The effect of electron withdrawing protecting groups at positions 4 and 6 on 1,2-cis galactosylation

Article abstract of DOI:10.1016/j.tet.2013.06.038

Ethyl 2,3,4-O-tribenzyl-6-O-chloroacetyl-1-d-thiogalactoside, phenyl 4,6-O-diacetyl-2,3-dibenzyl-1-d-thiogalactoside and phenyl 2,3-O-dibenzyl-4,6-O- dichloroacetyl-1-d-thiogalactoside were employed in the study of the stereoselectivity of the glycosylati

Full text of DOI:10.1016/j.tet.2013.06.038

Tetrahedron 69 (2013) 7090e7097
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The effect of electron withdrawing protecting groups at positions 4
and 6 on 1,2-cis galactosylation
*
Eva C. Lourenc¸ o, M. Rita Ventura
ꢀ
Instituto de Tecnologia Química e Biologica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 April 2013
Received in revised form 5 June 2013
Accepted 11 June 2013
Available online 18 June 2013
Ethyl 2,3,4-O-tribenzyl-6-O-chloroacetyl-1-
thiogalactoside and phenyl 2,3-O-dibenzyl-4,6-O-dichloroacetyl-1-
D
-thiogalactoside, phenyl 4,6-O-diacetyl-2,3-dibenzyl-1-
-thiogalactoside were employed in
the study of the stereoselectivity of the glycosylation reaction with several acceptors, ranging from
unhindered linear primary alcohols to other sugars, using NIS/TfOH as activator. Higher -selectivities
were obtained in the glycosylation reactions with phenyl 2,3-O-dibenzyl-4,6-O-dichloroacetyl-1- -thi-
D-
D
a
D
ogalactoside as the donor, showing that a stronger electron withdrawing 4-O-ester group had an in-
fluence in the anomeric selectivity favouring the formation of 1,2-cis galactosides.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
a
a
-Galactosides
-Galactosylation
Thiogalactosides
4-Chloroacetyl ester
1. Introduction
axial substituent as in galactose, leads to better solvation, in-
creasing the reactivity during the glycosylation reaction.10
Recently, we reported that NIS/TfOH mediated glycosylations of
ethyl 6-O-acetyl-2,3,4-O-tribenzyl-1- -thioglucoside afforded
higher -anomeric selectivities when compared with other 6-O-
We decided to explore the influence of C-6 and C-4 remote
neighbouring groups on the reactivity of some thiogalactosides and
hence attempt to improve the stereoselectivity of the glycosylation
reaction.11 The effect of having different electron withdrawing
groups (acetate and chloroacetate) at C-6 and at both C-4 and C-6
was studied.
D
1
a
protecting groups. The choice of solvent was also found to be very
important and ethyl ether was the solvent that afforded the higher
a
-selectivities.1 We believe that the 6-O-acetyl group being electron
withdrawing, reduced the reactivity at the anomeric position
compared to e.g., the tetrabenzylated thioglycoside and favoured
the formation of the
2. Results and discussion
a
-glucosides (1,2-cis glucosylation).1e3 It is
well established that the overall reactivity of the donor affects the
stereoselectivity of the glycosylation reaction, and the protecting
groups of the donor have a strong influence in the anomeric out-
come of the glycosylation reaction.4e6 The corresponding glyco-
Thiogalactoside 3, having a chloroacetate group at position C-6,
was obtained from donor 11 in two steps as described in Scheme 1.
Donor 512 with acetate groups at both C-4 and C-6 was prepared
as previously described. Donor 6 with chloroacetate groups at C-4
and C-6,13 was prepared from diol 412,14,15 by esterification with
chloroacetic anhydride (Scheme 2).
sylation reactions of ethyl 6-O-acetyl-2,3,4-O-tribenzyl-1-D-
thiogalactoside 7 in ethyl ether were generally less stereoselective
than those with the corresponding glucoside donor, and changing
the solvent or lowering the reaction temperature did not improve
the results.1 Thiogalactosides are more reactive than thio-
glucosides,1,7e9 and it has been hypothesised that this increased
reactivity results from the stabilisation of the oxacarbenium ion
and the related species5 by the axial substituents at C-4 of galac-
tose. The solvation of the leaving group and/or the promoter may
also play a role in the galactose/glucose reactivity difference, an
During a previous study with thiogalactoside 11 the reactions
were seen to be considerably more rapid in dichloromethane and
changing the solvent did not improve the stereoselectivity. Thus for
this study all of the glycosylation reactions were carried in this
solvent.
The results of the glycosylation reactions of donors 3, 5 and 6
with several acceptors using NIS/TfOH are described in Tables 1e3.
For donor 3, glycosylation with small secondary alcohols afforded
anomeric selectivities very similar to those obtained with donor 1.1
With a less hindered acceptor (Table 1, entries 2, 4, 5, 8, 9, EPA-
depiandrosterone), the stereoselectivity of the glycosylation re-
* Corresponding author. Tel.: þ351 214469775; e-mail address: rventura@itq-
b.unl.pt (M.R. Ventura).
action was lower and more b anomer was obtained. In the case of
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.038

E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
7091
Scheme 1. Synthesis of donor 3.
Scheme 2. Synthesis of donors 5 and 6.
Table 1
Table 2
Glycosylation reactions of thiogalactoside 3
Glycosylation reaction of thiogalactoside 5
Entry
1
ROH/product
t (min)
Yield (%)
86
a/b
Entry
1
ROH/product
t (min)
Yield (%)
68
a/b
5
1:0
5
2:4:1
2
3
5
77
69
1.2:1
1:0
2
3
5
5
63
70
1:2.27
1.4:1
30
4
5
6
EPA/10
Adamantanol/11
Benzyl (S)-mandelate/12
5
5
5
57
82
70
1:1.7
1:1.3
1:0
4
5
6
EPA/20
Adamantanol/21
Benzyl (S)-mandelate/22
5
5
5
91
98
68
2.2:1
6.5:1
1:0
7
30a
97
1:1
7
40a
99
1.9:1
8
9
10
L
-Menthol/14
Cyclohexanol/15
Boc- -serine methyl ester/16
5
5
5
85
93
91
1:1.5
1:1.2
2:1
8
9
10
L
-Menthol/24
Cyclohexanol/25
Boc- -serine methyl ester/26
5
50a
5
85
78
69
2.7:1
1.12:1
2:1
L
L
a
Additional equivalents of TfOH were added during the reaction.
a
Additional equivalents of TfOH were added during the reaction.
benzyl (S)-mandelate, only the
a
anomer was obtained (Table 1,
in glycosylation reactions with sugar and hindered primary alcohol
acceptors. Dibenzoyl ester groups at C-4 and C-6 on a galactosyl
trichloroacetimidate donor and a 2-naphthylmethyl (NAP) group at
entry 6).
Boons16 and co-workers reported that iodonium-ion promoted
glycosylations in 1,4-dioxane/toluene with a participating group at
C-2 and C-3 was less reactive, providing a higher a-selectivity with
C-4 in galactosyl donors afforded high
a
-anomeric selectivities, and
several sugar derived acceptors when compared with the same
donor with benzylidene protection at C-4 and C-6.17 We therefore
studied the glycosylation reaction of thiogalactoside 5, having
a second acetate group at C-4 (Table 2). The stereoselectivity
in his study the best results were obtained with electron-donating
groups. In another study11 using a galactosyl phosphite donor with
4- and 6-acyl groups, high a-anomeric selectivities were obtained

7092
E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
Table 3
stability of the intermediate carbocationic species. In this way co-
valent intermediates become more likely. Thus the increased
selectivity could derive from the preferential formation of the
triflate, which is then substituted by the nucleophilic alcohol in an
SN2 manner to afford the -galactoside. A coherent mechanism for
Glycosylation reaction of thiogalactoside 6
a
-
b
a
this remote control has not yet been established.
During this study it was observed that the structure of the ac-
ceptor had a strong influence on the stereoselectivity of the gly-
cosylation reaction. Most related studies4,6,16,24,25 have used sugars
as the acceptors in order to obtain di- and higher saccharides, and
Entry
1
ROH/product
t (min)
Yield (%)
69
a/b
in these cases the
selectivity. Indeed, when the acceptor was a sugar (Tables 2 and 3,
entry 3), the corresponding -galactoside was obtained exclusively.
a-galactosides were obtained with good to high
5
1:0
a
In general, more hindered small acceptors afforded higher
anomeric selectivities (Table 3, entries 1, 3, 6). On the other hand
lipophilic primary alcohols (Table 3, entries 2 and 7) did not afford
2
3
5
62
89
1.5:1
good
a selectivities. Lipids can aggregate easily, which changes
their reactivity26 and negatively influences the stereoselective
outcome of the glycosylation reaction.
15
1:0
3. Conclusion
In conclusion, there is not yet a general method for stereo-
selective a-galactosylation. The influence of the solvent, tempera-
ture and the nature and position of the protecting groups in the
donor have been a subject of study over many years, and the gly-
cosylation methods optimised accordingly. However, when these
4
5
6
EPA/30
Adamantanol/31
Benzyl (S)-mandelate/32
5
5
5
41
89
79
3.8:1
6.2:1
1:0
methods are applied to different acceptors the
a stereoselectivity is
not predictable in many cases. This must be due to the stereo-
electronic different natures of the reactive hydroxy groups on the
acceptor and inter and intramolecular interactions during the gly-
cosylation reaction. In fact it may be postulated that the reactivity
of the acceptor influences the nature of the reactive glycosyl donor
species that ultimately reacts.
7
60a
99
1.5:1
8
9
10
L
-Menthol/34
Cyclohexanol/35
Boc- -serine methyl ester/36
5
5
5
94
87
73
3.43:1
2.5:1
2:1
L
a
Additional equivalents of TfOH were added during the reaction.
4. Experimental section
increased remarkably in all examples studied, and in some exam-
ples (Table 2, entries 1, 3, 6) only the anomer was obtained.
4.1. General
a
Thiogalactosyl donor 6, with chloroacetyl esters at C-4 and C-6
1H NMR spectra were obtained at 400 MHz in CDCl3 with
was also tested in the same glycosylation reactions (Table 3).
chemical shift values (d) in parts per million downfield from tet-
Having stronger electron withdrawing esters, higher
a
-selectivity
ramethylsilane, and 13C NMR spectra were obtained at 100.61 MHz
in CDCl3. Assignments are supported by 2D correlation NMR
studies. Medium pressure preparative column chromatography:
Silica Gel Merck 60 H. Analytical TLC: Aluminium-backed Silica Gel
Merck 60 F254. Reagents and solvents were purified and dried
according to Ref. [27]. All the reactions were carried out under an
inert atmosphere (argon).
was expected. Indeed, this donor provided higher anomeric selec-
tivities than donor 3 (Table 1) and donor 5 (Table 2) for acceptors
EPA,
glycosylation reaction of each donor with N-Boc serine methyl ester
always afforded the same anomeric ratio ( 2:1). Poor selec-
tivity has been attributed to the decreased nucleophilicity of N-
L-menthol and cyclohexanol (Table 3, entries 4, 8, 9). The
a
/b
a/b
acylated b-hydroxy amino acids, due to hydrogen bonding between
the acceptor OH and NH groups.18 Higher anomeric selectivities
have been obtained with N-Fmoc serine allyl ester11,19 which we did
not test.
