Synthesis of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction

Article abstract of DOI:10.1016/j.tet.2016.12.035

Carotenoid pentynoates were coupled to protected and unprotected sugar azides via an azide-alkyne click-reaction using bis-triphenylphosphano-copper(I)-butyrate (C₃H₇COOCu(PPh₃)₂) complex. Protected sugars delivered the conjugates with excellent yields, whereas with unprotected ones amphipathic carotenoid-sugar derivatives were obtained in good or moderate yields in a simple way.

Full text of DOI:10.1016/j.tet.2016.12.035

Accepted Manuscript
Synthesis of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction
Attila Agócs, Éva Bokor, Anikó Takátsy, Tamás Lóránd, József Deli, László Somsák,
Veronika Nagy
PII:
S0040-4020(16)31323-0
10.1016/j.tet.2016.12.035
TET 28327
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 September 2016
Revised Date: 1 December 2016
Accepted Date: 16 December 2016
Please cite this article as: Agócs A, Bokor E, Takátsy A, Lóránd T, Deli J, Somsák L, Nagy V, Synthesis
of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction, Tetrahedron (2017), doi:
10.1016/j.tet.2016.12.035.
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Synthesis of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction
Attila Agócs, Éva Bokor, Anikó Takátsy, Tamás Lóránd, József Deli, László Somsák and Veronika
Nagy

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Synthesis of carotenoid-monosaccharide
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Attila Agócsa, Éva Bokorb, Anikó Takátsya, Tamás Lóránda, József Delia,c, László Somsákb and Veronika Nagya
a University of Pécs, Department of Biochemistry and Medical Chemistry, Szigeti út 12, H-7624 Pécs, Hungary
b University of Debrecen, Department of Organic Chemistry, POB 400, H-4002 Debrecen, Hungary
c University of Pécs, Department of Pharmacognosy, Rókus u. 2, H-7624 Pécs, Hungary

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction
Attila Agócsa, Éva Bokorb, Anikó Takátsya, Tamás Lóránda, József Delia,c, László Somsákb and Veronika
Nagya
a University of Pécs, Department of Biochemistry and Medical Chemistry, Szigeti út 12, H-7624 Pécs, Hungary
b University of Debrecen, Department of Organic Chemistry, POB 400, H-4002 Debrecen, Hungary
c University of Pécs, Department of Pharmacognosy, Rókus u. 2, H-7624 Pécs, Hungary
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Carotenoid pentynoates were coupled to protected and unprotected sugar azides via an azide-
alkyne click-reaction using bis-triphenylphosphano-copper(I)-butyrate (C3H7COOCu(PPh3)2)
complex. Protected sugars delivered the conjugates with excellent yields, whereas with
unprotected ones amphipathic carotenoid-sugar derivatives were obtained in good or moderate
yields in a simple way.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
amphipathic
carotenoid pentynoates
glycosides
click reaction
unprotected sugar
———
Corresponding author. Tel.: +36-72-536-001/31864 ext.; fax: +36-72-536-225; e-mail: vera.nagy@aok.pte.hu

2
Tetrahedron
1. Introduction
hydroxy carotenoids were planned to be esterified with propiolic
ACCEPTED MANUSCRIPT
acid according to Steglich’s method,16 however, in these
reactions unstable products formed in low yields. Hence, 4-
pentynoic acid was the reagent of choice, which, in the presence
of DCC and DMAP, gave crystalline carotenoid pentynoates in
acceptable yields (Table 1).
Glycosides and glycosyl esters of carotenoids have been
described as naturally occurring amphipathic molecules. Many of
them were found in extremophile microorganisms, and they are
believed to be partially responsible for the resistance of these
creatures against heat and/or high osmotic pressure.1
Thermoxanthins, carotenoid glycoside-branched fatty acid esters
of diverse structures, were investigated thoroughly as main
pigments of Thermus bacteria. The polar sugar moieties and the
length of these carotenoid derivatives facilitate their lateral
arrangement in cell membranes.2 Once incorporated in the
membrane they could change its fluidity and can act as
antioxidants, as well. Carotenoids are known as good
antioxidants, whilst hydrophilic carotenoids are even more so,3
therefore carotenoid glycosides in the cell membrane can play a
role in the inhibition of oxidative stress. Since carotenoid
glycosides and esters are of limited availability from natural
sources, their effect on oxidative stress has not been studied yet.
For the chemical synthesis of carotenoid glycosides only a
few examples were described. A classical Königs-Knorr reaction
with zeaxanthin resulted in a complex mixture containing mono-
and diglucosides in low yields.4 The total synthesis of
thermoxanthins via selective glucosidation of hydroxy-β-ionone
has also been reported, and their effect on the stability of cellular
phospholipid membrane was examined.5 Glycosides of
astaxanthin and adonixanthin have been prepared by recombinant
DNA techniques using modified E. coli.6 The target compounds
in the above procedures were obtained in very low overall yields
(2-8%) and/or required complicated isolation.
A new tentative approach for the synthesis of carotenoid
thioglucosides has been reported using β-carotene and
isozeaxanthin as starting materials.7 The products contained the
sugar moieties in position 4 and 4’ of the carotenoid ring, and
after deprotection, could be regarded as mimetics of naturally
occurring thermoxanthins. Some protected 3-O-glycosyl-
carotenoids have also been prepared in good or moderate yields
by modern glycosylation methods.8 These methods surpassed the
previous procedures in terms of yields, but cannot be considered
as a general methodology for all kind of carotenoids. Another
problem arose during deprotection of the acetyl/benzoyl
protected sugar moieties, the unprotected glycosides could be
obtained only in low yields.
Table 1. Preparation of 4-pentynoate esters of hydroxy
carotenoids
Carotenoid (Car-OH)
Product (yield)
5 mono-
pentynoate
(75%)a
6 dipentynoate
(53%)
7 mono-
pentynoate (90%)
8 dipentynoate
(59%)
a Yield calculated for two steps starting from 8’-apo-β-carotenal.
8’-Apo-β-carotenol pentynoate (5) was chosen as a model
compound for the preliminary experiments. Coupling with
peracetyl glycosyl azide (9) in the presence of CuI as catalyst was
not observed in dichloromethane, toluene/i-propanol or DMF,
even with triethylamine or ethyl-diisopropylamine (EDIPA).10
The use of bis-triphenylphosphano-copper(I)-butyrate in
dichloromethane, however, resulted in the formation of the
triazole 15 (Table 2). Under the same conditions other protected
and unprotected sugar azides (10-14) were reacted with 8’-apo-β-
carotenol pentynoate (5) giving the target triazoles (16-20). With
the exception of peracetylated 6-deoxy-6-triazolyl-glucose
derivative (18), the acyl protected glycosyl triazoles formed in
excellent yields.
Keeping the reactants in solution was described to be a crucial
requirement for a successful click-reaction.9,17 However, in our
experiments dichloromethane was found to be a suitable solvent
even in reactions with unprotected sugars that are insoluble in
this solvent, they delivered the products in lower but still
acceptable yields. These conditions allow the direct synthesis of
unprotected glycosyl triazoles, otherwise selective deacylation of
the sugar would be hard to achieve.
