column chromatography on silica gel (CHCl3/toluene/EtOAc,
H 6.34, N 1.60; found C 69.97, H 6.25, N, 1.55.
7:2:1–4:1:1) gave 38a (35 mg, 35%) and 38b (32 mg, 32%).
38a: [α]2D4 = 6.1 (c = 1.10, CHCl3). 1H NMR (400 MHz, CDCl3,
Disaccharides 37a and 37b. Method A at –40 °C: Glycosylation of
23 (42 mg, 0.085 mmol) with phenyl 2-acetyl-2-azido-6-O-benzyl-
4-O-chloroacetyl-2-deoxy-1-thio-β-d-glucopyranoside (36; 43 mg,
0.071 mmol) in CH2Cl2 (3 mL) in the presence of N-(phenylthio)-
ε-caprolactam (21 mg, 0.049 mmol), Tf2O (14 μL, 0.085 mmol),
and 4-Å molecular sieves (0.3 g) at –40 °C for 21 h, subsequent
work-up, and purification by preparative TLC (toluene/hexane/
EtOAc, 4:1:1) gave the α-linked disaccharide 37a (17 mg, 24%) and
the β-linked disaccharide 37b (7 mg, 10%).
3
25 °C): δ = 7.34–7.15 (m, 20 H, aromatic H), 5.13 (t, JH,H
=
3
10.4 Hz, 1 H, 4II-H), 5.00 (d, JH,H = 11.2 Hz, 1 H, O-CH2Ph),
4.92 (d, 3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.83–4.77 (m, 3 H), 4.63
3
(d, JH,H = 12.4 Hz, 1 H, O-CH2Ph), 4.58–4.50 (m, 3 H), 4.39 (t,
3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.11–4.07 (m, 2 H), 4.03–3.96
(m, 3 H), 3.74–3.66 (m, 3 H), 3.50–3.35 (m, 3 H), 3.38 (s, 3 H,
OCH3), 3.19 (dd, 3JH,H = 12.0, 2.8 Hz, 1 H), 2.07 (s, 3 H, COCH3),
2.03 (s, 3 H, COCH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ = 170.2, 168.9, 157.9, 138.3, 137.9, 137.6, 134.4, 128.8, 128.5,
128.4, 128.3, 128.3, 128.2, 128.0, 128.0, 127.8, 127.8, 127.6, 127.5,
98.2, 95.6, 82.0, 79.5, 77.2, 75.8, 74.8, 73.6, 73.5, 70.2, 70.0, 68.2,
66.6, 61.5, 60.1, 55.4, 47.9, 20.8 ppm. C46H51NO13 (825.90): calcd.
C 66.90, H 6.22, N 1.70; found C 66.87, H 6.05, N 1.58.
α-Linked Disaccharide 37a: [α]2D5 = +110 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.78–6.68 (m, 23 H, aromatic H), 5.74 (d,
3
3JH,H = 4.0 Hz, 1 H, 1II-H), 5.63 (d, JH,H = 8.5 Hz, 1 H, 1I-H),
3
3
5.43 (dd, JH,H = 10.5, 9.0 Hz, 1 H, 1I-H), 5.20 (t, JH,H = 9.5 Hz,
3
1 H, 4II-H), 4.82 (d, JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.65 (dd,
1
38b: [α]2D4 = 15.2 (c = 0.73, CHCl3). H NMR (500 MHz, CDCl3):
3
3JH,H = 10.5, 8.5 Hz, 1 H, 3I-H), 4.65 (d, JH,H = 12.0 Hz, 1 H, O-
3
δ = 7.39–7.22 (m, 20 H, aromatic H), 5.11 (t, JH,H = 8.8 Hz, 1 H,
CH2Ph), 4.55 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.54 (dd, 3JH,H
4II-H), 4.98 (d, J = 10.8 Hz, 1 H, O-CH2Ph), 4.86 (d, J = 11.6 Hz,
1 H, O-CH2Ph), 4.79 (d, J = 10.8 Hz, 1 H, O-CH2Ph), 4.78 (d,
3
= 10.5, 8.5 Hz, 1 H, 2I-H), 4.48 (d, JH,H = 11.5 Hz, 1 H, O-
CH2Ph), 4.46 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph), 4.23 (dd, 3JH,H
= 9.5, 8.5 Hz, 1 H, 4I-H), 4.19 (d, 3JH,H = 11.5 Hz, 1 H, O-CH2Ph),
3
3JH,H = 12.4 Hz, 1 H, O-CH2Ph), 4.61 (d, JH,H = 12.0 Hz, 1 H,
O-CH2Ph), 4.56 (d, 3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.54 (d, 3JH,H
3
4.01 (m, 1 H, 5II-H), 3.93 (dd, JH,H = 11.5, 3.5 Hz, 1 H, 6Ia-H),
3
= 6.0 Hz, 1 H), 4.51 (d, JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.37 (d,
3
3
3.82 (d, JH,H = 14.5 Hz, 1 H, N-CH2Ph), 3.81 (dd, JH,H = 11.5,
3
3JH,H = 8.0 Hz, 1 H, 1II-H), 4.25 (d, JH,H = 14.4 Hz, 1 H, N-
2.0 Hz, 1 H, 6Ib-H), 3.77 (m, 1 H, 5I-H), 3.71 (s, 3 H, PhOCH3),
CH2Ph), 4.15–4.10 (m, 3 H), 4.07–3.93 (m, 3 H), 3.82 (m, 1 H),
3
3
3.71 (d, JH,H = 14.5 Hz, 1 H, N-CH2Ph), 3.36 (dd, JH,H = 10.5,
3
3
3.60 (m, 1 H), 3.52 (t, JH,H = 5.6 Hz, 1 H), 3.45 (dd, JH,H = 9.6,
3.2 Hz, 1 H, 2I-H), 3.33 (s, 3 H, OCH3), 3.31–3.25 (m, 2 H), 2.06
(s, 3 H, Ac), 2.03 (s, 3 H, Ac) ppm. 13C NMR (100 MHz, CDCl3,
24 °C): δ = 170.3, 168.9, 158.0, 138.3, 137.9, 137.8, 134.9, 129.2,
128.8, 128.5, 128.4, 128.4, 128.3, 128.0, 127.9, 127.9, 127.8, 127.8,
127.6, 102.0, 98.1, 81.8, 79.8, 77.8, 77.2, 75.8, 74.8, 74.4, 73.5, 69.7,
68.6, 67.7, 62.1, 60.2, 55.6, 48.1, 20.8, 20.8 ppm. C46H51NO13
(825.90): calcd. C 66.90, H 6.22, N 1.70; found C 66.75, H 6.00,
N, 1.48.
