Stereoselective diversity-oriented syntheses of functionalized saccharides from bicyclic carbohydrate 1,2-lactones

Article abstract of DOI:10.1016/j.tet.2011.01.069

Bicyclic carbohydrate 1,2-lactones have been synthesized in only two steps and high yields by saponification and subsequent cyclization from known malonate addition products to glycals. The gluco-configured lactone serves as an important precursor for div

Full text of DOI:10.1016/j.tet.2011.01.069

Tetrahedron 67 (2011) 2447e2461
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective diversity-oriented syntheses of functionalized saccharides from
bicyclic carbohydrate 1,2-lactones
*
Jian Yin, Torsten Linker
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24e25, D-14476 Potsdam-Golm, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Bicyclic carbohydrate 1,2-lactones have been synthesized in only two steps and high yields by saponi-
fication and subsequent cyclization from known malonate addition products to glycals. The gluco-con-
figured lactone serves as an important precursor for diversity-oriented syntheses. Thus, stereoselective
opening of the lactone ring was realized with various nucleophiles in the presence of Sc(OTf)3. This
enabled the introduction of different substituents at the anomeric position, to afford a broad variety of 1-
Received 15 November 2010
Received in revised form 12 January 2011
Accepted 24 January 2011
Available online 28 January 2011
functionalized carbohydrates. On the other hand, stereoselective a-substitution of the gluco-configured
Keywords:
Carbohydrates
Lactones
Glycosides
Molecular diversity
Synthetic methods
lactone with different electrophiles and subsequent ring opening gives a collection of 2-functionalized
saccharides. More than 30 products have been isolated in analytically pure form, and their configurations
were unequivocally established by various NMR methods. Thus, carbohydrate 1,2-lactones are attractive
precursors for the stereoselective synthesis of diverse saccharides.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
1,5-lactone, representing a cheap chiral building block, is easily
prepared by oxidation of the anomeric position of
D
-glucose.9
Access to synthetic carbohydrates is an urgent need for the
development of carbohydrate-based drugs, vaccines, adjuvants as
well as novel drug delivery systems.1 Compared to nucleic acids and
peptides, carbohydrates remain relatively underexplored,2 which is
due in part to the difficulty associated with the synthesis of diverse
carbohydrates and related analogs.3 It is this complexity; however,
that makes carbohydrates a rich source of molecular diversity with
numerous biological applications. Since the early reports by
Schreiber et al.,4 diversity-oriented synthesis (DOS) has become
a new paradigm for developing structurally diverse small mole-
cules as probes to investigate biological pathways and also to
provide the chemical space in drug discovery issues.5
Carbohydrate-fused 1,7-lactones10 are available from uronic acids
and allow stereoselective glycosylations by nucleophilic opening at
the anomeric position.11
Carbohydrate-fused g-lactones found less attention with some
examples for 2,3-lactones 1, which were synthesized over many
steps.12 Besides two papers on functionalized 1,2-lactones 2 (Fig. 1,
R¼I or NHAr),13 our group published the first entry to unsubstituted
carbohydrate 1,2-lactones 3 (Fig. 1, R¼H) in two communications
very recently.14 Herein, we describe in full detail the scope of this
new method, various synthetic transformations, mechanistic
rationalizations of the stereoselectivities, and structural elucidation
of all products. Thus, bicyclic carbohydrate 1,2-lactones 3 are ideal
substrates for the stereoselective diversity-oriented syntheses of 1-
and 2-functionalized saccharides.
Lactones, especially g-lactones, as industrial intermediates and
enzyme inhibitors,6 represent an important class of organic com-
pounds and can be synthesized by various methods.7 Very recently,
Trabocchi et al. reported the generation of molecular diversity of
morpholine analogs by employing a bicyclic morpholine 2,3-lac-
tone,8 which suggests that lactones can serve as an important
precursor for diverse synthesis. However, only few carbohydrate-
based lactones were reported although such structures should
increase the water solubility and related bioavailability. D-Glucono-
* Corresponding author. Tel.: þ49 331 977 5212; fax: þ49 331 977 5056; e-mail
address: linker@uni-potsdam.de (T. Linker).
Fig. 1. Carbohydrate-fused g-lactones.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.069

2448
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2. Results and discussion
2.1. Synthesis of bicyclic carbohydrate 1,2-lactones
Toward our studies on transition-metal-mediated radical re-
actions,15 we developed a one-step entry to 2-C-branched carbo-
hydrates 4 by addition of dimethyl malonate to glycals in high yields
and stereoselectivities.16 Since we already succeeded in the cleavage
to the ester gluco-5 under drastic reaction conditions (Scheme 1),17
our initial synthetic effort on gluco-3 started with decarboxylation
product gluco-5. However, the desired lactone gluco-3 was obtained
in only moderate yield (Scheme 1). Therefore, we looked for a milder
and more convenient method. In the first step, saponification with
LiOH afforded the malonic acid gluco-6 quantitatively. Surprisingly,
the lactone gluco-3 was formed by simple heating to 110 ꢀC in high
yield (Scheme 1). This cyclization is forced by the elimination of
carbon dioxide and methanol entropically, and is superior to the
synthesis via ester gluco-5.
Scheme 2. Diversity-oriented syntheses from lactone gluco-3.
offer an easy entry to 1-functionalized saccharides. On the other
hand, 2-functionalized saccharides would be available by
a-sub-
stitution of the -lactone with different electrophiles and sub-
g
sequent ring opening (pathway 2).
2.2. Synthesis of 1-functionalized saccharides
First of all, we investigated the synthesis of 1-functionalized sac-
charides with commercially available trimethylsilyl cyanide (TMSCN)
11c,e
7a as nucleophile (Table 2). Lewis acids like TMSOTf11a,b or SnCl4
have been proven to be suitable catalysts for openings of 1,7-lac-
tones at the anomeric center.18 However, lactone gluco-3 gave no
conversion (TMSOTf, entry 1) or cleavage of the O-benzyl protecting
groups (SnCl4, entries 2 and 3) in either CH2Cl2 or CH3CN. In addition,
only decomposition products were formed when TiCl4 (entries 4 and
5) or BF3$OEt2 (entry 6) were used as catalysts. Finally, the best con-
18
dition was found with Sc(OTf)3 in CH2Cl2, which was previously
applied for the opening of substituted lactones 2 in CH3CN.13a In our
experiments, three solvents led to different results (Table 2, entries
7e9) indicating a remarkable solvent effect.19 The combination of Sc
(OTf)3 and CH2Cl2 proceeded smoothly and the ring-opened product
8a was isolated in 90% yield (entry 9). Thus, a nitrile group was easily
introduced at the anomeric center, and we could investigate the
applicability of a broad variety of other nucleophiles 7.
Scheme 1. Synthesis of carbohydrate 1,2-lactone gluco-3.
Table 2
Opening of carbohydrate 1,2-lactone gluco-3 with TMSCN
To optimize the synthesis and develop a general entry to car-
bohydrate 1,2-lactones glyco-3, different 2-C-branched saccharides
glyco-4 were investigated.17b The corresponding free dicarboxylic
acids glyco-6 were used without purification, and cyclized under
acidic conditions at 110 ꢀC (Table 1). The method is suitable for
hexoses (entries 1 and 2), pentoses (entries 3 and 4), and di-
saccharides (entries 5 and 6), and provides the hitherto unknown
carbohydrate 1,2-lactones glyco-3 in only two steps and high yields
from malonate addition products 4.14a
OBn
O
OBn
O
a
7a
BnO
BnO
BnO
BnO
CN
Lewis acid
solvent
O
COOH
3
gluco-
8a
O
Entry
Lewis acid
Solvent
Resultsb
1
2
3
4
5
6
7
8
9
TMSOTf
SnCl4
SnCl4
TiCl4
TiCl4
BF3$OEt2
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
CH2Cl2
CH2Cl2
CH3CN
CH2Cl2
CH3CN
CH2Cl2
THF
A
B
B
C
C
C
B
Table 1
Synthesis of carbohydrate 1,2-lactones 3
O
O
O
BnO
ii a
ia
BnO
BnO
HOOC
glyco-
OMe
OMe
CH3CN
CH2Cl2
A
90%c
O
MeOOC
COOMe
COOH
a
4
6
3
glyco-
glyco-
O
7a is TMSCN.
b
A: no conversion; B: cleavage of O-benzyl protecting group; C: decomposition of
gluco-3.
Entry
Malonate
Product
Yieldb [%]
c
Yields of analytically pure products, isolated by column chromatography.
1
2
3
4
5
6
gluco-4
galacto-4
xylo-4
arabino-4
malto-4
lacto-4
gluco-3
galacto-3
xylo-3
arabino-3
malto-3
lacto-3
92
91
88
88
87
84
C-Glycosides are of current interest in chemistry, biology, and
medicine.20 They possess a rich source of chirality and have been
used as building blocks in natural product synthesis.21 Therefore,
we investigated the reaction of lactone gluco-3 with various C-
nucleophiles 7bee in the presence of Sc(OTf)3 (Table 3). Indeed, we
could isolate 1,2-bis-C-branched glucose derivatives 8b,c in high
yields (entries 1 and 2). Additionally, electron rich arenes enabled
the simple synthesis of C-aryl glycosides 8d,e (entries 3 and 4), but
the transformation failed with electron poor anisole.22 The opening
a
(i) LiOH, MeOH/H2O, reflux, IR-120. (ii) HOAc, toluene, reflux.
Yields of analytically pure products, isolated by column chromatography.
b
Since lactone gluco-3 provides the most common configuration
in nature, we became interested in its selective functionalization by
two different methods (Scheme 2). One idea was the reaction with
nucleophiles at the anomeric center (pathway 1), which would
proceeded for all reactions stereoselectively to
subsequent epimerization was not observed.
b-anomers, and

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2449
Table 3
resulting in
b-anomers with free acid groups (entries 10 and 11).
Opening of lactone gluco-3 with C-nucleophiles 7beea
Herein we describe the mechanism of such reactions with Sc(OTf)3
Entry
1
C-Nucleophile 7
Product 8b (%)
for the first time, but similar a/b anomerizations have been pre-
viously reported in the presence of SnCl4.11e
BnO
Not only C- and O-glycosides, but also N- and S-glycosides are
very important compounds in current glycochemistry and glyco-
biology.9c,23 Thus, the third topic of our studies was the reaction of
lactone gluco-3 with various hetero-nucleophiles 7qeu in the
presence of Sc(OTf)3 (Table 5, entries 1e5). The reaction with
aqueous ammonia is especially attractive, since it opens simple
access to bicyclic lactam 8q (entry 1) in excellent yield. Glucosyl
azide 8r was formed with trimethylsilyl azide (7r) as nucleophile,
O
BnO
SiMe3
7b
7c
7d
8b (83)
8c (85)
8d (67)
BnO
HOOC
BnO
Me
Me
OMe
Me
Me
O
BnO
2
3
BnO
HOOC
OSiMe3
COOMe
BnO
OMe
OMe
OMe
O
BnO
BnO
HOOC
OMe
OMe
MeO
Table 4
MeO
O
BnO
Opening of lactone gluco-3 with O-nucleophiles 7fepa
BnO
4
7e
8e (77)
Product 8b (%)
BnO
HOOC
Entry O-Nucleophile 7
MeO
OMe
MeO
BnO
a
O
In the presence of Sc(OTf)3, procedure and conditions see Experimental.
Yields of analytically pure products, isolated by column chromatography.
BnO
BnO
1
2
MeOH
EtOH
7f
8fc (92)
8g (86)
OMe
OEt
b
MeOOC
BnO
O
BnO
BnO
7g
Next, the lactone opening was investigated with various alco-
EtOOC
hols (Table 4, entries 1e9) to provide biologically important
O-glycosides,9c,23 where the free carboxylic acid was directly
esterified under the reaction conditions after ring opening.
(α/β 25/75)
BnO
BnO
O
OiPr
BnO
3
4
i-PrOH
t-BuOH
7h
7i
8h (78)
8i (65)
Surprisingly,
O-nucleophiles and the reaction times. Methanol (7f) afforded the
-methyl glucoside 8f (entry 1) after 30 min in excellent yield,
whereas an epimerization to the -anomer, which was not sepa-
rable from the anomer, occurred after several hours. On the other
a/b selectivities strongly depend on the different
iPrO C(α/β 75/25)
2
b
BnO
a
O
BnO
b
BnO
OtBu
hand, ethanol (7g) and 2-propanol (7h) furnished anomeric mix-
tures (entries 2 and 3), which were separated by column chroma-
tography and isolated in analytically pure form (see Experimental).
Other alcohols 7ien, even sterically hindered tert-butyl alcohol (7i)
and cyclohexanol(7j), also reacted as nucleophiles under such
tBuO2C
BnO
O
BnO
BnO
OH
5
6
7j
8j (78)
8k (55)
O
O
O
conditions (Table 4, entries 4e9). Interestingly, a-glucosides 8ien
were isolated selectively after longer reaction times. Such an
anomerization is important for further transformations of the
products. Glycosides 8len, which contain two long alkyl chains and
represent mimics of carbohydrate-based phospholipids,24 were
obtained with octanol (entry 7), dodecanol (entry 8), and even
octadecanol (entry 9). Unfortunately, the reaction of lactone gluco-3
with protected carbohydrates 7o,p gave only low conversion
in dichloromethane. Thus, different solvents were investigated,
and the best result was found with 1,2-dichloroethane. Finally,
disaccharides 8o,p were isolated in moderate yields after 80 min
(Table 4, entries 10 and 11). The liability of the glycosidic bond
in the presence of Sc(OTf)3 required short reaction times, which
BnO
BnO
O
Cyclohexanol
7k
BnO
Oc-hex
c-hexO2C
BnO
O
BnO
BnO
7
8
CH3(CH2)7OH
CH3(CH2)11OH
7l
8l (60)
O(CH2)7CH3
CH3(CH2)7O2C
BnO
O
BnO
BnO
7m
8m (56)
O(CH2)11CH3
O(CH2)17CH3
CH3(CH2)11O2C
BnO
explains the selective formation of
esterification of the carboxylic acid group.
Our mechanistic rationale of anomerization during O-gly-
b-anomers and the absence of
O
BnO
BnO
9
CH3(CH2)17OH
7n
7o
7p
8n (52)
8o (53)
8p (30)
a/b
CH3(CH2)17O2C
cosylation is based on two possible intermediates A and B, with the
Sc(OTf)3 activated lactone A formed in the first step (Scheme 3).
O
R1
=
BnO
O
O
O
Fast reactions with nucleophiles like methanol afford
b
-anomers,
BnO
BnO
R1
10
O
O
due to the selective attack from the opposite face. On the other
hand, after longer reaction times, the intermediate A might open to
the anomeric cation B, which can be trapped by the nucleophile
from both sides. Under thermodynamic control, an equilibrium via
O
HOOC
O
O
BnO
O
O
BnO
BnO
R2
11
O
R2
=
O
intermediate B is possible, with the preferred formation of
a-
HOOC
O
anomers. For such long reaction times, a subsequent esterification
in the presence of the Lewis acid takes place (Table 4, entries 2e9).
The isolation of products 8o,p is in accordance to this hypothesis,
since the liability of the disaccharide requires short reaction times,
a
In the presence of Sc(OTf)3, procedure and conditions see Experimental.
Yields of analytically pure products, isolated by column chromatography.
Compound 8f is identical with compound 5.
b
c

2450
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2.3. Synthesis of 2-functionalized saccharides
In the next part of our diversity-oriented synthesis we became
interested in further functionalizations of the 2-position. The -al-
a
kylation of lactone gluco-3 seemed to be very attractive, since car-
bohydrate 2,3-lactones exhibit very good stereoselectivities.12c,29
Indeed, in our previous studies we established potassium hexame-
thyldisilazide (KHMDS) as a suitable base for the a-deprotonation of
lactone gluco-3 at low temperatures.14b Thus, methylated product
(7S)-9a was isolated in high yield as a sole diastereomer (Scheme 4).
Scheme 3. Proposed mechanism for a/b anomerization.
Table 5
Scheme 4. Stereoselective synthesis of 2-functionalized glucosides (7S)-10.
Opening of lactone gluco-3 with hetero-nucleophiles 7qeua
Entry
1
hetero-Nucleophile 7
Product 8b (%)
BnO
To extend the potential of our method and to determine the
structure of all products, we examined the assembly of hetero-
atoms at the 7-position of the glucose backbone. Thus, reaction
with trisyl azide30 afforded azide (7S)-9b in 88% yield. Un-
fortunately, MoO531 as oxidant gave no conversion of lactone gluco-
O
BnO
BnO
25% NH3/H2O
7q
8q (95)
NH
O
3, but with Davis reagent32 the
a-hydroxy ester (7S)-9c was
BnO
O
obtained in 87% yield in only one step (Scheme 4). Both reactions
proceeded again with excellent stereoselectivities, and the prod-
ucts were isolated in analytically pure form. Next, the lactone ring
was smoothly re-opened with methanol in the presence of Sc
(OTf)3. Under such conditions, the methyl esters (7S)-10 were iso-
lated in good yields without epimerization (Scheme 4). Therefore,
we developed a convenient method to prepare 2-functionalized
saccharides from the lactone gluco-3 in only few steps.
The exclusive formation of one diastereomer for all reactions
can be explained by steric interactions of the attacking electrophile
with the sugar backbone, as already postulated in our previous
communication.14b Herein we present detailed structural and
conformational elucidations by NMR methods. Due to the fixed
bicyclic structure of the lactone, coupling constants and NOE effects
are very distinctive. Thus, both lactones gluco-3 and (7S)-9a show
an unusually large coupling constant of J1,2¼5.0 Hz, being mid-way
between the normal values for axialeequatorial and axialeaxial
interactions (Fig. 2).
BnO
2
3
4
TMSN3
EtSH
7r
7s
7t
8r (75)
8s (82)
8t (85)
N3
SEt
SH
BnO
HOOC
BnO
BnO
O
O
BnO
EtSOC
BnO
BnO
(TMS)2S
BnO
HOOC
BnO
BnO
O
5
Et3SiH
7u
8u (78)
BnO
HOOC
a
In the presence of Sc(OTf)3, procedure and conditions see Experimental.
Yields of analytically pure products, isolated by column chromatography.
b
which can be applied in ‘click chemistry’25 or as precursor for
preparation of dendrimers.26 During this reaction, the intermediary
silyl ester was hydrolyzed during work-up (entry 2). Ethanethiol
(7s) afforded ethyl thioglucoside 8s (entry 3) as a potential glycosyl
donor27 in good yield. All reactions proceeded with excellent ster-
eoselectivities under exclusive formation of
b-anomers, of course
the hemithioacetal 8t is in equilibrium with its
a
form (entry 4).
This glycosyl thiol is a very useful building block for the synthesis
of certain glycoconjugates that may be considered as analogs of
glycopeptides and glycoproteins.28 Finally, 1-deoxy derivate 8u was
synthesized in 78% yield by hydride opening (entry 5).
Fig. 2. Structural comparison of lactones gluco-3 and (7S)-9a.
This indicates that the conformation of the pyranoside ring is
distorted by the lactone from a chair to something approaching
a half-chair.12c Additionally, lactone gluco-3 has two coupling con-
In summary, the opening of lactone gluco-3, which is easily
available from
D-glucal, with different nucleophiles proceeded
0
smoothly with high stereoselectivities in moderate to good yields.
Five C-glycosides (Tables 2 and 3), eleven O-glycosides (Table 4),
and five hetero-glycosides (Table 5) were isolated in analytically
pure form. Thus, a diverse set of more than 20 different 1-func-
tionalized saccharides was synthesized from the same precursor in
only few steps.
stants J2,7¼7.5 Hz and J2,7 ¼4.5 Hz, whereas lactone (7S)-9a shows
only J2,7¼5.8 Hz (Fig. 2). Since this value is in between 4.5 and 7.5 Hz,
again the conformation of the bicyclic ring system must have been
distorted, and a clear determination of the configuration at the
7-position was not possible by coupling constants. Therefore, we
performed detailed NOE studies with lactone 9a. Distinctive