In order to couple monosaccharides to carotenoids with good
yields, a new approximation was chosen, which would include
unprotected sugars and would give similar amphipathic
compounds in one single step. Therefore, we planned to use the
copper(I) catalyzed (3+2) azide-alkyne cycloaddition reaction
(CuAAC) for the coupling of sugar azides to carotenoid
pentynoates. Click chemistry, requiring mild reaction conditions
and providing a high yield of products,9 proved to be an
appropriate choice for the very sensitive carotenoids, which have
previously been coupled with polyethyleneglycol azides in click
reactions.10
With 1-carboxamido-β-D-glucopyranosyl azide (14) the
conversion of 8’-apo-β-carotenol pentynoate (5) was not
complete (~70%). Further experiments on coupling deprotected
sugar azides (13, 14) with other hydroxy carotenoid pentynoates
(6-8) were performed under the same conditions (Table 3). All
studied carotenoid pentynoates gave good yields with β-D-
Recently, the use of bis-triphenylphosphano-copper(I)-
butyrate (C3H7COOCu(PPh3)2) complex11 has been reported as an
efficient catalyst for the synthesis of 1-glycopyranosyl-4-
substituted-1,2,3-triazoles.12 This paper presents our studies on
the coupling of protected and free glycosyl azides with
carotenoid pentynoates using C3H7COOCu(PPh3)2 as a catalyst.
glucopyranosyl azide (13). Starting from a more hydrophilic
unprotected sugar was expected to improve the hydrophilicity of
the product. To achieve this, 1-carboxamido-β-D-glucopyranosyl
azide (14) was reacted under the same conditions, but
unfortunately yielded complex mixtures with only traces of the
triazoles. The low yields in the case of unprotected 1-
carboxamido-1-azido-D-glucose can be explained by its even
2. Results and discussion
worse solubility in dichloromethane, in addition to the steric
hindrance of the azido group as well as the hydrogen bond
between the azide and the CONH2.18,19 To optimize the
Acetyl/benzoyl protected and free glycosyl azides were
prepared according to known procedures.13-15 Hydroxy
carotenoids were treated with NaH and propargyl chloride in
DMF to give propargyl ethers, but no reaction was detected. The
conditions for 1-carboxamido-1-azido-
D-glucose (14) acetonitrile
was applied as a solvent in the presence or absence of

3
triethylamine, but no improvements were observed. We also tried
coupling of carotenoid pentynoates to sugar azides. In spite of
the low solubility, unprotected β-
used in these reactions, however, 1-carboxamido-β-
ACCEPTED MANUSCRIPT
to couple capsanthin dipentynoate (8) to 14 using CuI as a
catalyst in dichloromethane with EDIPA, however,
transformation of the starting materials was not detected.
D-glucopyranosyl azide can be
D-
glucopyranosyl azide is less suitable. This way unprotected
carotenyloxy-3-oxopropyl-1,2,3-triazol-1-yl glucosides were
prepared directly in a single coupling step. Our method provides
an easy and general way for the synthesis of these biologically
interesting molecules. The new sugar derivatives of capsanthin
are especially promising, because capsanthin is one of the best
3. Conclusion
Carotenoid pentynoates were synthesized by the Steglich
method, and coupled with protected and unprotected sugar azides
in a CuAAC reaction using bis-triphenylphosphano-copper(I)-
butyrate (C3H7COOCu(PPh3)2) catalyst in dichloromethane. No
other reaction conditions were found to be suitable for the
antioxidants
among
carotenoids.20
Table 2. CuAAC reaction of 8’-apo-β-carotenol-pentynoate with sugar azides
entry
sugar
9
10
11
12
R1
R2
X
N3
H
N3
H
N3
N3
Y
H
N3
CONH2
OAc
H
product R1
R2
X
Y
H
reaction time
1.5 h
2 h
7 h
8 h
yield
92%
95%
93%
63%
72%
49% a
1
2
3
4
5
6
OAc
OAc
OBz
OAc
OH
OAc
OAc
OBz
N3
OH
OH
15
16
17
18
19
20
OAc
OAc
OAc
OBz
triazole
OH
triazole
H
triazole CONH2
OAc
OBz
OAc
OH
triazole
H
OAc
H
13
14
triazole
triazole CONH2
1 day
2 days
OH
CONH2
OH
OH
a Conversion of 5 was ~70%
Table 3. CuAAC reaction of carotenol pentynoates with unprotected sugar azides
entry
sugar
13
13
13
14
carotenol pentynoate
reaction time
12 h
12 h
products (yields)
21 ditriazole (65%)
22 (76%)
1
2
3
4
5
6
zeaxanthin dipentynoate (6)
β-cryptoxanthin pentynoate (7)
capsanthin dipentynoate (8)
zeaxanthin dipentynoate (6)
β-cryptoxanthin pentynoate (7)
capsanthin dipentynoate (8)
12 h
23 ditriazole (71%)
2 days
2 days
2 days
24 mono-triazole (tracesa) and 25 ditriazole (tracesa)
no reaction
14
14
26 mono-triazole (tracesa) and 27 ditriazole (15%)
a detected by MS in the worked-up reaction mixture.
ionization of the samples. Mass spectra were monitored either in
positive or in negative mode (depending on the chemical
structure) with pulsed ionization (λ = 337 nm; nitrogen laser).
Spectra were measured in reflectron mode using a delayed
extraction of 120 nsec. The elemental analysis measurements
were performed on a Fisons EA 1110 CHNS apparatus.
Thin layer chromatography was performed on TLC Silica gel
60 F254 on Al sheets (Merck), and the spots were visualized under
UV light and by gentle heating. Preparative layer
chromatography was executed on PLC Silica gel 60 F254 1 mm on
glass plate (Merck). For column chromatography Kieselgel 60
(Merck, particle size 0.063-0.200 mm) was used. All reagents
used for synthesis were commercial and of analytically pure
quality and all organic solvents were of HPLC grade. Organic
solutions were dried over anhydrous Na2SO4 and concentrated
4. Experimental section
Melting points were measured on an HMK hot-stage (Franz
Küstner Nacht KG) and are uncorrected. NMR spectra were
recorded with a Bruker Avance III Ascend 500 spectrometer
(500/125 MHz for 1H/13C). The 13C and 1H NMR assignments for
5, 6, 7, 8 and 21 were made on the basis of 1D (1H, 13C APT) and
2D (COSY, HSQC) experiments, the assignments for the other
compounds were based on structural similarities with the above
molecules. Chemical shifts are referenced to the residual solvent
signals, or to Me4Si (1H). The IR spectra were run on an Impact
400 (Nicolet) FT-IR spectrophotometer in KBr pellets using a
KBr pellet as the background reference spectrum. Molar masses
were obtained by an Autoflex II MALDI instrument (Bruker
Daltonics). 2,5-Dihydroxy-benzoic acid (DHB) was used for the

4
Tetrahedron
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4.2. Zeaxanthin dipentynoate (6)
under reduced pressure at 40 ºC (bath temperature). Sugar
azides were prepared by published methods;13-15 the carotenoids
were isolated from red pepper Capsicuum anuum by standard
procedure.21 Crude 8’-apo-β-carotenol was freshly prepared from
commercially available 8’-apo-β-carotenal (Fluka), because the
alcohol is susceptible to oxidation.
Following the general procedure, zeaxanthin (2, 200 mg, 0.35
mmol) was dissolved in dry dichloromethane (10 mL). To the
stirred solution 4-pentynoic acid (69 mg, 0.7 mmol), DMAP (85
mg, 0.7 mmol) and DCC (145 mg, 0.7 mmol) were added. The
reaction was worked up, after stirring for 12 h, by addition of
some drops of water and 10 minutes later hexane (100 mL). After
filtration, drying and evaporation the product was crystallized.
Yield: 136 mg (53%); orange crystals; mp: 138 °C; Rf = 0.55
(hexane–acetone, 4:1). IR (KBr, cm-1): 1727 s (ν C=O, ester),
4.1. 8’-Apo-β-carotenol pentynoate (5)
8’-Apo-β-carotenal (300 mg, 0.72 mmol, UV (hexane) λmax
,
nm: 480, 454) was dissolved in toluene (200 mL) and 96%
ethanol (100 mL), NaBH4 (300 mg, 7.9 mmol) was added and the
mixture was vigorously stirred under nitrogen for 1 h. After the
solution became brighter and TLC showed complete conversion
to the more polar carotenol, KOH (1 g) was added to the solution.