3
4.0 Hz, 1 H, 2II-H), 3.28 (dd, JH,H = 10.5, 2.5 Hz, 1 H, 6IIa-H),
3
3.25 (dd, JH,H = 10.5, 3.5 Hz, 1 H, 6IIb-H), 2.08 (s, 3 H,
COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 170.2, 166.1,
155.5, 150.7, 138.1, 137.4, 137.4, 134.1, 131.4, 128.3–127.2, 118.8,
114.4, 97.7, 97.1, 81.0, 74.7, 74.4, 73.8, 73.7, 73.4, 70.5, 68.7, 67.2,
61.0, 55.9, 55.5, 40.4, 20.7 ppm. C52H51ClN4O14 (991.43): calcd. C
63.00, H 5.18, N 5.65; found C 63.03, H 5.18, N, 5.57.
β-Linked Disaccharide 37b: [α]2D5 = +40 (c = 0.5, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.81–6.68 (m, 23 H, aromatic H), 5.62 (d,
Disaccharide 39: Glycosylation of 22 (105 mg, 0.177 mmol) with 15
(100 mg, 0.212 mmol) in CH2Cl2 (8 mL) in the presence of
DTBMP (78 mg, 0.424 mmol), AgOTf (82 mg, 0.382 mmol), PhSCl
(30 μL, 0.254 mmol), and 4-Å molecular sieves (0.8 g) at 0 °C to
room temperature overnight, subsequent work-up, and purification
by size-exclusion chromatography (SX-3) and flash column
chromatography on silica gel (CHCl3/toluene/EtOAc, 7:2:1–4:1:1)
3
3JH,H = 8.0 Hz, 1 H, aromatic H), 5.11 (t, JH,H = 9.5 Hz, 1 H, 1I-
3
3
H), 4.87 (t, JH,H = 10.5 Hz, 1 H, 4II-H), 4.83 (d, JH,H = 12.0 Hz,
1 H, O-CH2Ph), 4.77 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.50 (d,
3JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.44 (d, 3JH,H = 8.5 Hz, 1 H, 1II-
3
3
H), 4.42 (dd, JH,H = 10.5, 8.0 Hz, 1 H, 2I-H), 4.42 (d, JH,H
=
12.0 Hz, 1 H, O-CH2Ph), 4.38 (d, 3JH,H = 12.0 Hz, 1 H, O-CH2Ph),
4.35 (dd, 3JH,H = 10.5, 8.5 Hz, 1 H, 3I-H), 4.32 (d, 3JH,H = 12.0 Hz,
1
gave 39 (139 mg, 82%). [α]2D4 = 64.8 (c = 1.95, CHCl3). H NMR
3
1 H, O-CH2Ph), 4.23 (dd, JH,H = 10.0, 8.5 Hz, 1 H, 4I-H), 3.95
(400 MHz, CDCl3, 25 °C): δ = 7.71–7.67 (m, 4 H, aromatic H),
3
3
(dd, JH,H = 11.5, 3.0 Hz, 1 H, 6Ia-H), 3.85 (dd, JH,H = 11.5,
3
7.31–6.89 (m, 15 H, aromatic H), 6.80 (d, JH,H = 9.2 Hz, 2 H,
3
1.5 Hz, 1 H, 6Ib-H), 3.84 (d, JH,H = 15.0 Hz, 1 H, COCH2Cl),
3
aromatic H), 6.69 (d, JH,H = 9.2 Hz, 2 H, aromatic H), 5.59 (d,
3
3.75 (d, JH,H = 15.0 Hz, 1 H, COCH2Cl), 3.73 (m, 1 H, 5I-H),
3
3JH,H = 7.6 Hz, 1 H, 1I-H), 5.43 (d, JH,H = 2.8 Hz, 1 H, 1II-H),
3
3.71 (s, 3 H, PhOCH3), 3.51 (dd, JH,H = 10.5, 4.0 Hz, 1 H, 6IIa-
3
3
5.14 (t, JH,H = 9.6 Hz, 1 H, 4II-H), 4.73 (d, JH,H = 11.6 Hz, 1 H,
3
3
H), 3.47 (dd, JH,H = 10.5, 8.5 Hz, 1 H, 2II-H), 3.40 (dd, JH,H
= 10.5, 4.0 Hz, 1 H, 6IIb-H), 3.31 (m, 1 H, 5II-H), 2.08 (s, 3H
COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 170.1 (COCH3),
166.3 (COCH2Cl), 155.4 (Phth, CO), 150.8 (Phth CO), 138.4,
137.8, 137.5, 133.7, 128.6–127.1, 123.3, 118.7, 114.3, 100.9 (C-1II),
97.6 (C-1I), 78.2 (C-4I), 77.0 (C-3I), 74.8 (C-5I, O-CH2Ph), 73.5 (O-
CH2Ph), 72.7 (C-3II), 72.3 (C-5II), 71.0 (C-4II), 68.2 (C-6II), 67.7
(C-6I), 64.4 (C-2II), 55.6 (C-2I, PhOCH3), 40.4 (COCH2Cl), 20.7
(COCH3) ppm. C52H51ClN4O14 (991.43): calcd. C 63.00, H 5.18, N
5.65; found C 62.82, H 5.10, N, 5.60.