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2451
cross-peaks of the methyl group with 2-H and even 1-H un-
equivocallyestablished the S-configuration at the 7-position (Fig. 3).
higher conversions and stereoselectivities. Finally, the best condi-
tion was found with the potassium salt, since the NMR spectra
indicated full conversion and the highly selective formation of
a sole product. Thus, the glycoside (7R)-10a was isolated in 90%
yield in analytically pure form (entry 7). To extend the scope of our
method, the assembly of heteroatoms at the 7-position of the
glucose backbone was investigated. Thus, electrophiles like trisyl
azide or the Davis reagent afforded the substituted methyl esters
(7R)-10b,c in 82% and 85% yield with excellent stereoselectivities,
respectively (Table 6, entries 8 and 9). All products were isolated in
analytically pure form.
The determination of the configurations of esters 10 was more
challenging than for lactones 9, since NOE measurements were not
possible, due to the free rotation around the C-2e7 bond. However,
very similar coupling constants for all S-isomers (J2,7¼5.8e6.6 Hz),
and R-isomers (J2,7¼1.8e2.1 Hz) clearly indicate that the configu-
rations of the newly formed stereogenic centers of all main prod-
ucts 10 are identical (Fig. 4).
Fig. 3. NOE measurements (600 MHz) of (7S)-9a.
To open a selective entry to the 7R-isomers, we became in-
terested in the direct
a-alkylation of ester gluco-5, which is easily
availablefrom
D
-glucalin only fewsteps.17 Now the methylenegroup
Fig. 4. Structural comparison of esters (7S)-10 and (7R)-10.
is not fixed within a bicyclic structure and the attack of the elec-
trophile can occur from different faces. Additionally, a suitable base
had to be found for deprotonation at low temperature (Table 6).
Furthermore, a direct comparison of the 1H NMR spectra of the
two isomers (7S)-10a, obtained from the lactone opening of 9a
(Scheme 4), and (7R)-10a exhibit remarkable differences (Fig. 5).
Thus, the chemical shifts of the methyl and CO2Me group differ by
more than 0.1 ppm. Therefore, both epimers can be easily distin-
guished by their 1H NMR spectra. Since ester (7S)-10a was obtained
Table 6
Deprotonation and trapping of ester gluco-5
OBn
O
OBn
O
from the known S-configured lactone 9a; all products from the a-
i. Base
ii. electrophile
THF, –78 °C
BnO
BnO
BnO
BnO
OMe
OMe
alkylation (Table 6) have exactly the opposite R-configuration. Thus,
the synthesis of both epimers from the same precursor has been
realized in only few steps.
THF, –78 °C
45 min
COOMe
gluco-5
R
COOMe
(7R)-10
The excellent stereoselectivities for all reactions can be ratio-
nalized by the formation of two different intermediates A or B
(Scheme 5). Chelation of the metal ion by the ester enolate and an
adjacent oxygen atom of the sugar backbone stabilizes the whole
system. Two possibilities to the anomeric center (A) and to the 3-
position (B) exist. From our studies with lactone gluco-3 we know,
that electrophiles attack the carbohydrate ring only from the top
face (Scheme 4). Thus, intermediate B must be clearly favored, since
it affords the R-configured products 10, which is indeed the case
(Table 6). The chelation proceeds most efficiently with potassium as
counterion, explaining the best selectivities with KHMDS (entries
7e9). This interpretation is in accordance to a recent study, where
the fixation of a potassium enolate to the 3-position and not to the
anomeric center was discussed as well.33 Overall, we developed
a new concept of chelation-control in carbohydrate chemistry and
realized a stereodivergent synthesis at the glucose backbone from
easily available precursors.
Entry
Base
Ra
Conv.b (%)
7R:7Sb
7R-10c (%)
1
2
3
4
5
6
7
8
9
LDA
Me
Me
Me
Me
Me
Me
Me
N3
50
55
50
60
90
88:12
89:11
91:9
90:10
92:8
7R-10a (30)
7R-10a (25)
7R-10a (32)
7R-10a (42)
7R-10a (71)
7R-10a (79)
7R-10a (90)
7R-10b (82)
7R-10c (85)
LDA/DMPU
LDA/HMPA
LDA/HMPT
LiHMDS
NaHMDS
KHMDS
95
95:5
>97
>97
>97
>97:3
>97:3
>97:3
KHMDS
KHMDS
OH
a
b
c
Electrophiles: iodomethane, 2-sulfonyloxaziridine or trisyl azide.
Determined by NMR spectra of the crude products.
Yields of analytically pure products, isolated by column chromatography.
Indeed, the reaction with lithium diisopropylamide (LDA) and
subsequent methylation already afforded the product 10a in a ratio
of 7R/7S¼88:12 (entry 1). However, the pure epimer (7R)-10a was
isolated in only 30% yield due to the low conversion of 50%. The
conversions and yields could not be improved by addition of 1,3-
dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) (entry
2), hexamethylphosphoramide (HMPA) (entry 3) or hexamethyl-
phosphorous triamide (HMPT) (entry 4). More efficient deproto-
nations were realized with stronger hexamethyldisilazides (HMDS)
(entries 5e7), and already the lithium salt provided remarkably
2.4. Synthesis of other functionalized saccharides
To obtain more diverse structures of functionalized saccharides,
we investigated some more transformations (Scheme 6). Thus, ni-
trile 8a was smoothly converted into the diester 11 in 86% yield.

2452
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
Fig. 5. Comparison of 1H NMR spectra of (7S)-10a and (7R)-10a.
Such 1,2-bis-C-branched glucose derivates with methyl ester
groups at the 1-positon are suitable intermediates in total syn-
thesis.34 Interestingly, allyl ester 8j is predestined for ring-closing
metathesis,35 since due to the selective
a/b anomerization during
the lactone opening, both double bonds occupy the same side of the
carbohydrate. Successfully, we synthesized macrolide 12, which,
Scheme 5. Proposed mechanism for the selective a-substitution of ester gluco-5.
Scheme 6. Transformations of carbohydrate analogs 8a, 8j, and 10b.

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2453
flanked by the saccharide, should possess interesting biological
properties.36 Finally, azides 10b were transformed into 2-C-
branched glyco-amino esters 13 by the convenient Staudinger re-
duction (Scheme 6).37 Such interesting compounds, which have
been synthesized by completely different reaction pathways pre-
viously,38 led to an additional structural proof for the configura-
tions at the 7-position.
acetate 3:1); 1H NMR (500 MHz, CDCl3):
d
¼2.40 (dd, J¼15.5, 7.5 Hz,
1H, 70-H), 2.53 (dd, J¼15.5, 4.5 Hz, 1H, 7-H), 2.58 (dddd, J¼10.5, 7.5,
5.0, 4.5 Hz, 1H, 2-H), 3.41 (ddd, J¼9.0, 4.5, 3.0 Hz, 1H, 5-H), 3.62 (dd,
J¼10.5, 2.0 Hz, 1H, 3-H), 3.72 (dd, J¼10.5, 3.0 Hz, 1H, 60-H), 3.73 (dd,
J¼10.5, 4.5 Hz, 1H, 6-H), 3.72 (dd, J¼9.0, 2.0 Hz, 1H, 4-H), 4.46
(d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼11.0 Hz, 1H, CH2ePh), 4.52
(d, J¼11.5 Hz, 1H, CH2ePh), 4.55 (d, J¼12.0 Hz, 1H, CH2ePh), 4.64
(d, J¼11.0 Hz, 1H, CH2ePh), 4.76 (d, J¼11.5 Hz, 1H, CH2ePh), 5.76
(d, J¼5.0 Hz, 1H, 1-H), 7.10e7.29 (m, 15H, arom, H); 13C NMR
3. Conclusion
(75 MHz, CDCl3):
74.1, 74.4 (3t, CH2ePh), 72.9, 76.5, 79.2 (3d, C-3, C-4, C-5), 101.4 (d,
C-1), 127.7, 127.9, 128.1, 128.4, 128.5, 128.6 (6d, arom, CeH), 137.6,
d
¼34.2 (t, C-7), 40.7 (d, C-2), 68.3 (t, C-6), 73.6,
In conclusion, we have developed a convenient and general
entry to bicyclic carbohydrate 1,2-lactones in only two steps from
malonates, which are easily available by radical additions to glycals.
Stereoselective diversity-oriented syntheses (DOS) of functional-
137.7, 137.8 (3s, arom, CeCH2O), 172.6 (s, COOR); IR (film):
n
¼3088,
3064, 3029, 2915, 2868, 1771, 1498, 1278 cmꢁ1; elemental analysis
(%) calcd for C29H30O6: C 73.40, H 6.37; found: C 73.25, H 6.42.
ized saccharides have been realized by using such
g-lactones as
important precursors. A broad variety of carbohydrate 1-analogs
have been obtained by ring opening with different nucleophiles at
the anomeric center. This pathway offers an opportunity to syn-
thesize biologically important C-, O-, and hetero-glycosides, which
can be used for attractive future applications. On the other hand,
4.2.2. (3aR,4R,5R,6R,7aR)-4,5-Dibenzyloxy-6-benzyloxymethyl-2-
oxo-hexahydro-furo[2,3-b]pyran (galacto-3). A white solid; mp
20
81e83 ꢀC; [
a
]
þ35.0 (c 1.00, CHCl3); Rf¼0.35 (c-hexane/ethyl
D
acetate 3:1); 1H NMR (500 MHz, CDCl3):
d
¼2.48 (dd, J¼17.5,
various 2-functionalized saccharides have been synthesized by
a
-
6.5 Hz, 1H, 70-H), 2.60 (dd, J¼17.5, 7.0 Hz, 1H, 7-H), 2.76 (dddd,
J¼10.5, 7.0, 6.5, 4.5 Hz, 1H, 2-H), 3.24 (dd, J¼10.5, 2.0 Hz, 1H, 3-H),
3.55 (dd, J¼9.0, 5.5 Hz, 1H, 60-H), 3.60 (dd, J¼9.0, 1.0 Hz, 1H, 6-H),
3.91 (dd, J¼7.5, 2.0 Hz, 1H, 4-H), 4.00 (ddd, J¼7.5, 5.5, 1.0 Hz, 1H, 5-
H), 4.32 (d, J¼11.5 Hz, 1H, CH2ePh), 4.40 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.46 (d, J¼12.0 Hz, 1H, CH2ePh), 4.55 (d, J¼11.5 Hz,
1H, CH2ePh), 4.64 (d, J¼11.5 Hz, 1H, CH2ePh), 4.78 (d,
J¼11.5 Hz, 1H, CH2ePh), 5.76 (d, J¼4.5 Hz, 1H, 1-H), 7.18e7.32 (m,
deprotonation of lactones or esters and subsequent trapping with
electrophiles. All products were isolated in good to high yields in
analytically pure form. The stereoselectivities are remarkably high
and can be controlled by the reaction pathway via lactone or ester.
Thus, R or S isomers are selectively available; their absolute con-
figurations were unequivocally determined by detailed NMR
studies. Overall more than 30 carbohydrate analogs have been
synthesized from one precursor, demonstrating the potential of
diversity-oriented syntheses in carbohydrate chemistry.
15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼34.8 (t, C-7), 37.2 (d,
C-2), 68.1 (t, C-6), 71.5, 73.5, 74.3 (3t, CH2ePh), 69.4, 72.4, 78.2
(3d, C-3, C-4, C-5), 102.2 (d, C-1), 127.8, 127.9, 128.0, 128.3, 128.4,
128.7 (6d, arom, CeH), 137.0, 137.7, 138.1 (3s, arom, CeCH2O),
4. Experimental
4.1. General
173.0 (s, COOR); IR (film):
n
¼3545, 3028, 2915, 1771, 1607, 1455,
1259 cmꢁ1; elemental analysis (%) calcd for C29H30O6: C 73.40, H
6.37; found: C 73.29, H 6.40.
All reactions were carried out under argon by using standard
Schlenk techniques. Solvents and commercially available chemicals
were purified by standard methods or used as purchased. Excess of
4.2.3. (3aR,4R,5R,7aR)-4,5-Dibenzyloxy-2-oxo-hexahydro-furo[2,3-
20
b]pyran (xylo-3). A colorless syrup; [
a
]
þ26.7 (c 0.92, CHCl3);
D
malonate was removed by a Kugelrohrofen (GKR-50, Buchi). TLC
Rf¼0.37 (c-hexane/ethyl acetate 3:1); 1H NMR (500 MHz, CDCl3):
€
was performed on aluminum sheets silica gel 60 F254 (Merck,
d
¼2.43 (dd, J¼16.0, 8.0 Hz, 1H, 60-H), 2.47 (dddd, J¼9.5, 8.0, 5.0,
Darmstadt). Silica gel (63e200
mm, Woelm, Erlangen) was used for
4.0 Hz, 1H, 2-H), 2.73 (dd, J¼16.0, 5.0 Hz, 1H, 6-H), 3.49e3.53 (m,
2H, 5-H, 50-H), 3.71 (ddd, J¼6.5, 3.0, 2.0 Hz,1H, 4-H), 3.83 (dd, J¼9.5,
3.0 Hz, 1H, 3-H), 4.49 (d, J¼12.0 Hz, 1H, CH2ePh), 4.52 (d, J¼11.5 Hz,
1H, CH2ePh), 4.58 (d, J¼12.0 Hz, 1H, CH2ePh), 4.69 (d, J¼11.5 Hz,
1H, CH2ePh), 5.59 (d, J¼4.0 Hz, 1H, 1-H), 7.18e7.30 (m, 10H, arom,
column chromatography. Optical rotations were measured on
€
a JASCO P-1020 polarimeter, melting points on a Buchi SMP 20
apparatus (uncorrected). IR spectra were recorded on a Per-
kineElmer 1600 FT-IR spectrometer. NMR spectra were recorded
either on a Bruker AC 300, AC 400 or AC 500 with CDCl3 as the
solvent and internal standard. Elemental analyses were performed
on an ELEMENTAR vario EL analysator. High resolution mass
spectroscopy (HRMS) was recorded on a Thermo Finnigan MAT 95
sectorfield spectrometer.
H); 13C NMR (75 MHz, CDCl3):
d¼32.1 (t, C-6), 40.4 (d, C-2), 61.9 (t,
C-5), 71.9, 73.6 (2t, CH2ePh), 74.7, 76.3 (2d, C-3, C-4), 100.1 (d, C-1),
127.7, 127.8, 128.0, 128.1, 128.6 (5d, arom, CeH), 137.5, 137.6 (2s,
arom, CeCH2O),174.1 (s, COOR); IR (film):
n
¼3068, 2931,1955, 1788,
1450, 1235 cmꢁ1; elemental analysis (%) calcd for C21H22O5: C 71.17,
H 6.26; found: C 71.32, H 6.16.
4.2. General procedure for the lactonization
4.2.4. (3aS,4S,5R,7aS)-4,5-Dibenzyloxy-2-oxo-hexahydro-furo[2,3-b]
20
A solution of addition product 4 (2.0 mmol) and LiOH$H2O
(210 mg, 5.0 mmol) in MeOH/H2O (4:1, 20 mL) was heated under
reflux for 1 h. After cooling to room temperature, the solvent was
removed under vacuum. Then the crude product was dissolved in
toluene and the pH value was adjusted to 3e4 with acetic acid. The
solution was heated under reflux for 1 h. After evaporating the
solvent the crude product was purified by flash chromatography
(cyclohexane/ethyl acetate 7:1) to afford the lactone 3 in analyti-
cally pure form.
pyran (arabino-3). A colorless syrup; [
a]
þ32.9 (c 0.96, CHCl3);
D
Rf¼0.39 (c-hexane/ethyl acetate 3:1); 1H NMR (500 MHz, CDCl3):
d
¼2.50 (dd, J¼17.5, 1.5 Hz, 1H, 60-H), 2.60 (dd, J¼17.5, 7.5 Hz, 1H, 6-
H), 2.76 (dddd, J¼9.5, 7.5, 4.5, 1.5 Hz, 1H, 2-H), 3.64 (dd, J¼12.5,
6.5 Hz, 1H, 50-H), 3.74 (ddd, J¼6.5, 3.0, 2.5 Hz, 1H, 4-H), 3.83 (dd,
J¼9.5, 2.5 Hz, 1H, 3-H), 4.00 (dd, J¼12.5, 3.0 Hz, 1H, 5-H), 4.29
(d, J¼11.5 Hz, 1H, CH2ePh), 4.54 (d, J¼11.5 Hz, 1H, CH2ePh), 4.56
(d, J¼12.0 Hz, 1H, CH2ePh), 4.68 (d, J¼12.0 Hz, 1H, CH2ePh), 5.77
(d, J¼4.5 Hz, 1H, 1-H), 7.18e7.32 (m, 10H, arom, H); 13C NMR
(75 MHz, CDCl3):
d
¼34.5 (t, C-6), 37.5 (d, C-2), 62.4 (t, C-5), 71.0,
4.2.1. (3aR,4R,5S,6R,7aR)-4,5-Dibenzyloxy-6-benzyloxymethyl-2-
71.3 (2t, CH2ePh), 68.9, 76.1 (2d, C-3, C-4), 102.0 (d, C-1), 127.8,
127.9, 128.2, 128.5, 128.6 (5d, arom, CeH), 137.2, 137.7 (2s, arom,
oxo-hexahydro-furo[2,3-b]pyran (gluco-3). A white solid; mp
20
87e89 ꢀC; [
a]
þ21.8 (c 0.99, CHCl3); Rf¼0.33 (c-hexane/ethyl
CeCH2O), 173.4 (s, COOR); IR (film):
n
¼3062, 2930, 1780, 1454,
D

