Y. Miao et al. / Polymer 52 (2011) 5018e5026
5019
various carbohydrates using an organic catalyst has never been
systematically studied as faras we know. Itis thus ofinterest to assess
an organic catalyst for this purpose. Organocatalysis has gained
much interest these last years, and numerous catalysts such as
organic acids, pyridines, nitrogen bases, phosphines, carbenes, and
phosphazenes have been assessed for the ring-opening polymeri-
zation of cyclic esters [26,27]. We choose 4-dimethylaminopyridine
(DMAP) as a catalyst. Mild polymerization conditions produce pol-
ylactides with predictable molecular weights and narrow dispersity
using this catalyst combined to an alcohol as co-initiator [28]. We
report herein the synthesis of various carbohydrate-functionalized
polylactides using DMAP as a catalyst for the ring-opening poly-
merization of lactide. To the best of our knowledge, several polymers
synthesized in this study have never been reported in the literature.
chromatography (eluent gradient, EtOAc/Petroleum ether 1/5 to 1/
3), to afford the compound 2 as a white solid (11 g, 78%).
2.2.3. Methyl 2,3,4 tri-O-benzyl-a-D-glucopyranoside (3 or Glc-1r)
A solution of 2 (11 g, 0.015 mol), in a mixture acetic acid/water
(9/1) was stirred at reflux during 5 h. The solvent was co-evapo-
rated with toluene and the residue was purified by chromatography
(eluent gradient, EtOAc/Petroleum ether 1/3 to 1/1), to afford the
compound 3 as a white solid (4.2 g, 60%).
The diol 6 (referred to as Glc-diol hereafter) was obtained in a 3
steps synthesis from the Methyl-a-D-glucopyranoside (Scheme 2).
The 4e6 benzylidene 4 was obtained in acidic condition by the
reaction with benzaldehyde dimethyl acetal, and then the position
O-2 and O-3 were methylated to give the fully protected compound
5. Selective cleavage of the benzylidene in aqueous acidic condi-
tions allowed us to obtain the diol 6.
2. Experimental section
2.2.4. Methyl 4,6-O-benzylidene-
a-
D
-glucopyranoside (4)
2.1. Materials
To solution of methyl
a
a-D-glucopyranoside (2.11 g,
10.87 mmol) in dry acetonitrile (60 mL) was added benzaldehyde
dimethyl acetal (2.80 g, 18.40 mmol) and the solution acidified with
camphorsulfonic acid (catalytic amount). After stirring at room
temperature overnight the mixture was neutralized with triethyl-
amine and concentrated in vacuo to dryness using toluene as
a cosolvent. The resulting residue was recrystallized from ethyl
acetate e hexane to afford compound 4 as a white crystalline solid
(2.22 g, 76%).
L
-lactide and D,L-lactide (Aldrich) were recrystallized three times
from toluene followed by sublimation under vacuum at 85 ꢀC.
4-dimethylaminopyridine (DMAP - Aldrich) was co-evaporated
three times with toluene followed by sublimation under vacuum
at 85 ꢀC before use. Chloroform (Aldrich) was washed with water,
dried with CaCl2, put under reflux with P2O5 and distilled.
Dichloromethane was taken from a solvent purification system
(MBraun MB SPS 800). All reagents and anhydrous solvents used for
the synthesis of the carbohydrates initiators were purchased from
SigmaeAldrich and used directly without any further purification.
