Synthesis of carbohydrate-grafted glycopolymers using a catalyst-free, perfluoroarylazide-mediated fast staudinger reaction

Article abstract of DOI:10.3390/molecules24010157

Glycopolymers have gained increasing importance in investigating glycan-lectin interactions, as drug delivery vehicles and in modulating interactions with proteins. The synthesis of these glycopolymers is still a challenging and rigorous exercise. In this

Full text of DOI:10.3390/molecules24010157

molecules
Article
Synthesis of Carbohydrate-Grafted Glycopolymers
Using a Catalyst-Free, Perfluoroarylazide-Mediated
Fast Staudinger Reaction
William Ndugire, Bin Wu and Mingdi Yan *
Department of Chemistry, University of Massachusetts Lowell, 1 University Ave., Lowell, MA 01854, USA;
William_Ndugire@student.uml.edu (W.N.); Bin_Wu1@student.uml.edu (B.W.)
* Correspondence: mingdi_yan@uml.edu; Tel.: +978-934-3647
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 5 December 2018; Accepted: 30 December 2018; Published: 3 January 2019
Abstract: Glycopolymers have gained increasing importance in investigating glycan-lectin
interactions, as drug delivery vehicles and in modulating interactions with proteins. The synthesis
of these glycopolymers is still a challenging and rigorous exercise. In this regard, the highly
efficient click reaction, copper (I)-catalyzed alkyne-azide cycloaddition, has been widely applied
not only for its efficiency but also for its tolerance of the appended carbohydrate groups. However,
a significant drawback of this method is the use of the heavy metal catalyst which is difficult to
remove completely, and ultimately toxic to biological systems. In this work, we present the synthesis
of carbohydrate-grafted glycopolymers utilizing a mild and catalyst-free perfluorophenyl azide
(PFPA)-mediated Staudinger reaction. Using this strategy, mannose (Man) and maltoheptaose (MH)
were grafted onto the biodegradable poly(lactic acid) (PLA) by stirring a PFAA-functionalized
PLA with a phosphine-derivatized Man or MH in DMSO at room temperature within an hour.
The glycopolymers were characterized by 1H-NMR, 19F-NMR, 31P-NMR and FTIR.
Keywords:
Glycopolymer; post-polymerization functionalization; perfluoroaryl azides;
Staudinger reaction
1. Introduction
Carbohydrates are not only the core of metabolism in many biological systems, but are
also integral in many cells as structural [
Synthetic carbohydrate-functionalized polymers, i.e., glycopolymers, has become an important
tool in fundamental glycobiology research, and in biomedical applications such as sensing [ ],
drug delivery [ ], and cryopreservation [ ]. Synthetic glycopolymers can be categorized broadly
into two types based on the mode of synthesis: (1) polymerization of carbohydrate-derivatized
monomers (such as allyl [ ], acrylamide [10] and acrylate [11]), and (2) grafting of carbohydrates
onto a polymer backbone [12 17]. The latter technique, typically referred to as post-polymerization
1], communication [2], and recognition [3] elements.
4,5
6
7,8
9
–
modification, allows facile synthesis of the polymer backbone and control over carbohydrate grafting
density. To successfully graft carbohydrates onto the polymer, the conjugation reaction must be highly
efficient, of high yield, and tolerant of the functional groups on the polymer. The popular ‘click’ type
of reactions, particularly the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC), meet these
requirements and have been applied in the synthesis of glycopolymers by post-polymerization and in
glycosylation of surfaces [18–20]. This reaction tolerates a wide variety of carbohydrate side groups.
Analytically, it offers the advantage in the form of the distinct chemical shift of the triazole proton
1
in H-NMR that facilitates straightforward characterization [21
,
22]. However, a drawback of this
reaction is the necessity of Cu (I) catalyst that has proved difficult to be removed completely from the
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products. While at least 2–5 mol% of Cu (I) is required to achieve a respectable reaction rate, even
small amounts of residual metal in the final product has been shown to denature proteins and cause
oxidative damage to cells [21,23,24]. Other click-type reactions that do not require metal catalysts
include SPAAC (strain-promoted azide-alkyne cycloaddition), azide-aryne based “benzyne click”
reaction, and iEDDA (inverse electron demand Diels–Alder) reaction [25
applied directly in the synthesis of glycopolymers.
–27], but these have not been
Another click-type reaction is the phosphine-azide Staudinger reaction [28]. The recent
improvement by Bertozzi via the introduction of an ester trap [29] rendered this bioorthogonal
reaction suitable for in vivo conjugations [30
,31] and in oligosaccharide metabolic engineering for
cell-surface labelling [29 32]. Despite its versatility, the Staudinger ligation suffers from a slow
,
reaction rate. To overcome this issue, we have recently shown that by using an electron-deficient
perfluoroaryl azide (PFPA), the rate of reaction can be increased up to four orders of magnitude
to give an iminophosphorane product [33]. The rate enhancement can be attributed to the highly
electronegative F atoms lowering the LUMO of PFPA thus accelerating the reactions with dienophiles
and nucleophiles [34–37]. In addition, the PFPA-iminophosphorane formed in this reaction was stable
and not readily hydrolyzed in vivo, as demonstrated in the metabolic labeling of A549 cells [33].
The fast reaction rate and high yield make this PFPA-Staudinger reaction an excellent candidate for
polymerization. In an earlier work, we demonstrated that the reaction of bis-PFPA and a bisphosphene
occurred at room temperature in 30 min to yield poly(iminophosphorane) having molecular weight
of over 59,000 and a narrow dispersity of 1.1–1.2 [38]. In this work, we applied this reaction in
the post-polymerization synthesis of carbohydrate–grafted glycopolymers. By taking advantage of
the fast reaction rate, mild reaction conditions, and high chemoselectivity of the PFPA-Staudinger
reaction, we conjugated maltoheptaose and mannose onto poly(lactic acid) (PLA), a biocompatible
and biodegradable glycopolymer.
2. Results and Discussion
While the availability of pendant functional groups like the hydroxyl on the polymer would be
suited for condensation with a carboxyl-modified sugar, this strategy is less desirable as it requires the
use of coupling agents that can be difficult to remove like DCC/DMAP [39] or strong acid [40] that
would hydrolyze the polymer.
Our design for grafting carbohydrates to PLA was to functionalize PLA with PFPA followed by
reaction with a phosphine-derivatized carbohydrate. A PLA-co-PLA-PFPA copolymer is synthesized so
that the density of PFPA and the carbohydrate can be varied and controlled. A hydroxy-functionalized
polylactide copolymer
carbohydrate. The benzyl-derivatized lactide monomer
Ring-opening copolymerization of lactide and lactide
catalyst gave polylactide copolymer in 74% yield [
so as to control the grafting density of carbohydrate on the PLA polymer. In this work, the polymer
obtained had a monomer ratio (m:n) of 1:22 for and after copolymerization. Deprotection of the
benzyl group on gave the hydroxy-functionalized polylactide copolymer in 63% yield [ ]. The m:n
ratio was calculated from the 1H-NMR spectrum of
(Figure 1A) by taking the ratio of the methine
4 (Scheme 1A) was synthesized to conjugate PFPA and subsequently graft the
1
was synthesized according to Scheme 1B.
1
2 in toluene using stannous octoate as the
4
5]. The ratio of the two monomers can be varied
1
2
3
4
5
4
protons (H-a and H-c) that overlap at 5.2 ppm. The integral value of the H-a is equivalent to methylene
protons H-b/2. Subtraction of this value from the overlapped (H-a + H-c) gives the integration of H-c
and therefore H-a/H-c can be calculated.