2454
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
1204 cmꢁ1; elemental analysis (%) calcd for C21H22O5: C 71.17, H
6.26; found: C 71.03, H 6.33.
NaHCO3 solution and the mixture was extracted with dichloro-
methane (3ꢂ20 mL), the combined organic extracts were dried
(Na2SO4) and concentrated. The crude product was purified by
flash chromatography. Compounds 8g and 8h are separable by
column.
4.2.5. (3aR,4R,5S,6R,7aR)-4-Benzyloxy-5-[2,3,4,6-tetra-O-benzyl-2-
deoxy-a-D-glucopyranosyl]-6-benzyloxymethyl-2-oxo-hexahydro-
furo[2,3-b] pyran (malto-3). A colorless syrup; [
a
]
20 þ58.5 (c 1.01,
D
CHCl3); Rf¼0.42 (c-hexane/ethyl acetate 3:1); 1H NMR (500 MHz,
4.3.1. [3,4,6-Tri-O-benzyl-2-deoxy-2-C-(acetic
acid)-b-D-glucopyr-
20
CDCl3):
d
¼2.18 (dd, J¼17.5, 9.5 Hz, 1H, 130-H), 2.79 (dddd, J¼10.5,
anosyl] carbonitrile (8a). A colorless syrup; [
a
]
þ34.1 (c 0.89,
D
9.5, 8.0, 6.5 Hz, 1H, 2-H), 2.85 (dd, J¼17.5, 8.0 Hz, 1H, 13-H), 3.31
(dd, J¼9.5, 2.0 Hz, 1H, 120-H), 3.43 (dd, J¼9.5, 3.5 Hz, 1H, 12-H),
3.49 (dd, J¼10.5, 7.5 Hz, 1H, 3-H), 3.50 (dd, J¼10.5, 7.5 Hz, 1H, 10-
H), 3.59 (dd, J¼9.5, 7.5 Hz, 1H, 4-H), 3.60 (ddd, J¼9.5, 6.5, 4.0 Hz,
1H, 5-H), 3.61 (ddd, J¼10.5, 3.5, 2.0 Hz, 1H, 11-H), 3.67 (dd, J¼12.5,
8.0 Hz, 1H, 60-H), 3.71 (dd, J¼12.5, 4.5 Hz, 1H, 6-H), 3.76
(dd, J¼10.0, 7.5 Hz, 1H, 9-H), 3.98 (dd, J¼10.0, 3.5 Hz, 1H, 8-H), 4.29
(d, J¼12.0 Hz, 1H, CH2ePh), 4.30 (d, J¼11.5 Hz, 1H, CH2ePh), 4.35
(d, J¼3.5 Hz, 1H, 7-H), 4.37 (d, J¼11.5 Hz, 1H, CH2ePh), 4.46
(d, J¼1.5 Hz, 2H, CH2ePh), 4.47 (d, J¼12.5 Hz, 1H, CH2ePh), 4.54
(d, J¼12.5 Hz, 1H, CH2ePh), 4.59 (d, J¼11.0 Hz, 1H, CH2ePh), 4.78
(d, J¼12.0 Hz, 1H, CH2ePh), 4.79 (d, J¼11.0 Hz, 1H, CH2ePh), 4.81
(d, J¼12.0 Hz, 1H, CH2ePh), 4.83 (d, J¼11.5 Hz, 1H, CH2ePh), 5.89
(d, J¼6.5 Hz, 1H, 1-H), 7.00e7.25 (m, 30H, arom, H); 13C NMR
CHCl3); Rf¼0.38 (c-hexane/ethyl acetate 1:1); 1H NMR
(400 MHz, CDCl3):
d
¼2.23 (dddd, J¼10.4, 9.6, 4.8, 4.0 Hz, 1H, 2-
H), 2.49 (dd, J¼17.6, 4.8 Hz, 1H, 70-H), 2.74 (dd, J¼17.6, 4.0 Hz,
1H, 7-H), 3.40 (ddd, J¼9.2, 6.0, 2.8 Hz, 1H, 5-H), 3.56 (dd, J¼11.6,
6.0 Hz, 1H, 60-H), 3.58 (dd, J¼9.2, 3.0 Hz, 1H, 4-H), 3.59 (dd,
J¼11.6, 2.8 Hz, 1H, 6-H), 3.64 (dd, J¼10.4, 3.0 Hz, 1H, 3-H), 4.39
(d, J¼10.4 Hz, 1H, CH2ePh), 4.43 (d, J¼9.6 Hz, 1H, 1-H), 4.46 (d,
J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼12.0 Hz, 1H, CH2ePh), 4.55
(d, J¼10.4 Hz, 1H, CH2ePh), 4.69 (d, J¼10.4 Hz, 1H, CH2ePh),
4.82 (d, J¼10.4 Hz, 1H, CH2ePh), 7.07e7.27 (m, 15H, arom, H);
13C NMR (75 MHz, CDCl3):
d
¼31.0 (t, C-7), 42.6 (d, C-2), 67.5 (d,
C-1), 68.3 (t, C-6), 73.7, 74.9, 75.2 (3t, CH2ePh), 79.0, 80.3, 81.0
(3d, C-3, C-4, C-5), 116.1 (s, C^N), 127.8, 127.9, 128.4, 128.5,
128.6 (5d, arom, CeH), 137.6, 137.7, 137.8 (3s, arom, CeCH2O),
(75 MHz, CDCl3):
d
¼30.2 (t, C-13), 36.1 (d, C-2), 68.1, 70.0 (2t, C-6,
175.9 (s, COOH); IR (film):
n
¼3030, 2949, 2235, 1731, 1456,
C-12), 71.0, 73.4, 73.5, 73.8, 75.0, 75.6 (6t, CH2ePh), 71.1, 71.4, 72.2,
74.2, 77.4, 79.6, 81.7 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 96.6,
99.6 (2d, C-1, C-7), 127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.3,
128.4, 128.7 (9d, arom, CeH), 137.5, 137.8, 137.9, 138.0, 138.2, 138.5
1259 cmꢁ1; elemental analysis (%) calcd for C30H31NO6: C 71.84,
H 6.23, N 2.79; found: C 71.55, H 6.06, N 2.84.
4.3.2. 3-[3,4,6-Tri-O-benzyl-2-deoxy-2-C-(formic
acid)-b-D-gluco-
þ35.7 (c 0.94,
20
(6s, arom, CeCH2O), 174.8 (s, COOR); IR (film):
n
¼3029, 2860, 1717,
pyranosyl]-1-propene (8b). A colorless syrup; [
a
]
D
1451, 1040 cmꢁ1; elemental analysis (%) calcd for C56H58O11: C
74.15, H 6.45; found: C 74.36, H 6.28.
CHCl3); Rf¼0.39 (c-hexane/ethyl acetate 1:1); 1H NMR (500 MHz,
CDCl3):
d
¼2.04e2.08 (m, 1H, CH2CH]CH2), 2.06 (dd, J¼16.0, 7.5 Hz,
1H, 70-H), 2.32e2.39 (m, 1H, CH2CH]CH2), 2.44 (dddd, J¼10.0, 7.5,
7.0, 4.5 Hz, 1H, 2-H), 2.57 (dd, J¼16.0, 7.0 Hz, 1H, 7-H), 3.49 (dd,
J¼9.5, 3.5 Hz, 1H, 4-H), 3.56 (dd, J¼14.0, 2.5 Hz, 1H, 60-H), 3.61 (dd,
J¼14.0, 6.5 Hz, 1H, 6-H), 3.63 (ddd, J¼9.5, 6.5, 2.5 Hz, 1H, 5-H), 3.69
(dd, J¼10.0, 3.5 Hz, 1H, 3-H), 4.04 (dt, J¼10.5, 4.5 Hz, 1H, 1-H), 4.42
(d, J¼12.0 Hz, 1H, CH2ePh), 4.44 (d, J¼11.0 Hz, 1H, CH2ePh), 4.53 (d,
J¼11.5 Hz, 1H, CH2ePh), 4.57 (d, J¼12.0 Hz, 1H, CH2ePh), 4.63 (d,
J¼11.0 Hz, 1H, CH2ePh), 4.78 (d, J¼11.5 Hz, 1H, CH2ePh), 5.00 (dt,
J¼16.0, 9.5 Hz, 2H, CH2CH]CH2), 5.71 (dddd, J¼17.0, 10.0, 7.0,
3.5 Hz, 1H, CH2CH]CH2), 7.06e7.27 (m, 15H, arom, H); 13C NMR
4.2.6. (3aR,4R,5S,6R,7aR)-4-Benzyloxy-5-[2,3,4,6-tetra-O-benzyl-2-
deoxy-b-D-galactopyranosyl]-6-benzyloxymethyl-2-oxo-hexahydro-
20
furo[2,3-b] pyran (lacto-3). A colorless syrup; [
a
]
þ66.1 (c 1.01,
D
CHCl3); Rf¼0.40 (c-hexane/ethyl acetate 3:1); 1H NMR (500 MHz,
CDCl3):
d
¼2.56 (dddd, J¼10.5, 8.5, 6.0, 4.5 Hz, 1H, 2-H), 2.57 (s, 2H,
13-H, 130-H), 3.32 (ddd, J¼10.5, 6.5, 3.0 Hz, 1H, 11-H), 3.38 (dd,
J¼8.5, 3.0 Hz, 2H, 12-H, 120-H), 3.44 (dd, J¼12.0, 7.5 Hz, 1H, 6-H),
3.48 (dd, J¼10.5, 6.5 Hz, 1H, 10-H), 3.50 (dd, J¼10.5, 7.5 Hz, 1H, 3-H),
3.57 (ddd, J¼10.0, 7.5, 3.5 Hz, 1H, 5-H), 3.67 (dd, J¼10.0, 7.5 Hz, 1H,
4-H), 3.72 (d, J¼7.5 Hz, 1H, 7-H), 3.73 (dd, J¼12.0, 3.5 Hz, 1H, 60-H),
3.81 (d, J¼3.0, 1H, 9-H), 3.98 (dd, J¼9.5, 6.5 Hz, 1H, 8-H), 4.24
(d, J¼11.5 Hz, 1H, CH2ePh), 4.27 (d, J¼12.0 Hz, 1H, CH2ePh), 4.31
(d, J¼11.5 Hz, 1H, CH2ePh), 4.40 (d, J¼11.0 Hz, 1H, CH2ePh), 4.47
(d, J¼12.0 Hz, 1H, CH2ePh), 4.48 (d, J¼11.5 Hz, 1H, CH2ePh), 4.64
(d, J¼11.0 Hz, 1H, CH2ePh), 4.65 (s, 2H, CH2ePh), 4.73 (d, J¼11.0 Hz,
1H, CH2ePh), 4.88 (d, J¼11.5 Hz,1H, CH2ePh), 4.90 (d, J¼11.5 Hz,1H,
CH2ePh), 5.74 (d, J¼4.5 Hz, 1H, 1-H), 7.11e7.29 (m, 30H, arom, H);
(75 MHz, CDCl3):
d
¼31.6 (t, CH2]CHCH2), 32.6 (t, C-7), 40.5 (d, C-2),
68.9 (t, C-6), 73.4, 74.2, 74.3 (3t, CH2ePh), 72.5, 73.0, 79.0 (3d, C-3,
C-4, C-5), 79.9 (d, C-1), 116.9 (t, CH2]CHCH2), 127.6, 127.7, 127.8,
128.3, 128.4 (5d, arom, CeH), 134.3 (d, CH2]CHCH2), 138.0, 138.1,
138.2 (3s, arom, CeCH2O), 177.8 (s, COOH); IR (film):
n
¼3031, 2968,
1737, 1453, 1267 cmꢁ1; elemental analysis (%) calcd for C32H36O6: C
74.39, H 7.02; found: C 74.45, H 7.16.
13C NMR (75 MHz, CDCl3):
d
¼33.6 (t, C-13), 39.8 (d, C-2), 67.9, 68.5
4.3.3. Methyl 2-[3,4,6-tri-O-benzyl-2-deoxy-2-C-(formic acid)-b-D-
20
(2t, C-6, C-12), 72.8, 73.2, 73.5, 73.9, 74.6, 75.4 (6t, CH2ePh), 72.6,
73.4, 73.6, 75.1, 78.2, 79.5, 82.4 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-
11), 101.0, 103.7 (2d, C-1, C-7), 127.4, 127.6, 127.7, 127.8, 127.9, 128.0,
128.2, 128.3, 128.4 (9d, arom, CeH), 137.9, 138.3, 138.4, 138.5, 138.7,
glucopyranosyl]-2-methylpropionate (8c). A colorless syrup; [a]
D
þ21.8 (c 0.92, CHCl3); Rf¼0.36 (c-hexane/ethyl acetate 1:1); 1H NMR
(400 MHz, CDCl3):
d
¼1.13, 1.20 (2s, 3H, each, CH3), 2.04 (dddd,
J¼10.4, 8.4, 6.8, 3.0 Hz, 1H, 2-H), 2.12 (dd, J¼17.2, 6.8 Hz, 1H, 70-H),
2.46 (dd, J¼17.2, 3.0 Hz,1H, 7-H), 3.39 (ddd, J¼9.6, 4.2, 2.0 Hz, 1H, 5-
H), 3.50 (d, J¼8.4 Hz, 1H, 1-H), 3.55 (s, 3H, COOMe), 3.59 (dd, J¼14.4,
2.0 Hz, 1H, 60-H), 3.66 (dd, J¼14.4, 4.2 Hz, 1H, 6-H), 3.72 (dd, J¼9.6,
3.0 Hz, 1H, 4-H), 3.75 (dd, J¼10.4, 3.0 Hz, 1H, 3-H), 4.47
(d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼11.2 Hz, 1H, CH2ePh), 4.53
(d, J¼11.2 Hz, 1H, CH2ePh), 4.55 (d, J¼12.0 Hz, 1H, CH2ePh), 4.66
(d, J¼11.2 Hz, 1H, CH2ePh), 4.85 (d, J¼11.2 Hz, 1H, CH2ePh),
138.8 (6s, arom, CeCH2O), 173.7 (s, COOR); IR (film):
n
¼3088, 2911,
1780,1498,1071 cmꢁ1; elemental analysis (%) calcd for C56H58O11: C
74.15, H 6.45; found: C 74.42, H 6.50.
4.3. General procedure for the opening of lactone
A solution of gluco-3 (1.0 mmol), Sc(OTf)3 (738 mg, 1.5 mmol,
1.5 equiv), and DrieriteÒ (20e40 mesh) (1.36 g, 10.0 mmol,
10.0 equiv) in absolute dry dichloromethane (20 mL) was stirred at
7.11e7.26 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼18.9, 24.2
(2q, CH3), 31.4 (t, C-7), 41.0 (d, C-2), 46.1 (s, (CH3)2CCOOMe), 52.0 (q,
COOMe), 69.3 (t, C-6), 73.3, 74.5, 74.7 (3t, CH2ePh), 79.3, 80.2, 80.7
(3d, C-3, C-4, C-5), 83.3 (d, C-1), 127.4, 127.7, 127.8, 128.3, 128.4 (5d,
arom, CeH), 138.2, 138.3, 138.5 (3s, arom, CeCH2O), 177.2, 177.4 (2s,
0 ꢀC with argon protection. After 30 min the nucleophile
7
(5.0 equiv) was added to the solution. Then the solution was stirred
at room temperature until TLC showed complete conversion of the
starting material. The reaction was quenched with saturated
COOH, COOMe); IR (film):
n
¼3031, 2952, 1787, 1453, 1266 cmꢁ1
;