Five minutes later the solution was washed with water (5 x 100
mL), dried (Na2SO4) and the solvent was evaporated under
reduced pressure. The residue (300 mg, UV (hexane) λmax, nm:
450, 425, 402) was immediately dissolved in dry
dichloromethane (150 mL). To the stirred solution 4-pentynoic
acid (140 mg, 1.43 mmol), dimethylaminopyridine (DMAP, 175
mg, 1.43 mmol) and dicyclohexyl carbodiimide (DCC, 296 mg,
1.43 mmol) were added. The mixture was stirred for 12 h under
nitrogen atmosphere, in darkness, at room temperature. Some
drops of water (~0.5 mL) and 10 minutes later hexane (150 mL)
were added to the reaction mixture, the obtained precipitate was
filtered out, the mother liquor was dried (Na2SO4) and evaporated
under reduced pressure. The product 5 was crystallized from
methanol/toluene mixture by the addition of some water. The
formed crystals were filtered off, dried in vacuum and stored in
closed ampoules under argon. Yield: 268 mg (75%) red plates;
mp: 108-109 °C; Rf = 0.60 (hexane–acetone, 4:1); IR (KBr, cm-
1
2120 w (ν C≡C), 3308 w (ν ≡CH). H-NMR (500 MHz, CDCl3):
δ = 1.08, 1.11 (2s, 12H, 16, 16’, 17, 17’-Me), 1.57-1.61 (m, 2H,
H-2ax, H-2’ax), 1.72 (s, 6H, 18, 18’-Me), 1.79 (ddd, 2H, J = 1.7
Hz, J = 3.3 Hz, J = 12.1 Hz, H-2eq, H-2’eq), 1.97, 1.98, 1.99 (3s,
14H, 19, 19’, 20, 20’-Me, 2 HC≡C), 2.13 (dd, 2H, J = 9.4 Hz, J =
16.9 Hz, H-4ax, H-4’ax), 2.44 (dd, 2H, J = 5.7 Hz, J = 17.1 Hz, H-
4eq, H-4’eq), 2.49-2.57 (m, 8H, 4 CH2 pentynoate), 5.07-5.13 (m,
2H, H-3, H-3’), 6.07-6.12 (m, 4H, H-7, 7’, 8, 8’), 6.16 (d, 2H, J =
11.7 Hz, H-10, 10’), 6.26 (d, 2H, J = 9.7 Hz, H-14, 14’), 6.37 (d,
2H, J = 14.9 Hz, H-12, 12’), 6.61-6.67 (m, 4H, H-11, 11’, 15,
15’). 13C-NMR (125 MHz, CDCl3): δ = 12.7, 12.8 (19, 19’, 20,
20’-Me), 14.4 (2 CH2-C≡C), 21.5 (18, 18’-Me), 28.5, 30.0 (16,
16’, 17, 17’-Me), 33.7 (2 CH2-CO), 36.7, 38.4, 44.0 (C-1, 1’, 2,
2’, 4, 4’), 68.9 (C-3, 3’), 69.0 (2 C≡CH), 82.6 (2 C≡CH), 124.9
(C-11, 11’), 125.2 (C-7, 7’), 125.5 (C-5, 5’), 130.1, 131.5, 132.6
(C-10, 10’, 14, 14’, 15, 15’), 136.5 (C-9, 9’), 137.7 (C-13, 13’),
137.7 (C-12, 12’), 137.9 (C-6, 6’), 138.7 (C-8, 8’), 171.4 (2
C=O). MS (MALDI-TOF, positive mode, with DHB matrix) m/z
= 728.3 (M+). Anal. calcd. for C50H64O4: C 82.37, H 8.85, found
C 82.32, H 8.47.
1
1): 1720 s (ν C=O, ester), 2119 w (ν C≡C), 3279 w (ν ≡CH); H-
4.3. β-Cryptoxanthin pentynoate (7)
NMR (500 MHz, CDCl3): δ = 0.93 (s, 6H, 16, 17-Me), 1.36-1.38
(m, 2H, H-2), 1.51-1.53 (m, 2H, H-3), 1.62 (s, 3H, 18-Me), 1.75
(s, 3H, 20’-Me), 1.85 (s, 1H, HC≡C), 1.87 (brs, 9H, 19, 19’, 20-
Me), 1.92 (t, 2H, J = 6.1 Hz, H-4), 2.41-2.44 (m, 2H, CH2
pentynoate), 2.48-2.51 (m, 2H, CH2 pentynoate), 4.50 (s, 2H, H-
8’), 6.01-6.58 (m, 12H, H-7, 8, 10, 10’, 11, 11’, 12, 12’, 14, 14’,
15, 15’). 13C-NMR (125 MHz, CDCl3): δ = 12.8, 12.8 (19, 19’,
20-Me), 14.4 (CH2-C≡C), 14.8 (20’-Me), 19.3 (C-3), 21.8 (18-
Me), 29.0 (16, 17-Me), 33.1, 33.4, 34.3 (C-1, C-4, CH2-CO), 39.7
(C-2), 69.1 (C≡CH), 70.2 (C-8’), 82.5 (C≡CH), 123.3, 125.3,
126.8, 129.3, 129.7, 130.5, 130.8, 132.3, 133.0, 137.1, 137.7,
138.6 (C-7, 8, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15, 15’), 129.4,
131.6, 135.7, 136.2, 136.8, 137.9 (C-5, 6, 9, 9’,13, 13’), 171.56
(C=O). MS (MALDI-TOF, positive mode, with DHB matrix)
m/z = 498.4 (M+). Anal. calcd. for C35H46O2: C 84.29, H 9.30,
found C 84.36, H 9.24.
Following the general procedure, β-cryptoxanthin (3, 70 mg,
0.13 mmol) was dissolved in dry dichloromethane (3.5 mL). To
the stirred solution 4-pentynoic acid (25 mg, 0.25 mmol), DMAP
(31 mg, 0.25 mmol) and DCC (52 mg, 0.25 mmol) were added.
The reaction was worked up, after stirring for 12 h, by addition of
some drops of water and 10 minutes later hexane (35 mL). After
filtration, drying and evaporation the product was crystallized.