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Scheme 1. Synthesis of (A) hydroxy-functionalized polylactide copolymer 4, and (B) lactide
monomer 1.
(A)
4
(B)
5
1
Figure 1. H-NMR spectra of copolymers 4 (A) and 5 (B) in CDCl3.
PFPA-functionalized PLA copolymer
5
was prepared by esterification of
4
with
carboxy-derivatized PFPA using DCC and a catalytic amount of DMAP giving
(Scheme 2).
5 in 86% yield

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Scheme 2. Synthesis of PFPA-PLA copolymer 5.
The 1H-NMR spectrum of
5
showed a near complete reaction as demonstrated by a marked shift
of the methylene proton H-b from 4.05 ppm to 4.83 ppm (Figure 1). No degradation of the copolymers
to the free lactic acid monomer was observed during the reaction, as evidenced by the absence of
peaks at ~1.2 ppm which belongs to the free lactic acid. In addition, the characteristic azide peak at
2133 cm−1 appeared in the Fourier transform-infrared spectroscopy (FTIR) spectrum of copolymer 5
(Figure 2).
4
5
Figure 2. FTIR spectra of PLA copolymers 4 and 5.
The phosphine-derivatized carbohydrates were prepared from an amine-derivatized carbohydrate
and the NHS-functionalized phosphine (Scheme 3). A monosaccharide, D-mannose (Man),
and an oligosaccharide, D-maltoheptaose (MH), were used as model carbohydrates in this study.
The amine-Man
detailed procedures in SI) [41]. The amine-MH
6
was synthesized according to previously reported procedure (see Scheme S2 and
was synthesized following the procedure in Scheme
7
S1 (see detailed procedures in SI). Reaction of NHS-functionalized triphenylphosphine with excess of
6 or 7 in DMSO at room temperature gave the triphenylphosphine-derivatized Man (8) or MH (9).