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2455
elemental analysis (%) calcd for C34H40O8: C 70.81, H 6.99; found: C
70.93, H 7.06.
hexane/ethyl acetate 4:1); 1H NMR (300 MHz, CDCl3):
d¼2.27 (dd,
J¼15.9, 9.0 Hz, 1H, 7-H), 2.61 (dd, J¼15.9, 5.1 Hz, 1H, 70-H), 2.80
(dddd, J¼10.8, 9.0, 5.1, 3.3 Hz, 1H, 2-H), 3.23 (s, 3H, OMe), 3.51 (s,
3H, COOMe), 3.54 (ddd, J¼9.9, 6.0, 3.6 Hz, 1H, 5-H), 3.55 (dd, J¼10.8,
9.0 Hz, 1H, 3-H), 3.58 (dd, J¼9.9, 9.0 Hz, 1H, 4-H), 3.82 (dd, J¼13.2,
3.6 Hz, 1H, 6-H), 3.85 (dd, J¼13.2, 6.0 Hz, 1H, 60-H), 4.37 (d,
J¼11.7 Hz, 1H, CH2ePh), 4.41 (d, J¼11.7 Hz, 1H, CH2ePh), 4.45 (d,
J¼11.4 Hz, 1H, CH2ePh), 4.48 (d, J¼11.4 Hz, 1H, CH2ePh), 4.63 (d,
J¼11.4 Hz, 1H, CH2ePh), 4.74 (d, J¼3.3 Hz, 1H, 1-H), 4.81 (d,
J¼11.4 Hz, 1H, CH2ePh), 7.16e7.30 (m, 20H); 13C NMR (75 MHz,
4.3.4. 2-[3,4,6-Tri-O-benzyl-2-deoxy-2-C-(formic
acid)-b-D-gluco-
20
pyranosyl]-1,5-dimethoxybenzene (8d). A colorless syrup;
[a]
D
þ47.8 (c 0.88, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate 1:1); 1H NMR
(300 MHz, CDCl3):
d
¼2.49 (dddd, J¼10.2, 8.4, 5.7, 3.0 Hz, 1H, 2-H),
2.54 (dd, J¼17.4, 3.0 Hz, 1H, 70-H), 2.86 (dd, J¼17.4, 5.7 Hz, 1H, 7-H),
3.19 (ddd, J¼9.9, 5.1, 3.6 Hz, 1H, 5-H), 3.58 (dd, J¼14.1, 3.6 Hz, 1H, 60-
H), 3.59 (dd, J¼9.9, 3.0 Hz, 1H, 4-H), 3.65 (s, 3H, OMe), 3.67 (dd,
J¼14.1, 5.1 Hz, 1H, 6-H), 3.71 (dd, J¼10.2, 3.0 Hz, 1H, 3-H), 3.73 (s,
3H, OMe), 4.31 (d, J¼11.1 Hz, 1H, CH2ePh), 4.33 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.43 (d, J¼11.1 Hz, 1H, CH2ePh), 4.57 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.58 (d, J¼11.1 Hz, 1H, CH2ePh), 4.74 (d, J¼11.1 Hz, 1H,
CH2ePh), 4.40 (d, J¼8.4 Hz, 1H, 1-H), 7.11e7.30 (m, 18H, arom, H);
CDCl3):
d
¼32.3 (t, C-7), 37.6 (d, C-2), 51.3 (q, COOMe), 55.2 (q, OMe),
69.6 (t, C-6), 71.5, 73.5, 74.4 (3t, CH2ePh), 69.6, 71.9, 78.3 (3d, C-3, C-
4, C-5), 100.3 (d, C-1), 127.5, 127.7, 127.8, 128.0, 128.2, 128.4 (6d,
arom, CeH), 138.0, 138.1, 138.2 (3s, arom, CeCH2O), 173.1 (s,
COOMe).
13C NMR (75 MHz, CDCl3):
d¼30.9 (t, C-7), 43.0 (d, C-2), 55.3, 55.8
(2q, OMe), 69.5, 69.7 (3d, arom, CeH), 71.2 (t, C-6), 73.2, 73.8, 74.2
(3t, CH2ePh), 76.0, 77.9, 78.5 (3d, C-3, C-4, C-5), 92.3 (d, C-1), 106.8
(s, C(MeOCCH)), 127.6, 127.7, 127.8, 128.0, 128.2, 128.3, 128.5 (7d,
arom, CeH), 137.3, 137.5, 138.1 (3s, arom, CeCH2O), 159.6, 160.9 (2s,
4.3.8. Ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(ethoxycarbonyl)-methyl]-
20
b
-
D
-glucopyranoside (
b
-8g). A colorless syrup; [
a
]
þ18.8 (c 0.91,
D
CHCl3); Rf¼0.43 (c-hexane/ethyl acetate 4:1); 1H NMR (300 MHz,
CDCl3):
d
¼1.10 (t, J¼3.0 Hz, COOCH2CH3), 1.13 (t, J¼3.9 Hz, OCH2CH3),
arom, CeOMe), 176.8 (s, COOH); IR (film):
n
¼3030, 2868, 1789, 1737,
2.09 (dddd, J¼10.5, 8.7, 6.3, 4.8 Hz, 1H, 2-H), 2.34 (dd, J¼15.3, 6.3 Hz,
1H, 70-H), 2.50 (dd, J¼15.3, 4.8 Hz, 1H, 7-H), 3.36e3.48 (m, 4H,
COOCH2CH3, OCH2CH3), 3.51 (dd, J¼14.1, 5.4 Hz, 1H, 60-H), 3.59 (ddd,
J¼9.3, 7.2, 5.4 Hz, 1H, 5-H), 3.65 (dd, J¼10.5, 6.9 Hz,1H, 3-H), 3.85 (dd,
J¼9.3, 6.9 Hz, 1H, 4-H), 3.95 (dd, J¼14.1, 7.2 Hz, 1H, 6-H), 4.31 (d,
J¼8.7 Hz,1H,1-H), 4.48 (d, J¼12.0 Hz, 1H, CH2ePh), 4.50 (d, J¼10.8 Hz,
1H, CH2ePh), 4.54 (d, J¼11.1 Hz, 1H, CH2ePh), 4.56 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.70 (d, J¼10.8 Hz, 1H, CH2ePh), 4.82 (d, J¼11.1 Hz, 1H,
CH2ePh), 7.08e7.28 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
1453, 1268, 1204 cmꢁ1; elemental analysis (%) calcd for C37H40O8: C
72.53, H 6.58; found: C 72.40, H 6.76.
4.3.5. 2-[3,4,6-Tri-O-benzyl-2-deoxy-2-C-(formic
acid)-b-D-gluco-
20
pyranosyl]-1,3,5-dimethoxybenzene (8e). A colorless syrup; [a]
D
þ41.6 (c 0.97, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate 1:1); 1H NMR
(300 MHz, CDCl3):
d
¼2.51 (dddd, J¼10.8, 8.1, 6.3, 2.7 Hz, 1H, 2-H),
2.57 (dd, J¼17.4, 2.7 Hz, 1H, 70-H), 2.85 (dd, J¼17.4, 6.3 Hz, 1H, 7-H),
3.26 (ddd, J¼9.6, 5.1, 4.2 Hz,1H, 5-H), 3.58 (dd, J¼14.7, 4.2 Hz,1H, 60-
H), 3.59 (dd, J¼9.6, 3.3 Hz, 1H, 4-H), 3.65 (s, 3H, OMe), 3.66 (s, 3H,
OMe), 3.67 (dd, J¼14.7, 5.1 Hz, 1H, 6-H), 3.71 (dd, J¼10.8, 3.3 Hz, 1H,
3-H), 3.73 (s, 3H, OMe), 4.33 (d, J¼1.2 Hz, 2H, CH2ePh), 4.43
(d, J¼11.1 Hz, 1H, CH2ePh), 4.57 (d, J¼11.1 Hz, 1H, CH2ePh), 4.58
(d, J¼11.1 Hz, 1H, CH2ePh), 4.74 (d, J¼11.1 Hz, 1H, CH2ePh), 4.43
(d, J¼8.1 Hz, 1H, 1-H), 7.11e7.30 (m, 17H, arom, H); 13C NMR
d
¼14.1, 14.9 (2q, COOCH2CH3, OCH2CH3), 32.0 (t, C-7), 44.8 (d, C-2),
60.2, 65.1 (2t, COOCH2CH3, OCH2CH3), 69.1 (t, C-6), 73.5, 74.6, 74.8 (3t,
CH2ePh), 75.1, 79.9, 82.0 (3d, C-3, C-4, C-5), 102.3 (d, C-1), 127.5,127.6,
127.7, 127.8, 128.3, 128.4 (6d, arom, CeH), 138.1, 138.2, 138.3 (3s, arom,
CeCH2O), 172.2 (s, COOCH2CH3); IR (film):
n
¼3031, 2952, 1738, 1731,
1497, 1435, 1268 cmꢁ1; elemental analysis (%) calcd for C33H40O7: C
72.24, H 7.35; found: C 72.65, H 7.11.
(75 MHz, CDCl3):
d
¼31.0 (t, C-7), 42.0 (d, C-2), 55.3, 55.5, 55.8 (3q,
OMe), 69.6 (2d, C(MeOCCH)2), 71.1 (t, C-6), 73.4, 74.1, 74.6 (3t,
CH2ePh), 75.9, 78.4, 78.8 (3d, C-3, C-4, C-5), 91.1 (d, C-1), 106.8 (s, C
(MeOCCH)2), 127.7, 127.8, 127.9, 128.0, 128.1, 128.4, 128.5 (7d, arom,
CeH), 137.6, 137.8, 138.0 (3s, arom, CeCH2O), 159.6, 159.8, 161.9 (3s,
4.3.9. Ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(ethoxycarbonyl)-methyl]-
20
a
-
D
-glucopyranoside (
a
-8g). A colorless syrup; [
a
]
þ24.2 (c 0.96,
D
CHCl3); Rf¼0.43 (c-hexane/ethyl acetate 4:1); 1H NMR (300 MHz,
CDCl3):
d
¼1.07 (t, J¼7.2 Hz, COOCH2CH3), 1.13 (t, J¼7.2 Hz, OCH2CH3),
arom, CeOMe), 177.7 (s, COOH); IR (film):
n
¼3031, 2952, 1737, 1729,
2.31 (dddd, J¼10.2, 9.0, 5.1, 3.0 Hz, 1H, 2-H), 2.32 (dd, J¼19.8, 5.1 Hz,
1H, 70-H), 2.54 (dd, J¼19.8, 9.0 Hz, 1H, 7-H), 3.34 (ddd, J¼9.6, 7.2,
3.3 Hz, 1H, 5-H), 3.56e3.67 (m, 4H, COOCH2CH3, OCH2CH3), 3.63 (dd,
J¼9.6, 6.6 Hz, 1H, 4-H), 3.69 (dd, J¼10.2, 6.6 Hz, 1H, 3-H), 3.93 (dd,
J¼14.4, 3.3 Hz, 1H, 60-H), 3.99 (dd, J¼14.4, 7.2 Hz, 1H, 6-H), 4.44 (d,
J¼11.1 Hz, 1H, CH2ePh), 4.45 (d, J¼12.0 Hz, 1H, CH2ePh), 4.55 (d,
J¼11.1 Hz, 1H, CH2ePh), 4.59 (d, J¼11.7 Hz, 1H, CH2ePh), 4.70 (d,
J¼11.1 Hz, 1H, CH2ePh), 4.83 (d, J¼3.0 Hz, 1H, 1-H), 4.84 (d, J¼11.1 Hz,
1H, CH2ePh), 7.04e7.30 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
1453, 1271 cmꢁ1; elemental analysis (%) calcd for C38H42O9: C 71.01,
H 6.59; found: C 71.41, H 6.78.
4.3.6. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(methoxy-carbonyl)-
20
methyl]-
b
-
D
-glucopyranoside (
b
-8f). A colorless syrup; [
a
]
D
þ14.2
(c 0.97, CHCl3); Rf¼0.42 (c-hexane/ethyl acetate 4:1); 1H NMR
(300 MHz, CDCl3):
d
¼2.09 (dddd, J¼10.8, 8.7, 5.7, 5.4 Hz, 1H, 2-H),
2.39 (dd, J¼15.3, 5.7 Hz, 1H, 7-H), 2.47 (dd, J¼15.3, 5.4 Hz, 1H, 70-H),
3.41 (s, 3H, OMe), 3.43 (ddd, J¼9.9, 5.4, 3.9 Hz, 1H, 5-H), 3.45 (dd,
J¼10.8, 9.0 Hz,1H, 3-H), 3.49 (s, 3H, COOMe), 3.56 (dd, J¼9.9, 9.0 Hz,
1H, 4-H), 3.67e3.70 (m, 2H, 6-H, 60-H), 4.22 (d, J¼8.7 Hz, 1H, 1-H),
4.50 (d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼11.7 Hz, 1H, CH2ePh),
4.54 (d, J¼11.7 Hz, 1H, CH2ePh), 4.59 (d, J¼12.0 Hz, 1H, CH2ePh),
4.71 (d, J¼11.1 Hz, 1H, CH2ePh), 4.84 (d, J¼11.1 Hz, 1H, CH2ePh),
d
¼14.1, 14.9 (2q, COOCH2CH3, OCH2CH3), 32.7 (t, C-7), 42.9 (d, C-2),
60.2, 63.5 (2t, COOCH2CH3, OCH2CH3), 68.8 (t, C-6), 73.5, 74.7, 75.0 (3t,
CH2ePh), 71.0, 79.8, 80.7 (3d, C-3, C-4, C-5), 98.4 (d, C-1), 127.5, 127.6,
127.7, 127.8, 128.3, 128.4 (6d, arom, CeH), 138.1, 138.2, 138.5 (3s, arom,
CeCH2O), 172.4 (s, COOCH2CH3); IR (film):
n
¼3030, 2948, 1739, 1728,
1473, 1435, 1260 cmꢁ1; elemental analysis (%) calcd for C33H40O7: C
72.24, H 7.35; found: C 72.25, H 7.30.
7.09e7.30 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼31.9
(t, C-7), 44.8 (d, C-2), 51.4 (q, COOMe), 56.9 (q, OMe), 69.0 (t, C-6),
73.5, 74.7, 74.8 (3t, CH2ePh), 75.2, 79.9, 82.1 (3d, C-3, C-4, C-5),
103.4 (d, C-1), 127.6, 127.7, 127.8, 128.3, 128.4 (5d, arom, CeH), 138.0,
138.2, 138.3 (3s, arom, CeCH2O), 172.6 (s, COOMe); IR (film):
4.3.10. iso-Propyl
carbonyl)-methyl]-
3,4,6-tri-O-benzyl-2-deoxy-2-C-[(iso-propoxy-
b-D-glucopyranoside (b-8h). A colorless syrup;
[a
]
20 þ22.5 (c 1.05, CHCl3); Rf¼0.44 (c-hexane/ethyl acetate 4:1); 1H
D
n
¼3030, 2949, 1736, 1452, 1260 cmꢁ1; elemental analysis (%) calcd
NMR (300 MHz, CDCl3):
d¼1.08 (t, J¼6.0 Hz, COOCH(CH3)2), 1.13 (t,
for C31H36O7: C 71.52, H 6.97; found: C 71.45, H 7.16.
J¼6.3 Hz, OCH(CH3)2), 2.02 (dddd, J¼10.5, 8.7, 5.4, 4.5 Hz, 1H, 2-H),
2.38 (dd, J¼15.6, 5.4 Hz, 1H, 70-H), 2.48 (dd, J¼15.6, 4.5 Hz, 1H, 7-H),
3.39 (ddd, J¼9.0, 6.0, 2.7 Hz, 1H, 5-H), 3.47e3.60 (m, 2H, COOCH
(CH3)2, OCH(CH3)2), 3.52 (dd, J¼10.5, 4.8 Hz, 1H, 3-H), 3.63 (dd,
4.3.7. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(methoxy-carbonyl)-
methyl]-
a-D
-glucopyranoside (a-8f). A colorless syrup; Rf¼0.42 (c-

2456
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
J¼9.0, 4.8 Hz, 1H, 4-H), 3.67 (dd, J¼12.3, 2.7 Hz, 1H, 60-H), 3.87
(dd, J¼12.3, 6.0 Hz, 1H, 6-H), 4.46 (d, J¼8.7 Hz, 1H, 1-H), 4.49
(d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼11.1 Hz, 1H, CH2ePh), 4.53
(d, J¼12.0 Hz, 1H, CH2ePh), 4.56 (d, J¼11.1 Hz, 1H, CH2ePh), 4.71
(d, J¼10.8 Hz, 1H, CH2ePh), 4.82 (d, J¼10.8 Hz, 1H, CH2ePh),
CH2ePh), 4.89 (d, J¼2.5 Hz, 1H, 1-H), 5.08 (dd, J¼10.5, 1.0 Hz, 1H,
0
OCH2CH]CH2 ), 5.12 (dd, J¼10.5,1.0 Hz,1H, OCH2CH]CH2), 5.16 (dd,
0
J¼3.5, 1.5 Hz, 1H, COOCH2CH]CH2 ), 5.19 (dd, J¼3.5, 1.5 Hz, 1H,
COOCH2CH]CH2), 5.73e5.82 (m, 2H, COOCH2CH]CH2, OCH2CH]
CH2), 7.05e7.29 (m,15H, arom, H); 13C NMR (75 MHz, CDCl3):
d¼32.5
7.10e7.29 (m,15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼21.7, 21.8,
(t, C-7), 42.8 (d, C-2), 65.0, 68.0 (2t, COOCH2CH]CH2, OCH2CH]
CH2), 68.7 (t, C-6), 73.4, 74.7, 75.0 (3t, CH2ePh), 71.1, 79.7, 80.5 (3d, C-
3, C-4, C-5), 97.9 (d, C-1), 117.0, 118.1 (2t, COOCH2CH]CH2,
OCH2CH]CH2), 127.5, 127.6, 127.7, 127.8, 128.3 (5d, arom, CeH),
132.2, 134.0 (2d, COOCH2CH]CH2, OCH2CH]CH2), 138.0, 138.1,
138.4 (3s, arom, CeCH2O), 171.9 (s, COOCH2CH]CH2); IR (film):
21.9, 23.5 (4q, COOCH(CH3)2, OCH(CH3)2), 31.7 (t, C-7), 44.8 (d, C-2),
69.1 (t, C-6), 67.6, 71.5 (2d, COOCH(CH3)2, OCH(CH3)2), 73.4, 74.6,
74.7 (3t, CH2ePh), 75.1, 80.1, 81.8 (3d, C-3, C-4, C-5), 100.8 (d, C-1),
127.5, 127.6, 127.7, 127.8, 128.3, 128.4 (6d, arom, CeH), 138.1, 138.3,
138.4 (3s, arom, CeCH2O), 171.7 (s, COOCH(CH3)2); IR (film):
n
¼3031, 2952,1792,1729,1453,1437,1272 cmꢁ1; elemental analysis
n
¼3031, 2959, 1732, 1678, 1455, 1268 cmꢁ1; elemental analysis (%)
(%) calcd for C35H44O7: C 72.89, H 7.69; found: C 73.03, H 7.42.
calcd for C35H40O7: C 73.40, H 7.04; found: C 73.48, H 6.99.
4.3.11. iso-Propyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(iso-propoxycar-
4.3.14. cyclo-Hexyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(cyclo-hexylox-
ycarbonyl)-methyl]-a-D-glucopyranoside (8k). A colorless syrup;
20
bonyl)-methyl]-
a
-
D
-glucopyranoside (
a
-8h). A colorless syrup; [
a
]
D
þ31.7 (c 1.02, CHCl3); Rf¼0.44 (c-hexane/ethyl acetate 4:1); 1H NMR
[
a
]
20 ꢁ15.8 (c 0.90, CHCl3); Rf¼0.40 (c-hexane/ethyl acetate 6:1); 1H
D
(300 MHz, CDCl3):
d
¼1.00 (t, J¼6.0 Hz, COOCH(CH3)2), 1.11 (t,
NMR (300 MHz, CDCl3):
d
¼1.16e1.74 (m, 20H, COOc-hex, Oc-hex),
J¼6.3 Hz, OCH(CH3)2), 2.25 (dd, J¼16.2, 6.9 Hz, 1H, 70-H), 2.31
(dddd, J¼10.5, 8.4, 6.9, 2.7 Hz, 1H, 2-H), 2.56 (dd, J¼16.2, 8.4 Hz, 1H,
7-H), 3.55 (ddd, J¼9.0, 6.0, 3.6 Hz, 1H, 5-H), 3.59e3.65 (m, 2H,
COOCH(CH3)2, OCH(CH3)2), 3.66 (dd, J¼12.0, 3.6 Hz, 1H, 60-H), 3.73
(dd, J¼10.5, 3.6 Hz, 1H, 3-H), 3.76 (dd, J¼9.0, 3.6 Hz, 1H, 4-H), 3.78
(dd, J¼12.0, 6.0 Hz, 1H, 6-H), 4.44 (d, J¼11.7 Hz, 1H, CH2ePh), 4.53
(d, J¼11.7 Hz, 1H, CH2ePh), 4.59 (d, J¼12.3 Hz, 1H, CH2ePh), 4.69 (d,
J¼10.8 Hz, 1H, CH2ePh), 4.84 (d, J¼10.8 Hz, 1H, CH2ePh), 4.88 (d,
J¼12.3 Hz, 1H, CH2ePh), 4.96 (d, J¼2.7 Hz, 1H, 1-H), 7.4e7.30 (m,
2.29 (dd, J¼17.7, 8.7 Hz,1H, 70-H), 2.47 (dddd, J¼10.5, 9.3, 8.7, 2.4 Hz,
1H, 2-H), 2.58 (dd, J¼17.7, 9.3 Hz, 1H, 7-H), 2.77 (dt, J¼8.4, 2.1 Hz,
1H, OCH), 3.47 (ddd, J¼8.7, 4.5, 3.3 Hz, 1H, 5-H), 3.54e3.66 (m, 2H,
6-H, 60-H), 3.60 (dd, J¼8.7, 3.6 Hz, 1H, 4-H), 3.73 (dd, J¼10.5, 3.6 Hz,
1H, 3-H), 3.83 (dt, J¼9.3, 1.5 Hz, 1H, COOCH), 4.44 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.49 (d, J¼10.8 Hz, 1H, CH2ePh), 4.54 (d, J¼11.1 Hz, 1H,
CH2ePh), 4.60 (d, J¼12.0 Hz, 1H, CH2ePh), 4.70 (d, J¼10.8 Hz, 1H,
CH2ePh), 4.85 (d, J¼11.1 Hz, 1H, CH2ePh), 5.01 (d, J¼2.4 Hz, 1H, 1-
H), 7.04e7.33 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼23.7,
15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼21.4, 21.7, 21.8, 23.3
23.9, 25.4, 25.7, 26.9, 31.2, 31.7, 33.1 (10t, COOc-hex, Oc-hex), 33.4 (t,
C-7), 43.0 (d, C-2), 69.0 (t, C-6), 71.0, 72.7 (2d, COOCH, OCH), 73.5,
74.8, 75.1 (3t, CH2ePh), 74.8, 79.9, 80.8 (3d, C-3, C-4, C-5), 96.7 (d, C-
1), 127.5, 127.6, 127.8, 127.9, 128.3, 128.4 (15d, arom, CeH), 138.1,
138.2, 138.6 (3s, arom, CeCH2O), 171.9 (s, COOc-hex); IR (film):
(4q, COOCH(CH3)2, OCH(CH3)2), 32.9 (t, C-7), 42.8 (d, C-2), 68.9 (t, C-
6), 67.6, 69.4 (2d, COOCH(CH3)2, OCH(CH3)2), 73.5, 74.8, 75.0 (3t,
CH2ePh), 70.9, 79.8, 80.7 (3d, C-3, C-4, C-5), 96.8 (d, C-1), 127.4,
127.5, 127.6, 127.8, 128.3, 128.4 (6d, arom, CeH), 138.1, 138.2, 138.6
(3s, arom, CeCH2O), 171.9 (s, COOCH(CH3)2); IR (film):
n
¼3030,
n
¼3031, 2948, 1737, 1453, 1437, 1260 cmꢁ1; ESI-HRMS (C41H52O7):
2948, 1800, 1729, 1453, 1437, 1272 cmꢁ1; elemental analysis (%)
calcd for C35H44O7: C 72.89, H 7.69; found: C 72.67, H 7.55.
calcd for [MþNa] 679.3611; found 679.3636.
4.3.15. Octyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(octyloxycarbonyl)-
4.3.12. tert-Butyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(tert-butoxycarbo-
methyl]-
a
-
D
-glucopyranoside (8l). A colorless syrup; [
a
]
20 þ54.2 (c
D
20
nyl)-methyl]-
a
-
D
-glucopyranoside (8i). A colorless syrup; [
a
]
þ20.6
0.98, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate 6:1); 1H NMR
D
(c 0.90, CHCl3); Rf¼0.44 (c-hexane/ethyl acetate 4:1); 1H NMR
(500 MHz, CDCl3):
J¼7.0 Hz, OCH2(CH2)6CH3), 1.12e1.28 (m, 24H, COOCH2(CH2)6CH3,
OCH2(CH2)6CH3), 1.42e1.56 (m, 4H, COOCH2(CH2)6CH3,
d
¼0.79 (t, J¼6.5 Hz, COOCH2(CH2)6CH3), 0.82 (t,
(300 MHz, CDCl3):
d¼1.14, 1.33 (s, 9H, each, OC(CH3)3), 2.12 (dd,
J¼15.6, 5.1 Hz, 1H, 70-H), 2.24 (dddd, J¼10.5, 5.1, 3.3, 3.0 Hz, 1H, 2-H),
2.52 (dd, J¼15.6, 3.0 Hz, 1H, 7-H), 3.50e3.60 (m, 2H, 6-H, 60-H), 3.63
(dd, J¼9.6, 3.9 Hz, 1H, 4-H), 3.74 (dd, J¼10.5, 3.9 Hz, 1H, 3-H), 3.90
(ddd, J¼9.6, 3.3,1.8 Hz,1H, 5-H), 4.43 (d, J¼12.0 Hz, 1H, CH2ePh), 4.45
(d, J¼10.8 Hz, 1H, CH2ePh), 4.53 (d, J¼11.1 Hz, 1H, CH2ePh), 4.61
(d, J¼12.0 Hz, 1H, CH2ePh), 4.70 (d, J¼10.8 Hz, 1H, CH2ePh), 4.84
(d, J¼11.1 Hz, 1H, CH2ePh), 5.18 (d, J¼3.3 Hz, 1H, 1-H), 7.04e7.30 (m,
OCH2(CH2)6CH3), 2.29 (dd, J¼16.0, 9.0 Hz, 1H, 70-H), 2.60 (dd,
J¼16.0, 5.5 Hz, 1H, 7-H), 2.79 (dddd, J¼11.0, 9.0, 5.5, 3.5 Hz, 1H, 2-
H), 3.23 (ddd, J¼9.0, 6.5, 3.5 Hz, 1H, 5-H), 3.49 (dd, J¼12.5, 3.5 Hz,
1H, 60-H), 3.56 (dd, J¼9.0, 3.5 Hz, 1H, 4-H), 3.86 (dd, J¼12.5, 6.5 Hz,
1H, 6-H), 3.92 (dd, J¼11.0, 3.5 Hz, 1H, 3-H), 4.36 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.38 (d, J¼11.5 Hz, 1H, CH2ePh), 4.44 (d, J¼12.0 Hz, 1H,
CH2ePh), 4.48 (d, J¼11.5 Hz, 1H, CH2ePh), 4.63 (d, J¼11.5 Hz, 1H,
CH2ePh), 4.81 (d, J¼11.5 Hz, 1H, CH2ePh), 4.85 (d, J¼3.5 Hz, 1H,
1-H), 7.15e7.28 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
15H, arom, H); 13C NMR (75 MHz, CDCl3):
d¼28.1, 28.6 (6q, CH3), 33.7
(t, C-7), 43.4 (d, C-2), 69.0 (t, C-6), 74.6 (s, OC(CH3)3), 73.5, 74.8, 75.1
(3t, CH2ePh), 80.2 (s, COOC(CH3)3), 70.5, 80.0, 80.6 (3d, C-3, C-4, C-5),
93.0 (d, C-1), 127.5, 127.6, 127.8, 127.9, 128.3, 128.4 (6d, arom, CeH),
138.2, 138.3, 138.6 (3s, arom, CeCH2O), 171.8 (s, COOC(CH3)3); IR
d
¼14.0, 14.1 (2q, CH3), 22.6, 22.7, 25.9, 26.2, 26.9, 28.6, 29.1, 29.2,
29.3, 29.4, 29.5, 31.8, 31.9 (12t, COOCH2(CH2)6CH3,
OCH2(CH2)6CH3), 32.8 (t, C-7), 37.6 (d, C-2), 64.4, 67.9 (2t,
COOCH2(CH2)6CH3, OCH2(CH2)6CH3), 69.5 (t, C-6), 71.5, 73.5, 74.3
(3t, CH2ePh), 69.6, 71.9, 78.6 (3d, C-3, C-4, C-5), 99.0 (d, C-1),
127.4, 127.6, 127.8, 128.0, 128.2, 128.4 (6d, arom, CeH), 138.1,
138.3, 138.9 (3s, arom, CeCH2O), 171.9 (s, COOCH2(CH2)6CH3); IR
(film):
n
¼3027, 2922, 1631, 1496, 1452, 1361, 1257 cmꢁ1; elemental
analysis (%) calcd for C37H48O7: C 73.48, H 8.00; found: C 73.84, H 7.87.
4.3.13. Allyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(allyloxycarbonyl)-meth
20
yl]-
a
-
D
-glucopyranoside (8j). A colorless syrup; [
a
]
þ9.5 (c 0.93,
D
CHCl3); Rf¼0.43 (c-hexane/ethyl acetate 4:1); 1H NMR (500 MHz,
(film):
n
¼3031, 2952, 1737, 1729, 1453, 1437, 1272, 1206 cmꢁ1
;
CDCl3):
d
¼2.33 (dddd, J¼11.5, 8.0, 6.5, 2.5 Hz, 1H, 2-H), 2.35 (dd,
elemental analysis (%) calcd for C45H64O7: C 75.38, H 9.00;
found: C 75.35, H 9.09.
J¼19.0, 6.5 Hz, 1H, 70-H), 2.58 (dd, J¼19.0, 8.0 Hz, 1H, 7-H), 3.59e3.66
(m, 4H, COOCH2CH]CH2, OCH2CH]CH2), 3.72 (dd, J¼10.5, 5.5 Hz,
1H, 4-H), 3.84 (ddd, J¼10.5, 5.5, 2.0 Hz, 1H, 5-H), 4.07 (dd, J¼13.0,
2.0 Hz, 1H, 60-H), 4.35 (dd, J¼13.0, 5.5 Hz, 1H, 6-H), 4.42 (dd, J¼11.5,
5.5 Hz, 1H, 3-H), 4.45 (d, J¼11.5 Hz, 1H, CH2ePh), 4.46 (d, J¼11.5 Hz,
1H, CH2ePh), 4.55 (d, J¼11.5 Hz, 1H, CH2ePh), 4.59 (d, J¼11.5 Hz, 1H,
CH2ePh), 4.70 (d, J¼11.5 Hz, 1H, CH2ePh), 4.85 (d, J¼11.0 Hz, 1H,
4.3.16. Dodecyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(dodecyloxycarbonyl)-
20
methyl]-
a
-
D
-glucopyranoside (8m). A colorless syrup; [
a
]
þ50.1 (c
D
0.88, CHCl3); Rf¼0.39 (c-hexane/ethyl acetate 6:1); 1H NMR
(300 MHz, CDCl3):
d¼0.80 (t, J¼6.9 Hz, COOCH2(CH2)10CH3), 0.81 (t,
J¼6.0 Hz, OCH2(CH2)10CH3), 1.12e1.28 (m, 40H, COOCH2(CH2)10CH3,