Yield: 72 mg (90%); red crystals; mp: 139-140 °C; Rf = 0.65
(hexane–acetone, 4:1). IR (KBr, cm-1): 1728 vs (ν C=O, ester),
1
2121 w (ν C≡C), 3305 w (ν ≡CH). H-NMR (500 MHz, CDCl3):
δ = 1.03, 1.07, 1.11 (3s, 12H, 16, 16’, 17, 17’-Me), 1.45-1.48 (m,
2H, H-2’), 1.59-1.63 (m, 2H, H-2ax, H-3’), 1.72 (2s, 6H, 18, 18’-
Me), 1.79 (d, 1H, J = 12.0 Hz, H-2eq), 1.97 (brs, 13H, 19, 19’, 20,
20’-Me, HC≡C), 2.02 (t, 2H, J = 6.3 Hz, H-4’), 2.13 (dd, 1H, J =
9.4 Hz, J = 16.9 Hz, H-4ax), 2.44 (dd, 1H, J = 5.7 Hz, J = 17.1
Hz, H-4eq), 2.50-2.54 (m, 4H, 2 CH2 pentynoate), 5.07-5.13 (m,
1H, H-3), 6.06-6.19 (m, 6H, H-7, 7’, 8, 8’, 10, 10’), 6.24-6.25
(m, 2H, H-14, 14’), 6.36 (dd, 2H, J = 7.1 Hz, J = 14.9 Hz, H-12,
12’), 6.57-6.68 (m, 4 H, H-11, 11’, 15, 15’). 13C-NMR (125
MHz, CDCl3): δ = 12.8 (19, 19’, 20, 20’-Me), 14.4 (CH2-C≡C),
19.3 (C-3’), 21.5, 21.8 (18, 18’-Me), 28.5, 29.0, 30.0 (16, 16’, 17,
17’-Me), 33.2 (C-4’), 33.7, 34.3 (C-1,1’), 36.7 (CH2-C=O), 38.4
(C-4), 39.7 (C-2’), 44.1 (C-2), 68.9 (C-3), 69.0 (HC≡C), 82.6
(HC≡C), 124.8, 125.1, 125.2, 126.7 (C-7, 7’, 11, 11’), 129.9,
130.2, 130.8, 131.5, 132.4, 132.7 (C-10, 10’, 14, 14’, 15, 15’),
125.5, 129.4, 135.5, 136.1, 136.3, 136.6, 138.0 (C-5, 5’, 6, 6’, 9,
9’, 13, 13’), 137.2, 137.7, 137.8, 138.7 (C-8, 8’, 12, 12’), 171.44
(C=O). MS (MALDI-TOF, positive mode, with DHB matrix)
m/z = 632.6 (M+). Anal. calcd. for C45H60O2: C 85.39, H 9.55,
found C 85.80, H 9.54.
General procedure for carotenoid pentynoates
The hydroxy carotenoids were dissolved in dry
dichloromethane (20 mg/mL). To the stirred solution 4-pentynoic
acid (2 equiv), DMAP (2 equiv) and DCC (2 equiv) were added.
The mixture was stirred for 12 h under nitrogen atmosphere, in
darkness, at room temperature. Some drops of water (~0.5 mL)
and 10 minutes later hexane (0.5 mL/mg carotenol) were added
to the reaction mixture, the obtained precipitate was filtered out,
the mother liquor was dried (Na2SO4) and evaporated under
reduced pressure. The products were crystallized from
methanol/toluene mixture by the addition of some water. The
formed crystals were filtered off, dried in vacuum and stored in
closed ampoules under argon.

5
4.4. Capsanthin dipentynoate (8)
3), 20.1, 20. 5, 20.6, 21.7 (4 Ac-Me, C-18), 20.9 (CH2-C=C
ACCEPTED MANUSCRIPT
propanoyl), 28.9 (16, 17-Me), 33.0, 33.4, 34.2 (C-1, C-4, CH2-
CO), 39.6 (C-2), 61. 5 (C-6”), 67.6 (C-2”), 70.0 (C-8’), 70.1 (C-
3”), 72.6 (C-4”), 75.0 (C-5”), 85.5 (C-1”), 119.5 (CH triazole),
123.3, 125.1, 126.6, 129.1, 129.6, 130.4, 130.7, 132.1, 132.9,
137.1, 137.7, 138.4 (C-7, 8’, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15,
15’), 129.3, 131.7, 135.6, 136.0, 136.7, 137.8 (C-5, 6, 9, 9’, 13,
13’), 147.0 (C=CH triazole), 168.8, 169.3, 169.8, 170.4 (4 Ac
C=O), 172.2 (C=O, propanoyl). MS (MALDI-TOF, positive
mode, with DHB matrix) m/z = 871.3 (M+). Anal. calcd. for
C49H65N3O11: C 67.49, H 7.51, N 4.82, found C 67.51, H 7.52, N
4.90.
Following the general procedure, capsanthin (4, 200 mg, 0.34
mmol) was dissolved in dry dichloromethane (10 mL). To the
stirred solution 4-pentynoic acid (67 mg, 0.68 mmol), DMAP (84
mg, 0.68 mmol) and DCC (141 mg, 0.68 mmol) were added. The
reaction was worked up, after stirring for 12 h, by addition of
some drops of water and 10 minutes later hexane (100 mL). After
filtration, drying and evaporation the product was crystallized.
Yield: 150 mg (59%); red crystals; mp: 128-129 °C; Rf = 0.52
(hexane–acetone, 4:1). IR (KBr, cm-1): 1686 m (ν C=O, ketone),
1
1728 vs (ν C=O, ester), 2120 w (ν C≡C), 3298 w (ν ≡CH). H-
NMR (500 MHz, CDCl3): δ = 0.86, 1.70, 1.10, 1.17 (4s, 12H, 16,
16’, 17, 17’-Me), 1.32 (s, 3H, 18’-Me), 1.57-1.62 (m, 2H, H-2ax,
H-4’β), 1.72 (s, 3H, 18-Me), 1.73-1.80 (m, 2H, H-2eq, H-2’β),
1.95, 1.97, 1.99 (3s, 14H, 19, 19’, 20, 20’-Me, 2 HC≡C), 2.06-
2.16 (m, 2H, H-4ax, H-2’α), 2.44 (dd, 1H, J = 5.6 Hz, J = 17.2
Hz, H-4eq), 2.51-2.55 (m, 8H, 4 CH2 pentynoate), 2.98 (dd, 1H, J
= 8.8 Hz, J = 14.9 Hz, H-4’α), 5.07-5.13 (m, 1H, H-3), 5.26-5.30
(m, 1H, H-3’), 6.08-6.12 (m, 2H, H-7, H-8), 6.16 (d, 1H, J = 11.3
Hz, H-10), 6.26 (d, 1H, J = 11.3 Hz, H-14), 6.35-6.38 (m, 2H, H-
12, H-14’), 6.42 (d, 1H, J = 15.1 Hz, H-7’), 6.50-6.73 (m, 6H, H-
10’, 11, 11’, 12’, 15, 15’), 7.33 (d, 1H, J = 15.0 Hz, H-8’). 13C-
NMR (125 MHz, CDCl3): δ = 12.7, 12.8, 12.9 (19, 19’, 20, 20’-
Me), 14.4, 14.5 (2 CH2-C≡C), 20.8, 21.5 (18, 18’-Me), 24.8, 25.6
(17, 17’-Me), 28.5, 30.0 (16, 16’-Me), 33.6, 33.7 (2 CH2-CO),
36.7, 38.4, 42.2, 43.7, 44.0, 47.6 (C-1, 1’, 2, 2’, 4, 4’), 68.9 (C-3),
68.9, 69.0 (2 C≡CH), 74.0 (C-3’), 82.5 (2 C≡CH), 120.6, 124.1,
125.5 (C-7, 7’, 11, 11’), 129.7, 131.4, 131.7, 132.4 (C-10, 10’,
15, 15’), 125.6, 133.6, 135.9, 136.0, 137.6, 137.9 (C-5, 5’, 6, 9,
9’, 13, 13’), 135.3, 137.5, 138.6, 140.9, 142.1, 147.1 (C-8, 8’, 12,
12’, 14, 14’), 171.4, 171.4 (2 C=O), 202.4 (C-6’). MS (MALDI-
TOF, positive mode, with DHB matrix) m/z = 744.3 (M+). Anal.
calcd. for C50H64O5: C 80.60, H 8.66, found C 80.11, H 8.43.