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OH
O
HN
O
P
O
N
P
F
O
N
F
O
P
F
O
O
5
O
O
NH2
O
O
HO
N
HO
F
H
DMSO, r.t., 3 h
DMSO, r.t., 1 h
O
O
6/7
O
8/9
O
n
m
10/11
OH
O
HO
HO
OH
O
OH
O
HO
HO
HO
OH
O
HO
O
S
HO
HO
O
O
O
O
HO
5
O
NH2
O
NH2
HO
7
6
Scheme 3. Synthesis of phosphine-derivatized mannose
8
and maltoheptaose
9, and subsequent
grafting to PFPA-PLA copolymer
5 to yield mannose-polymer 10 and maltoheptaose-polymer
11, respectively.
To prepare Man- or MH-grafted PLA 10 and 11, copolymer
5 was added directly to the reaction
mixture of or in DMSO and stirred at room temperature for 1 h. The products were purified by
8
9
dialysis for 48 h and dried by lyophilization. After the carbohydrate was grafted, the aromatic and the
carbohydrate peaks appeared in the 1H-NMR spectra of 10 and 11 at 7.5–7.7 ppm and 3.0–6.0 ppm,
respectively (Figure 3). In the 31P-NMR spectra of the products (Figure 4), a new peak was observed at
13 ppm after conjugation of the phosphine onto the copolymer. The absence of any peaks higher than
13 ppm confirmed the absence of byproducts resulting from the oxidation of phosphine.
The yield of conjugation was obtained from the 1H-NMR spectrum by taking the ratio of peak
integration of the phenyl protons (Ph) at 7.5–7.7 ppm and the methyl protons H-b at 1.48 ppm, together
with the previously calculated monomer ratio of m:n = 1:22 to give the formula:
!
Ph
× 22
3
14
(%)coupling yield =
× 100
(1)
H−b
Using this equation, the yields were calculated to be 25% and 35% for the Man-grafted
PLA copolymer 10 and MH-grafted PLA copolymer 11, respectively (see Figures S5 and S6 for
peak integrations).

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b
a
OH
carbohydrate
O
Ph
HN
Ph
Ph
O
P
Ph
F
N
F
F
O
O
carbohydrate
F
O
O
O
a
b
O
n
m
Figure 3. 1H-NMR spectra of Man- and MH-grafted copolymers 10
(top) and 11 (bottom) in DMSO-d6.
Figure 4. 31P-NMR spectra of copolymer 10 (top) and 11 (bottom) in DMSO-d6.
3. Conclusions
In this work, we utilized an electron-deficient perfluorophenyl azide-mediated fast
Staudinger reaction to efficiently synthesize carbohydrate grafted-polylactide glycopolymers
by post-polymerization modification. A polylactide copolymer was synthesized by stannous
octoate-catalyzed cationic ring-opening copolymerization, which was subsequently modified
with PFPA. Conjugation with a phosphine-derivatized carbohydrate yield mannose- and
maltoheptaose-grafted polylactide glycopolymers in 35% and 25% yields. These yields are comparable
to those obtained by other groups in post-polymerization synthesis of glycopolymers using other
techniques [42,43]. The main limiting factor of efficient grafting being steric hindrance between ligands
and the polymer backbone restricting access to the reactive sites. In our work, this occurs between
carbohydrate-phosphines reaction with the pendant PFPA groups, which is further complicated by the
difference in polarity between the PLA and D-mannose/maltoheptaose. However, the grafting reaction
is fast, carried out under mild conditions without the use of any catalyst. This metal catalyst-free
approach to glycopolymer synthesis is significant as it eliminates the concerns over the potential
toxicity of heavy metals, making these glycopolymers attractive for biomedical applications.