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2457
OCH2(CH2)10CH3),
1.42e1.56
(m,
4H,
COOCH2(CH2)10CH3,
(3s, arom, CeCH2O), 174.9 (s, COOH); IR (film):
n
¼3031, 2949, 1729,
OCH2(CH2)10CH3), 2.29 (dd, J¼16.0, 9.0 Hz, 1H, 70-H), 2.60 (dd,
J¼16.0, 5.5 Hz, 1H, 7-H), 2.79 (dddd, J¼11.0, 9.0, 5.5, 3.5 Hz, 1H, 2-
H), 3.23 (ddd, J¼9.0, 6.5, 3.5 Hz, 1H, 5-H), 3.49 (dd, J¼12.5, 3.5 Hz,
1H, 60-H), 3.56 (dd, J¼9.0, 3.5 Hz, 1H, 4-H), 3.86 (dd, J¼12.5,
6.5 Hz, 1H, 6-H), 3.92 (dd, J¼11.0, 3.5 Hz, 1H, 3-H), 4.33 (d,
J¼12.0 Hz, 1H, CH2ePh), 4.39 (d, J¼11.5 Hz, 1H, CH2ePh), 4.45 (d,
J¼12.0 Hz, 1H, CH2ePh), 4.47 (d, J¼11.5 Hz, 1H, CH2ePh), 4.66
(d, J¼11.5 Hz, 1H, CH2ePh), 4.80 (d, J¼11.5 Hz, 1H, CH2ePh), 4.84
(d, J¼4.0 Hz, 1H, 1-H), 7.04e7.30 (m, 15H, arom, H); 13C NMR
1452, 1437, 1271, 1207 cmꢁ1; elemental analysis (%) calcd for
C41H50O12: C 67.01, H 6.86; found: C 66.74, H 7.08.
4.3.19. 3,4,6-Tri-O-benzyl-2-deoxy-2-C-(formic acid)-
anosyl-(1/3)-(1,2:5,6-di-O-isopropylidene)- -glucopyranoside
þ34.7 (c 0.96, CHCl3); Rf¼0.43
(c-hexane/ethyl acetate 2:1); 1H NMR (400 MHz, CDCl3):
¼1.24,
b-D-glucopyr-
a-D
20
(8p). A colorless syrup; [a]
D
d
1.29, 1.37, 1.42 (4s, each, 3H, O2C(CH3)2), 2.38e2.46 (m, 1H, 130-H),
2.45 (ddt, J¼10.8, 7.6, 7.2 Hz, 1H, 8-H), 2.54 (dd, J¼16.0, 7.2 Hz, 1H,
13-H), 3.41 (ddd, J¼8.0, 6.0, 2.8 Hz, 1H, 5-H), 3.61e3.73 (m, 2H, 12-
H, 120-H), 3.62 (d J¼10.4 Hz, 1H, 11-H), 3.71 (dd, J¼9.6, 2.4 Hz, 1H,
10-H), 3.72 (dd, J¼8.4, 1.6 Hz, 1H, 3-H), 3.91 (dd, J¼10.8, 5.2 Hz, 1H,
9-H), 4.00 (dd, J¼8.0, 1.6 Hz, 1H, 4-H), 4.09 (dd, J¼8.4, 2.0 Hz, 1H, 2-
H), 4.25 (dd, J¼13.6, 2.8 Hz, 1H, 60-H), 4.27 (dd, J¼13.6, 6.0 Hz, 1H, 6-
H), 4.46 (d, J¼7.6 Hz, 1H, 7-H), 4.49 (d, J¼12.0 Hz, 1H, CH2ePh), 4.51
(d, J¼12.0 Hz, 1H, CH2ePh), 4.52 (d, J¼11.2 Hz, 1H, CH2ePh), 4.55
(d, J¼11.6 Hz, 1H, CH2ePh), 4.64 (d, J¼11.2 Hz, 1H, CH2ePh), 4.76
(d, J¼11.6 Hz, 1H, CH2ePh), 5.77 (d, J¼4.8 Hz, 1H, 1-H), 7.10e7.26
(75 MHz, CDCl3):
d
¼14.2, 14.3 (2q, CH3), 22.5, 22.8, 25.7, 26.2, 26.9,
28.6, 29.3, 29.4, 29.5, 29.6, 29.7, 31.9 (12t, COOCH2(CH2)10CH3,
OCH2(CH2)10CH3), 32.7 (t, C-7), 43.0 (d, C-2), 64.6, 67.8 (2t,
COOCH2(CH2)10CH3, OCH2(CH2)10CH3), 68.9 (t, C-6), 73.5, 74.8,
75.0 (3t, CH2ePh), 71.0, 79.8, 80.8 (3d, C-3, C-4, C-5), 98.6 (d, C-1),
127.5, 127.6, 127.8, 128.3, 128.4 (5d, arom, CeH), 138.1, 138.2, 138.6
(3s, arom, CeCH2O), 172.5 (s, COOCH2(CH2)10CH3); IR (film):
n
¼3030, 2950, 1736, 1452, 1436, 1206 cmꢁ1; elemental analysis (%)
calcd for C53H80O7: C 76.77, H 9.72; found: C 76.15, H 9.12.
(m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
d¼25.8, 26.4, 27.2,
4.3.17. Octadecyl
carbonyl)-methyl]-
3,4,6-tri-O-benzyl-2-deoxy-2-C-[(octadecyloxy-
a-D-glucopyranoside (8n). A colorless syrup;
27.4 (4q, CH3), 33.5 (t, C-13), 46.5 (d, C-8), 70.3, 70.8 (2t, C-6, C-12),
75.0, 76.1, 76.3 (3t, CH2ePh), 69.5, 71.8, 72.2, 72.9, 76.6, 81.0, 83.5
(7d, C-2, C-3, C-4, C-5, C-9, C-10, C-11), 97.9, 104.7 (2d, C-1, C-7),
110.5, 110.9 (2s, (CH3)2COO), 129.0, 129.2, 129.3, 129.8, 129.9 (5d,
arom, CeH), 139.5, 139.6, 139.7 (3s, arom, CeCH2O), 176.4 (s,
[
a
]
20 þ37.9 (c 0.96, CHCl3); Rf¼0.42 (c-hexane/ethyl acetate 6:1); 1H
D
NMR (300 MHz, CDCl3):
d¼0.80 (t, J¼6.9 Hz, COOCH2(CH2)16CH3),
0.82 (t, J¼6.6 Hz, OCH2(CH2)16CH3), 1.12e1.28 (m, 64H, COOCH2(CH2)16
CH3, OCH2(CH2)16CH3), 1.43e1.50 (m, 4H, COOCH2(CH2)16CH3,
OCH2(CH2)16CH3), 2.31 (dd, J¼19.5, 5.7 Hz, 1H, 70-H), 2.54 (dd, J¼19.5,
8.7 Hz, 1H, 7-H), 3.24 (dddd, J¼10.5, 8.7, 5.7, 3.6 Hz, 1H, 2-H), 3.55 (dd,
J¼12.9, 6.3 Hz, 1H, 60-H), 3.57 (ddd, J¼9.3, 6.3, 4.8 Hz, 1H, 5-H), 3.59
(dd, J¼10.5, 3.3 Hz,1H, 3-H), 3.60 (dd, J¼12.9, 4.8 Hz, 1H, 6-H), 3.71 (dd,
J¼9.3, 3.3 Hz, 1H, 4-H), 3.92 (d, J¼10.8 Hz, 1H, CH2ePh), 3.93 (d,
J¼3.6 Hz, 1H, 1-H), 4.45 (d, J¼12.0 Hz, 1H, CH2ePh), 4.55 (d, J¼11.1 Hz,
1H, CH2ePh), 4.59 (d, J¼12.0 Hz, 1H, CH2ePh), 4.69 (d, J¼10.8 Hz, 1H,
CH2ePh), 4.85 (d, J¼11.1 Hz, 1H, CH2ePh), 7.04e7.30 (m, 15H, arom, H);
COOH); IR (film):
mental analysis (%) calcd for C41H50O12: C 67.01, H 6.86; found: C
67.32, H 6.97.
n
¼3030, 2951, 1729, 1437, 1271, 1207 cmꢁ1; ele-
4.3.20. (2R,3S,4R,4aR,7aR)-2-Benzyoxymethyl-3,4-dibenzyoxy-6-
oxo-hexahydro-pyrano[2,3-b] pyrrole (8q). A white solid; mp
159e161 ꢀC; [
a
]
D
20 þ7.4 (c 1.00, DMSO); Rf¼0.36 (dichloromethane/
methanol 10:1); 1H NMR (500 MHz, DMSO-d6):
d
¼2.14 (dddd,
J¼10.0, 5.0, 4.0, 3.0 Hz, 1H, 2-H), 2.15 (dd, J¼14.5, 5.0 Hz, 1H, 70-
H), 2.88 (dd, J¼14.5, 3.0 Hz, 1H, 7-H), 3.41 (ddd, J¼9.5, 4.5, 1.5 Hz,
1H, 5-H), 3.54 (dd, J¼9.5, 3.5 Hz, 1H, 4-H), 3.59 (dd, J¼10.5,
1.5 Hz, 1H, 60-H), 3.66 (dd, J¼10.5, 4.5 Hz, 1H, 6-H), 3.89 (dd,
J¼10.0, 3.5 Hz, 1H, 3-H), 4.47 (d, J¼12.0 Hz, 1H, CH2ePh), 4.53 (d,
J¼12.0 Hz, 1H, CH2ePh), 4.54 (d, J¼11.0 Hz, 1H, CH2ePh), 4.57
(d, J¼11.0 Hz, 1H, CH2ePh), 4.71 (d, J¼11.0 Hz, 1H, CH2ePh), 4.77
(d, J¼11.0 Hz, 1H, CH2ePh), 6.45 (d, J¼4.0 Hz, 1H, 1-H), 6.77 (s,
1H, NH), 7.20e7.34 (m, 15H, arom, H); 13C NMR (75 MHz, DMSO-
13C NMR (75 MHz, CDCl3):
d¼14.1, 14.2 (2q, CH3), 22.4, 22.7, 25.7,
25.9, 26.2, 26.9, 28.6, 29.3, 29.4, 29.5, 29.6, 29.7, 31.9 (12t,
COOCH2(CH2)16CH3, OCH2(CH2)16CH3), 32.7 (t, C-7), 43.0 (d, C-2), 64.6,
67.8 (2t, COOCH2(CH2)16CH3, OCH2(CH2)16CH3), 68.9 (t, C-6),
73.5, 74.8, 75.0 (3t, CH2ePh), 71.0, 79.8, 80.8 (3d, C-3, C-4, C-5),
98.7 (d, C-1), 127.5, 127.6, 127.7, 127.8, 127.9, 128.3, 128.4 (15d,
arom, CeH), 138.1, 138.2, 138.6 (3s, arom, CeCH2O), 172.5 (s,
COOCH2(CH2)16CH3); IR (film):
n
¼3030, 2952, 1799, 1454, 1432,
1206 cmꢁ1; ESI-HRMS (C65H104O7): calcd for [MþH] 997.7860;
d6):
d
¼32.9 (t, C-7), 42.7 (d, C-2), 69.1 (t, C-6), 72.2, 73.7, 73.9 (3t,
found 997.7811.
CH2ePh), 70.0, 79.8, 79.9 (3d, C-3, C-4, C-5), 91.7 (d, C-1), 127.3,
127.4, 127.5, 128.1, 128.2, 128.3 (6d, arom, CeH), 138.2, 138.3,
4.3.18. 3,4,6-Tri-O-benzyl-2-deoxy-2-C-(formic acid)-
anosyl-(1/6)-(1,2:3,4-di-O-isopropylidene)- -galactopyranoside
þ48.9 (c 0.98, CHCl3); Rf¼0.42 (c-
b
-
D
-glucopyr-
138.5 (3s, arom, CeCH2O), 173.1 (s, CONHR); IR (film):
n
¼3030,
a
-
D
2949, 1736, 1452, 1260 cmꢁ1; elemental analysis (%) calcd for
C29H31NO5: C 73.55, H 6.60, N 2.96; found: C 73.50, H 6.88,
N 3.06.
20
(8o). A colorless syrup; [
a]
D
hexane/ethyl acetate 2:1); 1H NMR (500 MHz, CDCl3):
d
¼1.23, 1.25,
1.36, 1.49 (4s, each, 3H, O2C(CH3)2), 2.18 (dddd, J¼10.5, 8.5, 7.5,
4.5 Hz, 1H, 8-H), 2.34 (dd, J¼15.0, 7.5 Hz, 1H, 130-H), 2.52 (dd,
J¼15.0, 4.5 Hz, 1H, 13-H), 3.39 (ddd, J¼8.0, 7.0, 2.5 Hz, 1H, 5-H), 3.42
(dd, J¼10.5, 3.5 Hz, 1H, 9-H), 3.54e3.65 (m, 2H, 12-H, 120-H), 3.62
(dd, J¼9.0, 3.5 Hz, 1H, 10-H), 3.68 (dd, J¼11.0, 7.0 Hz, 1H, 60-H), 3.90
(dd, J¼7.5, 1.5 Hz, 1H, 11-H), 4.01 (dd, J¼11.0, 2.5 Hz, 1H, 6-H), 4.12
(dd, J¼8.0, 2.0 Hz, 1H, 4-H), 4.23 (dd, J¼5.0, 2.0 Hz, 1H, 3-H), 4.26
(dd, J¼5.0, 2.0 Hz, 1H, 2-H), 4.34 (d, J¼8.5 Hz, 1H, 7-H), 4.46
(d, J¼12.0 Hz, 1H, CH2ePh), 4.50 (d, J¼11.0 Hz, 1H, CH2ePh), 4.56
(d, J¼11.5 Hz, 1H, CH2ePh), 4.57 (d, J¼12.0 Hz, 1H, CH2ePh), 4.70
(d, J¼11.0 Hz, 1H, CH2ePh), 4.82 (d, J¼11.5 Hz, 1H, CH2ePh), 5.42
(d, J¼5.0 Hz, 1H, 1-H), 7.09e7.290 (m, 15H, arom, H); 13C NMR
4.3.21. Azido 3,4,6-tri-O-benzyl-2-deoxy-2-C-(formic acid)-b-D-glu-
20
copyranoside (8r). A colorless syrup; [
a
]
þ19.9 (c 0.87, CHCl3);
D
Rf¼0.41 (c-hexane/ethyl acetate 1:1); 1H NMR (400 MHz, CDCl3):
d
¼2.00 (dddd, J¼10.8, 9.6, 5.2, 4.8 Hz, 1H, 2-H), 2.42 (dd, J¼16.8,
4.8 Hz, 1H, 70-H), 2.50 (dd, J¼16.8, 5.2 Hz, 1H, 7-H), 3.50 (ddd, J¼9.2,
6.4, 2.1 Hz, 1H, 5-H), 3.52 (dd, J¼15.6, 2.1 Hz, 1H, 60-H), 3.58 (dd,
J¼15.6, 6.4 Hz, 1H, 6-H), 3.63 (dd, J¼9.2, 2.0 Hz, 1H, 4-H), 3.69 (dd,
J¼10.8, 2.0 Hz, 1H, 3-H), 4.51 (d, J¼12.0 Hz, 1H, CH2ePh), 4.53
(d, J¼11.2 Hz, 1H, CH2ePh), 4.56 (d, J¼11.2 Hz, 1H, CH2ePh), 4.59
(d, J¼12.0 Hz, 1H, CH2ePh), 4.63 (d, J¼9.6 Hz, 1H, 1-H), 4.71
(d, J¼11.2 Hz, 1H, CH2ePh), 4.84 (d, J¼11.2 Hz, 1H, CH2ePh),
(75 MHz, CDCl3):
d
¼24.2, 24.3, 24.9, 25.9 (4q, CH3), 32.0 (t, C-13),
7.10e7.30 (m,15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼31.2 (t, C-
45.0 (d, C-8), 68.8, 69.3 (2t, C-6, C-12), 73.5, 74.6, 74.8 (3t, CH2ePh),
68.0, 70.3, 70.7, 71.4, 75.1, 79.5, 82.0 (7d, C-2, C-3, C-4, C-5, C-9, C-
10, C-11), 96.4, 103.2 (2d, C-1, C-7), 109.0, 109.4 (2s, (CH3)2COO),
127.5, 127.7, 127.8, 128.3, 128.4 (5d, arom, CeH), 138.0, 138.1, 138.2
7), 44.2 (d, C-2), 68.5 (t, C-6), 73.6, 74.8, 75.0 (3t, CH2ePh), 77.3,
79.3, 81.3 (3d, C-3, C-4, C-5), 89.2 (d, C-1), 127.7, 127.8, 128.0, 128.4,
128.5 (5d, arom, CeH), 137.8, 137.9, 138.0 (3s, arom, CeCH2O), 176.7
(s, COOH); IR (film):
n
¼3030, 2952, 1800, 1738, 1453, 1268 cmꢁ1
;