From Tables 2 and 3 it can be seen that an ester at C-4 is very
important for the stereoselectivity of the glycosylation reaction
with thiogalactosides, and a more electron withdrawing ester af-
fords better results. Although the 4-O-chloroacetyl group could
4.2. Ethyl 2,3,4-tri-O-benzyl-1-thio-a/b-D-galactopyranoside 2
A solution of NaOMe 1 N (1.28
added to a stirred solution of ethyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-
thio- -galactopyranoside (1.150 g, 2.14 mmol) in MeOH (4 mL)
mL, 1.28 mmol) in MeOH was
a/b-D
at 0 ꢀC. After 1 h the reaction mixture was neutralised with satd
aq NH4Cl. The aqueous phase was extracted with EtOAc (3ꢁ10 mL)
and the combined organic extracts were dried (MgSO4), filtered and
the solvent was removed. The crude product was purified by flash
column chromatography on silica gel (20:80, EtOAc/Hex) to afford
disarm the system slightly, the higher
a-stereoselectivity can be
attributed to a remote stereocontrolling and electronic effect of the
C-4 ester in the galactoside donor.20e22 Crich and co-workers
studied possible neighbouring group participation in glycosyla-
tion reactions for esters in non-vicinal positions in several glycosyl
donors23 and ruled out neighbouring group participation from axial
the product 2 (0.856 g, 81%,
a
:
b
¼2.6:1) as a white solid.
a anomer:
20
mp 84.0e85.1 ꢀC. [
a]
þ145.2 (c 1.03, CH2Cl2). FT-IR (KBr disk):
D
3422e3508 cmꢂ1 (OeH). 1H NMR (CDCl3):
d
7.41e7.28 (m, 15H),
esters at C-4. Thus, the
a
-anomeric selectivity obtained with donors
5.51 (d, 1H, J¼3.5 Hz, H-1 ( )), 4.97 (d, 1H, J¼7.3 Hz), 4.87 (d, 1H,
a
5 and 6 could not be attributed to the direct participation of the
ester at C-4, but to stereoelectronic and conformational in-
fluences.23 These electron withdrawing groups will lower the
J¼7.5 Hz), 4.72 (q, 2H, J¼7.3 Hz, J¼9.3 Hz), 4.64 (d, 1H, J¼7.3 Hz),
4.30 (dd, 1H, J¼3.3 Hz, J¼3.5 Hz), 4.13e4.10 (m, 1H), 3.88e3.87 (m,
1H), 3.73 (dd, 1H, J¼3.3 Hz, J¼4.0 Hz), 3.53 (dd, 1H, J¼3.3 Hz,

E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
7093
J¼3.8 Hz), 2.61e2.45 (m, 2H), 1.27 (t, 3H, J¼4.5 Hz). 13C NMR
column chromatography on silica gel on silica gel (80:20 EtOAc/
hexane) afforded the product 5 as a viscous colourless foam
(CDCl3):
d
138.6, 138.2, 138.1, 128.5e127.6, 83.4 (C-1), 79.5, 76.2,
20
75.2, 74.5, 73.7, 72.8, 70.5, 62.5, 23.5, 14.6. Anal. Calcd for
C29H34O5S: C, 70.42; H, 6.93; S, 6.48. Found: C, 69.93; H, 6.86; S,
(0.488 g, 69%). [
a
]
þ23.6 (c 0.59, CH2Cl2). FT-IR (film): 1747,
D
1762 cmꢂ1 (C]O). 1H NMR (CDCl3)
(m, 13H), 5.56 (d, 1H, J¼2.9 Hz), 4.79e4.71 (m, 3H), 4.66 (d, 1H,
J¼9.3 Hz, H-1 ( )), 4.52 (d, 1H, J¼10.9 Hz), 4.36e4.24 (m, 2H),
4.18e4.09 (m, 2H), 4.05 (s, 2H), 3.87 (t, 1H, J¼6.5 Hz), 3.70e3.61 (m,
2H). 13C NMR (CDCl3)
167.0, 166.9, 137.9, 137.0, 132.9, 132.5, 128.9,
d 7.57e7.54 (m, 2H), 7.40e7.28
6.18.
b
anomer: mp 100.3e101.4 ꢀC. [
a
]
D
20 þ6.6 (c 0.89, CH2Cl2). FT-IR
(KBr disk): 3420e3510 cmꢂ1 (OeH). 1H NMR (CDCl3):
d
7.41e7.28
b
(m, 15H), 4.97 (d, 1H, J¼7.3 Hz), 4.90 (d, 1H, J¼6.3 Hz), 4.81 (d, 1H,
J¼6.3 Hz), 4.80e4.74 (m, 2H), 4.43 (d, 1H, J¼6.3 Hz, H-1 (
b
)),
d
3.87e3.76 (m, 3H), 3.58 (dd, 1H, J¼1.8 Hz, J¼4.0 Hz), 3.47 (dd, 1H,
J¼3.3 Hz, J¼3.8 Hz), 3.42e3.39 (m, 1H), 2.82e2.67 (m, 2H), 1.30 (t,
128.5e127.9, 87.7 (C-1), 80.6, 76.5, 75.9, 73.9, 72.5, 68.7, 63.5, 40.7,
40.5. HRMS: calcd for C30H30Cl2O7SNaþ [MþþNa]: 627.0987; found:
627.0982.
3H, J¼4.5 Hz). 13C NMR (CDCl3):
d 138.3, 138.2, 138.19, 128.5e127.6,
85.4 (C-1), 84.1, 78.6, 78.5, 75.8, 74.1, 73.1, 73.0, 62.2, 24.9, 15.1. Anal.
Calcd for C29H34O5S: C, 70.42; H, 6.93; S, 6.48. Found: C, 70.17; H,
6.97; S, 6.32.
4.6. General glycosylation procedure
A suspension of thioglycoside donor (0.15 mmol), acceptor
ꢁ
4.3. Ethyl 2,3,4-tri-O-benzyl-6-O-chloroacetyl-1-thio-
a
/b-D
-
(0.15 mmol) and 4 A MS in the solvent/mixture of solvents in-
galactopyranoside 3
dicated in Tables 1e3 (1 mL) was stirred for 1 h at room tempera-
ture then cooled to the indicated temperature (Tables 1e3). N-
To a stirred solution of 2 (0.845 g, 1.70 mmol) in pyridine (5 mL)
at 0 ꢀC was added chloroacetic anhydride (0.320 g, 1.87 mmol).
After complete conversion of the starting material water was
added. The mixture was extracted with EtOAc, dried (MgSO4) and
concentrated to furnish a yellow viscous residue. Purification by
column chromatography on silica gel (90:10 EtOAc/hexane) affor-
Iodosuccinimide (0.19 mmol) and TfOH (0.9 mL) were added and
when the reaction was complete (TLC), 10% Na2S2O3 aqueous so-
lution (2 mL) and satd aq NaHCO3 (1 mL) were added and the
mixture was extracted with CH2Cl2 (35 mL); the combined organic
phases were dried (MgSO4), filtered and the solvent was removed
under vacuum. The crude product was purified by preparative TLC
ded the product 3 as a viscous colourless foam (0.878 g, 90%).
(3:7 EtOAc/hexane). The a/b ratio of the isolated product was
20
a
anomer: [
a
]
D
þ104.00 (c 1.60, CH2Cl2). FT-IR (film): 1745 cmꢂ1
measured by comparison of the integral of the
NMR (400 MHz, CDCl3) spectra. Yields and
described in Tables 1e3.
a
and
b
signals in 1H
(C]O). 1H NMR (CDCl3):
d
7.40e7.28 (m, 15H), 5.47 (d, 1H, J¼5.4 Hz,
a/b ratio values are
H-1), 4.96 (d, 1H, J¼11.6 Hz), 4.87 (d, 1H, J¼11.8 Hz), 4.76e4.67 (m,
3H), 4.62 (d, 1H, J¼11.6 Hz), 4.32e4.25 (m, 3H), 4.15e4.06 (m, 1H),
3.96e3.88 (m, 2H), 3.85e3.83 (m, 1H), 3.79 (dd, 1H, J¼9.7 Hz,
J¼2.8 Hz), 2.62e2.35 (m, 2H), 1.26 (t, 3H, J¼7.4 Hz). 13C NMR
4.6.1. Methyl (2R)-1,3-di-O-tert-butyldiphenylsilyl-2-O-(2,3,4-tri-O-
benzyl-6-O-chloroacetyl- -galactopyranosyl)-1,2,3-
trihydroxypropane 7. FT-IR (film): 1746, 1763 cmꢂ1 (C]O). 1H NMR
(CDCl3): )),
7.66e7.57 (m), 7.40e7.11 (m), 5.11 (d, J¼3.4 Hz, H-1 (
)), 4.08e3.72
a/b-D
(CDCl3):
d 166.8, 138.5, 138.1, 138.0, 128.5e127.6, 83.2 (C-1), 79.2,
20
76.2, 74.4, 74.3, 73.8, 72.6, 68.5, 64.9, 40.6, 23.5,14.7.
b
anomer: [
a
]
d
a
D
þ2.03 (c 1.02, CH2Cl2). FT-IR (film): 1747 (C]O) cmꢂ1
.
1H NMR
4.96e4.79 (m), 4.73e4.56 (m), 4.45 (d, J¼7.7 Hz, H-1 (
b
(CDCl3):
d
7.40e7.28 (m, 15H), 4.99 (d, 1H, J¼11.8 Hz), 4.89 (d, 1H,
(m), 3.69 (br s), 3.64 (d, J¼15.0 Hz), 3.56 (d, J¼15.0 Hz), 3.42 (dd,
J¼10.2 Hz), 4.83e4.75 (m, 3H), 4.65 (d, 1H, J¼11.8 Hz), 4.42 (d, 1H,
J¼9.64 Hz, H-1), 4.31 (dd, 1H, J¼11.1 Hz, J¼6.8 Hz), 4.10 (dd, 1H,
J¼11.1 Hz, J¼7.4 Hz), 3.96e3.81 (m, 4H), 3.59e3.55 (m, 2H),
J¼2.8 Hz, J¼9.7 Hz), 3.34 (t, J¼6.4 Hz), 1.03 (s), 1.02 (s), 1.00 (s), 0.98
(s). 13C NMR (CDCl3):
d 166.5, 138.8, 138.46, 138.41, 138.2, 138.1,
135.6e135.5, 133.7e133.0, 129.8e129.5, 128.6e127.5, 103.2 (C-1
)), 96.2 (C-1 ( )), 81.9, 80.7, 79.4, 78.7, 77.2, 76.4, 74.9, 74.3, 74.2,
2.81e2.65 (m, 2H), 1.30 (t, 3H, J¼7.4 Hz). 13C NMR (CDCl3):
d
166.8,
(b
a
138.1, 128.5e127.6, 85.4 (C-1 (
b
)), 84.0, 78.3, 75.8, 75.5, 74.1, 73.3,
73.7, 73.6, 72.9, 72.8, 71.4, 67.7, 64.6, 64.2, 63.9, 63.7, 63.2, 62.9, 40.5,
40.4, 26.9, 26.84, 26.82, 26.7, 19.3, 19.2, 19.1.
72.9, 64.8, 40.6, 24.9, 15.1. HRMS: calcd for C31H35ClO6SNaþ
[MþþNa] 593.1740; found 593.1735.