4.6. 8’-(1-(2”,3”,4”,6”-tetra-O-acetyl-α-d-glucopyranosyl)-
1,2,3-triazol-4-yl)-propanoyloxy)-8’-apo-β-carotene (16)
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 45 mg, 0.09 mmol) was dissolved in dry
dichloromethane (1.5 mL) with 2,3,4,6-tetra-O-acetyl-α-D-
glucopyranosyl azide (10, 34 mg, 0.09 mmol) and
C3H7COOCu(PPh3)2 (3 mg, 0.004 mmol). After stirring for 2 h
under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by column chromatography (SiO2, EtOAc–hexane, 1:2). Yield:
1
75 mg (95%); red syrup; Rf = 0.49 (EtOAc–hexane, 1:1). H-
NMR (500 MHz, CDCl3): δ = 1.00 (s, 6H, 16, 17-Me), 1.42-1.46
(m, 2H, H-2), 1.57-1.61 (m, 2H, H-3), 1.69 (s, 3H, Me-18), 1.80,
18.5 (2s, 6H, Me-20, 20’), 1.92, 1.95 (2s, overlayed), 1.98-2.05
(m) (20H, H-4, Me-19, 19’-Me, 4 Ac-Me), 2.77 (t, 2H, J = 7.1
Hz, CH2 propanoyl), 3.07 (t, 2H, J = 7.1 Hz, CH2 propanoyl),
3.99 (dd, 1H, J = 1.9 Hz, J = 12.6 Hz, H-6”), 4.23 (dd, 1H, J =
3.7 Hz, J = 12.7 Hz, H-6”), 4.32-4.36 (m, 1H, H-5”), 4.55 (s, 2H,
H-8’), 5.21-5.28 (m, 2H, H-2”, H-4”), 6.08-6.67 (m, 14H, H-1”,
H-3”, H-7, 8, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15, 15’), 7.43 (s,
1H, triazole). 13C-NMR (125 MHz, CDCl3): δ = 12.7, 12.8, 14.1,
14.7 (19, 19’, 20, 20’-Me), 19.2 (C-3), 20.2, 20.5, 20.6, 21.7 (4
Ac-Me, C-18), 20.7 (CH2-C=C propanoyl), 28.9 (16, 17-Me),
33.0, 33.3, 34.2 (C-1, C-4, CH2-CO), 39.6 (C-2), 61.2 (C-6”),
67.9, 69.8, 70.4, 71.0 (C-2”, C-3”, C-4”, C-5”), 70.1 (C-8’), 81.1
(C-1”), 123.2, 123.5, 125.2, 126.7, 129.2, 129.6, 130.5, 130.7,
132.1, 133.0, 137.1, 137.7, 138.6 (C-7, 8’, 10, 10’, 11, 11’, 12,
12’, 14, 14’, 15, 15’), 129.3, 131.5, 135.6, 136.1, 136.6, 137.8
(C-7, 8’, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15, 15’), 145.8 (C=CH
triazole), 169.5, 169.6, 170.1, 170.4 (4 Ac C=O), 172.2 (C=O,
propanoyl). MS (MALDI-TOF, positive mode, with DHB
matrix) m/z = 871.2 (M+). Anal. calcd. for C49H65N3O11: C 67.49,
H 7.51, N 4.82, found C 67.81, H 7.25, N 4.80.
General procedure for CuAAC reactions
The carotenoid pentynoates were dissolved in dry
dichloromethane (0.06 mmol/mL) with sugar azide (1 equiv) and
bis-triphenylphosphano-copper(I)-butyrate (C3H7COOCu(PPh3)2)
(5 mol%). The reaction mixture was stirred under nitrogen
atmosphere in darkness. When TLC showed the disappearance of
the starting materials, the solvent was evaporated in vacuum, and
the residue was purified by chromatography.
4.5. 8’-(1-(2”,3”,4”,6”-tetra-O-acetyl-β-d-glucopyranosyl)-
1,2,3-triazol-4-yl)-propanoyloxy)-8’-apo-β-carotene (15)
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 45 mg, 0.09 mmol) was dissolved in dry
dichloromethane (1.5 mL) with 2,3,4,6-tetra-O-acetyl-β-D-
4.7. 8’-(1-(2”,3”,4”,6”-tetra-O-benzoyl-1”-carboxamido-β-d-
glucopyranosyl)-1,2,3-triazol-4-yl)-propanoyloxy)-8’-apo-β-
carotene (17)
glucopyranosyl azide (9, 34 mg, 0.09 mmol) and
C3H7COOCu(PPh3)2 (3 mg, 0.004 mmol). After stirring for 1.5 h
under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by column chromatography (SiO2, EtOAc–hexane, 2:3). Yield:
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 45 mg, 0.09 mmol) was dissolved in dry
dichloromethane (2 mL) with 2,3,4,6-tetra-O-benzoyl-1-
carboxamido-β-D-glucopyranosyl azide (11, 60 mg, 0.09 mmol)
1
73 mg (92%); red syrup; Rf = 0.45 (EtOAc–hexane, 1:1). H-
and C3H7COOCu(PPh3)2 (3 mg, 0.004 mmol). After stirring for 7
h under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by column chromatography (SiO2, EtOAc–hexane, 2:3). Yield:
NMR (500 MHz, CDCl3): δ = 1.05 (s, 6H, 16, 17-Me), 1.43-1.46
(m, 2H, H-2), 1.57-1.62 (m, 2H, H-3), 1.69 (s, 3H, Me-18), 1.80,
1.84 (2s, 6H, Me-20,20’), 1.92, 1.95, 2.04 (3s, overlayed), 1.98-
2.02 (m) (20H, H-4, 19, 19’-Me, 4 Ac-Me), 2.75 (t, 2H, J = 7.3
Hz, CH2 propanoyl), 3.04 (t, 2H, J = 7.4 Hz, CH2 propanoyl),
3.96-4.00 (m, 1H, H-5”), 4.07-4.13 (m, 1H, H-6”), 4.28 (dd, 1H,
J = 4.9 Hz, J = 12.7 Hz, H-6”), 4.56 (s, 2H, H-8’), 5.22 (t, 1H, J
= 9.7 Hz, H-4”), 5.36-5.44 (m, 2H, H-2”, H-3”), 5.83 (d, 1H, J =
8.8 Hz, H-1”), 6.08-6.67 (m, 12H, H-7, 8, 10, 10’, 11, 11’, 12,
12’, 14, 14’, 15, 15’), 7.58 (s, 1H, triazole). 13C-NMR (125 MHz,
CDCl3): δ = 12.7, 12.8 (19, 19’, 20-Me), 14.7 (20’-Me), 19.2 (C-
1
98 mg (93%); red syrup; Rf = 0.51 (EtOAc–hexane, 1:1). H-
NMR (500 MHz, CDCl3): δ = 1.03 (s, 6H, 16, 17-Me), 1.47 (ps,
2H, H-2), 1.61 (ps, 2H, H-3), 1.72, 1.80 (2s, 6H, Me-18, 20’),
1.95-2.03 (m, 11H, H-4, Me-19, 19’, 20-Me), 2.67 (ps, 2H, CH2
propanoyl), 2.97 (ps, 2H, CH2 propanoyl), 4.55 (s, 3H, 2 H-8’, H-
6”), 4.89 (d, 1H, J = 11.4 Hz, H-6”), 5.26 (pd, 1H, J = 8.5 Hz, H-
5”), 5.88 (t, 1H, J = 8.3 Hz, H-4”), 6.16-6.70 (m, 15H, H-2”, H-
3”, CONH2, H-7, 8, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15, 15’),

6
Tetrahedron
ACCEPTED MANUSCRIPT
6.95 (s, 1H, CONH2), 7.26-8.11 (m, 21H, triazole, 4 Bz
3.89 (m, 2H, H-2”, H-6”), 4.58 (s, 2H, H-8’), 5.55 (t, 1H, J = 9.2
aromatics). 13C-NMR (125 MHz, CDCl3): δ = 12.7, 12.8 (19, 19’,
20-Me), 14.7 (20’-Me), 19.2 (C-3), 20.8 (CH2-C=C propanoyl),
21.7 (C-18), 28.9 (16, 17-Me), 33.0, 33.2, 34.2 (C-1, C-4, CH2-
CO), 39.6 (C-2), 62.4 (C-6”), 70.0 (C-8’), 68.2, 71.1, 72.3, 73.9
(C-2”-C-5”), 89.2 (C-1”), 120.2, 123.3, 125.1, 126.6, 137.1 (CH
triazole, C-7, 8’, 10, 10’, 11, 11’, 12, 12’, 14, 14’, 15, 15’),
128.2-133.6 (Bz aromatics), 129.3, 131.6, 135.7, 136.0, 136.7,
137.8 (C-5, 6, 9, 9’, 13, 13’), 146.4 (C=CH triazole), 164.2,
164.9, 165.0, 166.0, 166.4 (4 Bz C=O, CONH2), 172.1 (C=O,
propanoyl). MS (MALDI-TOF, negative mode, without matrix)
m/z = 1161.6 (M+-1). Anal. calcd. for C70H74N4O12: C 72.27, H
6.41, N 4.82, found C 72.48, H 6.59, N 4.66.