2458
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
elemental analysis (%) calcd for C29H31N3O6: C 67.30, H 6.04, N 8.12;
found: C 67.05, H 6.06, N 8.64.
(75 MHz, CDCl3):
6), 73.6, 74.8, 74.9 (3t, CH2ePh), 79.8, 79.9, 84.0 (3d, C-3, C-4, C-5),
127.7, 127.8, 127.9, 128.0, 128.4, 128.6, 128.8 (7d, arom, CeH), 137.9,
d
¼32.6 (t, C-7), 39.3 (d, C-2), 69.0, 69.8 (2t, C-1, C-
4.3.22. Ethylthio 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(ethylthioxycarbo-
138.0, 138.1 (3s, arom, CeCH2O), 177.1 (s, COOH); IR (film):
n
¼3030,
20
nyl)-methyl]-
b
-
D
-glucopyranoside (8s). A colorless syrup;
[
a
]
2946, 1738, 1451, 1258 cmꢁ1; elemental analysis (%) calcd for
C29H32O6: C 73.09, H 6.77; found: C 73.00, H 6.89.
D
þ11.4 (c 0.98, CHCl3); Rf¼0.49 (c-hexane/ethyl acetate 1:1); 1H NMR
(400 MHz, CDCl3):
d
¼1.11 (t, J¼7.2 Hz, 3H, SCH2CH3), 1.15 (t,
J¼7.2 Hz, 3H, SCH2CH3), 2.28e2.38 (m, 4H, SCH2CH3), 2.43 (dd,
J¼16.4, 7.6 Hz, 1H, 70-H), 2.45 (dddd, J¼10.8, 8.0, 7.6, 4.4 Hz, 1H, 2-
H), 2.57 (dd, J¼16.4, 4.4 Hz, 1H, 7-H), 2.64 (ddd, J¼9.6, 5.2, 3.6 Hz,
1H, 5-H), 3.57 (dd, J¼10.0, 5.2 Hz, 1H, 60-H), 3.65 (dd, J¼9.6, 4.0 Hz,
1H, 4-H), 3.68 (dd, J¼10.0, 3.6 Hz, 1H, 6-H), 3.96 (dd, J¼10.8, 4.0 Hz,
1H, 3-H), 4.44 (d, J¼12.4 Hz, 1H, CH2ePh), 4.47 (d, J¼12.4 Hz, 1H,
CH2ePh), 4.50 (d, J¼11.6 Hz, 1H, CH2ePh), 4.51 (d, J¼11.6 Hz, 1H,
CH2ePh), 4.54 (d, J¼11.6 Hz, 1H, CH2ePh), 4.63 (d, J¼11.6 Hz, 1H,
CH2ePh), 4.86 (d, J¼8.0 Hz, 1H, 1-H), 7.16e7.28 (m, 15H, arom, H);
4.4. General procedure for the deprotonation of lactone 3 and
ester 5, subsequent trapping with electrophiles
A solution of lactone 3 (235 mg, 0.5 mmol) or ester 5 (258 mg,
0.5 mmol) in dry tetrahydrofuran (10 mL) was cooled to ꢁ78 ꢀC
under an argon atmosphere. At this temperature potassium hex-
amethyldisilazide (1.5 mL, 0.75 mmol) was added slowly. After
45 min, iodomethane (0.16 mL, 2.5 mmol), 2-phenylsulfonyl-3-
phenyloxaziridine (Davis reagent, 265 mg, 1.0 mmol) or trisyl azide
(310 mg, 1.0 mmol) was added dropwise within 10 min. The solu-
tion was stirred until TLC showed complete conversion of the
starting material. A saturated solution of ammonium chloride
(10 mL) was added, and the mixture was extracted with dichloro-
methane (3ꢂ10 mL). The combined organic extracts were dried
(Na2SO4) and concentrated. The crude products 9 and 10 were
analyzed by NMR spectroscopy and purified by flash chromatog-
raphy (c-hexane/ethyl acetate 7:1).
13C NMR (75 MHz, CDCl3):
SCH2CH3), 33.5 (t, C-7), 41.8 (d, C-2), 70.4 (t, C-6), 73.5, 73.6, 73.9 (3t,
CH2ePh), 55.0, 70.5, 79.8 (3d, C-3, C-4, C-5), 82.2 (d, C-1), 127.9,
128.0, 128.1, 128.5, 128.6, 128.7 (6d, arom, CeH), 137.3, 137.4, 137.6
d
¼14.2,14.3 (2q, SCH2CH3), 24.4, 25.0 (2t,
(3s, arom, CeCH2O), 186.1 (s, COSR); IR (film):
n
¼3031, 2952, 1800,
1738, 1731, 1453, 1268, 1215 cmꢁ1; elemental analysis (%) calcd for
C33H40O5S2: C 68.24, H 6.94, S 11.04; found: C 68.05, H 6.66, S 10.78.
4.3.23. Thio 3,4,6-tri-O-benzyl-2-deoxy-2-C-(formic acid)-b-D-glu-
copyranoside (8t). A colorless syrup (mixed isomers); [
0.98, CHCl3); Rf¼0.38 (c-hexane/ethyl acetate 1:1);
NMR (300 MHz, CDCl3):
a
b
]
20 þ11.4 (c
4.4.1. (3S,3aS,4R,5S,6R,7aR)-4,5-Dibenzyloxy-6-benzyloxymethyl-3-
D
-isomer: 1H
methyl-2-oxo-hexahydro-furo[2,3-b]pyran
(7S-9a). A colorless
20
d
¼2.08 (dddd, J¼11.1, 8.1, 6.0, 4.8 Hz, 1H, 2-
syrup; [
a]
D
ꢁ2.4 (c 0.63, CHCl3); Rf¼0.36 (c-hexane/ethyl acetate
H), 2.10 (dd, J¼15.6, 4.8 Hz, 1H, 70-H), 2.23 (dd, J¼15.6, 6.0 Hz, 1H, 7-
H), 2.64 (ddd, J¼9.9, 6.6, 4.2 Hz, 1H, 5-H), 3.50 (dd, J¼11.1, 8.7 Hz,
1H, 3-H), 3.60 (dd, J¼12.3, 6.6 Hz, 1H, 60-H), 3.67 (dd, J¼12.3, 4.2 Hz,
1H, 6-H), 4.11 (dd, J¼9.9, 8.7 Hz, 1H, 4-H), 4.49 (d, J¼11.4 Hz, 1H,
CH2ePh), 4.52 (d, J¼3.3 Hz, 2H, CH2ePh), 4.53 (d, J¼11.4 Hz, 1H,
CH2ePh), 4.54 (d, J¼8.1 Hz, 1H, 1-H), 4.69 (d, J¼10.8 Hz, 1H,
CH2ePh), 4.71 (d, J¼10.8 Hz, 1H, CH2ePh), 7.06e7.29 (m, 15H, arom,
3:1); 1H NMR (300 MHz, CDCl3):
d¼1.16 (d, J¼7.5 Hz, 3H, CH3), 2.33
(dt, J¼11.7, 5.7 Hz, 1H, 2-H), 2.68 (qd, J¼7.5, 5.7 Hz, 1H, 7-H), 3.48
(ddd, J¼10.5, 4.8, 3.0 Hz, 1H, 5-H), 3.60e3.70 (m, 2H, 3-H, 4-H), 3.69
(dd, J¼12.9, 4.8 Hz, 1H, 60-H), 3.72 (dd, J¼12.9, 3.0 Hz, 1H, 6-H), 4.42
(d, J¼11.4 Hz, 1H, CH2ePh), 4.44 (d, J¼12.0 Hz, 1H, CH2ePh), 4.48 (d,
J¼12.0 Hz, 1H, CH2ePh), 4.53 (d, J¼11.4 Hz, 1H, CH2ꢁPh), 4.54 (d,
J¼12.0 Hz, 1H, CH2ꢁPh), 4.67 (d, J¼12.0 Hz, 1H, CH2ꢁPh), 5.76 (d,
J¼5.7 Hz, 1H, 1-H), 7.08e7.31 (m, 15H, arom, H); 13C NMR (75 MHz,
H); 13C NMR (75 MHz, CDCl3):
d
¼33.9 (t, C-7), 48.0 (d, C-2), 68.8 (t,
C-6), 73.5, 74.7, 74.9 (3t, CH2ePh), 79.5, 79.6, 79.8 (3d, C-3, C-4, C-5),
82.7 (d, C-1), 127.6, 127.7, 127.8, 127.9, 128.4 (5d, arom, CeH), 137.8,
CDCl3):
d
¼15.4 (q, CH3), 38.9 (d, C-7), 46.6 (d, C-2), 68.7 (t, C-6),
73.2, 73.3, 73.5 (3t, CH2ꢁPh), 72.3, 75.8, 77.5 (3d, C-3, C-4, C-5), 99.3
(d, C-1), 127.7, 127.8, 128.0, 128.4, 128.5, 128.6 (6d, arom, CꢁH),
137.6, 137.7, 137.8 (3s, arom, CꢁCH2O), 177.1 (s, COOR); IR (film):
137.9, 138.0 (3s, arom, CeCH2O), 177.3 (s, COOH); a
-isomer: 1H NMR
(300 MHz, CDCl3):
d
¼2.20 (dd, J¼16.5, 7.5 Hz, 1H, 70-H), 2.21
(dddd, J¼10.8, 7.5, 5.1, 2.7 Hz, 1H, 2-H), 2.52 (dd, J¼16.5, 5.1 Hz, 1H,
7-H), 2.68 (ddd, J¼9.3, 7.5, 4.5 Hz, 1H, 5-H), 3.43 (dd, J¼11.1, 7.2 Hz,
1H, 3-H), 3.66 (d, J¼3.6 Hz, 2H, 6-H, 60-H), 4.05 (dd, J¼9.3, 7.2 Hz,
1H, 4-H), 4.45 (d, J¼12.3 Hz, 1H, CH2ePh), 4.51 (d, J¼3.3 Hz, 2H,
CH2ePh), 4.57 (d, J¼12.3 Hz, 1H, CH2ePh), 4.59 (d, J¼2.7 Hz, 1H, 1-
H), 4.85 (d, J¼11.1 Hz, 1H, CH2ePh), 4.85 (d, J¼11.1 Hz, 1H,
CH2ePh), 7.06e7.29 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
n
¼3452, 3032, 1963, 1771, 1710, 1624, 1490, 1447, 1345, 1094 cmꢁ1
;
elemental analysis calcd (%) for C30H32O6 (488.57): C 73.75, H 6.60;
found: C 74.05, H 6.76.
4.4.2. (3S,3aS,4R,5S,6R,7aR)-3-Azido-4,5-dibenzyloxy-6-benzylox-
ymethyl-2-oxo-hexahydro-furo[2,3-b] pyran (7S-9b). A colorless
20
syrup; [
a]
ꢁ2.6 (c 0.89, CHCl3); Rf¼0.38 (c-hexane/ethyl acetate
D
d
¼33.3 (t, C-7), 43.1 (d, C-2), 68.5 (t, C-6), 73.5, 74.7, 75.3 (3t,
3:1); 1H NMR (300 MHz, CDCl3):
d
¼2.44 (ddd, J¼11.7, 5.4, 4.8 Hz,
CH2ePh), 72.1, 79.4, 79.8 (3d, C-3, C-4, C-5), 79.9 (d, C-1), 127.6,
127.7, 127.8, 127.9, 128.4 (5d, arom, CeH), 137.8, 137.9, 138.0 (3s,
1H, 2-H), 3.48 (ddd, J¼10.5, 4.5, 2.4 Hz, 1H, 5-H), 3.60 (dd, J¼12.9,
4.5 Hz, 1H, 60-H), 3.64 (dd, J¼11.7, 8.1 Hz, 1H, 3-H), 3.68 (dd, J¼10.5,
8.1 Hz, 1H, 4-H), 3.72 (dd, J¼12.9, 2.4 Hz, 1H, 6-H), 3.98 (d, J¼4.8 Hz,
1H, 7-H), 4.43 (d, J¼11.4 Hz, 1H, CH2ꢁPh), 4.46 (d, J¼11.7 Hz, 1H,
CH2ꢁPh), 4.47 (d, J¼12.0 Hz, 1H, CH2ꢁPh), 4.51 (d, J¼12.0 Hz, 1H,
CH2ꢁPh), 4.54 (d, J¼11.4 Hz, 1H, CH2ꢁPh), 4.65 (d, J¼11.7 Hz, 1H,
CH2ꢁPh), 5.83 (d, J¼5.4 Hz, 1H, 1-H), 7.09e7.33 (m, 15H, arom, H);
arom, CeCH2O), 177.0 (s, COOH); IR (film):
n
¼2953, 1796, 1734,
1726, 1452, 1268, 1207 cmꢁ1; ESI-HRMS (C29H32O6S): calcd for
[MþH] 509.1998; found 509.1994.
4.3.24. 3,4,6-Tri-O-benzyl-1-deoxy-2-deoxy-2-C-(formic acid)-b-D-
glucopyranoside (8u). A colorless syrup; [
a
]
20 þ26.9 (c 0.93, CHCl3);
13C NMR (75 MHz, CDCl3):
d
¼45.2 (d, C-2), 60.3 (d, C-7), 68.3 (t, C-
D
Rf¼0.45 (dichloromethane/methanol 8:1); 1H NMR (300 MHz,
6), 73.3, 73.4, 73.5 (3 t, CH2ꢁPh), 72.8, 75.2, 75.3 (3d, C-3, C-4, C-5),
99.8 (d, C-1), 127.8, 127.9, 128.0, 128.1, 128.3, 128.4, 128.5, 128.7 (8d,
arom, CꢁH), 137.2, 137.3, 137.7 (3s, arom, CꢁCH2O), 170.4 (s, COOR);
CDCl3):
d
¼2.02 (dd, J¼15.6, 8.1 Hz, 1H, 70-H), 2.23 (dddt, J¼11.1, 8.7,
7.8, 4.5 Hz, 1H, 2-H), 2.47 (dd, J¼15.6, 4.5 Hz, 1H, 7-H), 3.10 (dd,
J¼11.4, 4.2 Hz, 1H, 10-H), 3.33 (dd, J¼14.4, 6.3 Hz, 1H, 60-H), 3.55 (dd,
J¼11.4, 9.3 Hz, 1H, 1-H), 3.61 (dd, J¼14.4, 3.3 Hz, 1H, 6-H), 3.87 (ddd,
J¼9.6, 6.3, 3.3 Hz, 1H, 5-H), 3.95 (dd, J¼9.6, 4.8 Hz, 1H, 4-H), 4.00
(dd, J¼11.1, 4.8 Hz, 1H, 3-H), 4.46 (d, J¼12.3 Hz, 1H, CH2ePh), 4.47
(d, J¼11.1 Hz, 1H, CH2ePh), 4.55 (d, J¼12.3 Hz, 1H, CH2ePh), 4.56
(d, J¼11.4 Hz, 1H, CH2ePh), 4.70 (d, J¼11.1 Hz, 1H, CH2ePh), 4.86
(d, J¼11.4 Hz, 1H, CH2ePh), 6.98e7.27 (m, 15H, arom, H); 13C NMR
IR (film):
n
¼3424, 3058, 3032, 2952, 1738, 1456, 1438, 1149, 1087,
1021 cmꢁ1; HRMS(ES) (C29H29N3O6): calcd for [MþNa] 538.1954;
found 538.1945.
4.4.3. (3S,3aS,4R,5S,6R,7aR)-4,5-Dibenzyloxy-6-benzyloxymethyl-3-
hydroxy-2-oxo-hexahydro-furo[2,3-b]pyran (7S-9c). A colorless
20
syrup; [
a
]
ꢁ0.6 (c 0.86, CHCl3); Rf¼0.25 (c-hexane/ethyl acetate
D