4.6.2. Methyl 15-O-(2,3,4-tri-O-benzyl-6-O-chloroacetyl-
actopyranosyl)decapentanoate 8. FT-IR (film): 1736 cmꢂ1 (C]O). 1H
NMR (CDCl3): 7.41e7.26 (m), 4.98e4.89 (m), 4.85e4.80 (m), 4.80
(d, J¼3.2 Hz, H-1 ( )), 4.77e4.73 (m), 4.67e4.60 (m), 4.33 (d,
J¼7.6 Hz, H-1 (
J¼7.1 Hz, J¼11.1 Hz, H-6 (
a/b-D-gal-
4.4. Phenyl 4,6-di-O-acetyl-2,3-di-O-benzyl-1-thio-b-D-gal-
actopyranoside 5
d
a
To a stirred solution of 4 (0.810 g, 1.78 mmol) in pyridine (5 mL)
at 0 ꢀC was added acetic anhydride (0.507 mL, 5.36 mmol) and
a catalytic amount of DMAP. After complete conversion of the
starting material water was added. The mixture was extracted with
EtOAc, dried (MgSO4) and concentrated to furnish a viscous residue.
Purification by column chromatography on silica gel (70:30 EtOAc/
hexane) afforded the product 5 as a viscous colourless foam
b
)), 4.29 (dd, J¼6.4 Hz, J¼11.0 Hz, H-6 (
b)), 4.22 (dd,
b)),
b)), 3.66 (s),
a
)), 4.10 (dd, J¼6.4 Hz, J¼11.0 Hz, H0-6 (
4.07e4.01 (m), 3.96e3.81 (m), 3.75 (d, J¼2.1 Hz, H-4 (
3.62e3.40 (m), 2.29 (t, J¼7.5 Hz), 1.67e1.55 (m), 1.39e1.24 (m). 13C
NMR (CDCl3): d 174.5,174.3,166.82,166.80,138.7,138.6,138.5,138.4,
138.1, 128.6e127.5, 103.9 (C-1 (b)), 97.4 (C-1 (a)), 82.1, 79.4, 78.9,
76.6, 75.2, 74.4, 74.3, 74.1, 73.6, 73.5, 73.3, 72.5, 71.5, 70.1, 68.4, 67.9,
65.1, 64.4, 51.4, 40.6, 34.1, 29.7e29.1, 26.2, 26.1, 24.9.
(0.960 g, 100%). [
a
]
D
20 þ29.5 (c 0.50, CH2Cl2). FT-IR (film): 1741 cmꢂ1
(C]O). HRMS: calcd for C30H32O7SNaþ [MþþNa]: 559.1766; found:
559.1761. The 1H and 13C NMR data were identical to those de-
scribed in the literature.28
4.6.3. Methyl (2R)-3-O-tert-butyldiphenylsilyl-2-O-[2,3,4-tri-O-ben-
zyl-6-O-chloroacetyl-
a/b-D-galactopyranosyl-(1/6)-2,3,4-tri-O-ben-
zyl-1-O- -glucopyranosyl]-2,3-dihydroxypropanoate
a
-
D
9. FT-IR
4.5. Phenyl 2,3-di-O-benzyl-4,6-di-O-chloroacetyl-1-thio-
b-D
-
(film): 1751 cmꢂ1 (C]O). 1H NMR (CDCl3):
d
7.70e7.66 (m),
galactopyranoside 6
7.43e7.08 (m), 5.23 (d, J¼3.4 Hz, H-10
a
Glucose), 5.15 (d, J¼3.5 Hz,
H-10
a Glucose), 4.99e4.89 (m), 4.93 (m, H-1a Galactose), 4.90e4.89
To a stirred solution of 4 (0.530 g, 1.17 mmol) in pyridine (3 mL)
at 0 ꢀC was added chloroacetic anhydride (0.440 g, 2.57 mmol).
After complete conversion of the starting material water was
added. The mixture was extracted with EtOAc, dried (MgSO4) and
concentrated to furnish a yellow viscous residue. Purification by
(m), 4.86e4.80 (m), 4.78e4.46 (m), 4.26e4.19 (m), 4.20 (d, J¼7.8 Hz,
H-1 Galactose), 4.15e3.42 (m), 3.72 (s), 3.57 (s), 1.02 (s), 1.01 (s).
13C NMR (CDCl3):
170.3, 170.2, 166.8, 166.7, 139.0e138.1, 135.7,
135.6, 133.1e132.9, 129.8, 129.7, 128.5e127.2, 104.0 (C-1 Galac-
tose), 97.9 (C-1
Galactose), 94.5 (C-10 Glucose), 94.4 (C-10
b
d
b
a
a
a

7094
E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
Glucose), 82.1, 81.7, 81.6, 79.6, 79.2, 79.0, 78.3, 77.6, 77.5, 76.5, 75.7,
75.6, 75.3, 74.7, 74.6, 74.5, 74.47, 74.43, 74.40, 74.2, 73.5, 73.4, 72.9,
72.5, 71.9, 71.8, 71.7, 70.8, 70.1, 68.3, 68.2, 66.2, 65.1, 64.8, 64.4, 52.0,
51.8, 40.6, 40.5, 26.7, 19.2.
4.10e4.01 (m), 3.98e3.91 (m), 3.87 (dd, J¼14.8 Hz, J¼18.4 Hz, AcCl),
3.77 (dd, J¼7.8 Hz, J¼11.0 Hz, H-2 (
3.53e3.48 (m), 3.38 (td, J¼4.2 Hz, J¼10.6 Hz, CHeO menthol (
3.32 (td, J¼4.3 Hz, J¼10.6 Hz, CHeO menthol (
CH(CH3)2 menthol), 2.12e2.09 (m, CHCH2CH
2.05e2.02 (m, CHCH2CH ( ) menthol), 1.67e1.56 (m, CH2CH2
b
)), 3.72 (d, J¼2.3 Hz, H-4 (
b
)),
b
)),
a
)), 2.43e2.32 (m,
menthol),
(b)
4.6.4. 3-O-(2,3,4-Tri-O-benzyl-6-O-chloroacetyl-
anosyl)-epiandrosterone 10. FT-IR (film): 1737 cmꢂ1 (C]O). 1H NMR
(CDCl3): )),
7.41e7.27 (m), 4.98e4.92 (m), 4.89 (d, J¼3.7 Hz, H-1 (
4.89e4.72 (m), 4.68e4.60 (m), 4.45 (d, J¼7.7 Hz, H-1 ( )), 4.29 (dd,
J¼6.6 Hz, J¼11.0 Hz, H-6 ( )), 4.23e4.18 (m, H-6 ( )), 4.11e4.00 (m),
3.96e3.95 (m), 3.92 (d, J¼5.3 Hz, AcCl ( )), 3.88 (d, J¼5.1 Hz, AcCl
)), 3.65e3.57 (m),
a
/
b
-
D
-galactopyr-
a
menthol), 1.41e1.21 (m, CHCH3, CHCH(CH3)2 menthol), 1.03e1.75
d
a
(m), 0.83 (d, J¼7.1 Hz), 0.72 (d, J¼6.8 Hz), 0.68 (d, J¼6.9 Hz). 13C NMR
b
(CDCl3): d 166.9, 166.8, 138.7, 138.68, 138.61, 138.5, 138.25, 138.23,
b
a
128.6e128.2, 127.8e127.4, 101.9 (C-1 (b)), 99.3 (C-1 (a)), 82.5, 80.6,
a
79.3, 78.96, 78.92, 76.8, 75.2, 74.5, 74.4, 74.1, 73.7, 73.6, 73.1, 73.0,
(
b
)), 3.86e3.80 (m), 3.74 (d, J¼2.3 Hz, H-4 (
b
71.5, 68.2, 65.4, 64.8, 48.8 (CHCH(CH3)2
(CHCH(CH3)2 ) menthol), 42.9 (CHCH2CH (
(CHCH2CH ( ) menthol), 40.63 (AcCl (
34.2, 31.7 (CHCH3 menthol ( )), 31.5 (CHCH3 menthol (
(CH(CH3)2 menthol ( )), 24.5 (CH(CH3)2 menthol (
22.4, 22.2, 21.1, 16.0, 15.5.
(
a
a
)
menthol), 47.9
3.53e3.47 (m), 2.43 (dd, J¼8.7 Hz, J¼19.1 Hz), 2.13e2.01 (m),
1.95e1.88 (m), 1.84e1.19 (m), 1.14e1.03 (m), 1.01e0.90 (m), 0.85 (s),
0.83 (s), 0.67 (ddd, J¼3.4 Hz, J¼11.4 Hz, J¼11.4 Hz). 13C NMR (CDCl3):
(b
) menthol), 41.2
b
a)), 40.62 (AcCl (b)), 34.4,
a
b)), 24.8
d
165.8, 165.7,137.7,137.5,137.1,127.5e126.4,101.2 (C-1 (
b
)), 94.5 (C-
b
a)), 23.0, 22.9,
1 (a)), 81.2, 78.5, 78.0, 75.4, 75.3, 74.4, 73.0, 72.6, 72.2, 71.5, 70.4,
66.9, 64.3, 63.4, 53.4, 50.3, 46.7, 44.2, 39.5, 35.8, 34.8, 34.7, 34.0,
33.6, 30.5, 29.8, 28.4, 27.4, 26.3, 20.7, 19.4, 12.7, 11.3.
4.6.9. O-1-Cyclohexyl-2,3,4-tri-O-benzyl-6-O-chloroacetyl-
galactopyranoside 15. FT-IR (film): 1759, 1744 cmꢂ1 (C]O). 1H NMR
(CDCl3): 7.41e7.21 (m), 4.98 (s, H-1 ( )), 4.98e4.73 (m), 4.68e4.60
(m), 4.44 (d, J¼7.6 Hz, H-1 ( )), 4.32e4.27 (m, H-6 ( )), 4.23e4.19
(m, H-6 ( )), 4.09e4.01 (m), 3.96e3.80 (m), 3.73 (s, H-4 ( )),
3.70e3.62 (m), 3.52e3.50 (m), 1.95e1.89 (m), 1.82e1.73 (m),
1.54e1.12 (m). 13C NMR (CDCl3):
166.8, 166.7, 138.8, 138.7, 138.6,
138.4, 138.2, 138.1, 128.7e128.2, 127.9e127.5, 102.2 (C-1 ( )), 95.6
(C-1 ( )), 82.3 (C-3 ( )), 79.4 (C-2 ( )), 79.0 (C-3 ( )), 77.8, 76.5 (C-2
)), 75.8, 75.2, 74.4 (C-4 ( )), 74.1, 73.6, 73.1, 72.5 (C-4 ( )), 71.5 (C-5
)), 67.9 (C-5 ( )), 65.3 (C-6 ( )), 64.5 (C-6 ( )), 40.6 (AcCl), 33.6,
a/b-D-
4.6.5. 1-O-Adamantanyl-2,3,4-tri-O-benzyl-6-O-chloroacetyl-
galactopyranose 11. FT-IR (film): 1741, 1743 (C]O st) cmꢂ1. 1H NMR
(CDCl3): )), 4.99e4.94 (m),
7.41e7.25 (m), 5.31 (d, J¼3.4 Hz, H-1 (
4.88 (d, J¼11.6 Hz, Bn ( )), 4.82 (d, J¼11.7 Hz, Bn ( )), 4.76e4.70 (m),
4.67e4.59 (m), 4.60 (d, J¼7.6 Hz, H-1 ( )), 4.28 (dd, J¼7.1 Hz,
J¼11.0 Hz, H-6 ( )), 4.28 (dd, J¼7.1 Hz, J¼10.5 Hz, H-6 ( )), 4.15 (t,
J¼5.3 Hz ( )), 4.07e3.95 (m), 3.92e3.87 (m), 3.81 (t, J¼9.6, H-2 ( )),
3.72 (d, J¼2.4 Hz, H-4 ( )), 3.53e3.49 (m), 2.12 (br s), 1.91e1.76 (m),
1.65e1.57 (m). 13C NMR (CDCl3):
165.8, 165.7, 137.8, 137.7, 137.5,
137.4,137.3,137.1,127.7e127.2,126.9e126.4, 95.5 (C-1 ( )), 89.5 (C-1
)), 81.5, 78.4, 78.0, 75.4, 74.2, 74.1, 73.5, 73.4, 73.3, 73.0, 72.6, 72.3,
a
/
b
-
D
-
d
a
b
b
d
a
b
b
a
b
b
d
b
a
b
a
b
a
b
b
a
b
(
(
a
b
a
b
d
a
a
b
b
33.3, 31.9, 31.6, 25.6, 25.5, 24.5, 24.2, 24.0, 23.9.