Hz, H-1”), 6.10-6.73 (m, 12H, H-7, 8, 10, 10’, 11, 11’, 12, 12’,
14, 14’, 15, 15’), 7.97 (s, 1H, triazole). 13C-NMR (125 MHz,
CD3OD + CDCl3): δ = 13.0 (19, 19’, 20-Me), 14.9 (20’-Me), 20.1
(C-3), 21.6 (CH2-C=C propanoyl), 22.0 (18-Me), 29.4 (16, 17-
Me), 33.8, 34.2, 35.0 (C-1, C-4, CH2-CO), 40.5 (C-2), 62.2 (C-
6”), 71.0 (C-8’), 70.5, 73.7, 78.1, 80.6 (C-2”, 3”, 4”, 5”), 89.2 (C-
1”), 122.3, 124.2, 126.0, 127.4, 130.1, 130.7, 131.4, 131.8, 133.2,
133.9, 138.2, 138.9, 139.4 (CH triazole, C-7, 8’, 10, 10’, 11, 11’,
12, 12’, 14, 14’, 15, 15’), 132.5, 136.6, 137.5 (C-5, 6, 9, 9’, 13,
13’), 147.1 (C=CH triazole), 173.7 (C=O, propanoyl). MS
(MALDI-TOF, positive mode, with DHB matrix) m/z = 703.52
(M+). Anal. calcd. for C41H57N3O7: C 69.96, H 8.16, N 5.97,
found C 69.73, H 7.93, N 5.72.
4.8. 6”-deoxy-6”-(4-(3-(8’-apo-β-caroten-8’-yloxy)-3-
oxopropyl)-1,2,3-triazol-1-yl)-1”,2”,3”,4”-tetra-O-acetyl-α-d-
glucopyranose (18)
4.10. 8’-(1-(1”-carboxamido-β-d-glucopyranosyl)-1,2,3-triazol-
4-yl)-propanoyloxy)-8’-apo-β-carotene (20)
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 45 mg, 0.09 mmol) was dissolved in dry
dichloromethane (2 mL) with 6-deoxy-6-azido-1,2,3,4-tetra-O-
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 30 mg, 0.06 mmol) was dissolved in dry
dichloromethane (1 mL) with 1-carboxamido-β-D-glucopyranosyl
acetyl-α-D-glucopyranose (12, 34 mg, 0.09 mmol) and
azide (14, 15 mg, 0.06 mmol) and C3H7COOCu(PPh3)2 (2 mg,
0.003 mmol). After stirring for 2 days under nitrogen atmosphere
in darkness, the solvent was evaporated under reduced pressure,
and the residue was purified by preparative thin layer
chromatography (SiO2, CH2Cl2–MeOH, 9:1). Yield: 22 mg
(49%); red syrup; Rf = 0.70 (CH2Cl2–MeOH, 4:1). 1H-NMR (500
MHz, CD3OD): δ = 1.03 (s, 6H, 16, 17-Me), 1.48-1.50 (m, 2H,
H-2), 1.63-1.65 (m, 2H, H-3), 1.71, 1.82 (2s, 6H, Me-18,20’),
1.95, 1.96, 1.97 (3s, 9H, 19, 19’, 20-Me), 2.04 (t, 2H, J = 6.1 Hz,
H-4), 2.78 (t, 2H, J = 7.4 Hz, CH2 propanoyl), 3.04 (t, 2H, J = 7.4
Hz, CH2 propanoyl), 3.48-3.79 (m, 4H, H-3”, 4”, 5”, 6”), 3.91
(dd, 1H, J = 1.5 Hz, J = 12.2 Hz, H-6”), 4.00 (d, 1H, J = 9.8 Hz,
H-2”), 4.58 (s, 2H, H-8), 6.09-6.72 (m, 12H, H-7, 8, 10, 10’, 11,
11’, 12, 12’, 14, 14’, 15, 15’), 8.07 (s, 1H, triazole). 13C-NMR
(125 MHz, CD3OD): δ = 12.8, 12.9, 14.8 (19, 19’, 20, 20’-Me),
20.4 (C-3), 21.9 (CH2-C=C propanoyl), 22.0 (C-18), 29.5 (16,
17-Me), 34.0, 34.4, 35.3 (C-1, C-4, CH2-CO), 40.9 (C-2), 62.3
(C-6”), 71.2 (C-8’), 70.5, 76.0, 77.2, 79.5 (C-2”-C-5”), 90.6 (C-
1”), 122.3, 124.6, 126.2, 127.6, 130.3, 131.7, 132.3, 133.7, 134.2,
137.8, 138.7, 139.5, 139.7 (CH triazole, C-7, 8’, 10, 10’, 11, 11’,
12, 12’, 14, 14’, 15, 15’), 130.1, 133.1, 136.8, 137.0, 139.3 (C-5,
6, 9, 9’, 13, 13’), 147.5 (C=CH triazole), 169.4 (CONH2), 174.0
(C=O, propanoyl). MS (MALDI-TOF, positive mode, with DHB
matrix) m/z = 747.1 (M+). Anal. calcd. for C42H58N4O8: C 67.54,
H 7.83, N 7.50, found C 67.86, H 8.09, N 7.36.