3
O-CH2Ph), 4.63 (d, JH,H = 12.4 Hz, 1 H, O-CH2Ph), 4.58–4.51
(m, 5 H), 4.35 (d, JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.21 (t, JH,H
= 9.2 Hz, 1 H), 4.13–3.98 (m, 5 H), 3.80 (d, JH,H = 11.2 Hz, 1 H,
O-CH2Ph), 3.69 (s, 3 H, OCH3), 3.21 (dd, JH,H = 12.4, 2.8 Hz, 1
3
3
3
3
H, 2II-H), 2.10 (s, 3 H, COCH3), 2.11 (s, 3 H, COCH3) ppm. 13C
NMR (100 MHz, CDCl3, 24 °C): δ = 170.2, 168.9, 157.7, 155.4,
150.5, 137.7, 137.1, 134.1, 133.9, 131.3, 128.9, 128.6, 128.3, 128.2,
128.1, 127.6, 127.5, 127.3, 123.4, 118.8, 114.3, 97.8, 95.8, 78.9, 75.0,
73.5, 73.5, 71.2, 68.5, 68.4, 62.0, 60.4, 60.0, 55.6, 55.1, 47.8, 21.2,
20.9 ppm. C45H48NO13 (810.86): calcd. C 66.66, H 5.97, N 1.73;
found C 66.45, H 5.78, N 1.50.
Disaccharides 38a and 38b: Glycosylation of 20 (82 mg,
0.177 mmol) with 15 (100 mg, 0.212 mmol) in CH2Cl2 (8 mL) in Disaccharide 41: Glycosylation of 40 (82 mg, 0.177 mmol) with 15
the presence of DTBMP (78 mg, 0.424 mmol), AgOTf (82 mg, (100 mg, 0.212 mmol) in CH2Cl2 (8 mL) in the presence of
Eur. J. Org. Chem. 2011, 497–516
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
511

S. Manabe, K. Ishii, Y. Ito
FULL PAPER
DTBMP (78 mg, 0.424 mmol), AgOTf (82 mg, 0.382 mmol), PhSCl
(30 μL, 0.254 mmol), and 4-Å molecular sieves (0.8 g) at 0 °C to
room temperature overnight, subsequent work-up, and purification
by size-exclusion chromatography (SX-3) and flash column
chromatography on silica gel (CHCl3/toluene/EtOAc, 7:2:1–4:1:1)
EtOAc. The combined layers were washed with satd. NaHCO3 and
brine. After drying the mixture over Na2SO4, the solvent was re-
moved in vacuo. The residue was purified by silica gel column
chromatography (EtOAc to EtOAc/MeOH, 1:1) to give the
162.4 mg (90%) of the product as a colorless oil.
1
gave 41 (107 mg, 73%). [α]2D4 = 39.3 (c = 1.95, CHCl3). H NMR
MPEG-Bound Disaccharides 51a and 51b: PhSCl (40 μL,
0.0868 mmol) was added to a mixture of MPEG-bound acceptor
49 (120.6 mg, 0.0868 mmol), thioglycoside 11 (188 mg,
0.347 mmol), AgOTf (89 mg, 0.347 mmol), DTBMP (107 mg,
0.521 mmol), and 4-Å molecular sieves (300 mg) in toluene (1 mL)
and dioxane (3 mL) at 0 °C. The mixture was stirred at room tem-
perature overnight and the mixture was diluted with EtOAc and
satd. NaHCO3. The mixture was filtered though Celite and the
filtrate was separated. The aqueous layer was extracted with
EtOAc. The combined layers were washed with brine and dried
with Na2SO4. The residue was purified by silica gel column
chromatography (EtOAc to EtOAc/MeOH, 1:1) to give 160.0 mg
(quant.) of the product.
(400 MHz, CDCl3, 25 °C): δ = 7.40–7.10 (m, 20 H, aromatic H),
5.13–5.08 (m, 2 H), 4.85–4.80 (m, 3 H), 4.74–4.65 (m, 3 H), 4.56–
3
4.51 (m, 3 H), 4.19 (s, 1 H), 3.93–3.88 (m, 4 H), 3.72 (dd, JH,H
=
8.4, 2.6 Hz, 1 H, 2II-H), 3.52 (t, JH,H = 10.0 Hz, 1 H), 3.54–3.42
(m, 2 H), 3.37 (s, 3 H, COCH3), 3.18 (dd, JH,H = 12.0, 2.4 Hz, 1
3
3
H), 2.04 (s, 3 H), 2.03 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3,
24 °C): δ = 170.2, 168.9, 158.3, 137.9, 137.1, 134.1, 129.8, 128.9,
128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.1, 128.1, 128.0, 128.0,
127.9, 127.9, 127.7, 127.6, 127.6, 127.2, 98.5, 95.5, 75.6, 75.4, 73.8,
73.7, 73.4, 73.3, 70.3, 68.2, 67.8, 67.5, 61.0, 60.0, 55.6, 47.5, 21.9,
20.8 ppm. C46H51NO13: (825.90): calcd. C 66.90, H 6.22, N 1.70;
found C 66.69, H 6.20, N 1.50.