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4. Experimental Procedures
4.1. Materials and Instruments
All chemicals and solvents were purchased from Sigma-Aldrich (St. Louis, MO, USA),
TCI America (Portland, Oregon, USA) or Fisher Scientific (Hampton, NH, USA), and were used
without further purification unless otherwise noted. Dichloromethane (DCM), dimethylformamide
(DMF), ethyl acetate (EtOAc) and dimethyl sulfoxide (DMSO) were purified by distillation over
CaH2. Deuterated solvents were acquired from Cambridge Isotope Lab., Inc. (Tewksbury, MA, USA).
Amberlite IRC-120H+ resin was activated by washing with NaOH and HCl, followed by water, ethanol
and toluene.
Nuclear magnetic resonance spectroscopy data were collected on either a Bruker 500 MHz
spectrometer (1H-NMR) or a Bruker 200 MHz spectrometer (19F- and 31P-NMR) (Bruker Corporation,
Billerica, MA, USA). FT-IR spectra were recorded on a Nicolet 6700 FT-IR spectrometer (Thermo Fisher
Scientific, Waltham, MA, USA).
4-Azido-2,3,5,6-tetrafluorobenzoic
following our previously developed protocol
1-(2-(2-(2-aminoethoxy)ethoxy)ethoxy- -D-mannopyranoside
acid
(PFPA-COOH)
44 45]. The detailed synthesis of
Scheme S2) 41 46 and
, Scheme S1) can be found in the
was
synthesized
[
,
α
(
6,
[ , ]
1-(2-(2-(2-aminoethoxy)ethoxy)ethoxy-maltoheptaoside (
Supporting Information.
7
4.2. Synthesis of 3-benzyloxy-2-hydroxypropionic acid (II)
Synthesized according to literature procedure [47]. To a 200 mL of 0.7 M aqueous solution of
trifluoroacetic acid, H-Ser(benzyl)-OH ( , 10.0 g, 52 mmol) was added, and the mixture was stirred at
I
room temperature until all solids were dissolved. Then, 50 mL of aqueous NaNO2 (5.3 g, 77 mmol)
was added dropwise with a syringe pump under Ar protection and the reaction was stirred for another
3 h. After confirming of the consumption of starting material by TLC, NaCl (10 g) was added and
the mixture was extracted with ethyl acetate three times followed by washing with brine and dried
over MgSO4. After passing through a flash column using CH2Cl2/MeOH/AcOH (v/v/v 100:8:1),
compound II was obtained (7.2 g, 72%).3 1H-NMR (500 MHz, DMSO-d6)
δ 7.35–7.26 (m, 5H, Ar-H),
4.60 (s, 2H, PhCH2O-), 4.38 (s, 1H, -OCH2CH(COOH)O-) 3.83 (d, J = 15 Hz, 2H, -OCH2CH-). IR: 3324,
3070, 3032, 2925, 2871, 2645, 2537, 1693, 1495, 1455, 1412, 1379, 1274, 1225, 1202, 1161, 1019, 1001, 973,
926, 827, 791, 732, 610, 529 cm−1
.
4.3. Synthesis of 3-(benzyloxy)-2-(2-bromopropanoyloxy)propanoic acid (III)
Synthesized per literature [47]. Compound II (10.0 g, 51 mmol) and 2-bromopropionyl chloride
(6.3 mL, 61.2 mmol) were mixed in a 50-mL round-bottom flask backfilled with Ar. The reaction
◦
mixture was heated to 70 C and stirred for 6 h. Upon the completion of the reaction, the crude product
was heated at 60 ◦C under reduced pressure to remove unreacted 2-bromopropionyl chloride and
2-bromopropionyl acid. After cooling to room temperature, the residue was washed with water and
extracted with ethyl acetate 3 times. The combined organic phase was washed with brine and dried
over MgSO4. Compound III was obtained as a brown oil after further purification by flash column
1
CH2Cl2/MeOH/AcOH (v/v/v 100:2:0.5) (12.6 g, 75%). H-NMR (500 MHz, CDCl3): 7.35–7.25 (m,
5H, Ar-H), 5.34–5.32 (m, 1H, -OCH2CH(COOH)O-), 4.62–4.38 (m, 3H, PhCH2O- and -OCCH(Br)CH3),
3.97–3.85 (m, 2H, -OCH2CH-), 1.88–1.83 (m, 3H, -CH(Br)CH3). IR: 3442, 3031, 2928, 2871, 1732, 1452,
1362, 1211, 1155, 1097, 1070, 985, 910, 738, 697, 610 cm−1
.
4.4. Synthesis of 3-(benzyloxy)-2-(2-iodopropanoyloxy)propanoic acid (IV)
Prepare following literature procedures [47]. Compound III (8.0 g, 24 mmol) and potassium
iodide (40 g, 0.24 mol) were mixed with 100 mL of anhydrous acetone. The mixture was heated at
60 ◦C overnight under Ar. The solid salt was removed by passing through a layer of Celite® and the