(a
72.0, 71.6, 70.3, 66.5, 64.2, 63.7, 41.6, 41.4, 39.6, 39.5, 35.2, 35.2, 29.7,
29.6.
4.6.10. 3-O-(2,3,4-Tri-O-Benzyl-6-O-chloroacetyl-
anosyl)-N-Boc-
-ser-methyl ester 16. FT-IR (film) 1714, 1747 cmꢂ1
(C]O). 1H NMR (CDCl3):
7.40e7.25 (m), 5.73 (d, J¼8.6 Hz, NHBoc
)), 5.46 (d, J¼7.8 Hz, NHBoc ( )), 4.96 (d, J¼11.5 Hz, Bn), 4.87e4.83
(m), 4.80e4.72 (m), 4.76 (s, H-1 ( )), 4.65e4.59 (m), 4.45e4.43 (m,
CH serine), 4.32 (d, J¼7.6 Hz, H-1 ( )), 4.29e4.19 (m), 4.15e3.96 (m),
3.92e3.73 (m), 3.74 (s, CO2Me ( )), 3.66 (s, CO2Me ( )), 3.53e3.50
(m), 1.43 (s, t-Bu ( )), 1.42 (s, t-Bu ( 170.8,
)). 13C NMR (CDCl3):
170.7, 167.0, 166.8, 155.5, 138.4, 138.37, 138.30, 138.1, 137.9,
128.6e128.2, 127.9e127.5, 104.3 (C-1 ( )), 99.7 (C-1 ( )), 81.9, 78.9,
78.5, 76.3, 75.4, 74.5, 74.3, 74.2, 73.5, 73.4, 72.5, 71.8, 71.1, 69.0, 65.0
a/b-D-galactopyr-
L
d
4.6.6. Benzyl (2S)-2-O-(2,3,4-tri-O-benzyl-6-O-chloroacetyl-
a
-
D
-gal-
(a
b
actopyranosyl)-2-phenylacetate 12. [
a
]
20 þ72.9 (c 0.82, CH2Cl2). FT-
a
b
b
D
IR (film): 1748 cmꢂ1 (C]O). 1H NMR (CDCl3):
d
7.52e7.49 (m, 2H),
7.43e7.18 (m, 23H), 5.15 (s, 1H, CH mandelate), 5.12 (dd, 1H,
J¼6.5 Hz, J¼16.5 Hz, CO2Bn), 4.96 (d, J¼11.6 Hz, Bn), 4.92 (d,
a
a
b
d
J¼11.6 Hz, Bn), 4.87 (d, J¼3.6 Hz, H-1 ( )), 4.78 (d, J¼11.6 Hz, Bn),
a
4.66 (d, J¼11.7 Hz, Bn), 4.60 (d, J¼11.6 Hz, Bn), 4.48 (d, J¼11.7 Hz,
b
a
Bn), 4.18e4.10 (m, 3H, H-3, H-5, H-6), 4.05e3.99 (m, 2H, H-2, H0-6),
3.91e3.82 (m, 3H, H-4, AcCl). 13C NMR (CDCl3):
d
169.9, 166.8, 138.6,
(C-6 (
a
)), 64.3 (C-6 (
b
)), 54.2 (CH serine (
a
)), 53.9 (CH serine (
b
)),
)),
138.2, 138.1, 135.5, 135.4, 128.8e128.2, 127.9e127.5, 96.4 (C-1 ( )),
a
52.6 (CO2Me (
b
)), 52.4 (CO2Me ( )), 40.7 (AcCl (a
a
)), 40.6 (AcCl (
b
78.7 (C-3), 77.4 (CH mandelate), 76.2 (C-2), 74.4, 74.3 (C-4), 73.6,
73.1, 68.9 (C-5), 66.8 (CO2CH2Ph), 64.8 (C-6), 40.6 (CH2Cl). HRMS:
calcd for C44H43ClO9Naþ [MþþNa]: 773.2493; found: 773.2485.
28.3 (t-Bu).
4.6.11. (2R)-1,3-Di-O-tert-butyldiphenylsilyl-2-O-(4,6-di-O-acetyl-
2,3-di-O-benzyl-a-D-galactopyranosyl)-1,2,3-trihydroxypropane
4.6.7. 1-
-galactopyranoside 13. FT-IR (film): 1715, 1757 cmꢂ1 (C]O). 1H
NMR (CDCl3): 7.41e7.26 (m), 4.98e4.94 (m), 4.91e4.88 (m), 4.90
(d, J¼3.5 Hz, H-1 ( )),
u
-Methoxy-PEG550yl-2,3,4-tri-O-benzyl-6-O-chloroacetyl-
a/
17. [
a
]
20 þ62.4 (c 2.63, CH2Cl2). FT-IR (film): 1744 cmꢂ1 (C]O). 1H
D
b-
D
NMR (CDCl3): d 7.67e7.61 (m, 8H), 7.41e7.11 (m, 22H), 5.43 (d, 1H,
d
J¼2.9 Hz), 5.10 (d, 1H, J¼3.5 Hz, H-1 ( )), 4.68 (d, 1H, J¼10.9 Hz),
a
a
)), 4.84e4.60 (m), 4.40 (d, J¼7.6 Hz, H-1 (
b
4.67 (d, 1H, J¼11.9 Hz), 4.55 (d, 1H, J¼11.9 Hz), 4.49 (d, 1H,
J¼11.0 Hz), 4.23 (t, 1H, J¼6.7 Hz), 3.99e3.75 (m, 8H), 3.72 (dd, 1H,
J¼3.6 Hz, J¼10.0 Hz), 2.08 (s, 3H), 1.91 (s, 3H), 1.00 (s, 18H). 13C NMR
4.28 (dd, J¼6.6 Hz, J¼11.0 Hz), 4.21 (dd, J¼7.0 Hz, J¼11.0 Hz),
4.12e3.82 (m), 3.77e3.50 (m), 3.37 (s, OMe). 13C NMR (CDCl3):
d
166.88, 166.81, 138.7, 138.5, 138.3, 138.1, 138.0, 128.6e128.1,
(CDCl3): d 170.4, 170.3, 138.4, 138.1, 135.6, 135.4, 133.4, 133.3, 133.2,
127.9e127.5, 104.0 (C-1 ( )), 97.6 (C-1 ( )), 81.9, 79.2, 78.8, 76.4,
b
a
133.1, 129.7, 128.3e127.5, 96.2 (C-1 (a)), 77.3, 75.7, 75.4, 73.0, 72.3,
75.0, 74.4, 74.3, 73.6, 73.5, 73.2, 72.6, 71.9, 71.6, 70.5, 70.4, 70.3, 70.2,
68.9, 68.0, 66.9, 64.9, 64.4, 59.0 (OMe), 40.7 (AcCl), 40.6 (AcCl).
HRMS: calcd for C54H81ClO19Naþ [MþþNa]: 1091.4953; found:
1091.4934.
67.8, 66.4, 64.0, 62.8, 62.1, 26.84, 26.82, 20.9, 20.6, 19.2, 19.1. HRMS:
calcd for C59H70O10Si2Naþ [MþþNa]: 1017.4405; found: 1017.4400.
4.6.12. Methyl 15-O-(4,6-di-O-acetyl-2,3-di-O-benzyl-
yranosyl)decapentanoate 18. FT-IR (film): 1740 cmꢂ1 (C]O). 1H
NMR (CDCl3): )), 5.49 (d,
7.33e7.25 (m), 5.55 (d, J¼3.1 Hz, H-4 (
J¼2.3 Hz, H-4 ( )), 4.88 (d, J¼10.8 Hz), 4.82 (d, J¼11.2 Hz), 4.81 (d,
J¼3.5 Hz, H-1 ( )), 4.76e4.70 (m), 4.62 (d, J¼12.0 Hz), 4.56 (d,
J¼11.1 Hz), 4.53 (d, J¼11.4 Hz), 4.38 (d, J¼6.9 Hz, H-1 ( )), 4.16e4.09
(m), 4.07e4.04 (m), 3.99e3.91 (m), 3.78e3.73 (m), 3.66 (s),
a/b-D-galactop
4.6.8. O-1-
L
-Menthyl-2,3,4-tri-O-benzyl-6-O-chloroacetyl-
a
/
b
-
D
-gal-
d
a
actopyranoside 14. FT-IR (film): 1762 cmꢂ1 (C]O). 1H NMR (CDCl3):
b
a
d
7.40e7.27 (m), 5.01 (d, J¼3.5 Hz, H-1 (
)), 4.94 (d, J¼10.8 Hz, Bn ( )), 4.88e4.64 (m), 4.61 (d, J¼11.6 Hz, Bn
)), 4.37 (d, J¼7.7 Hz, H-1 ( )), 4.27e4.22 (m, H-6 ( ), H-6 ( )),
a
)), 4.97 (d, J¼11.8 Hz, Bn
(b
a
b
(a
b
a
b

E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
7095
3.65e3.42 (m), 2.29 (t, J¼7.5 Hz), 2.14 (s), 2.11 (s), 2.07 (s), 2.05 (s),
1.70e1.54 (m), 1.41e1.25 (m). 13C NMR (CDCl3):
174.3, 170.57,
170.53, 170.48, 170.40, 138.6, 138.5, 138.1, 137.7, 128.3e127.6, 103.8
(C-1 ( )), 97.6 (C-1 ( )), 79.0, 78.8, 76.0, 75.6, 75.3, 73.4, 72.3, 72.2,
169.7, 138.3, 138.0, 135.39, 135.34, 128.8e128.0, 127.9e127.3, 96.7
(C-1 ( )), 77.8 (CH mandelate), 75.9 (C-3), 75.3 (C-2), 73.3, 72.2, 67.7
(C-4), 67.4 (C-5), 66.9 (CO2CH2Ph), 62.2 (C-6), 20.8 (Ac), 20.7 (Ac).
HRMS: calcd for C39H40O10Naþ [MþþNa]: 691.2519; found:
691.2504.
d
a
b
a
70.6, 70.5, 68.6, 67.9, 66.6, 66.5, 62.6, 62.0, 51.4, 34.1, 29.7e29.1,
26.2, 26.1, 24.9, 20.93, 20.90, 20.7.