MPEG-Bound Compound 46: BF3·OEt2 (20 μL, 0.157 mmol) was
n-Pent-4-yl 2,3,4-O-Tribenzyl-6-O-(tert-butyldiphenylsilyl)-β-D-glu-
added to
a solution of MPEG-bound linker 43 (288 mg,
copyranoside (53): NaOMe solution (28% in MeOH, 0.2 mL) was
added dropwise in the presence of phenolphthalein to a solution of
tetraacetate 52 (15.00 g, 36.08 mmol) in MeOH (30 mL) and THF
(30 mL). After stirring the mixture for 4 h, the mixture was neutral-
ized with Amberlyst 15E. After filtration, the solvent was evapo-
rated and dried under high vacuum. Then TBDPSCl (11.1 mL.
43.30 mmol) was added to a solution of the resulting tetraol and
imidazole (5.70 g, 72.12 mmol) in DMF (30 mL) at 0 °C. The mix-
ture was stirred at room temperature overnight. Satd. NaHCO3
and EtOAc were added. After separation, the aqueous layer was
extracted with EtOAc. The combined layers were washed with
brine and dried with NaSO4. After filtration and concentration, the
residue was purified by silica gel column chromatography (CHCl3/
EtOAc, 1:1) to give 14.02 g of the TBDPS ether. NaH (4.61 g,
115.40 mmol) was added to a solution of the triol (14.02 g,
28.85 mmol) and benzyl bromide (13.71 mL, 115.40 mmol) in
DMF (50 mL) at 0 °C. The mixture was stirred under N2 at room
temperature overnight. Triethylamine was added to the mixture to
destroy the excess benzyl bromide. Then satd. NH4Cl was added
and the aqueous layer was extracted with EtOAc. The combined
layers were washed with brine and dried with Na2SO4. After fil-
tration and concentration, the residue was purified by silica gel
column chromatography (hexane/EOAc, 20:1–10:1) to give 21.25 g
0.314 mmol) and imidate 44 (335 mg, 0.471 mmol) in CH2Cl2
(2 mL) at 0 °C. After stirring the mixture overnight, satd. NaHCO3
and EtOAc were added. The combined layers were washed with
brine and dried with Na2SO4. After concentration, the residue was
purified by silica gel column chromatography (AcOEt/EtOAc/
MeOH, 1:1) to give 451 mg (97%) of MPEG-bound compound 46
as a colorless oil.
MPEG-Bound Compound 47: BF3·OEt2 (18 μL, 0.144 mmol) was
added to
a solution of MPEG-bound linker 43 (264 mg,
0.288 mmol) and imidate 45 (307 mg, 0.432 mmol) in CH2Cl2
(2 mL) at 0 °C. The mixture was stirred at 0 °C overnight. Then
satd. NaHCO3 and EtOAc were added. The aqueous layer was ex-
tracted with EtOAc and the combined layers were washed with
brine. After drying the mixture over Na2SO4, the solvent was re-
moved in vacuo. The residue was purified by silica gel column
chromatography (EtOAc to MeOH/EtOAc, 1:1) to give 420.6 mg
(98%) of compound 47 as a colorless oil.
MPEG-Bound Compound 48: NaOMe (1 drop, 28% MeOH solu-
tion) was added in the presence of phenolphthalein to a solution
of MPEG-bound chloroacetate 46 (220 mg, 0.148 mmol) in
MeOH. After 1 h, Amberlist 15E was added. The resin was filtered
and washed with MeOH and CHCl3. The filtrate was concentrated
and the residue was purified by silica gel column chromatography
(AcOEt to AcOEt/MeOH, 1:1) to give 200 mg (98%) of the alcohol
48 as a colorless oil.
1
(78%) of 53 as a colorless oil. [α]2D4 = 0.20 (c = 1.48, CHCl3). H
3
NMR (400 MHz, CDCl3, 23 °C): δ = 7.73 (d, JH,H = 6.8 Hz, 1 H,
3
aromatic H), 7.70 (d, JH,H = 6.8 Hz, 1 H, aromatic H), 7.67–7.15
(m, 21 H, aromatic H), 5.81 (m, 1 H, allyl), 5.05–4.85 (m, 6 H,
MPEG-Bound Compound 49: NaOMe (1 drop, 28% MeOH solu-
tion) was added in the presence of phenolphthalein to a solution
of MPEG-bound chloroacetate 47 (220 mg, 0.148 mmol) in
MeOH. After 1.5 h, Amberlist 15E was added. The resin was fil-
tered and washed with MeOH and CHCl3. The filtrate was concen-
trated and the residue was purified by silica gel column chromatog-
raphy (AcOEt to AcOEt/MeOH, 1:1) to give 200 mg (98%) of the
MPEG-bound alcohol 49 as a colorless oil.