Molecules 2019, 24, 157
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filtrate was concentrated under vacuum. Ethyl acetate was added to the oily residue and the solution
was filtered again to remove trace potassium iodide/potassium bromide. The organic phase was
washed with 2 M aq. Na2S2O3 for 3 times and dried over MgSO4. After removing the solvent from
the filtrate, the product IV was obtained and used directly in the next step without purification (7.5 g,
82%). 1H-NMR (500 MHz, CDCl3):
δ 10.26 (s, 1H, -COOH), 7.50–7.16 (m, 5H, Ar-H), 5.39 (m, 1H,
-OCH2CH(COOH)O-), 4.84–4.41 (m, 3H, PhCH2O- and –OCCH(Br)CH3), 3.94 (dd, J = 48.3, 10.4 Hz,
2H, -OCH2CH-), 2.29–1.87 (m, 3H, -CH(I)CH3). IR: 2923, 1728, 1496, 1452, 1362, 1197, 1124, 1094, 1043,
1026, 977, 909, 737, 697, 633, 603, 582, 570, 563, 554, 548, 538, 529, 526 cm−1
.
4.5. Synthesis of 3-(benzyloxymethyl)-6-methyl-1,4-dioxane-2,5-dione (Monomer 1)
Synthesized as described in literature [ ]. A solution of compound IV (10.0 g, 26.8 mmol) in
7
dry CH2Cl2 (100 mL) was added dropwise to refluxing dry acetone (1 L) containing DIEA (8.8 mL,
53.6 mmol) under Ar. It took 10 h to finish the addition and the reaction was refluxed for another
hour. The solvents were removed under reduced pressure and ether was added to dissolve the crude
product. Insoluble ammonium iodide was filtered and the filtrate was concentrated. After purification
by flash column chromatography using hexanes/ethyl acetate (v/v 4:1), the title compound
obtained as a yellow oil (2.1 g, 31%). The diastereomers were used directly without separation.
1H-NMR (500 MHz, CDCl3): (SS)
7.34–7.26 (m, 5H, Ar H), 5.24–5.04 (2H; -OCCH(CH2O-)O- and
- OCCH(CH3)O-), 4.61–4.56 (2H; ArCH2O-), 3.97 (2H; -OCH2CH-), 1.63 (3H; -CHCH3). IR: 2993 (w,
1 was
δ
ν
s(aromatic C-H)), 2942 (w,
ν
as(-CH2- and –CH3)), 2872 (w,
νs(-CH2- and aliphatic -CH-)), 1748 (vs,
ν
s(ester C=O)), 1453 (m,
δ
s(-CH2-)), 1365 (w), 1268 (w), 1182 (s), 1084 (vs), 1046 (m), 865 (w), 739 (m,
ω(aromatic C-H)), 698 (m, τ(aromatic ring)) cm−1
.
4.6. Synthesis of PLA copolymer 3
Monomer 1 (1.0 g, 4.0 mmol), recrystallized L-lactide (2, 1.0 g, 6.9 mmol) and Sn(Oct)2 (10 mg in
1 mL anhydrous toluene) were added into a 5-mL round-bottom flask. The mixture was heated to
70 ◦C under vacuum for 1 h. Ar was filled in the flask and the temperature was increased to 140 ◦C.
The mixture was stirred until the stir bar stopped moving. After cooling to room temperature, the solid
was dissolved in CH2Cl2 and hexanes was added. The precipitate was re-dissolved in CH2Cl2, and
this dissolution/precipitation was repeated three times, and the precipitate was finally dried under
vacuum to give copolymer 1c as a dark brown solid (1.48 g, 74%). 1H-NMR (500 MHz, CDCl3)
δ
5.20 (-OCH2CH(COOH)O- and -OCH(CH3)CO-), 4.59 (PhCH2O-), 3.90 (-OCH2CH-), 1.56 (-CHCH3).
IR (ATR) 2942, 1747, 1497, 1452, 1365, 1192, 1084, 1046, 865, 739, 698 cm−1
.
4.7. Synthesis of PLA copolymer 4
Following literature synthesis [47]. Copolymer
3 (1.0 g) was dissolved in 50 mL ethyl
acetate/methanol (3:1), and catalytic amount of Pd/C was added. The mixture was purged with Ar for
20 min and filled with H2 under vigorous stirring. After 12 h, the solution was passed through a pile of
Celite to remove Pd/C and the filtrate was dried under vacuum to give copolymer
4 as a light brown
1
solid (630 mg, 63%). H-NMR (500 MHz, CDCl3):
δ 5.0–5.5 (-OCH(CH2OH)CO- and -OCH(CH3)CO-),
3.78 (HOCH2CH-), 1.49 (-CHCH3). IR (ATR): ~3500 (br, w), 2995 (m), 2945 (m), 1744 (s), 1452 (m), 1380
(w), 1182 (s), 1129 (s), 1084 (s), 864 (m), 743 (m) cm−1
.
4.8. Synthesis of PFPA-grafted PLA copolymer 5
Copolymer
4 (100 mg) and PFPA-COOH (20 mg, 0.09 mmol) were added together with DCC
(41 mg, 0.2 mmol) and DMAP (2.4 mg, 0.02 mmol) to 10 mL anhydrous dichloromethane under Ar,
and the mixture was stirred at room temperature overnight. The solution was then concentrated
to 3 mL and was poured into 50 mL of hexane/methanol (v/v 9:1) to precipitate the crude product.
The yellow precipitate was dissolved in dichloromethane and was precipitated in hexane/methanol.
This dissolution/ precipitation was repeated for a total of 3 times. Finally, the precipitate was