4.6.17. 1-
-galactopyranoside 23. FT-IR (film): 1716, 1742 cmꢂ1 (C]O). 1H
NMR (CDCl3): )), 5.48 (d,
7.37e7.26 (m), 5.55 (d, J¼2.6 Hz, H-4 (
J¼2.4 Hz, H-4 ( )), 4.90 (d, J¼10.8 Hz),
u-Methoxy-PEG550yl-4,6-di-O-acetyl-2,3-di-O-benzyl-a/b-
4.6.13. Methyl (2R)-3-O-tert-butyldiphenylsilyl-2-O-[4,6-di-O-ace-
D
tyl-2,3-di-O-benzyl-
1-O- -glucopyranosyl]-2,3-dihydroxypropanoate 19. [
2.06 (c 0.88, CH2Cl2). FT-IR (film): 1744 cmꢂ1 (C]O). 1H NMR
a-
D
-galactopyranosyl-(1/6)-2,3,4-tri-O-benzyl-
d
a
20
a-
D
a
]
þ11
b
)), 4.91 (d, J¼3.6 Hz, H-1 (
a
D
4.80 (d, J¼12.0 Hz), 4.74 (d, J¼11.1 Hz), 4.71 (d, J¼12.3 Hz), 4.64 (d,
J¼12.0 Hz), 4.56 (d, J¼11.0 Hz), 4.52 (d, J¼11.4 Hz), 4.44 (d, J¼7.2 Hz,
(CDCl3):
d 7.70e7.67 (m, 4H), 7.39e7.17 (m, 31H), 5.46 (d, 1H,
J¼3.0 Hz), 5.14 (d, 1H, J¼3.5 Hz, H-10
J¼10.8 Hz), 4.97 (d, 1H, J¼1.8 Hz, H-1 (
(a
) Glucose), 4.98 (d, 1H,
H-1 (b)), 4.21e4.18 (m), 4.15e4.10 (m), 4.06e4.01 (m), 3.98 (dd,
a
) Galactose), 4.87 (d, 1H,
J¼3.4 Hz, J¼9.9 Hz, H-3 (
a)), 3.81e3.53 (m), 3.37 (s, OMe), 2.13 (s,
Ac), 2.11 (s, Ac), 2.07 (s, Ac), 2.06 (s, Ac). HRMS: calcd for C49H79O20
J¼11.5 Hz), 4.83 (d, 1H, J¼11.6 Hz), 4.74 (d, 1H, J¼10.7 Hz), 4.70 (d,
1H, J¼11.3 Hz), 4.69 (d, 1H, J¼12.1 Hz), 4.60 (d, 1H, J¼12.1 Hz), 4.59
(d, 1H, J¼11.6 Hz), 4.53 (d, 1H, J¼11.5 Hz), 4.52 (d, 1H, J¼11.3 Hz),
4.48 (dd, 1H, J¼4.0 Hz, J¼5.9 Hz), 4.09e3.86 (m, 8H), 3.77e3.60 (m,
4H), 3.75 (s, 3H), 3.48 (dd, 1H, J¼3.6 Hz, J¼9.5 Hz), 2.09 (s, 3H), 1.94
[MþþH]: 987.5165; found: 987.5157.
4.6.18. O-1-
actopyranoside 24. FT-IR (film): 1746 cmꢂ1 (C]O). 1H NMR (CDCl3):
7.36e7.25 (m), 5.56 (d, J¼2.6 Hz, H-4 ( )), 5.46 (s, H-4 ( )), 5.02 (d,
J¼3.5 Hz, H-1 ( )), 4.87 (d, J¼10.7 Hz, Bn ( )), 4.80 (d, J¼11.6 Hz, Bn
)), 4.73 (d, J¼11.0 Hz, Bn ( )), 4.68 (d, J¼10.7 Hz, Bn ( )), 4.62 (d,
J¼11.6 Hz, Bn ( )), 4.56e4.50 (m), 4.42 (d, J¼6.2 Hz, H-1 ( )), 4.29 (t,
J¼6.2 Hz, H-5 ( )), 4.14e4.04 (m, 2H-6 ( ), 2H-6 ( )), 3.99 (dd,
J¼3.0 Hz, J¼10.0 Hz, H-3 ( )), 3.77 (dd, J¼3.5 Hz, J¼10.0 Hz, H-2 ( )),
3.72 (t, J¼6.6 Hz, H-5 ( )), 3.57e3.50 (m, H-2 ( ), H-3 ( )), 3.41 (td,
J¼4.1 Hz, J¼10.6 Hz, CHeO menthol ( )), 3.34 (td, J¼4.2 Hz,
J¼10.6 Hz, CHeO menthol ( )), 2.44e2.31 (m, CH(CH3)2 menthol),
2.14e2.05 (m, CHCH2CH menthol), 2.14 (s, Ac ( )), 2.11 (s, Ac ( )),
2.07 (s, Ac ( )), 2.05 (s, Ac ( )), 1.67e1.60 (m, CH2CH2 menthol),
L-Menthyl-4,6-di-O-acetyl-2,3-di-O-benzyl-a/b-D-gal-
(s, 3H), 1.02 (s, 9H). 13C NMR (CDCl3):
d
170.5, 170.4, 170.2, 138.9,
d
a
b
138.7, 138.6, 138.3, 138.0, 135.7, 135.6, 133.1, 132.8, 129.7,
a
b
128.3e127.3, 98.0 (C-1 ( ) Glucose), 81.7,
a
) Galactose), 94.5 (C-10 (
a
(a
a
b
79.5, 75.7, 75.5, 75.3, 74.7, 74.5, 72.7, 72.0, 71.9, 70.8, 67.9, 66.7, 66.1,
64.7, 62.5, 52.0, 26.7, 20.9, 20.7, 19.2. HRMS: calcd for
C71H80O16SiNaþ [MþþNa]: 1239.5113; found: 1239.5108.
a
b
a
a
b
a
a
b
b
b
4.6.14. 3-O-(4,6-Di-O-acetyl-2,3-di-O-benzyl-
anosyl)-epiandrosterone 20. FT-IR (film): 1741 cmꢂ1 (C]O). 1H NMR
(CDCl3): )), 5.47 (d,
7.36e7.27 (m), 5.55 (d, J¼3.0 Hz, H-4 (
J¼2.8 Hz, H-4 ( )), 4.97 (d, J¼3.6 Hz, H-1 ( )), 4.88 (d, J¼10.9 Hz, Bn
)), 4.80 (d, J¼12.0 Hz, Bn ( )), 4.75e4.71 (m), 4.62 (d, J¼12.0 Hz,
Bn ( )), 4.23 (t,
)), 4.54 (t, J¼11.3 Hz), 4.48 (d, J¼7.2 Hz, H-1 (
J¼6.4 Hz, H-5 ( )), 4.19e4.10 (m), 4.03 (dd, J¼7.3 Hz, J¼11.1 Hz, H-6
)), 3.77e3.73 (m),
a
/
b
-
D
-galactopyr-
b
a
d
a
b
a
b
a
a
b
(b
a
1.42e1.25 (m, CHCH3, CHCH(CH3)2 menthol), 1.08e0.80 (m), 0.75
a
b
(d, J¼6.7 Hz), 0.68 (d, J¼6.8 Hz). 13C NMR (CDCl3):
d 170.6, 170.59,
a
170.58, 170.4, 138.66, 138.62, 138.1, 137.9, 128.3e128.0, 127.9e127.4,
(
a
)), 3.95 (dd, J¼3.3 Hz, J¼10.0 Hz, H-3 (
a
101.7 (C-1 (
menthol ( )), 79.3, 78.7, 76.1 (C-3 (
71.8, 70.4 (C-5 ( )), 68.0 (C-4 ( )), 66.8 (C-5 (
(C-6 ( )), 62.3 (C-6 ( )), 48.7 (CHCH(CH3)2
(CHCH(CH3)2 ) menthol), 42.9 (CHCH2CH (
(CHCH2CH ( ) menthol), 34.3, 34.2, 31.7 (CHCH3 menthol (
(CHCH3 menthol ( )), 25.0 (CH(CH3)2 menthol ( )), 24.4 (CH(CH3)2
menthol ( )), 23.0, 22.9, 22.4, 22.2, 21.0, 20.98 (Ac), 20.92 (Ac), 20.8
(Ac), 20.7 (Ac), 16.0, 15.5.
b
)), 99.5 (C-1 (
a
)), 81.2 (CHeO menthol (
)), 76.0 (C-2 ( )), 75.3, 73.8, 72.3,
)), 66.7 (C-4 ( )), 63.0
) menthol), 47.9
) menthol), 41.3
)), 31.5
a)), 79.5 (CHeO
3.64e3.48 (m), 2.43 (dd, J¼8.9 Hz, J¼19.2 Hz), 2.13 (s), 2.10 (s), 2.06
(s), 2.05 (s), 2.11e2.01 (m), 1.95e1.43 (m), 1.40e1.20 (m), 1.15e1.07
(m), 1.01e0.91 (m), 0.68 (ddd, J¼3.3 Hz, J¼11.5 Hz, J¼11.5 Hz). 13C
b
a
a
b
a
a
b
a
b
(a
a
NMR (CDCl3):
d
170.5, 170.4, 138.6, 138.5, 138.1, 137.8, 128.3e127.6,
(b
102.3 (C-1 ( )), 96.2 (C-1 (
b
a
)), 79.7, 79.2, 78.9, 76.1, 75.5, 75.4, 73.3,
b
a
72.3, 72.2, 70.5, 67.9, 66.6, 66.5, 62.7, 62.0, 54.4, 51.4, 47.8, 45.2, 44.8,
36.9, 35.85, 35.8, 35.0, 34.7, 31.5, 30.9, 29.5, 28.5, 28.4, 27.5, 21.7,
20.9, 20.7, 20.5, 13.8, 12.3, 12.2.
b
b
a
4.6.15. 1-O-Adamantanyl-4,6-di-O-acetyl-2,3-di-O-benzyl-
galactopyranose 21. FT-IR (film): 1744, 1745 cmꢂ1 (C]O). 1H NMR
(CDCl3): )), 5.46 (d,
7.36e7.25 (m), 5.56 (d, J¼2.9 Hz, H-4 (
J¼2.4 Hz, H-4 ( )), 5.32 (d, J¼3.8 Hz, H-1 ( )), 4.92 (d, J¼10.9 Hz, Bn
)), 4.77e4.70 (m), 4.68e4.60 (m), 4.56e4.50 (m), 4.35 (t, J¼6.6 Hz,
H-5 ( )), 3.75
)), 4.18e4.03 (m), 3.99 (dd, J¼3.4 Hz, J¼10.0 Hz, H-3 (
(dd, J¼3.8 Hz, J¼10.0 Hz, H-2 ( )), 3.61e4.53 (m), 2.15 (m), 2.13 (s),
2.10 (s), 2.04 (s), 1.93e1.78 (m), 1.69e1.59 (m). 13C NMR (CDCl3):
170.5, 170.4, 138.6, 138.2, 137.8, 128.9e127.5, 96.3 (C-1 ( )), 90.7
(C-1 ( )), 79.5, 78.8, 76.1, 75.6, 75.5, 75.4, 73.1, 72.3, 72.1, 70.4, 68.0,
a
/
b
-
D
-
4.6.19. O-1-
actopyranoside 25. FT-IR (film): 1744 cmꢂ1 (C]O). 1H NMR (CDCl3):
7.36e7.25 (m), 5.56 (d, J¼2.8 Hz, H-4 ( )), 5.48 (d, J¼2.3 Hz, H-4
)), 4.99 (d, J¼3.6 Hz, H-1 ( )), 4.91 (d, J¼10.8 Hz, Bn), 4.79 (d,
J¼12.0 Hz, Bn), 4.75e4.69 (m), 4.62 (d, J¼12.0 Hz, Bn), 4.57e4.49
(m), 4.48 (d, J¼7.2 Hz, H-1 ( )), 4.23 (t, J¼6.2 Hz, H-5 ( )), 4.20e4.09
(m), 4.03 (dd, J¼7.4 Hz, J¼11.2 Hz), 3.97 (dd, J¼3.3 Hz, J¼10.0 Hz, H-
3 ( )), 3.78e3.73 (m), 3.70e3.63 (m), 3.61e3.49 (m), 2.13 (s, Ac),
L-Cyclohexyl-4,6-di-O-acetyl-2,3-di-O-benzyl-a/b-D-gal-
d
a
d
a
b
a
(b
a
(
b
a
a
b
a
a
a
d
b
2.10 (s, Ac), 2.06 (s, Ac), 2.05 (s, Ac), 1.99e1.84 (m), 1.77e1.75 (m),
a
1.62e1.17 (m). 13C NMR (CDCl3):
137.8, 128.3e127.5, 102.1 (C-1 (
(CH cyclohexanol), 76.3 (CH cyclohexanol), 76.1 (H-3 (
d
170.58, 170.56, 170.4, 138.6, 138.1,
)), 95.9 (C-1 ( )), 79.4, 78.8, 78.5
)), 75.6 (H-2
)), 66.6 (C-4 ( ), C-5
)), 62.6, 62.0, 33.7, 33.3, 32.0, 31.6, 25.58, 25.55, 24.5, 24.2, 24.1,
66.7, 66.2, 62.6, 62.2, 42.6, 42.4, 36.2, 35.8, 31.1, 30.6, 20.98, 20.92,
20.7.