3
3
allyl), 4.80 (d, JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.73 (d, JH,H
=
10.8 Hz, 1 H, O-CH2Ph), 4.65 (d, 3JH,H = 11.2 Hz, 1 H, O-CH2Ph),
3
4.55 (s, 2 H), 4.39 (d, JH,H = 8.0 Hz, 1 H, 1-H), 4.00–3.74 (m, 3
3
3
H), 3.72 (t, JH,H = 8.0 Hz, 1 H), 3.64 (t, JH,H = 9.2 Hz, 1 H),
3
3.60–3.51 (m, 1 H), 3.43 (t, JH,H = 8.0 Hz, 1 H, 2-H), 3.31 (m, 1
H, 5-H), 2.20 (m, 2 H, CH2), 1.83 (m, 2 H, CH2), 1.04 (s, 9 H,
tBu) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.4, 138.0, 137.9,
135.7, 135.4, 133.5, 133.0, 129.4, 128.3, 128.2, 127.9, 127.9, 127.8,
127.6, 127.6, 127.5, 127.5, 127.4, 114.9, 103.4, 84.7, 82.6, 77.7, 77.2,
75.9, 75.6, 75.1, 74.9, 72.1, 69.0, 62.8, 30.5, 29.2, 26.9, 19.4 ppm.
HRMS: C48H56O6Si + Na [M + Na]+ 779.3738; found 779.3742.
MPEG-Bound Disaccharide 50: Tf2O (67 mL, 0.397 mmol) was
added to a mixture of thioglycoside 11 (214 mg, 0.394 mmol),
MPEG-bound acceptor 48 (137 mg, 0.0986 mmol), N-phenylthio-
ε-caprolactam
(88 mg,
0.397 mmol),
DTBMP
(81 mg,
0.397 mmol), and 4-Å molecular sieves (300 mg) in CH2Cl2 (3 mL)
at 4 °C. The mixture was stirred at room temperature overnight
and then diluted with satd. NaHCO3 and EtOAc. The mixture was
filtered through Celite. After filtration, the Celite was washed with
EtOAc. After separation, the aqueous layer was extracted with
n-Pent-4-enyl 2,3,4-O-Tribenzyl-6-O-chloroacetyl-β-D-glucopyrano-
side (54): TBAF (1.0 m THF solution, 10 mL, 10.0 mmol) was
added to a solution of TBDPS ether 53 (5.44 g, 7.19 mmol) in THF
(10 mL). The mixture was stirred at room temperature overnight.
The mixture was diluted with EtOAc and washed with 1 m HCl.
512
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 497–516

1,2-cis-Selective Glycosylation Reactions
The aqueous layer was extracted with EtOAc. The combined layers
were washed with brine and dried with Na2SO4. After filtration
and concentration, the residue was purified by silica gel column
Jones’ reagent was added to a solution of the aldehyde (261.4 mg,
0.439 mmol) in acetone (2 mL) at 0 °C until the color of the mix-
ture turned brown. Excess of the reagent was destroyed by adding
chromatography (hexane/EtOAc, 4:1–7:3) to give the product iPrOH and the mixture was diluted with CHCl3 and filtered
(3.71 g, 99%). [α]2D4 = 2.1 (c = 0.52, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.27–7.19 (m, 15 H, aromatic H), 5.74 (m, 1 H, allyl),
through Celite. The Celite was washed with CHCl3. After concen-
tration, the mixture was purified by silica gel column chromatog-
1
4.98–4.86 (m, 4 H, allyl), 4.80 (d, 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), raphy (hexane/EtOAc, 7:3–1:1) to give (203 mg, 76%) of the acid
4.75 (d, 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.67 (d, 3JH,H = 10.8 Hz, 55. [α]2D4 = 27.2 (c = 0.92, CHCl3). 1H NMR (400 MHz, CDCl3,
3
1 H, O-CH2Ph), 4.57 (d, 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.37 (d, 22 °C): δ = 7.26–7.17 (m, 15 H, aromatic H), 4.89 (d, JH,H
=
3JH,H = 8.0 Hz, 1 H, 1-H), 3.87 (m, 1 H), 3.78 (m, 1 H), 3.66 (m, 10.8 Hz, 1 H, O-CH2Ph), 4.84 (d, 3JH,H = 11.2 Hz, 1 H, O-CH2Ph),
3
3
1 H), 3.61 (t, JH,H = 8.8 Hz, 1 H), 3.50 (m, 2 H), 3.95 (t, JH,H
=
4.80 (d, 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.73 (d, 3JH,H = 10.8 Hz,
1 H, O-CH2Ph), 4.65 (d, 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.51 (d,
3
8.8 Hz, 1 H, 2-H), 3.31 (m, 1 H, 5-H), 2.15 (m, 2 H), 1.82 (t, JH,H
= 7.6 Hz, 2 H, CH2), 1.70 (m, 2 H, CH2) ppm. 13C NMR 3JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.37–4.31 (m, 2 H), 4.19 (dd,
3
(100 MHz, CDCl3): δ = 138.4, 138.3, 137.9, 137.8, 128.4, 128.3, 3JH,H = 11.6, 3.6 Hz, 1 H), 3.96 (d, JH,H = 14.8 Hz, 1 H,
3
128.0, 127.9, 127.8, 127.6, 127.6, 115.0, 103.6, 84.5, 82.3, 77.6, 75.7,
75.1, 75.0, 74.9, 69.6, 62.1, 30.2, 29.0 ppm. HRMS: calcd. for
[C32H38O6 + Na]+ 541.2561; found 541.2558.