C3H7COOCu(PPh3)2 (3 mg, 0.004 mmol). After stirring for 8 h
under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by column chromatography (SiO2, EtOAc–hexane, 1:1). Yield:
50 mg (63%); orange amorphous product; Rf = 0.19 (EtOAc–
1
hexane, 1:1). H-NMR (500 MHz, CDCl3): δ = 1.01 (s, 6H, 16,
17-Me), 1.43-4.47 (m, 2H, H-2), 1.58-1.62 (m, 2H, H-3), 1.70,
1.81 (2s, 6H, Me-18, 20’), 1.93-2.10 (m, 23H, H-4, Me-19, 19’,
20-Me, 4 Ac-Me), 2.76 (t, 2H, J = 7.4 Hz, CH2 propanoyl), 3.04
(t, 2H, J = 7.3 Hz, CH2 propanoyl), 4.23-4.37 (m, 2H, H-5”, H-
6”), 4.50-4.55 (m, 3H, H-8’, H-6”), 4.81 (t, 1H, J = 9.6 Hz, H-
2”/4”), 5.01 (dd, 1H, J = 3.7 Hz, J = 10.3 Hz, H-4”/2”), 5.45 (t,
1H, J = 9.8 Hz, H-3”), 6.09-6.68 (m, 13H, H-1”, H-7, 8, 10, 10’,
11, 11’, 12, 12’, 14, 14’, 15, 15’), 7.41 (s, 1H, triazole). 13C-NMR
(125 MHz, CDCl3): δ = 12.7, 12.8 (19, 19’, 20-Me), 14.7 (20’-
Me), 19.2 (C-3), 20.4, 20.6, 20.6, 20.7, 21.7 (4 Ac-Me, C-18),
21.0 (CH2-C=C propanoyl), 28.9 (16, 17-Me), 33.06, 33.52,
34.22 (C-1, C-4, CH2-CO), 39.59 (C-2), 50.26 (C-6”), 69.0, 69.2,
69.5, 70.3 (C-2”-C-5”), 69.9 (C-8’), 88.6 (C-1”), 122.7, 123.3,
125.1, 126.7, 129.0, 129.6, 130.4, 130.7, 132.2, 132.9, 137.1,
137.7, 138.4 (CH triazole, C-7, 8’, 10, 10’, 11, 11’, 12, 12’, 14,
14’, 15, 15’), 129.3, 131.8, 135.7, 136.1, 136.7, 137.8 (C-5, 6, 9,
9’, 13, 13’), 146.6 (C=CH triazole), 168.6, 169.4, 169.6, 170.0 (4
Ac C=O), 172.3 (C=O, propanoyl). MS (MALDI-TOF, positive
mode, with DHB matrix) m/z = 871.4 (M+). Anal. calcd. for
C49H65N3O11: C 67.49, H 7.51, N 4.82, found C 67.71, H 7.50, N
4.93.
4.11. 3,3’-bis(1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl)-
propanoyloxy)-β,β-carotene (21)
Following the general procedure, zeaxanthin dipentynoate (6,
30 mg, 0.04 mmol) was dissolved in dry dichloromethane (1 mL)
with β-D-glucopyranosyl azide (13, 8.5 mg, 0.04 mmol) and
4.9. 8’-(1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl)-
propanoyloxy)-8’-apo-β-carotene (19)
Following the general procedure, 8’-apo-β-carotenol
pentynoate (5, 30 mg, 0.06 mmol) was dissolved in dry
dichloromethane (1 mL) with β-D-glucopyranosyl azide (13, 12
C3H7COOCu(PPh3)2 (1.4 mg, 0.002 mmol). After stirring for 12
h under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by preparative thin layer chromatography (SiO2, CH2Cl2–MeOH,
9:1). Yield: 30 mg (65%); orange plate crystals; mp: 198-199 °C;
Rf = 0.34 (CH2Cl2–MeOH, 4:1). 1H-NMR (500 MHz, (CD3)2SO):
δ = 1.06, 1.08 (2s, 12H, 16, 16’, 17, 17’-Me), 1.53 (t, 2H, J =
11.4 Hz, H-2, 2’ax), 1.71 (s, 6H, 18, 18’-Me), 1.75-1.78 (m, 2H,
H-2, 2’eq), 1.94 (s, 12H, Me-19, 19’, 20, 20’-Me), 2.10-2.15 (m,
2H, H-4, 4’ax), 2.37-2.41 (m, 2H, H-4, 4’eq), 2.68 (brs, 4H, CH2
propanoyl), 2.90 (brs, 4H, CH2 propanoyl), 3.20-3.71 (m, 12H,
H-2”, 3”, 4”, 5”, 2x6”), 4.65 (brs, 2H, OH), 4.98 (brs, 2H, H-3,
3’), 5.24 (brs, 2H, OH), 5.41 (brs, 2H, OH), 5.47 (d, 2H, J = 9.0
Hz, H-1”), 6.10-6.26 (m, 6H, H-7, 7’, 8, 8’, 10, 10’), 6.33-6.42
(m, 4H, H-12, 12’, 14, 14’), 6.64-6.72 (m, 4H, 11, 11’, 15, 15’),
mg, 0.06 mmol) and C3H7COOCu(PPh3)2 (2 mg, 0.003 mmol).
After stirring for 1 day under nitrogen atmosphere in darkness,
the solvent was evaporated under reduced pressure, and the
residue was purified by column chromatography (SiO2, CH2Cl2–
MeOH, 95:5). Yield: 30 mg (72%); orange plate crystals; mp:
147-148 °C; Rf = 0.75 (CH2Cl2–MeOH, 4:1). 1H-NMR (500
MHz, CD3OD): δ = 1.04 (s, 6H, 16, 17-Me), 1.48-1.51 (m, 2H,
H-2), 1.62-1.66 (m, 2H, H-3), 1.71 (s, 3H, Me-18), 1.82 (s, 3H,
Me-20’), 1.96, 1.97, 1.98 (3s, 6H, Me-19, 19’, 20-Me), 2.04 (t,
2H, J = 6.1 Hz, H-4), 2.78 (t, 2H, J = 7.4 Hz, CH2 propanoyl),
3.05 (t, 2H, J = 7.4 Hz, CH2 propanoyl), 3.48-3.57 (m, 3H, H-3”,
H-4”, H-5”), 3.71 (dd, 1H, J = 5.4 Hz, J = 12.1 Hz, H-6”), 3.85-

7
8.05 (s, 1H, triazole). 13C-NMR (125 MHz, (CD3)2SO): δ = 12.4,
12.5 (19, 19’, 20, 20’-Me), 20.5 CH2-C=C propanoyl), 21.1 (C-
18, 18’), 28.2, 29.7 (16, 16’, 17, 17’-Me), 33.0 (CH2-CO
propanoyl), 36.1 (C-4, 4’), 37.9 (C-1, 1’), 43.5 (C-2, 2’), 60.6 (C-
6”), 67.6 (C-3), 69.5, 72.0, 76.8, 79.8 (C-2”-C-5”), 87.3 (C-1”),
121.0 (triazole), 124.9, 125.0 (C-7, 7’, 11, 11’), 125.5 (C-5,5’),
130.3, 131.5, 132.6 (C-10, 10’, 14, 14’, 15, 15’), 135.2, 136.1,
137.2 (C-6, 6’, 9, 9’, 13, 13’), 137.4, 137.9 (C-8, 8’, 12, 12’),
145.1 (C=CH triazole), 171.6 (C=O, propanoyl). MS (MALDI-
TOF, positive mode, with DHB matrix) m/z = 1161.6 (M++Na+).
Anal. calcd. for C62H86N6O14: C 65.36, H 7.61, N 7.38, found C
65.07, H 7.75, N 7.58.
125.5 (C-11, 11’, 7, 7’), 125.6 (C-5, 5’), 122.0, 122.8, 122.8,
ACCEPTED MANUSCRIPT
125.3, 126.5, 126.6, 131.2, 132.9, 133.1, 136.8, 138.9, 140.3,
142.6, 143.8 (CH triazole, C-7, 7’, 8, 10, 10’, 11, 11’, 12, 12’, 14,
14’, 15, 15’), 126.8, 135.0, 136.8, 137.3, 138.8, 139.3 (C-5, 5’, 6,
9, 9’, 13, 13’), 147.6 (C=CH triazole), 148.6 (C-8’), 173.9, 174.0
(2 C=O propanoyl), 205.1 (C-6’). MS (MALDI-TOF, positive
mode, with DHB matrix) m/z = 1177.4 (M++Na+), 1193.4
(M++K+). Analysis calc. for C62H86N6O15: C 64.45, H 7.50, N
7.27, found C 64.23, H 7.51, N 7.38.