b
a
a
(a
)), 75.3, 73.2, 72.2, 70.5 (C-5 (
b
)), 68.0 (C-4 (
a
b
4.6.16. Benzyl (2S)-2-O-4,6-di-O-acetyl-2,3-di-O-benzyl-
a
-
D
-galacto
(a
20
pyranosyl-2-phenylacetate 22. [
(film): 1743 cmꢂ1 (C]O). 1H NMR (CDCl3):
5.57 (d, 1H, J¼3.0 Hz, H-4), 5.19e5.09 (m, 3H, CH mandelate,
a
]
þ101.8 (c 1.57, CH2Cl2). FT-IR
24.0, 20.97 (Ac), 20.92 (Ac), 20.77 (Ac), 20.75 (Ac).
D
d
7.44e7.15 (m, 20H),
4.6.20. 3-O-(4,6-Di-O-acetyl-2,3-di-O-benzyl-
a/b-D-galactopyr-
CO2CH2Ph), 4.88 (d, 1H, J¼3.6 Hz, H-1 (
a
)), 4.75 (d, 1H, J¼10.8 Hz,
anosyl)-N-Boc- -ser-methyl ester 26. anomer: [
L
a
a]
20 þ99.0 (c 1.25,
D
Bn), 4.69 (d, 1H, J¼11.8 Hz, Bn), 4.58 (d, 1H, J¼10.8 Hz, Bn), 4.45 (d,
1H, J¼11.8 Hz, Bn), 4.37 (t, 1H, J¼6.4 Hz, H-5), 4.13 (dd, 1H, J¼3.2 Hz,
J¼10.0 Hz, H-3), 4.08 (dd,1H, J¼6.0 Hz, J¼11.2 Hz, H-6), 3.96 (dd,1H,
J¼6.9 Hz, J¼11.1 Hz, H-60), 3.77 (dd, 1H, J¼3.6 Hz, J¼9.9 Hz, H-2),
CH2Cl2). FT-IR (film): 1715, 1745 cmꢂ1 (C]O). 1H NMR (CDCl3):
d
7.32e7.26 (m,10H), 5.62 (d,1H, J¼8.2 Hz, NHBoc), 5.55 (s,1H, H-4),
4.80 (s, 1H, H-1 (
a
)), 4.77 (d, 1H, J¼12.0 Hz, Bn), 4.73 (d, 1H,
J¼11.1 Hz, Bn), 4.58 (d, 1H, J¼11.9 Hz, Bn), 4.53 (d, 1H, J¼11.0 Hz, Bn),
2.09 (s, 3H, Ac), 2.03 (s, 3H, Ac). 13C NMR (CDCl3):
d 170.5, 170.3,
4.47e4.45 (m, 1H, CH serine), 4.17e4.02 (m, 4H, H-5, H-6, H0-6, CH2

7096
E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
serine), 3.90e3.83 (m, 2H, H-3, CH2 serine), 3.77e3.74 (m, 1H, H-2),
3.66 (s, 3H, CO2Me), 2.10 (s, 3H, Ac), 2.04 (s, 3H, Ac), 1.45 (s, 3H, t-
HRMS: calcd for C71H78O16Cl2SiNaþ [MþþNa]: 1307.4334; found:
1307.4328.
Bu). 13C NMR (CDCl3):
d
170.7, 170.5, 170.2, 155.4, 138.4, 137.9,
128.36, 128.34, 127.9, 127.7, 127.6, 99.2 (C-1 ( )), 75.6 (C-3), 75.4 (C-
2), 73.4, 72.1, 70.2 (CH2 serine), 67.5 (C-4), 67.3 (C-5), 62.3 (C-6), 54.1
a
4.6.24. 3-O-(2,3-Di-O-benzyl-4,6-di-O-chloroacetyl-
actopyranosyl)-epiandrosterone 30. FT-IR (film): 1737, 1764 cmꢂ1
(C]O). 1H NMR (CDCl3):
7.35e7.27 (m), 5.58 (d, J¼2.7 Hz, H-4 ( )),
5.50 (d, J¼1.9 Hz, H-4 ( )), 4.97 (d, J¼3.7 Hz, H-1 ( )), 4.88 (d,
J¼10.9 Hz, Bn ( )), 4.79 (d, J¼12.0 Hz, Bn ( )), 4.74e4.69 (m), 4.54 (d,
J¼11.3 Hz), 4.50 (d, J¼7.4 Hz, H-1 ( )), 4.34e4.30 (m), 4.25e4.20 (m),
4.15e4.04 (m), 3.99 (dd, J¼10.0 Hz, J¼3.4 Hz, H-3 ( )), 3.83 (t,
)), 3.57e3.48
a/b-D-gal-
(CH serine), 52.5 (CO2Me), 28.3 (t-Bu), 20.8 (Ac), 20.7 (Ac).
d
a
20
b
anomer: [
a
]
D
þ38.8 (c 0.57, CH2Cl2). FT-IR (film): 1715,
b
a
1744 cmꢂ1 (C]O). 1H NMR (CDCl3):
d
7.39e7.28 (m, 10H), 5.48 (s,
b
a
2H, NHBoc, H-4), 4.80 (d, 1H, J¼10.7 Hz, Bn), 4.75e4.69 (m, 2H, Bn),
b
4.50 (d,1H, J¼11.3 Hz, Bn), 4.49e4.46 (m,1H, CH serine), 4.36 (d,1H,
a
J¼7.1 Hz, H-1 (
b
)), 4.35e4.31 (m, 1H, CH2 serine), 4.13 (d, 2H,
J¼7.0 Hz, H-5 (
b
)), 3.73 (dd, J¼10.0 Hz, J¼3.7 Hz, H-2 (
a
J¼6.5 Hz, H-6, H0-6), 3.83 (dd, 1H, J¼3.4 Hz, J¼10.4 Hz, CH2 serine),
3.75 (s, 3H, CO2Me), 3.75e3.72 (m, 1H, H-5), 3.58e3.52 (m, 2H, H-2,
H-3), 2.14 (s, 3H, Ac), 2.08 (s, 3H, Ac), 1.42 (s, 3H, t-Bu). 13C NMR
(m), 2.44 (dd, J¼19.2 Hz, J¼8.5 Hz), 2.11e2.01 (m), 1.96e1.63 (m),
1.59e1.43 (m),1.39e1.20 (m),1.15.1.07 (m),1.02e0.91 (m), 0.68 (ddd,
J¼0.63 Hz, J¼11.4 Hz, J¼11.4 Hz). 13C NMR (CDCl3):
d
167.2, 167.0,
(CDCl3):
127.8, 127.7, 104.1 (C-1 (
d
170.7, 170.5, 170.3, 155.4, 138.2, 137.5, 128.3, 128.1, 128.0,
)), 79.0, 78.3, 75.4, 72.1, 70.8 (C-5), 70.3
166.9, 138.4, 138.3, 137.8, 128.4e127.7, 102.2 (C-1 (
b
)), 95.8 (C-1 ( )),
a
b
79.7, 78.8, 77.1, 75.7, 75.4, 75.2, 73.4, 72.6, 70.1, 70.0, 68.7, 66.0, 63.9,
63.2, 54.4, 51.4, 47.8, 45.2, 44.7, 40.8, 40.7, 40.5, 36.8, 35.8, 35.7, 35.0,
31.5, 30.8, 29.5, 28.4, 27.4, 21.7, 20.5, 14.2, 13.8, 12.9, 12.3. HRMS:
calcd for C43H54Cl2O9Naþ [MþþNa]: 807.3043; found: 807.3018.
(CH2 serine), 66.3 (C-4), 61.9 (C-6), 54.0 (CH serine), 52.6 (CO2Me),
28.3 (t-Bu), 20.8 (Ac), 20.7 (Ac).
4.6.21. (2R)-1,3-Di-O-tert-butyldiphenylsilyl-2-O-(4,6-di-O-chlor-
oacetyl-2, 3-di-O-benzyl-
a
-
D
-galactopyranosyl)-1, 2, 3-
4.6.25. 1-O-Adamantanyl-2,3-di-O-benzyl-4,6-di-O-chloroacetyl-
-galactopyranoside 31. FT-IR (film): 1743, 1747, 1762, 1763 cmꢂ1
(C]O). 1H NMR (CDCl3):
7.34e7.25 (m), 5.59 (d, J¼2.4 Hz, H-4 ( )),
5.49 (d, J¼2.2 Hz, H-4 ( )), 5.30 (d, J¼3.7 Hz, H-1 ( )), 4.91 (d,
J¼10.9 Hz, Bn ( )), 4.75e4.66 (m), 4.63 (d, J¼11.9 Hz, Bn ( )), 4.57 (d,
J¼10.6 Hz, Bn ( )), 4.53 (d, J¼11.2 Hz, Bn ( )), 4.43 (t, J¼6.5 Hz, H-5
)), 4.29 (dd, J¼7.4 Hz, J¼11.2 Hz, H-6 ( )), 4.24e4.16 (m),
4.14e4.08 (m), 4.05 (s), 4.02 (dd, J¼3.4 Hz, J¼10.0 Hz), 3.83 (t,
J¼6.5 Hz, H-5 ( )), 3.72 (dd, J¼3.7 Hz, J¼10.0 Hz, H-2 ( )), 3.60e3.53
(m), 2.15 (br s), 1.91e1.76 (m), 1.67e1.59 (m). 13C NMR (CDCl3):
167.2, 167.0, 166.9, 138.4, 138.3, 137.9, 137.4, 128.4e127.6, 96.3 (C-1
)), 90.6 (C-1 ( )), 79.0, 78.5, 75.8, 75.7, 75.4, 75.3, 74.9, 73.2, 72.7,
a/
20
trihydroxypropane 27. [
1747, 1766 cmꢂ1 (C]O). 1H NMR (CDCl3):
7.43e7.27 (m,18H), 7.18e7.14 (m, 4H), 5.39 (d,1H, J¼2.9 Hz), 5.06 (d,
a]
þ66.9 (c 12.15, CH2Cl2). FT-IR (film):
b-D
D
d
7.63e7.61 (m, 8H),
d
a
b
a
a
1H, J¼3.5 Hz, H-1 (
a
)), 4.64 (d, 2H, J¼11.4 Hz), 4.54 (d, 1H,
b
a
J¼11.9 Hz), 4.50 (d, 1H, J¼10.9 Hz), 4.26 (t, 1H, J¼6.6 Hz), 4.14e3.91
(m, 6H), 3.88e3.72 (m, 6H), 3.67 (dd, 1H, J¼3.4 Hz, J¼10.0 Hz), 1.01
b
(a
b
(s, 18H). 13C NMR (CDCl3):
d 167.0, 166.6, 138.1, 137.8, 135.6e135.5,
133.3, 133.2, 133.0, 129.83, 129.80, 128.3, 128.2, 128.0, 127.8e127.6,
b
a
96.2 (C-1 (a)), 77.6, 75.4, 75.1, 73.1, 72.6, 70.0, 65.8, 64.1, 63.2, 62.8,
40.7, 40.4, 26.9, 26.8, 19.3, 19.1. HRMS: calcd for C59H68O10Cl2Si2Naþ
d
[MþþNa]: 1085.3626; found: 1085.3620.