COCH2Cl), 3.90 (d, JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.86 (m, 1
H), 3.60–3.52 (m, 2 H), 3.45–3.44 (m, 2 H), 3.36 (t, 3JH,H = 8.8 Hz,
3
1 H, 2-H), 2.42 (t, JH,H = 7.2 Hz, 2 H, CH2), 1.91 (m, 2 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3, 22 °C): δ = 178.6 (car-
boxylic acid), 166.8, 138.1, 138.0, 137.4, 128.4, 128.3, 128.1, 128.9,
127.9, 127.9, 127.9, 127.7, 127.6, 127.6, 103.4, 84.6, 82.1, 76.8, 75.7,
74.9, 74.9, 72.5, 68.7, 64.5, 40.8, 31.6, 24.9 ppm. HRMS: calcd. for
[C33H37ClO9 + Na]+ 635.2018; found 635.2017.
Chloroacetic anhydride (1.46 g, 8.54 mmol) was added to a solution
of the resulting alcohol (3.71 g, 7.16 mmol) in pyridine (3 mL) and
CH2Cl2 (20 mL) was added at 0 °C. After stirring overnight at
room temperature, the mixture was diluted with EtOAc and washed
with 1 m HCl. The aqueous layer was extracted with EtOAc and
the extract was washed with brine and dried with Na2SO4. After
filtration, the residue was purified by silica gel column chromatog-
raphy (hexane/EtOAc, 4:1) to give 4.25 g (quant.) of chloroacetate
54. [α]2D4 = 26.0 (c = 0.85, CHCl3). 1H NMR (400 MHz, CDCl3,
22 °C): δ = 7.31–7.22 (m, 15 H, aromatic H), 5.80–5.78 (m, 1 H,
Immobilization: 1-Methylimidazole (32 μL, 0.4 mmol) and MSNT
(59.2 mg, 0.2 mmol) were added to a suspension of resin 57
(500 mg, 0.115 mmol) and acid 55 (150 mg, 0.245 mmol) in DMF
(1 mL). The mixture was shaken overnight. The resin was then fil-
tered and washed with DMF, CHCl3, and MeOH. The resins were
dried in vacuo overnight. The weight of resin 58 obtained was
552 mg.
3
allyl), 5.00–4.92 (m, 4 H, allyl), 4.85 (d, JH,H = 10.8 Hz, 1 H, O-
3
3
CH2Ph), 4.78 (d, JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.70 (d, JH,H
3
= 10.8 Hz, 1 H, O-CH2Ph), 4.56 (d, JH,H = 11.0 Hz, 1 H, O-
Detection of Chloroacetyl by the PNBP Method: Some resin was
transferred to a plastic microtube. Then a PNBP toluene solution
(80 mg/10 mL, ca. 0.3 mL) was added. After 5 min, the resin was
spread over a TLC plate. After heating on a hot plate (1 min), a
10% piperidine solution (toluene) was sprayed over the sample. Af-
ter heating the resin for 10 s, the color was observed with the naked
eye or a computer analysis was performed by using a microscope
equipped with a CCD camera [280ϫ, CCD Micro Scope Inf-550
(Moritex)].
3
CH2Ph), 4.39 (m, 1 H), 4.37 (d, JH,H = 7.8 Hz, 1 H, COCH2Cl),
4.26 (dd, 3JH,H = 11.7, 4.4 Hz, 1 H), 4.01 (d, 3JH,H = 14.8 Hz, 1 H,
3
N-CH2Ph), 3.94 (d, JH,H = 14.8 Hz, 1 H, COCH2Cl), 3.88 (m, 1
H), 3.88–3.49 (m, 3 H), 3.42 (t, JH,H = 9.6 Hz, 1 H), 2.13 (m, 2
3
H, CH2), 1.75 (m, 2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3,
23 °C): δ = 166.9, 137.8, 137.6, 128.5, 128.3, 128.2, 128.0, 128.0,
127.8, 127.7, 115.0, 103.6, 84.7, 82.1, 75.7, 74.9, 74.9, 72.5, 69.6,
64.6, 40.8, 30.2, 29.0 ppm. HRMS: calcd. for C34H39ClO7 + Na [M
+ Na]+ 617.2277; found 617.2277.
Capping: Benzoyl isocyanate (0.2 mL) was added to a suspension
of the resin (550 mg) in CH2Cl2 (14 mL) and the mixture was
shaken for 1 h. After the reaction, the resin was filtered and washed
with CH2Cl2, MeOH, CH2Cl2, and diethyl ether, and dried at high
vacuum. The weight of the resin obtained was 550 mg.
3-Carboxypropyl 2,3,4-O-Tribenzyl-6-O-chloroacetyl-β-D-glucopyr-
anoside (55): O3 was passed through a solution of alkene 54
(350 mg, 0.589 mmol) in CH2Cl2 (5 mL) and MeOH (5 mL) at
–78 °C until the reaction mixture turned pale blue. After removal
of O3 by O2 gas, Me2S (0.2 mL) was added. The reaction mixture
was warmed to room temperature and stirred overnight. After
evaporation, the crude mixture was purified by silica gel column
chromatography (hexane/EtOAc, 4:1–3:2) to give 261.4 mg (75%)
Deprotection of Chloroacetate by HDTC: Freshly prepared HDTC
solution (0.37 m, 2 mL) was added to a suspension of the resin
(540 mg) in DMF (10 mL). The mixture was shaken for 3 h at room
temperature. The resin was filtered and washed with DMF, MeOH,
CH2Cl2, and diethyl ether, and dried in vacuo. The weight of resin
59 obtained was 530 mg.