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2459
2:1); 1H NMR (300 MHz, CDCl3):
d
¼2.71 (ddd, J¼11.1, 6.9, 5.7 Hz,1H,
2849, 1737, 1631, 1494, 1452, 1204, 1065 cmꢁ1
(C31H35N3O7): calcd for [MþNa] 584.2373; found 584.2349.
;
HRMS(ES)
2-H), 3.57 (dd, J¼9.3, 9.0 Hz, 1H, 4-H), 3.56e3.66 (m, 2H, 6-H, 60-H),
3.61 (ddd, J¼9.3, 5.7, 2.7 Hz, 1H, 5-H), 3.63 (dd, J¼11.1, 9.0 Hz, 1H, 3-
H), 3.73 (d, J¼6.9 Hz, 1H, 7-H), 4.37 (d, J¼12.0 Hz, 1H, CH2ePh), 4.40
(d, J¼11.4 Hz, 1H, CH2ePh), 4.44 (d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d,
J¼11.4 Hz, 1H, CH2ePh), 4.52 (d, J¼12.0 Hz, 1H, CH2ePh), 4.61 (d,
J¼12.0 Hz, 1H, CH2ePh), 5.94 (d, J¼5.7 Hz, 1H, 1-H), 7.08e7.32 (m,
4.5.3. Methyl (7S)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(hydroxy)-(me-
thoxy-carbonyl)-methyl]-
b
-
D
-glucopyranoside (7S-10c). A colorless
20
syrup; [
a]
D
ꢁ3.1 (c 0.79, CHCl3); Rf¼0.28 (c-hexane/ethyl acetate
2:1); 1H NMR (300 MHz, CDCl3):
d
¼2.21 (ddd, J¼11.1, 8.7, 6.6 Hz, 1H,
15H, arom, H); 13C NMR (75 MHz, CDCl3):
d
¼46.1 (d, C-2), 68.8 (t,
2-H), 3.35 (s, 3H, OMe), 3.36 (ddd, J¼10.5, 5.1, 3.6 Hz, 1H, 5-H), 3.49
(s, 3H, COOMe), 3.64 (dd, J¼10.5, 9.0 Hz,1H, 4-H), 3.68e3.72 (m, 2H,
6-H), 3.80 (dd, J¼11.1, 9.0 Hz, 1H, 3-H), 4.32 (d, J¼8.7 Hz, 1H, 1-H),
4.42 (d, J¼10.8 Hz, 1H, CH2ePh), 4.50 (d, J¼12.3 Hz, 1H, CH2ePh),
4.51 (d, J¼6.6 Hz, 1H, 7-H), 4.52 (d, J¼10.8 Hz, 1H, CH2ePh), 4.60
(d, J¼12.3 Hz, 1H, CH2ePh), 4.68 (d, J¼10.8 Hz, 1H, CH2ePh), 4.85
(d, J¼10.8 Hz, 1H, CH2ePh), 7.03e7.30 (m, 15H, arom, H); 13C NMR
C-6), 70.1 (d, C-7), 72.7, 73.0, 73.5 (3t, CH2ePh), 72.7, 74.9, 75.3 (3d,
C-3, C-4, C-5), 99.6 (d, C-1), 127.8, 127.9, 128.1, 128.4, 128.6, 128.6
(6d, arom, CeH), 137.3, 137.5, 137.8 (3s, arom, CeCH2O), 174.5
(s, COOR); IR (film):
n
¼3029, 2863, 1748, 1496, 1453, 1361, 1208,
1027 cmꢁ1; ESI-HRMS (C29H30O7): calcd for [MþNa] 513.1889;
found 513.1874.
(75 MHz, CDCl3):
d
¼50.8 (d, C-2), 52.4 (q, COOMe), 57.0 (q, OMe),
4.5. General procedure for the opening of lactones 9
66.6 (d, C-7), 68.8 (t, C-6), 73.5, 74.7, 74.9 (3t, CH2ePh), 74.3, 74.8,
80.4 (3d, C-3, C-4, C-5), 101.6 (d, C-1), 127.4, 127.6, 127.7, 127.8, 128.1,
128.3, 128.4 (7d, arom, CeH),137.9,138.2,138.3 (3s, arom, CeCH2O),
A mixture of lactone 9 (0.5 mmol) and DrieriteÒ (20e40 mesh)
(680 mg) in dry methanol (10 mL) was stirred at 0 ꢀC under argon
atmosphere. At this temperature Sc(OTf)3 (370 mg, 0.75 mmol,
1.5 equiv) was added and after 30 min TLC showed complete
conversion. The reaction was quenched with saturated sodium
hydrogen carbonate solution (10 mL) and the mixture was
extracted with dichloromethane (3ꢂ20 mL). The combined or-
ganic extracts were dried (Na2SO4) and concentrated and the
crude products 10 were purified by flash chromatography (c-
hexane/ethyl acetate 7:1).
175.3 (s, COOMe); IR (film):
n
¼3441, 3030, 2869, 1723, 1605, 1496,
1453, 1361, 1261, 1207, 1055 cmꢁ1; ESI-HRMS (C31H36O8): calcd for
[MþH] 537.2488; found 537.2478.
4.5.4. Methyl
bonyl)-ethyl]-
(7R)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(methoxy-car-
20
b-D-glucopyranoside (7R-10a). A colorless syrup; [a]
D
ꢁ8.7 (c 1.11, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3):
d¼0.87 (d, J¼7.2 Hz, 3H, CH3), 2.35 (ddd, J¼11.4,
8.7, 2.1 Hz, 1H, 2-H), 2.79 (qd, J¼7.2, 2.1 Hz, 1H, 7-H), 3.33 (ddd, J¼9.0,
6.3, 3.6 Hz, 1H, 5-H), 3.34 (s, 3H, OMe), 3.42 (dd, J¼9.0, 9.3 Hz, 1H, 4-
H), 3.48 (dd, J¼12.6, 3.6 Hz, 1H, 60-H), 3.56 (s, 3H, COOMe), 3.61 (dd,
J¼12.6, 6.3 Hz, 1H, 6-H), 3.67 (dd, J¼11.4, 9.3 Hz, 1H, 3-H), 4.12
(d, J¼8.7 Hz, 1H, 1-H), 4.48 (d, J¼12.0 Hz, 1H, CH2ePh), 4.52
(d, J¼10.8 Hz, 1H, CH2ePh), 4.56 (d, J¼11.1 Hz, 1H, CH2ePh), 4.58
(d, J¼12.0 Hz, 1H, CH2ePh), 4.72 (d, J¼10.8 Hz, 1H, CH2ePh), 4.86
(d, J¼11.1 Hz, 1H, CH2ePh), 7.11e7.29 (m, 15H, arom, H); 13C NMR
4.5.1. Methyl
(7S)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(methoxy-car-
bonyl)-ethyl]-b-D-glucopyranoside (7S-10a). A colorless syrup;
20
[
a
]
ꢁ3.5 (c 0.88, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate 3:1);
D
1H NMR (300 MHz, CDCl3):
d
¼1.13 (d, J¼7.2 Hz, 3H, CH3), 2.25
(ddd, J¼11.1, 8.7, 5.8 Hz, 1H, 2-H), 2.89 (qd, J¼7.2, 5.8 Hz, 1H, 7-
H), 3.35 (dt, J¼9.3, 3.3 Hz, 1H, 5-H), 3.37 (s, 3H, OMe), 3.43 (s,
3H, COOMe), 3.58 (dd, J¼9.3, 8.7 Hz, 1H, 4-H), 3.60 (dd, J¼11.1,
8.7 Hz, 1H, 3-H), 3.69 (d, J¼3.3 Hz, 2H, 6-H), 4.18 (d, J¼8.7 Hz, 1H,
1-H), 4.50 (d, J¼12.0 Hz, 1H, CH2ePh), 4.52 (d, J¼10.8 Hz,
1H, CH2ePh), 4.57 (d, J¼10.8 Hz, 1H, CH2ePh), 4.59 (d, J¼12.0 Hz,
1H, CH2ePh), 4.67 (d, J¼10.8 Hz, 1H, CH2ePh), 4.84 (d,
J¼10.8 Hz, 1H, CH2ePh), 7.04e7.31 (m, 15H, arom, H); 13C NMR
(75 MHz, CDCl3):
d
¼10.0 (q, CH3), 35.3 (d, C-7), 48.7 (d, C-2), 51.5 (q,
COOMe), 57.0 (q, OMe), 69.1 (t, C-6), 73.5, 74.3, 74.7 (3t, CH2ePh), 75.1,
79.5, 80.2 (3d, C-3, C-4, C-5), 102.0 (d, C-1), 127.6, 127.8, 127.9, 128.0,
128.3, 128.4, 128.5 (7d, arom, CeH), 138.0, 138.1, 138.2 (3s, arom,
CeCH2O), 175.7 (s, COOMe); IR (film):
n
¼3456, 3024, 2922, 2858,
1801, 1738, 1490, 1453, 1358, 1270, 1064 cmꢁ1; elemental analysis
calcd (%) for C32H38O7 (534.64): C 71.89, H 7.16; found: C 72.05, H 7.23.
(75 MHz, CDCl3):
d
¼12.3 (q, CH3), 35.6 (d, C-7), 49.5 (d, C-2), 51.4
(q, COOMe), 56.7 (q, OMe), 69.0 (t, C-6), 73.5, 74.5, 74.6 (3t,
CH2ePh), 75.1, 79.5, 80.6 (3d, C-3, C-4, C-5), 102.5 (d, C-1), 127.4,
127.6, 127.7, 127.8, 128.2, 128.3, 128.4 (7d, arom, CeH), 138.0,
138.2, 138.4 (3s, arom, CeCH2O), 175.3 (s, COOMe); IR (film):
4.5.5. Methyl
(7R)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(azido)-(me-
-glucopyranoside (7R-10b). A colorless
þ12.0 (c 0.81, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate
thoxy-carbonyl)-methyl]-
b-D
20
syrup; [
a]
D
n
¼3463, 3024, 2926, 2949, 1738, 1456, 1362, 1217, 1054 cmꢁ1
;
3:1); 1H NMR (300 MHz, CDCl3):
d
¼2.25 (ddd, J¼11.1, 8.4, 2.1 Hz,1H,
elemental analysis calcd (%) for C32H38O7 (534.64): C 71.89, H
7.16; found: C 71.77, H 6.96.
2-H), 3.32 (dd, J¼12.0, 3.0 Hz, 1H, 60-H), 3.33 (s, 3H, OMe), 3.56
(ddd, J¼9.3, 6.3, 3.0 Hz, 1H, 5-H), 3.58 (dd, J¼9.3, 7.5 Hz, 1H, 4-H),
3.64 (s, 3H, COOMe), 3.65 (dd, J¼12.0, 6.3 Hz, 1H, 6-H), 4.20 (dd,
J¼11.1, 7.5 Hz, 1H, 3-H), 4.21 (d, J¼10.8 Hz, 1H, CH2ePh), 4.47
(d, J¼12.0 Hz, 1H, CH2ePh), 4.53 (d, J¼2.1 Hz, 1H, 7-H), 4.56
(d, J¼11.4 Hz, 1H, CH2ePh), 4.56 (d, J¼8.4 Hz, 1H, 1-H), 4.57
(d, J¼12.0 Hz, 1H, CH2ePh), 4.73 (d, J¼10.8 Hz, 1H, CH2ePh), 4.88
(d, J¼11.4 Hz, 1H, CH2ePh), 7.09e7.32 (m, 15H, arom, H); 13C NMR
4.5.2. Methyl
(7S)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(azido)-(me-
-glucopyranoside (7S-10b). A colorless
þ4.9 (c 1.09, CHCl3); Rf¼0.37 (c-hexane/ethyl acetate
thoxy-carbonyl)-methyl]-
b-D
20
syrup; [
a]
D
3:1); 1H NMR (300 MHz, CDCl3):
d¼2.35 (ddd, J¼11.4, 8.7, 6.0 Hz,
1H, 2-H), 3.29 (s, 3H, OMe), 3.36 (ddd, J¼9.9, 5.7, 2.7 Hz, 1H, 5-H),
3.47 (s, 3H, COOMe), 3.58 (dd, J¼9.9, 8.1 Hz, 1H, 4-H), 3.58 (dd,
J¼12.6, 5.7 Hz, 1H, 60-H), 3.66 (dd, J¼12.6, 2.7 Hz, 1H, 6-H), 4.05 (dd,
J¼11.4, 8.1 Hz, 1H, 3-H), 4.44 (d, J¼11.4 Hz, 1H, CH2ePh), 4.50
(d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼6.0 Hz, 1H, 7-H), 4.59
(d, J¼12.0 Hz, 1H, CH2ePh), 4.63 (d, J¼8.7 Hz, 1H, 1-H), 4.65
(d, J¼11.4 Hz, 1H, CH2ePh), 4.80 (d, J¼11.1 Hz, 1H, CH2ePh), 4.84
(d, J¼11.1 Hz, 1H, CH2ePh), 7.00e7.26 (m, 15H, arom, H); 13C NMR
(75 MHz, CDCl3):
d
¼49.2 (d, C-2), 52.3 (q, COOMe), 57.3 (d, C-7),
58.5 (q, OMe), 68.8 (t, C-6), 73.6, 74.7, 75.1 (3t, CH2ePh), 74.9, 78.8,
79.9 (3d, C-3, C-4, C-5),101.0 (d, C-1),127.6,127.8,128.0,128.1,128.3,
128.4, 128.6 (7d, arom, CeH), 137.9, 138.0, 138.1 (3s, arom, CeCH2O),
170.4 (s, COOMe); IR (film):
n
¼3437, 3058, 3028, 2951, 1801, 1738,
1494, 1454, 1439, 1264, 1213 cmꢁ1; ESI-HRMS (C31H35N3O7): calcd
for [MþNa] 584.2373; found 584.2336.
(75 MHz, CDCl3):
d
¼45.9 (d, C-2), 52.3 (q, COOMe), 57.1 (d, C-7),
60.4 (q, OMe), 69.1 (t, C-6), 71.1, 73.4, 73.5 (3t, CH2ePh), 72.1, 74.3,
78.0 (3d, C-3, C-4, C-5),100.9 (d, C-1),127.4,127.7,127.8,127.9,128.0,
128.1, 128.2, 128.4 (8d, arom, CeH), 137.8, 137.9, 138.6 (3s, arom,
4.5.6. Methyl (7R)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(hydroxy)-(me-
thoxy-carbonyl)-methyl]-
b
-
D
-glucopyranoside (7R-10c). A colorless
20
syrup; [
a]
D
ꢁ6.8 (c 1.11, CHCl3); Rf¼0.28 (c-hexane/ethyl acetate
CeCH2O), 176.3 (s, COOMe); IR (film):
n
¼3435, 3079, 3053, 2924,
2:1); 1H NMR (300 MHz, CDCl3):
d¼2.14 (ddd, J¼11.1, 8.7, 1.8 Hz, 1H,