(b
a
72.5, 70.2, 69.9, 68.9, 65.7, 63.9, 63.5, 42.6, 42.4, 40.8, 40.7, 40.6,
40.5, 36.2, 30.7, 30.6. HRMS: calcd for C34H40Cl2O8Naþ [MþþNa]:
669.1998; found: 669.1986.
4.6.22. Methyl 15-O-(2,3-di-O-benzyl-4,6-di-O-chloroacetyl-
galactopyranosyl)decapentanoate 28. FT-IR (film): 1736, 1764 cmꢂ1
(C]O). 1H NMR (CDCl3):
7.35e7.27 (m), 5.57 (d, J¼3.3 Hz, H-4 ( )),
5.51 (d, J¼2.1 Hz, H-4 ( )), 4.87 (d, J¼10.8 Hz), 4.807 (d, J¼3.6 Hz, H-
1 (
)), 4.80 (d, J¼12.0 Hz), 4.73 (d, J¼11.0 Hz), 4.72 (d, J¼10.9 Hz),
4.70 (d, J¼10.4 Hz), 4.61 (d, J¼12.2 Hz), 4.58 (d, J¼11.0 Hz), 4.54 (d,
J¼11.2 Hz), 4.39 (d, J¼7.1 Hz, H-1 ( )), 4.34e4.19 (m), 4.15 (d,
J¼2.2 Hz, AcCl ( )), 4.10 (d, J¼2.8 Hz, AcCl ( )), 4.08 (s, AcCl ( )), 4.06
(s, AcCl ( )), 3.95e3.90 (m),
)), 4.00 (dd, J¼3.4 Hz, J¼10.0 Hz, H-3 (
3.83 (t, J¼7.0 Hz, H-5 ( )), 3.73 (dd, J¼3.6 Hz, J¼10.0 Hz, H-2 ( )),
3.66 (s), 3.63e3.43 (m), 2.29 (t, J¼7.5 Hz), 1.67e1.57 (m), 1.42e1.24
(m). 13C NMR (CDCl3):
174.3, 167.1, 167.0, 166.9, 166.8, 138.3, 137.7,
137.4, 128.4e127.7, 103.7 (C-1 ( )), 97.6 (C-1 ( )), 78.6, 78.5, 75.7,
a/b-D-
d
a
b
4.6.26. Benzyl (2S)-2-O-(4,6-di-O-chloroacetyl-2,3-di-O-benzyl-a-D-
20
a
galactopyranosyl)-2-phenylacetate 32. [
FT-IR (film): 1747 cmꢂ1 (C]O). 1H NMR (CDCl3):
20H), 5.58 (d, 1H, J¼3.0 Hz, H-4), 5.18e5.11 (m, 3H, CH mandelate,
a
]
þ80.5 (c 2.10, CH2Cl2).
D
d
7.49e7.13 (m,
b
b
a
b
CO2CH2Ph), 4.87 (d, 1H, J¼3.6 Hz, H-1 ( )), 4.73 (d, 1H, J¼10.8 Hz,
a
a
a
Bn), 4.66 (d, 1H, J¼11.8 Hz, Bn), 4.63 (d, 1H, J¼10.8 Hz, Bn),
4.45e4.42 (m, 2H, H-5, Bn), 4.18e4.04 (m, 3H, H-3, H-6, H0-6), 4.08
(s, 2H, AcCl), 4.02 (s, 2H, AcCl), 3.73 (dd, 1H, J¼3.6 Hz, J¼10.0 Hz, H-
b
a
d
2). 13C NMR (CDCl3):
d 169.7, 166.9, 166.8, 138.1, 137.7, 135.3, 135.1,
b
a
128.9e128.0, 127.9e127.4, 96.7 (C-1 (a)), 78.0 (CH mandelate), 75.5
75.4, 75.3, 73.4, 72.7, 72.6, 70.6, 70.0, 68.7, 68.6, 66.0, 63.7, 63.1, 51.4,
40.8, 40.7, 40.6, 40.5, 34.1, 29.6e29.1, 26.2, 26.1, 24.9. HRMS: calcd
for C40H56Cl2O10Naþ [MþþNa]: 789.3143; found: 789.3119.
(C-3), 75.1 (C-2), 73.3, 72.6, 69.9 (C-4), 67.0 (CO2CH2Ph), 66.9 (C-5),
63.4 (C-6), 40.7 (AcCl), 40.5 (AcCl). HRMS: calcd for C39H40Cl2
O10Naþ [MþþNa]: 759.1740; found: 759.1726.
4.6.23. Methyl (2R)-3-O-tert-butyldiphenylsilyl-2-O-[2,3-di-O-ben-
4.6.27. 1-
zyl- -galactopyranoside 33. FT-IR (film): 1716, 1760 (C]O st)
cmꢂ1. 1H NMR (CDCl3):
5.50 (br s, H-4 (
)), 4.90 (d, J¼10.5 Hz), 4.89 (d, J¼3.6 Hz, H-1 (
4.83e4.53 (m), 4.47 (d, J¼6.7 Hz, H-1 (
(m), 4.04e3.97 (m), 3.90e3.53 (m), 3.37 (s, OMe). 13C NMR (CDCl3):
167.1, 167.0, 166.9, 138.4, 138.2, 137.7, 137.3, 128.4e128.0,
127.9e127.6, 103.8 (C-1 ( )), 97.7 (C-1 ( )), 78.5, 78.4, 75.5 (C-3 ( )),
75.1, 73.4, 72.6, 72.5, 71.9, 71.8, 70.4, 70.3, 70.1, 70.0 (C-4 ( )), 69.3,
68.6 (C-4 ( )), 67.3, 66.0 (C-5 ( )), 63.5 (C-6 ( )), 63.1 (C-6 ( ), 59.0
(OMe), 40.77 (AcCl), 40.75 (AcCl), 40.6 (AcCl), 40.5 (AcCl).
u-Methoxy-PEG550yl-4,6-di-O-chloroacetyl-2,3-di-O-ben-
zyl-4,6-di-O-chloroacetyl-
a
-
D
-galactopyranosyl-(1/6)-2,3,4-tri-O-
a/b-D
20
benzyl-1-O-
a
-
D
-glucopyranosyl]-2,3-dihydroxypropanoate 29. [
a
]
d
7.46e7.25 (m), 5.58 (d, J¼2.7 Hz, H-4 (
a
a
)),
)),
D
þ98.5 (c 0.76, CH2Cl2). FT-IR (film): 1751 cmꢂ1 (C]O). 1H NMR
b
(CDCl3):
d
7.69e7.68 (m, 4H), 7.40e7.17 (m, 31H), 5.48 (d, 1H,
b)), 4.32e4.19 (m), 4.16e4.06
J¼2.9 Hz, H-4 Galactose), 5.15 (d, 1H, J¼3.3 Hz, H-10 (
a) Glucose),
4.98 (d, 1H, J¼10.6 Hz), 4.92 (d, 1H, J¼3.2 Hz, H-1 (
a
) Galactose),
d
4.88 (d, 1H, J¼11.6 Hz), 4.84 (d, 1H, J¼11.5 Hz), 4.73 (d, 1H,
J¼10.6 Hz), 4.67 (d, 2H, J¼11.8 Hz), 4.60 (d, 1H, J¼11.4 Hz), 4.58 (d,
1H, J¼12.0 Hz), 4.53 (d, 1H, J¼11.2 Hz), 4.52 (d, 1H, J¼11.6 Hz),
4.48e4.46 (m, 1H), 4.19e3.88 (m, 13H), 3.76 (s, 3H), 3.74e3.58 (m,
4H), 3.51 (dd, 1H, J¼3.4 Hz, J¼9.4 Hz), 1.03 (s, 9H). 13C NMR (CDCl3):
b
a
a
a
b
a
a
b
d
170.2, 167.0, 166.7, 138.8, 138.6, 138.4, 138.2, 137.7, 135.6, 135.5,
4.6.28. O-1-
L-Menthyl-4,6-di-O-chloroacetyl-2,3-di-O-benzyl-a/b-D-
133.0, 132.8, 129.7, 128.3e127.3, 97.8 (C-1 (
), Glucose), 81.7, 79.5, 77.4, 75.7, 75.3, 75.0, 74.7, 74.5, 72.8, 72.4,
71.9, 70.8, 70.1, 66.3, 66.2, 64.7, 63.7, 52.0, 40.7, 40.5, 26.7, 19.2.
a
), Galactose), 94.4 (C-10
galactopyranoside 34.