1
of aldehyde. [α]2D4 = 26.5 (c = 0.88, CHCl3). H NMR (400 MHz,
CDCl3, 21 °C): δ = 9.66 (s, 1 H, aldehyde), 7.26–7.17 (m, 15 H,
3
aromatic H), 4.73 (d, JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.82 (d,
3
3JH,H = 9.2 Hz, 1 H, O-CH2Ph), 4.80 (d, JH,H = 10.4 Hz, 1 H,
Glycosylation: DMTST (60 mg) was added to a suspension of the
resin (528 mg) and donor 11 (382 mg, 0.690 mmol) in CH2Cl2
(3 mL). The mixture was shaken at room temperature overnight.
The resin was filtered and washed with DMF, MeOH, CH2Cl2, and
diethyl ether, and dried at high vacuum. This procedure was re-
peated twice. The weight of the resin 60 obtained was 585 mg.
3
3
CH2Ph), 4.73 (d, JH,H = 10.8 Hz, 1 H, O-CH2Ph), 4.67 (d, JH,H
3
= 10.8 Hz, 1 H, O-CH2Ph), 4.52 (d, JH,H = 10.8 Hz, 1 H, O-
3
3
CH2Ph), 4.36 (d, JH,H = 12.0 Hz, 1 H, O-CH2Ph), 4.31 (d, JH,H
3
= 8.0 Hz, 1 H, 1-H), 4.19 (m, 1 H), 3.97 (d, JH,H = 15.2 Hz, 1 H,
COCH2Cl), 3.91 (d, JH,H = 15.2 Hz, 1 H, COCH2Cl), 3.81 (m, 1
H), 3.60–3.43 (m, 4 H), 3.35 (t, JH,H = 7.6 Hz, 1 H, 2-H), 2.47 (t,
3
3
3JH,H = 7.2 Hz, 2 H), 1.89 (m, 2 H), 1.19 (t, JH,H = 7.2 Hz, 1 Disaccharide Cleavage from the Resin: Sodium methoxide (0.15 mL,
3
H) ppm. 13C NMR (100 MHz, CDCl3, 23 °C): δ = 201.61 (alde- 28% MeOH solution) was added to a suspension of the resin
hyde), 168.89, 138.17, 137.50, 128.45, 128.35, 128.13, 128.03,
(580 mg) in MeOH (2 mL) and THF (3 mL) at room temperature.
127.98, 127.84, 127.81, 127.69, 127.67, 103.42, 84.63, 82.14, 77.21, The mixture was stirred at room temperature overnight and then
76.88, 75.73, 74.90, 72.58, 68.92, 64.48, 40.74, 40.57, 22.41 ppm.
HRMS: calcd. for [C33H37ClO8 + Na]+ 619.2069; found 619.2064.
Amberlyst 15E was added to neutralize the mixture. The resins
were filtered and washed with CH2Cl2 and MeOH. After evapora-
Eur. J. Org. Chem. 2011, 497–516
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
513

S. Manabe, K. Ishii, Y. Ito
FULL PAPER
tion, the crude material was purified by preparative TLC (hexane/
perature overnight, concentrated with toluene, and purified by flash
column chromatography on silica gel (EtOAc/CHCl3, 4:1) to give
64 (42 mg, 92%) as a colorless foam. [α]2D4 = +147 (c = 1.0, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 6.26 (d, J = 9.5 Hz, 1 H,
EtOAc, 3:2) to give 61a (42 mg, 39%) and 61b (20 mg, 19%). Di-
1
saccharide 61a: [α]2D4 = 27.8 (c = 1.1, CHCl3). H NMR: δ = 7.32–
3
7.24 (m, 25 H, aromatic H), 4.93 (d, JH,H = 10.8 Hz, 1 H), 4.89–
3
3
3
3
4.78 (m, 5 H), 4.68 (d, JH,H = 10.8 Hz, 1 H, 1-H), 4.60 (d, JH,H NHCOCH3), 5.48 (t, JH,H = 10.0 Hz, 1 H, 3I-H), 5.20 (t, JH,H
=
3
= 14.8 Hz, 1 H, N-CH2Ph), 4.60–4.55 (m, 3 H), 4.49–4.34 (m, 2
9.5 Hz, 1 H, 3II-H), 5.15 (t, JH,H = 10.0 Hz, 1 H, 4I-H), 5.12 (t,
3
3
H), 4.23 (d, JH,H = 14.8 Hz, 1 H, N-CH2Ph), 3.97–3.94 (m, 3 H),
3JH,H = 10.0 Hz, 1 H, 4II-H), 5.06 (d, JH,H = 3.5 Hz, 1 H, 1II-H),
3.67 (s, 3 H, CO2CH3), 3.94–3.62 (m, 10 H), 3.44 (t, 3JH,H = 9.6 Hz,
4.92 (d, 3JH,H = 4.0 Hz, 1 H, 1I-H), 4.79 (dd, 3JH,H = 10.0, 4.0 Hz,
3
3
1 H), 3.36–3.34 (m, 2 H), 3.15 (dd, JH,H = 12.0, 2.8 Hz, 1 H, 2II- 1 H, 2I-H), 4.40 (m, 1 H, 2II-H), 4.22 (dd, JH,H = 12.5, 4.5 Hz, 1
H), 2.75 (m, 2 H, CH2), 1.95 (m, 2 H, CH2) ppm. 13C NMR: δ =
173.5, 158.7, 138.3, 138.2, 138.1, 137.9, 137.7, 137.7, 137.4, 134.9,
128.6, 128.3, 128.3, 128.2, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8,
127.7, 127.6, 127.5, 103.5, 95.5, 84.6, 82.3, 77.5, 76.2, 75.7, 75.1,
74.9, 74.4, 73.6, 73.0, 69.7, 69.1, 68.9, 68.6, 66.1, 62.0, 60.1, 51.8,
48.0, 30.6, 25.2 ppm. HRMS: calcd. for [C53H59NO13 + Na]+
940.3879; found 940.3880. Disaccharide 61b: [α]2D4 = –5.1 (c = 0.96,
CHCl3). 1H NMR: δ = 7.36–7.9 (m, 25 H, aromatic H), 4.86 (d,