2460
J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2-H), 3.32 (s, 3H, OMe), 3.38 (ddd, J¼9.6, 6.3, 2.4 Hz, 1H, 5-H), 3.58
(dd, J¼9.6, 8.7 Hz, 1H, 4-H), 3.65 (dd, J¼12.3, 6.3 Hz, 1H, 60-H), 3.66
(s, 3H, COOMe), 3.68 (dd, J¼12.3, 2.4 Hz, 1H, 6-H), 3.76 (dd, J¼11.1,
8.7 Hz, 1H, 3-H), 4.33 (d, J¼8.7 Hz, 1H, 1-H), 4.39 (d, J¼1.8 Hz, 1H, 7-
H), 4.47 (d, J¼12.0 Hz, 1H, CH2ePh), 4.52 (d, J¼11.1 Hz, 1H, CH2ePh),
4.56 (d, J¼12.0 Hz, 1H, CH2ePh), 4.65 (d, J¼11.1 Hz, 1H, CH2ePh),
4.75 (d, J¼11.1 Hz, 1H, CH2ePh), 4.87 (d, J¼11.1 Hz, 1H, CH2ePh),
CH2ePh), 4.93 (d, J¼3.5 Hz, 1H, 1-H), 5.72 (dt, J¼12.0, 2.5 Hz, 2H,
OCH2CH]CHCH2O), 7.15e7.36 (m, 15H, arom, H); 13C NMR
(75 MHz, CDCl3):
d
¼32.4 (t, C-7), 42.9 (d, C-2), 63.5, 67.0 (2t,
OCH2CH]CHCH2O), 68.7 (t, C-6), 73.5, 74.7, 75.2 (3t, CH2ePh),
71.1, 79.6, 80.4 (3d, C-3, C-4, C-5), 97.5 (d, C-1), 127.4, 128.1 (2d,
OCH2CH]CHCH2O), 127.6, 127.7, 127.9, 128.3, 128.4 (5d, arom,
CeH), 138.0, 138.2, 138.4 (3s, arom, CeCH2O), 171.9 (s, COOR); IR
7.10e7.28 (m, 15H, arom, H); 13C NMR (75 MHz, CDCl3):
d¼50.6 (d,
(film):
n
¼3031, 2952, 1799, 1737, 1729, 1453, 1271, 1207 cmꢁ1
;
C-2), 52.4 (q, COOMe), 57.3 (q, OMe), 66.3 (d, C-7), 69.0 (t, C-6), 73.5,
74.7, 75.4 (3t, CH2ePh), 75.0, 79.6, 79.7 (3d, C-3, C-4, C-5), 100.8 (d,
C-1), 127.5, 127.7, 127.8, 128.3, 128.4 (5d, arom, CeH), 138.1, 138.2,
elemental analysis (%) calcd for C33H36O7: C 72.77, H 6.66; found:
C 72.68, H 6.80.
138.3 (3s, arom, CeCH2O), 175.7 (s, COOMe); IR (film):
n
¼3028,
4.8. Reduction of azides (7R)- or (7S)-10b
2921, 2853,1735,1497,1453,1358, 1294, 1250,1213,1183 cmꢁ1; ESI-
HRMS (C31H36O8): calcd for [MþH] 537.2488; found 537.2477.
To a solution of azido-sugars (7R)-10b or (7S)-10b (280 mg,
0.5 mmol) in freshly distilled tetrahydrofuran (10 mL) were added
water (0.11 mL, 6 mmol) and triphenylphosphine (395 mg,
1.5 mmol) under argon atmosphere. The mixture was stirred at
room temperature until TLC showed complete conversion of the
starting material. The solvent was removed, and the residue was
purified by flash chromatography (c-hexane/ethyl acetate 1:1) to
afford the corresponding protected amino acids 13.
4.6. Pinner reaction
A solution of 8a (501 mg, 1.0 mmol) in an HCleMeOH mixture
[prepared by slow addition of AcCl (1.0 mL) to anhydrous MeOH
(20 mL) at 0 ꢀC] was heated to 65 ꢀC until TLC showed complete
conversion of starting material. After cooling to room temperature,
the solvent was evaporated. The crude product was purified by
flash chromatography (c-hexane/ethyl acetate 8:1).
4.8.1. Methyl
(7S)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(amino)-(me-
thoxy-carbonyl)-methyl]-
b-D-glucopyranoside (7S-13). A colorless
4.6.1. Methyl
thoxy-carbonyl methyl)-
2,6-anhydro-4,5,7-tri-O-benzyl-2-deoxy-2-C-(me-
-gluco- -glycero-hepturonate (11). A col-
þ19.1 (c 1.02, CHCl3); Rf¼0.29 (c-hexane/ethyl
syrup; [
a]
20 ꢁ19.2 (c 0.92, CHCl3); Rf¼0.22 (c-hexane/ethyl acetate
D
D
D
1:2); 1H NMR (300 MHz, CDCl3):
d
¼2.35 (ddd, J¼11.4, 8.7, 6.0 Hz,
20
orless syrup; [
a]
D
1H, 2-H), 3.29 (s, 3H, OMe), 3.36 (ddd, J¼9.9, 5.7, 2.7 Hz, 1H, 5-H),
3.47 (s, 3H, COOMe), 3.58 (dd, J¼9.9, 8.1 Hz, 1H, 4-H), 3.58 (dd,
J¼12.6, 5.7 Hz, 1H, 60-H), 3.66 (dd, J¼12.6, 2.7 Hz, 1H, 6-H), 4.05 (dd,
J¼11.4, 8.1 Hz, 1H, 3-H), 4.44 (d, J¼11.4 Hz, 1H, CH2ePh), 4.50
(d, J¼12.0 Hz, 1H, CH2ePh), 4.51 (d, J¼6.0 Hz, 1H, 7-H), 4.59
(d, J¼12.0 Hz, 1H, CH2ePh), 4.63 (d, J¼8.7 Hz, 1H, 1-H), 4.65
(d, J¼11.4 Hz, 1H, CH2ePh), 4.80 (d, J¼11.1 Hz, 1H, CH2ePh), 4.84
(d, J¼11.1 Hz, 1H, CH2ePh), 7.00e7.26 (m, 15H, arom, H); 13C NMR
acetate 4:1); 1H NMR (400 MHz, CDCl3):
d¼2.29 (dddd, J¼10.0, 8.4,
5.6, 4.8 Hz, 1H, 2-H), 2.37 (dd, J¼16.8, 4.8 Hz, 1H, 70-H), 2.45 (dd,
J¼16.8, 5.6 Hz, 1H, 7-H), 3.45 (ddd, J¼9.6, 6.0, 5.6 Hz, 1H, 5-H), 3.47
(s, 3H, CO2Me), 3.53 (dd, J¼10.0, 6.4 Hz, 1H, 3-H), 3.57 (dd, J¼9.6,
6.4 Hz, 1H, 4-H), 3.59e3.66 (m, 2H, 6-H, 60-H), 3.64 (s, 3H, CO2Me),
3.94 (d, J¼11.4 Hz, 1H, CH2ePh), 4.49 (d, J¼10.6 Hz, 1H, CH2ePh),
4.52 (d, J¼8.4 Hz, 1H, 1-H), 4.54 (d, J¼11.6 Hz, 1H, CH2ePh), 4.55
(d, J¼11.6 Hz, 1H, CH2ePh), 4.69 (d, J¼10.6 Hz, 1H, CH2ePh), 4.85
(d, J¼11.4 Hz, 1H, CH2ePh), 7.06e7.28 (m, 15H, arom, H); 13C NMR
(75 MHz, CDCl3):
d
¼44.7, 44.8 (2d, C-2, C-7), 51.4 (q, COOMe), 56.9
(q, OMe), 69.0 (t, C-6), 73.5, 74.7, 74.8 (3t, CH2ePh), 75.2, 79.9, 82.0
(3d, C-3, C-4, C-5), 103.4 (d, C-1), 127.5, 127.6, 127.7, 127.8, 128.3,
128.4 (6d, arom, CeH), 138.0, 138.1, 138.2 (3s, arom, CeCH2O), 176.6
(75 MHz, CDCl3):
d
¼31.2 (t, C-7), 41.4 (d, C-2), 51.5, 52.1 (2q,
COOMe), 68.8 (t, C-6), 73.4, 74.7, 74.9 (3t, CH2ePh), 78.5, 79.5, 79.6
(3d, C-3, C-4, C-5), 82.6 (d, C-1), 127.5, 127.6, 127.7, 127.8, 127.9,
128.3, 128.4 (7d, arom, CeH), 137.8, 138.0, 138.1 (3s, arom, CeCH2O),
(s, COOMe); IR (film):
n
¼3471, 3088, 3062, 3028, 2952, 1738, 1494,
1453,1435,1358,1213,1153 cmꢁ1; ESI-HRMS (C31H37NO7): calcd for
169.5, 171.8 (2s, COOMe); IR (film):
n
¼3031, 2952, 1800, 1738, 1731,
[MþH] 536.2648; found 536.2633.
1453, 1268 cmꢁ1; elemental analysis (%) calcd for C32H36O8: C
70.06, H 6.61; found: C 70.12, H 6.68.
4.8.2. Methyl
(7R)-3,4,6-tri-O-benzyl-2-deoxy-2-C-[(amino)-(me-
-glucopyranoside (7R-13). A colorless
ꢁ12.5 (c 1.04, CHCl3); Rf¼0.21 (c-hexane/ethyl acetate
thoxy-carbonyl)-methyl]-
b-D
4.7. Ring-closing metathesis
20
syrup; [
a]
D
1:2); 1H NMR (300 MHz, CDCl3):
d
¼2.17 (ddd, J¼10.8, 8.7, 2.1 Hz,1H,
A solution of 8j (572 mg, 1.0 mmol) and Grubbs’ catalyst (A)
(83 mg, 0.1 mmol) in dry and degassed CH2Cl2 (20 mL) was stirred
at room temperature for 48 h. The solvent was removed under
reduced pressure. The crude product was purified by flash chro-
matography (c-hexane/ethyl acetate 6:1).
2-H), 3.31 (s, 3H, OMe), 3.36 (ddd, J¼9.3, 6.6, 3.6 Hz, 1H, 5-H), 3.58
(s, 3H, COOMe), 3.59 (dd, J¼9.3, 9.0 Hz, 1H, 4-H), 3.60 (d, J¼2.1 Hz,
1H, 7-H), 3.61e3.68 (m, 2H, 6-H), 3.73 (dd, J¼10.8, 9.0 Hz, 1H, 3-H),
4.26 (d, J¼8.7 Hz, 1H, 1-H), 4.47 (d, J¼12.0 Hz, 1H, CH2ePh), 4.53 (d,
J¼10.8 Hz, 1H, CH2ePh), 4.57 (d, J¼12.0 Hz, 1H, CH2ePh), 4.63 (d,
J¼11.7 Hz, 1H, CH2ePh), 4.75 (d, J¼10.8 Hz, 1H, CH2ePh), 4.86 (d,
J¼11.7 Hz, 1H, CH2ePh), 7.12e7.29 (m, 15H, arom, H); 13C NMR
4.7.1. (8aR,9R,10S,11R,12aS,Z)-9,10-Bis(benzyloxy)-11-(benzylox-
ymethyl)-8a,9,10,11-tetra-hydro-2H-pyrano[2,3-b][1,6]dioxecin-7(5H,
(75 MHz, CDCl3):
d
¼50.1, 50.4 (2d, C-2, C-7), 51.9 (q, COOMe), 57.0
20
8H, 12aH)-one (12). A colorless syrup; [
a]
ꢁ39.6 (c 1.00, CHCl3);
D
(q, OMe), 69.0 (t, C-6), 73.4, 73.5, 73.6 (3t, CH2ePh), 74.9, 78.5, 80.2
(3d, C-3, C-4, C-5), 101.2 (d, C-1), 127.5, 127.7, 127.8, 128.3, 128.4,
128.5 (6d, arom, CeH), 138.1, 138.2, 138.3 (3s, arom, CeCH2O), 176.1
Rf¼0.35 (c-hexane/ethyl acetate 2:1); 1H NMR (500 MHz, CDCl3):
d
¼2.36 (dddd, J¼10.5, 6.0, 4.0, 3.5 Hz, 1H, 2-H), 2.47 (dd, J¼15.5,
6.0 Hz, 1H, 70-H), 2.73 (dd, J¼15.5, 4.0 Hz,1H, 7-H), 3.68 (ddd, J¼10.0,
6.0, 2.5 Hz, 1H, 5-H), 3.70 (dd, J¼10.0, 6.0 Hz, 1H, 4-H), 3.71 (dd,
J¼13.5, 6.0 Hz, 1H, 60-H), 3.78 (dd, J¼13.5, 2.5 Hz, 1H, 6-H), 3.79 (dd,
J¼10.5, 6.0 Hz, 1H, 3-H), 3.83 (dd, J¼12.0, 1.5 Hz, 1H, OCH2CH]
CHCH2O), 4.19 (d, J¼13.0 Hz, 1H, OCH2CH]CHCH2O), 4.43 (d,
J¼13.0 Hz, 1H, OCH2CH]CHCH2O), 4.52 (d, J¼11.5 Hz, 1H, CH2ePh),
4.54 (d, J¼11.0 Hz, 1H, CH2ePh), 4.63 (d, J¼11.5 Hz,1H, CH2ePh), 4.66
(d, J¼12.5 Hz, 1H, CH2ePh), 4.71 (d, J¼12.0 Hz, 1H, OCH2CH]
CHCH2O), 4.79 (d, J¼11.0 Hz, 1H, CH2ePh), 4.91 (d, J¼12.5 Hz, 1H,
(s, COOMe); IR (film):
n
¼3434, 3083, 3062, 3027, 2922, 1728, 1709,
1496, 1453, 1362, 1102, 1028 cmꢁ1; ESI-HRMS (C31H37NO7): calcd
for [MþH] 536.2648; found 536.2653.
Acknowledgements
This work was generously supported by the Deutsche For-
schungsgemeinschaft (Li 556/7-3) and the University of Potsdam.

J. Yin, T. Linker / Tetrahedron 67 (2011) 2447e2461
2461
16. (a) Linker, T.; Hartmann, K.; Sommermann, T.; Scheutzow, D.; Ruckdeschel, E.
Angew. Chem. 1996, 108, 1819e1821; Angew. Chem., Int. Ed. 1996, 35, 1730e1732;
(b) Linker, T.; Sommermann, T.; Kahlenberg, F. J. Am. Chem. Soc. 1997, 119,
9377e9384.
17. (a) Yin, J.; Spindler, J.; Linker, T. Chem. Commun. 2007, 2712e2713; (b) Yin, J.;
Sommermann, T.; Linker, T. Chem.dEur. J. 2007, 13, 10152e10167.
18. Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; WILEY-VCH: Weinheim,
2000.
References and notes
1. (a) Lepenies, B.; Yin, J.; Seeberger, P. H. Curr. Opin. Chem. Biol. 2010, 14, 404e411;
(b) Buskas, T.; Thompson, P.; Boons, G.-J. Chem. Commun. 2009, 5335e5349; (c)
Stallforth, P.; Lepenies, B.; Adibekian, A.; Seeberger, P. H. J. Med. Chem. 2009, 52,
5561e5577;(d) Boltje, T. J.; Buskas, T.; Boons, G.-J. Nat. Chem. 2009,1, 611e622; (e)
Hecht, M.-L.; Stallforth, P.; Silva, D. V.; Adibekian, A.; Seeberger, P. H. Curr. Opin.
Chem. Biol. 2009, 13, 354e359; (f) Seeberger, P. H.; Werz, D. B. Nature 2007, 446,
1046e1051; (g) Werz, D. B.; Seeberger, P. H. Chem.dEur. J. 2005, 11, 3194e3206.
2. Insight. Nature 2007, 446, 999e1051.
3. (a) Pilobello, K. T.; Mahal, L. K. Curr. Opin. Chem. Biol. 2007, 11, 300e305; (b) Le,
G. T.; Abbenante, G.; Becker, B.; Grathwohl, M.; Halliday, J.; Tometzki, G.; Zuegg,
J.; Meutermans, W. Drug Discovery Today 2003, 8, 701e709; (c) Nicolaou, K. C.;
Mitchell, H. J. Angew. Chem. 2001, 113, 1624e1672; Angew. Chem., Int. Ed. 2001,
40, 1576e1624.
4. (a) Schreiber, S. L. Science 2000, 287, 1964e1969; (b) Burke, M. D.; Berger, E. M.;
Schreiber, S. L. Science 2003, 302, 613e618; (c) Burke, M. D.; Schreiber, S. L.
Angew. Chem. 2004, 116, 48e60; Angew. Chem., Int. Ed. 2004, 43, 46e58.
5. (a) Galloway, W. R. J. D.; Bender, A.; Welch, M.; Spring, D. R. Chem. Commun.
2009, 2446e2462; (b) Kumar, K. Chem. Biol. 2009, 39e53; (c) Thomas, G. L.;
Wyatt, E. E.; Spring, D. R. Curr. Opin. Drug Discovery Dev. 2006, 9, 700e712; (d)
Tan, D. S. Nat. Chem. Biol. 2005, 1, 74e84; (e) Shang, S.; Tan, D. S. Curr. Opin.
Chem. Biol. 2005, 9, 248e258.
19. Solvent Effects in Organic Chemistry; Reichardt, C., Ed.; WILEY-VCH: Weinheim,
1990.
20. (a) Postema, M. H. D. C-Glycoside Synthesis; CRC: Boca Raton, 1995; (b) Levy, D.
E.; Tang, C. The Chemistry of C-Glycosides; Elsevier: Oxford, 1995.
21. (a) Hanessian, S.; Pernet, A. G. Adv. Carbohydr. Chem. Biochem. 1976, 33, 111e188;
(b) Postema, M. H. D. Tetrahedron 1992, 48, 8545e8599; (c) Beau, J.-M.; Gal-
lagher, T. Top. Curr. Chem. 1997, 187, 1e54; (d) Nicotra, F. Top. Curr. Chem. 1997,
187, 55e83; (e) Du, Y.; Linhardt, R. J.; Vlahov, I. R. Tetrahedron 1998, 54,
9913e9959.
22. (a) Beyer, J.; Madsen, R. J. Am. Chem. Soc. 1998, 120, 12137e12138; (b) Beyer, J.;
Skaanderup, P. R.; Madsen, R. J. Am. Chem. Soc. 2000, 122, 9575e9583.
23. The Organic Chemistry of Sugars; Levy, D. E., Fuegedi, P., Eds.; CRC: Boca Raton,
2006.
24. (a) Hird, G. S.; McIntosh, T. J.; Grinstaff, M. W. J. Am. Chem. Soc. 2000, 122,
8097e8098; (b) Hird, G. S.; McIntosh, T. J.; Ribeiro, A. A.; Grinstaff, M. W. J. Am.
Chem. Soc. 2002, 124, 5983e5992.
6. Konaklieva, M. I.; Plotkin, B. J. Mini-Rev. Med. Chem. 2005, 5, 73e95.
25. (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. 2001, 113, 2056e2075;
Angew. Chem., Int. Ed. 2001, 40, 2004e2021; (b) Moses, J. E.; Moorhouse, A. D.
Chem. Soc. Rec. 2007, 36, 1249e1262.
€
€
7. (a) Kroper, H. In Houben-Weyl, Methoden der Organischen Chemie; Muller, E., Ed.;
Thieme: Stuttgart, 1963; Vol. VI/2, pp 561e852; (b) Grieco, P. A. Synthesis 1975,
67e82; (c) Ogliaruso, M. A.; Wolfe, J. F. Synthesis of Lactones and Lactams; WI-
LEY: New York, NY, 1993; (d) Seitz, M.; Reiser, O. Curr. Opin. Chem. Biol. 2005, 9,
285e292; (e) Burstein, C.; Tschan, S.; Xie, X.; Glorius, F. Synthesis 2006,
2418e2439.
€
26. Rockendorf, N.; Lindhorst, T. K. J. Org. Chem. 2004, 69, 4441e4445.
27. Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52, 179e266.
28. Bernardes, G. J. L.; Gamblin, D. P.; Davis, B. G. Angew. Chem. 2006, 118,
4111e4115; Angew. Chem., Int. Ed. 2006, 45, 4007e4011.
29. (a) Wood, W. W.; Rashid, A. Tetrahedron Lett. 1987, 28, 1933e1936; (b) Ibrahim-
Ouali, M.; Parrain, J.-L.; Santelli, M. Org. Prep. Proced. 1999, 31, 467e505.
30. (a) Evans, D. A.; Britton, T. C.; Ellman, J. A.; Dorow, R. L. J. Am. Chem. Soc. 1990,
112, 4011e4030; (b) Stone, M. J.; Maplestone, R. A.; Rahman, S. K.; Williams, D.
H. Tetrahedron Lett. 1991, 32, 2663e2666.
31. (a) Kang, K. H.; Cha, M. Y.; Pae, A. N.; Choi, K. I.; Cho, Y. S.; Koh, H. Y.; Chung, B. Y.
Tetrahedron Lett. 2000, 41, 8137e8140; (b) Hua, D. H.; Huang, X.; Chen, Y.;
Battina, S. K.; Tamura, M.; Noh, S. K.; Koo, S. I.; Namatame, I.; Tomoda, H.;
Perchellet, E. M.; Perchellet, J. P. J. Org. Chem. 2004, 69, 6065e6078.
32. (a) Davis, F. A.; Chen, B. C. Chem. Rev. 1992, 92, 919e934; (b) Narayanan, J.;
Hayakawa, Y.; Fan, J.; Kirk, K. L. Bioorg. Chem. 2003, 31, 191e197; (c) Davis, F. A. J.
Org. Chem. 2006, 71, 8993e9003.
8. Lalli, C.; Trabocchi, A.; Sladojevich, F.; Menchi, G.; Guarna, A. Chem.dEur. J.
2009, 15, 7871e7875.
9. (a) Lehmann, J. Kohlenhydrate, Chemie und Biologie, 2. Aufl.; Thieme: Stuttgart,
1996; (b) Bols, M. Carbohydrate Building Blocks; WILEY: New York, NY, 1996; (c)
Lindhorst, T. K. Essentials of Carbohydrate Chemistry and Biochemistry, 3. Aufl.;
WILEY-VCH: Weinheim, 2007.
10. The term ‘carbohydrate x,y-lactone’ and not the IUPAC name is used in this full
paper.
11. (a) Gaertzen, O.; Misske, A. M.; Wolbers, P.; Hoffmann, H. M. R. Synlett 1999,
1041e1044; (b) Gaertzen, O.; Misske, A. M.; Wolbers, P.; Hoffmann, H. M. R.
ꢀ
ꢀ
Tetrahedron Lett. 1999, 40, 6359e6363; (c) Polakova, M.; Pitt, N.; Tosin, M.;
Murphy, P. V. Angew. Chem. 2004, 116, 2572e2575; Angew. Chem., Int. Ed. 2004,
43, 2518e2521; (d) Rat, S.; David, M.; Michaud, P.; Kovensky, J.; Wadouachi, A.
Tetrahedron 2007, 63, 12424e12428; (e) O’Brien, C.; Polakova, M.; Pitt, N.; Tosin,
M.; Murphy, P. V. Chem.dEur. J. 2007, 13, 902e909.
33. Akashi, Y.; Takao, K.; Tadano, K. Tetrahedron Lett. 2009, 50, 1139e1142.
34. (a) Terauchi, T.; Kimijima, K.; Nakamura, Y.; Hayashi, G.; Tanaka, T.; Kanoh, N.;
Nakata, M. Tetrahedron Lett. 2001, 42, 5505e5508; (b) Ciblat, S.; Kim, J.; Stewart,
C. A.; Wang, J.; Forgione, P.; Clyne, D.; Paquette, L. A. Org. Lett. 2007, 9, 719e722.
ꢀ
ꢀ
12. (a) Yeung, B. W. A.; Alonso, R.; Vite, G. D.; Fraser-Reid, B. J. Carbohydr. Chem.
1989, 8, 413e427; (b) Alker, D.; Jones, D. N.; Taylor, G. M.; Wood, W. W. Tet-
rahedron Lett. 1991, 32, 1667e1670; (c) Alker, D.; Jones, D. N.; Taylor, G. M.;
Wood, W. W. J. Chem. Soc., Perkin Trans. 1 1992, 1119e1126; (d) Yu, M.;
Pagenkopf, B. L. Tetrahedron 2003, 59, 2765e2771.
€
35. (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413e4450; (b) Furstner, A.
Angew. Chem. 2000,112, 3140e3172; Angew. Chem., Int. Ed. 2000, 39, 3013e3043;
(c) Connon, S. J.; Blechert, S. Top. Organomet. Chem. 2004,11, 93e124; (d) Schmidt,
B.; Hermanns, J. Top. Organomet. Chem. 2004, 13, 223e267.
ꢀ
13. (a) Jimenez, O.; de la Rosa, G.; Lavilla, R. Angew. Chem. 2005, 117, 6679e6683;
36. Ruttens, B.; Blom, P.; Van Hoof, S.; Hubrecht, I.; Van der Eycken, J. J. Org. Chem.
2007, 72, 5514e5522.
37. (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635e646; (b) Scriven, E. F.
V.; Turnbull, K. Chem. Rev. 1988, 88, 297e368.
38. (a) Shridhar, P. R.; Ashalu, K. C.; Chandrasekaran, S. Org. Lett. 2004, 6,
1777e1779; (b) Sommermann, T.; Kim, B. G.; Peters, K.; Peters, E.-M.; Linker, T.
Chem. Commun. 2004, 2624e2625.
Angew. Chem., Int. Ed. 2005, 44, 6521e6525; (b) Haveli, S. D.; Sridhar, P. R.;
Suguna, P.; Chandrasekaran, S. Org. Lett. 2007, 9, 1331e1334.
14. (a) Yin, J.; Linker, T. Chem.dEur. J. 2009, 15, 49e52; (b) Yin, J.; Linker, T. Org.
Biomol. Chem. 2009, 7, 4829e4831.
15. (a) Linker, U.; Kersten, B.; Linker, T. Tetrahedron 1995, 51, 9917e9926; (b) Linker,
T.; Linker, U. Angew. Chem. 2000, 112, 934e936; Angew. Chem., Int. Ed. 2000, 39,
902e904; (c) Linker, T. J. Organomet. Chem. 2002, 661, 159e167.