a
anomer: [
a]
20 þ52.8 (c 2.48, CH2Cl2). FT-IR
D
(a
(film): 1748, 1765 cmꢂ1 (C]O). 1H NMR (CDCl3):
d
7.32e7.26 (m,
10H), 5.58 (s, 1H, H-4), 5.00 (d, 1H, J¼3.0 Hz, H-1 (
a)), 4.77 (d, 1H,

E.C. Lourenc¸ o, M.R. Ventura / Tetrahedron 69 (2013) 7090e7097
7097
J¼11.6 Hz, Bn), 4.71 (d,1H, J¼10.9 Hz, Bn), 4.62 (d,1H, J¼11.6 Hz, Bn),
4.6.30. 3-O-(4,6-Di-O-chloroacetyl-2,3-di-O-benzyl-
actopyranosyl)-N-Boc-
1747 (C]O st) cmꢂ1. 1H NMR (CDCl3):
J¼8.2 Hz, NHBoc, H-4 ( )), 5.49 (d, J¼2.7 Hz, H-4 (
NHBoc ( )), 4.79 (s, H-1 (
)), 4.80 (d, J¼10.7 Hz, Bn (
4.59e4.51 (m), 4.48e4.45 (m, CH serine), 4.37 (d, J¼7.6 Hz, H-1 (
4.31e4.16 (m), 4.15e4.06 (m), 3.92 (dd, J¼3.3 Hz, J¼10.0 Hz, H-3 (
3.86e3.80 (m), 3.78e3.71 (m, H-2 ( )), 3.76 (s, CO2Me (
CO2Me ( )), 3.53 (dd, J¼9.3 Hz,
)), 3.59 (dd, J¼3.0 Hz, J¼9.6 Hz, H-3 (
J¼17.0 Hz, H-2 ( )),1.45 (s, t-Bu ( )),1.42 (s, t-Bu (
)).13C NMR (CDCl3):
170.7,167.0,166.99,166.94,138.1,137.5,137.1,128.4e127.7,104.0 (C-1
)), 99.3 (C-1 ( )), 78.6 ( ), 78.0 ( ), 75.5 ( ), 75.3 (C-3 ( )), 75.1 (C-2
)), 73.5 ( ), 72.59 ( ), 72.52 ( ), 70.6 (CH2 serine ( )), 70.4 (CH2
)), 70.2 (C-5 ( )), 69.7 (C-4 ( )), 68.4 (C-4 ( )), 66.8 (C-5 (
63.5 (C-6 ( )), 63.0 (C-6 ( )), 54.1 (CH serine ( )), 54.0 (CH serine (
52.6 (CO2Me ( )), 52.5 (CO2Me ( )), 40.7 (AcCl ( )), 40.67 (AcCl (
40.61 (AcCl ( )), 40.5 (AcCl (
a
/
b
-
D
-gal-
4.57 (d, 1H, J¼10.9 Hz, Bn), 4.36 (t, 1H, J¼6.4 Hz, H-5), 4.25e4.15 (m,
2H, H-6, H0-6), 4.11 (s, 2H, AcCl), 4.07 (s, 2H, AcCl), 4.02 (dd, 1H,
J¼2.0 Hz, J¼10.0, H-3), 3.73 (dd, 1H, J¼2.9 Hz, J¼10.0 Hz, H-2), 3.34
(td, 1H, J¼4.0 Hz, J¼10.5 Hz, CHeO menthol), 2.41e2.35 (m, 1H,
CH(CH3)2 menthol), 2.06e2.03 (m, 1H, CHCH2CH menthol),
1.64e1.57 (m, 3H, CH2CH2 menthol), 1.43e1.35 (m, 1H, CHCH3),
1.30e1.25 (m, 1H, CHCH(CH3)2 menthol), 1.07e0.77 (m, 2H,
CHCH2CH menthol, CH2CH2 menthol), 0.91 (d, 3H, J¼6.5 Hz, CHCH3
menthol), 0.83 (d, 3H, J¼6.6 Hz, CH(CH3)2 menthol), 0.69 (d, 3H,
L
-ser-methyl ester 36. FT-IR (film): 1714, 1715,
7.37e7.27 (m), 5.58 (d, 2H,
)), 5.44 (d, J¼7.9 Hz,
)), 4.77e67 (m),
d
a
b
b
b
a
b)),
a)),
a
b)), 3.67 (s,
a
b
b
a
b
J¼6.7 Hz, CH(CH3)2 menthol). 13C NMR (CDCl3):
d
167.0, 166.9, 138.3,
)), 81.3
d
137.7, 128.3, 128.2, 128.0, 127.7, 127.6, 127.5, 99.4 (C-1 (
a
(b
a
b
b
b
a
a
(CHeO menthol), 75.78, 75.75, 73.8, 72.2, 70.1 (C-4), 66.2 (C-5), 63.9
(C-6), 48.7 (CHCH(CH3)2 menthol), 42.8 (CH2(CH)2), 40.7 (AcCl),
40.5 (AcCl), 34.2 (CH2CH2 menthol), 31.7 (CH(CH3) menthol), 24.5
(CH(CH3)2 menthol), 22.9 (CH2CH2 menthol), 22.4 (CHCH3), 21.0
(CH(CH3)2), 16.0 (CH(CH3)2. HRMS: calcd for C34H44Cl2O8Naþ
[MþþNa]: 673.2311; found: 673.2294.
(a
a
b
b
a
serine (
b
a
b
a
b
a
)),
)),
)),
a
b
a
b
a
a
b
b
)), 28.3 (t-Bu). HRMS: calcd for
C33H41Cl2O12NNaþ [MþþNa]: 736.1904; found: 736.1889.
b
anomer: [
a
]
20 ꢂ0.75 (c 0.53, CH2Cl2). FT-IR (film): 1763 cmꢂ1
D
(C]O). 1H NMR (CDCl3):
d 7.36e7.27 (m, 10H), 5.49 (d, 1H,
Acknowledgements
J¼3.2 Hz, H-4), 4.87 (d, 1H, J¼10.8 Hz, Bn), 4.71 (d, 1H, J¼11.2 Hz,
Bn), 4.67 (d, 1H, J¼10.8 Hz, Bn), 4.54 (d, 1H, J¼11.2 Hz, Bn), 4.44 (d,
~
^
This work was supported by Fundac¸ ao para a Ciencia e a Tec-
nologia (FCT) through grant PEst-OE/EQB/LA0004/2011. E.L. ac-
knowledges FCT for a PhD grant SFRH/47702/2008. We thank
CERMAX for the use of the NMR spectrometers, which were pur-
chased within the framework of the National Programme for Sci-
entific Re-equipment, contract REDE/1517/RMN/2005, with funds
from POCI 2010 (FEDER) and FCT. This work was motivated by
collaboration with Professor Helena Santos.
1H, J¼7.6 Hz, H-1 (
b
)), 4.28e4.12 (m, 4H, AcCl, H-6, H06), 4.05 (s,
2H, AcCl), 3.80 (t, 1H, J¼6.4 Hz, H-5), 3.57 (dd, 1H, J¼3.4 Hz,
J¼9.6 Hz, H-3), 3.50 (dd, 1H, J¼7.6 Hz, J¼9.5 Hz, H-2), 3.42 (td, 1H,
J¼4.2 Hz, J¼10.7 Hz, CHeO menthol), 2.34e2.26 (m, 1H, CH(CH3)2
menthol), 2.11e2.08 (m, 1H, CHCH2CH menthol), 1.67e1.64 (m, 2H,
CH2CH2 menthol), 1.39e1.24 (m, 2H, CHCH3, CHCH(CH3)2 men-
thol), 1.02e0.80 (m, 9H), 0.74 (d, 3H, J¼6.8 Hz, CH(CH3)2). 13C NMR
(CDCl3):
127.8, 127.6, 101.4 (C-1 (
d
167.2, 166.9, 138.4, 137.5, 128.4, 128.2, 128.17, 128.14,
)), 79.1 (CHeO menthol), 79.0 (C-3), 78.5
b
References and notes
(C-2), 75.3, 72.7, 69.2 (C-5), 68.9 (C-4), 63.4 (C-6), 47.9
(CHCH(CH3)2 menthol), 41.1 (CHCH2CH menthol), 40.8 (AcCl), 40.5
(AcCl), 34.3, 31.5 (CHCH3 menthol), 25.1 (CH(CH3)2), 23.0, 22.1,
21.0, 15.6.
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4.6.29. O-1-Cyclohexyl-4,6-di-O-chloroacetyl-2,3-di-O-benzyl-a/b-D-
galactopyranoside 35.
a
anomer: [
a]
20 þ94.0 (c 1.06, CH2Cl2). FT-IR
D
ꢀ
(film): 1744, 1762 cmꢂ1 (C]O). 1H NMR (CDCl3):
d 7.32e7.28 (m,
10H), 5.58 (d, 1H, J¼2.9 Hz, H-4), 4.98 (d, 1H, J¼3.6 Hz, H-1 (
a)), 4.77
6. Kumar, R.; Whitfield, D. M. J. Org. Chem. 2012, 77, 3724e3729.
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(d, 1H, J¼11.9 Hz, Bn), 4.71 (d, 1H, J¼10.7 Hz, Bn), 4.63e4.57 (m, 2H,
Bn), 4.31 (t, 1H, J¼6.4 Hz, H-5), 4.24e4.17 (m, 2H, H-6, H0-6),
4.14e4.06 (m, 4H, AcCl), 4.00 (dd, 1H, J¼3.3 Hz, J¼10.0 Hz, H-3),
3.73 (dd, 1H, J¼3.3 Hz, J¼10.0 Hz, H-2), 3.56e3.49 (m, 1H, CH
cyclohexanol), 1.92e1.74 (m, 4H), 1.58e1.53 (2H, m), 1.47e1.14 (m,
ꢀ
8. Bohe, L.; Crich, D. C. R. Chim. 2011, 14, 3e16.
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316, 201e205.
4H). 13C NMR (CDCl3):
127.7, 95.8 (C-1 (
d
167.0, 166.9, 138.3, 137.8, 128.3, 128.0, 127.8,
a
)), 76.4 (CH cyclohexanol), 75.7 (C-3), 75.3 (C-2),
73.3, 72.6, 70.1 (C-4), 66.0 (C-5), 63.8 (C-6), 40.7 (AcCl), 40.5 (AcCl),
16. Demchenko, A.; Rousson, E.; Boons, G.-J. Tetrahedron Lett. 1999, 40, 6523e6526.
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4411e4414.
33.3, 31.5, 25.5, 24.4, 24.1. HRMS: calcd for C30H36Cl2O8Naþ
[MþþNa]: 617.1685; found: 617.1675.
20
ꢂ
18. Polt, R.; Szabo, L.; Treiberg, J.; Li, Y.; Hruby, V. J. J. Am. Chem. Soc. 1992, 114,
b
anomer: [
a
]
þ22.7 (c 0.65, CH2Cl2). FT-IR (film): 1748,
D
10249e10258.
1760 cmꢂ1 (C]O). 1H NMR (CDCl3):
1H, J¼1.8 Hz, H-4), 4.90 (d, 1H, J¼10.8 Hz, Bn), 4.70 (t, 2H, J¼11.4 Hz,
)), 4.32
d 7.35e7.27 (m, 10H), 5.50 (d,
ꢂ
19. Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.;
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118, 6826e6840.
20. Baek, J. Y.; Lee, B.-Y.; Jo, M. G.; Kim, K. S. J. Am. Chem. Soc. 2009, 131,
17705e17713.
Bn), 4.54 (d, 1H, J¼11.2 Hz, Bn), 4.49 (d, 1H, J¼7.4 Hz, H-1 (
b
(dd, 1H, J¼6.9 Hz, J¼11.2 Hz, H-6), 4.23 (dd, 1H, J¼6.5 Hz, J¼11.2 Hz,
H0-6), 4.15 (dd, 2H, J¼15.1 Hz, J¼18.1 Hz, AcCl), 4.07 (s, 2H, AcCl),
3.82 (t, 1H, J¼6.7 Hz, H-5), 3.70e3.63 (m, 1H, CH cyclohexanol),
3.60e3.53 (m, 2H, H-2, H-3), 1.98e1.91 (m, 2H), 1.79e1.74 (m, 2H),
1.57e1.50 (m, 2H), 1.47e1.37 (m, 2H), 1.34e1.17 (m, 2H). 13C NMR
21. Ma, Y.; Lian, G.; Li, Y.; Yu, B. Chem. Commun. 2011, 7515e7517.
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27. Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, fifth ed.;
Elsevier.
(CDCl3):
127.7, 102.1 (C-1 (
70.0 (C-5), 68.7 (C-4), 63.2 (C-6), 40.8 (AcCl), 40.5 (AcCl), 33.6, 31.9,
25.5, 24.0, 23.9.
d
167.2,166.9,138.3,137.4,128.4,128.3,128.15,128.11,127.8,
)), 78.8, 78.6 (CH cyclohexanol), 78.5, 75.3, 72.6,
b
28. Li, Z.; Gildersleeve, J. G. J. Am. Chem. Soc. 2006, 128, 11612e11619.