H, 6IIa-H), 4.10 (dd, JH,H = 12.5, 2.5 Hz, 1 H, 6IIb-H), 3.98 (m,
3
3
1 H, 5II-H), 3.97 (m, 1 H, 5I-H), 3.76 (dd, JH,H = 12.5 H, 2.0 Hz,
3
1 H, 6Ia-H), 3.72 (dd, JH,H = 12.5, 4.0 Hz, 1 H, 6Ib-H), 3.41 (s, 3
H, OCH3), 2.10 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 2.08 (s, 3
H, COCH3), 2.04 (s, 3 H, COCH3), 2.02 (s, 6 H, COCH3), 2.00
(s, 3 H, COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 171.1
(COCH3), 170.6 (COCH3), 170.2 (oxazolidinone C=O), 170.0
(COCH3), 169.9 (COCH3), 169.9 (COCH3), 169.3 (COCH3), 97.0
(C-1II), 96.7 (C-1I), 71.0 (C-3II), 70.9 (C-2I), 70.2 (C-3I), 68.5 (C-
4I), 68.4 (C-5I), 68.0 (C-4II), 67.9 (C-5II), 64.3 (C-6I), 61.9 (C-6II),
3
3JH,H = 10.4 Hz, 1 H, O-CH2Ph), 4.81 (d, JH,H = 10.8 Hz, 1 H,
O-CH2Ph), 4.78 (d, 3JH,H = 11.6 Hz, 1 H, O-CH2Ph), 4.70 (d, 3JH,H
3
= 10.4 Hz, 1 H, O-CH2Ph), 4.62 (d, JH,H = 10.4 Hz, 1 H, O- 55.5 (OCH3), 51.5 (C-2II), 22.8 (COCH3), 20.7 (COCH3), 20.6
3
CH2Ph), 4.54–4.42 (m, 5 H), 4.28–4.23 (m, 2 H), 3.97 (d, JH,H
=
(COCH3) ppm. C27H39NO17 (649.60): calcd. C 49.92, H, 6.05, N
9.6 Hz, 1 H, 1-H), 3.91–3.61 (m, 4 H), 3.57 (s, 3 H, CO2CH3), 3.56–
2.16; found C 49.92, H 6.05, N, 2.16.
3.41 (m, 5 H), 3.41 (t, 3JH,H = 8.8 Hz, 1 H), 3.29 (t, 3JH,H = 8.0 Hz,
CCDC-790330 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
Cambridge Crystallographic Data Centre via http:www.ccdc.cam.-
ac.uk/datarequest/cif.
3
1 H), 3.07 (dd, JH,H = 11.2, 6.8 Hz, 1 H), 2.83 (br. s, 1 H), 2.29–
2.26 (m, 2 H, CH2), 1.82 (m, 1 H), 1.79 (m, 2 H, CH2) ppm. 13C
NMR: δ = 173.2, 158.7, 138.1, 138.0, 137.6, 137.1, 135.4, 129.4,
128.4, 128.3, 128.3, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6,
103.3, 102.0, 84.4, 82.1, 79.5, 78.0, 77.2, 76.3, 75.8, 74.9, 74.9, 74.7,
73.8, 69.7, 68.9, 68.5, 51.7, 48.0, 30.5, 25.2 ppm. HRMS: calcd. for
C53H59NO13 + Na [M + Na]+ 940.3879; found 940.3878.
Supporting Information (see also the footnote on the first page of
this article): Experimental procedures and spectroscopic data for
the prepared compounds.
Chloroacetyl Detection by the PNBP Method: Some resin was
transferred to a plastic microtube. Then a PNBP toluene solution
(80 mg/10 mL, ca. 0.3 mL) was added. After 5 min, the resin was
spread over a TLC plate. After heating on a hot plate (1 min), a
10% piperidine solution (toluene) was sprayed over the sample. Af-
ter heating the resin for 10 s, the color was observed with the naked
eye or a computer analysis was performed by using a microscope
equipped with a CCD camera [280ϫ, CCD Micro Scope Inf-550
(Moritex)].
Acknowledgments
We thank Dr. Teiji Chihara and his staff for elemental analyses,
Dr. Kaori Otsuki and Dr. Masaya Usui for high-resolution MS
measurements, and Daisuke Hashizume for X-ray analyses. We also
thank Ms. A. Takahashi for her technical assistance. S. M. thanks
matching funds from RIKEN for PRESTO, the President’s Discre-
tionary Fund from RIKEN, and Grants-in-Aid for Scientific Re-
search (C) from the Japan Society for the Promotion of Science
(grant numbers 19590032 and 21590036).
Hydroxy Group Detection by the Disperse Red Method: The resin
was transferred to a plastic tube and THF (ca. 0.1 mL) was added.
Then a solution of Disperse Red (13 mg/13 mL in THF, 0.1 mL)
and 1 drop of 0.5% iPr2NEt in THF solution were added. After
10 min, the solution was discarded. Then the resin was washed with
THF and DMF several times. The color of the resin was observed
with the naked eye or a computer analysis was performed by using
a microscope with equipped with a CCD camera.
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Received: September 13, 2010
Published Online: December 9, 2010
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