2.2.5. Methyl 4,6-O-benzylidene-2,3-di-O-methyl-a-D-
glucopyranoside (5)
Methyl 4,6-O-benzylidene-a-D-glucopyranoside (500 mg,
2.2. Carbohydrates synthesis
1.77 mmol) was dissolved in dry DMF (20 mL) under a nitrogen
atmosphere. To this was added 60% NaH suspended in oil (260 mg,
6.50 mmol) followed by the dropwise addition of methyl iodide
The different carbohydrates synthesized for this study are pre-
sented in Fig. 1. Classical carbohydrates protection and deprotection
(340 mL, 5.46 mmol) and the reaction was left to stir for 16 h under
strategies were used for this purpose. The Methyl-
a
-
D
-glucopyr-
a nitrogen atmosphere at room temperature. After this time, the
reaction was quenched with water (40 mL) and the aqueous layer
was washed with ethyl acetate (3 ꢁ 50 mL). The combined organic
layers were then washed with saturated NaHCO3 (3 ꢁ 50 mL) and
water (3 ꢁ 50 mL). The combined organic layers were dried
(MgSO4), filtered, and the solvent removed in vacuo and the
residue recrystallized from ethanol to furnish 5 as a white solid
(270 mg, 49%).
anoside is a commercially available compound used as received for
carbohydrate synthesis and purified by toluene distillation.
The compound 3 (referred to as Glc-1r hereafter) is easily ob-
tained in 3 steps from the Methyl-a-D-glucopyranoside after
selective tritylation of the O-6 position and benzylation of the
position O-2, O-3 and O-4 in well established conditions in a 66%
and 78% yield respectively (Scheme 1). The trityl group is selec-
tively removed by refluxing in a mixture of acetic acid and water to
give the compound 3 in a 60% yield.
2.2.6. Methyl 2,3-di-O-methyl-
a
-D-glucopyranoside (6 or Glc-diol)
To methyl 4,6-O-benzylidene-2,3-di-O-methyl-
a-D-glucopyr-
2.2.1. Methyl-6-O-trityl-
a
-
D
-glucopyranoside - (1)
-glucopyranoside (6.0 g, 0.03 mol),
anoside (250 mg, 0.81 mmol) was added a solution of 80% acetic
acid in water (15 mL) and the mixture was heated to 50 ꢀC. After
a period of 4 h, the reaction mixture was cooled, concentrated in
vacuo, and then co-evaporated with toluene (3 ꢁ 20 mL). The
residue was recrystallized from ethyl acetate e Petroleum ether to
give the desired compound 6 as a white solid (73 mg, 41%).
The required compound 10 (referred to as Glc-2r), partially
A solution of methyl-
a-D
tritylchloride (11 g, 1.2 eq.), triethylamine (8 mL), and DMAP
(290 mg, 0.5 eq.) in DMF (50 ml) was stirred overnight at room
temperature under nitrogen. After 12 h stirring, the reaction
mixture was poured into ice-water and extracted with dichloro-
methane. The organic extracts were washed with water, and dried
with magnesium sulfate. After removal of the solvents, the solid
was recrystallized from ethanol to give 8.9 g, (66%) of compound 1
as a white solid.
protected benzyl-b-D-glucopyranoside, was prepared in 6 steps
synthesis from commercial glucose pentaacetate by the orthoester
procedure (Scheme 3). The O-benzyl orthoester 7 was obtained
under LemieuxeMorgan conditions, the acetyl groups of 7 were
replaced by benzyl groups, and the orthoester 8 was rearranged
2.2.2. Methyl 2,3,4 tri-O-benzyl-6-O-trityl-a-D-glucopyranoside (2)
A solution of 1 (8.9 g, 0.03 mol) in DMF was added at 0 ꢀC to NaH
(60% in mineral oil, 3.6 g, 4.5 eq.). After 30 min BnBr (10.5 ml,
4.5 eq) was added and the reaction mixture was stirred overnight at
room temperature. The reaction was then quenched with water
(40 mL) and the aqueous layer was washed with ethyl acetate
(4 ꢁ 50 mL). The organic extracts were dried with magnesium
sulfate. After removal of the solvents, the residue was purified by
into the corresponding benzyl-
trimethylsilyl triflate followed by de-O-acetylation at O-2.
b-glycoside 10 by treatment with
2.2.7. 3,4,6-Tri-O-acetyl-a-D-glucopyranose 1,2-(benzyl
orthoacetate) (7)
Glucose pentaacetate (5 g, 0.013 mol) was dissolved in a solu-
tion of HBr (33%) in acetic acid (15 mL), after 3 h at room