Molecules 2019, 24, 157
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dried under vacuum to give PFPA-grafted PLA copolymer
5
as a bright yellow solid (104 mg,
86%). 1H-NMR (500 MHz, CDCl3):
δ 5.56 (-OCH(-CH2OCOPFPA)CO-), 5.19 (-OCH(CH3)CO),
4.83 (-OCH2(OCOPFPA)CH-), 1.59 (-CHCH3). 19F-NMR (188 MHz, CDCl3): δ −137.5 (doublet),
−
149.62 (singlet). FTIR (ATR): 2995 (m), 2945 (m), 2133 (m), 1747 (s), 1648 (w), 1563 (m), 1490 (s), 1381
(m), 1363 (m), 1258 (s), 1182 (s), 1128 (s), 1082 (s), 1044 (s), 957 (w), 865 (m), 751 (s), 667 (m) cm−1
4.9. Synthesis of Man- or MH-grafted PLA glycopolymers 10 or 11
General Procedures
.
The mole ratio of N-succinimidyl 2-(diphenylphosphanyl)benzoate:amine-carbohydrate: PFPA in
polymer 10 or 11 was set as 4:6:1. N-Succinimidyl 2-(diphenylphosphanyl) benzoate and amine-Man
6
or amine-MH
7
were added to 5 mL anhydrous DMSO, and the solution was stirred for 3 h. Then,
. Afterwards, the mixture was
the mixture was added to a DMSO solution containing copolymer
5
stirred for another hour. The mixture was transferred into a dialysis tube (molecule cutoff: 3500) and
dialyzed in water for 2 days. Finally, the product was obtained after lyophilization.
1
Polymer 10: yellow powder (yield: 92%). H-NMR (500 MHz, DMSO-d6):
δ 7.70–7.20 (Ar-H),
5.21 (-OCH(CH3)CO-), 5.80–3.00 (carbohydrate), 1.48 (-CHCH3); IR (ATR): 3362, 2945, 1747, 1651, 1489,
1451, 1381, 1515, 1184, 1082, 1043, 865, 749, 695 cm−1
.
1
Polymer 11: a white powder (yield: 94%). H-NMR (500 MHz, DMSO-d6): 7.75–7.40 (Ar-H), 5.21
(-OCH(CH3)CO-), 4.90–3.00 (carbohydrate), 1.48 (-CHCH3); IR (ATR): 3371, 2945, 1748, 1651, 1503,
1452, 1381, 1133, 1084, 865, 752, 695 cm−1
.
Supplementary Materials: Supporting information including detailed synthetic protocols, 1H, 19F and 31P NMR
and IR spectra are available online.
Author Contributions: The authors contributed as follows M.Y., B.W. and W.N. in conceptualization, visualization
and methodology and synthesis, W.N. and M.Y. in writing—original draft preparation, M.Y., B.W. and W.N. in
writing—review and editing; supervision, project administration, and funding acquisition, M.Y.
Funding: This study was supported in part by the National Institute of Health (R15GM128164) and National
Science Foundation (CHE-1808671).
Acknowledgments: The authors thank Xuan Chen for his help in the synthesis.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are not currently available from the authors.
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