4.14. 3-(1-(1”-carboxamido-β-d-glucopyranosyl)-1,2,3-triazol-4-
yl)-propanoyloxy)-3’-hydroxy-β,β-carotene (24) and 3,3’-bis(1-
(1”-carboxamido-β-d-glucopyranosyl)-1,2,3-triazol-4-yl)-
propanoyloxy)-β,β-carotene (25)
4.12. 3-(1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl)-
propanoyloxy)-β,β-carotene (22)
Following the general procedure, zeaxanthin dipentynoate (6,
30 mg, 0.04 mmol) was dissolved in dry dichloromethane (1 mL)
with 1-carboxamido-β-D-glucopyranosyl azide (14, 10 mg, 0.04
Following the general procedure, β-cryptoxanthin pentynoate
(7, 30 mg, 0.047 mmol) was dissolved in dry dichloromethane (1
mmol) and C3H7COOCu(PPh3)2 (1.4 mg, 0.002 mmol). After
stirring for 2 days under nitrogen atmosphere in darkness, the
solvent was evaporated under reduced pressure. Compounds 24
and 25 were detected in the worked up reaction mixture by MS.
Compound 24: Rf = 0.65 (CH2Cl2–MeOH, 4:1); MS (MALDI-
TOF, positive mode, with DHB matrix) m/z = 976.4 (M+).
Compound 25: Rf = 0.15 (CH2Cl2–MeOH, 4:1); MS (MALDI-
TOF, positive mode, with DHB matrix) m/z = 1247.2 (M++Na+).
mL) with β-D-glucopyranosyl azide (13, 9.7 mg, 0.047 mmol)
and C3H7COOCu(PPh3)2 (1.6 mg, 0.0024 mmol). After stirring
for 12 h under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by preparative thin layer chromatography (SiO2, CH2Cl2–MeOH,
9:1). Yield: 30 mg (76%); red plate crystals; mp: 178-179°C; Rf =
1
0.57 (CH2Cl2–MeOH, 4:1). H-NMR (500 MHz, CDCl3): δ =
1.02, 1.05, 1.09 (3s, 12H, 16, 16’, 17, 17’-Me), 1.24 (s, 3H, 18’-
Me), 1.47, 1.61 (2brs, 5H, 2 H-2, 2’, H-3’), 1.71 (s, 3H, 18-Me),
1.95-2.08 (m, 15H, Me-19, 19’, 20, 20’-Me, 2 H-4’, H-4ax), 2.39-
2.42 (m, 1H, H-4eq), 2.63, 2.93 (2brs, 4H, 2 CH2 propanoyl),
3.65-4.13 (m, 6H, H-2”, 3”, 4”, 5”, 2x6”), 5.04 (brs, 2H, H-3,
OH), 5.56 (brs, 4H, H-1”, 3OH), 6.07-6.35 (m, 10H, H-7, 7’, 8,
8’, 10, 10’, 14, 14’, 12, 12’), 6.60 (brs, 4H, H-11, 11’, 15, 15’),
7.71 (brs, 1H, triazole). MS (MALDI-TOF, positive mode, with
DHB matrix) m/z = 837.4 (M+), 860.4 (M++Na+). Analysis calc.
for C51H71N3O7: C 73.09, H 8.54, N 5.01, found C 73.37, H 8.75,
N 4.75.
4.15. 3,3’-bis(1-(1”-carboxamido-β-d-glucopyranosyl)-1,2,3-
triazol-4-yl)-propanoyloxy)-β,κ-carotene (27)
Following the general procedure, capsanthin dipentynoate (8,
30 mg, 0.04 mmol) was dissolved in dry dichloromethane (1 mL)
with 1-carboxamido-β-D-glucopyranosyl azide (14, 10 mg, 0.04
mmol) and C3H7COOCu(PPh3)2 (1.4 mg, 0.002 mmol). After
stirring for 2 days under nitrogen atmosphere in darkness, the
solvent was evaporated under reduced pressure, and the residue
was purified by preparative thin layer chromatography (SiO2,
CH2Cl2–MeOH, 4:1). Yield: 7.5 mg of compound 27 (15%); red
syrup; Rf = 0.14 (CH2Cl2–MeOH, 4:1). 1H-NMR (500 MHz,
CD3OD): δ = 0.87, 1.09, 1.11, 1.33 (5s, 15H, 16, 16’, 17, 17’,18’-
Me), 1.55-1.60 (m, 2H, H-2ax, H-4’β), 1.74 (s, 3H, 18-Me), 1.76-
1.80 (m, 2H, H-2eq, H-2’β), 1.90, 1.98, 1.99 (3s, 12H, 19, 19’, 20,
20’-Me), 2.03-2.16 (m, 2H, H-4ax, H-2’α), 2.41 (dd, 1H, J = 6.0
Hz, J = 14.8 Hz, H-4eq), 2.71-2.73 (m, 4H, 2 CH2 pentynoate),
2.89 (dd, 1H, J = 8.7 Hz, J = 14.7 Hz, H-4’α), 3.01-3.05 (m, 4H,
2 CH2 pentynoate), 3.46-4.02 (m, 12H, H-2”, 3”, 4”, 5”, 2x6”),
5.04-5.10 (m, 1H, H-3), 5.21-5.25 (m, 1H, H-3’), 6.15 (ps, 2H,
H-7, H-8), 6.19 (d, 1H, J = 11.1 Hz, H-10), 6.32 (d, 1H, J = 11.4
Hz, H-14), 6.40-6.44 (m, 2H, H-12, H-14’), 6.55 (d, 1H, J = 15.1
Hz, H-7’), 6.61-6.64 (m, 2H, H-10’, 12’), 6.69-6.81 (m, 4H, 11,
11’, 15, 15’), 7.31 (d, 1H, J = 14.9 Hz, H-8’), 8.05, 8.07 (2s, 2H,
triazoles), 8.55 (s, 2H, CONH2). MS (MALDI-TOF, positive
mode, with DHB matrix) m/z = 1263.4 (M++Na+). Analysis calc.
for C64H88N8O17: C 61.92, H 7.15, N 9.03, found C 61.66, H 7.26,
N 8.84. Compound 26 was detected in the worked up reaction
mixture by MS. Rf = 0.57 (CH2Cl2–MeOH, 4:1); MS (MALDI-
TOF, positive mode, with DHB matrix) m/z = 1015.4 (M++Na+).
4.13. 3,3’-bis(1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl)-
propanoyloxy)-β,κ-carotene (23)
Following the general procedure, capsanthin dipentynoate (8,
30 mg, 0.04 mmol) was dissolved in dry dichloromethane (1 mL)
with β-D-glucopyranosyl azide (13, 8.5 mg, 0.04 mmol) and
C3H7COOCu(PPh3)2 (1.4 mg, 0.002 mmol). After stirring for 12
h under nitrogen atmosphere in darkness, the solvent was
evaporated under reduced pressure, and the residue was purified
by preparative thin layer chromatography (SiO2, CH2Cl2–MeOH,
4:1). Yield: 33 mg (71%); red syrup; Rf = 0.57 (CH2Cl2–MeOH,
1
4:1). H-NMR (500 MHz, CD3OD): δ = 0.87, 1.08, 1.11, 1.18
(4s, 12H, 16, 16’, 17, 17’-Me), 1.33 (s, 3H, 18’-Me), 1.57 (t, 2H,
J = 11.8 Hz, H-2ax, H-4’β), 1.74 (s, 3H, 18-Me), 1.78-1.80 (m,
2H, H-2eq, H-2’β), 1.97, 1.99, 2.00 (3s, 12H, 19, 19’, 20, 20’-
Me), 2.03-2.16 (2m, 2H, H-4ax, H-2’α), 2.41 (dd, 1H, J = 5.8 Hz,
J = 17.0 Hz, H-4eq), 2.70-2.74 (m, 4H, 2 CH2 pentynoate), 2.89
(dd, 1H, J = 8.5 Hz, J = 14.7 Hz, H-4’α), 3.01-3.03 (m, 4H, 2
CH2 pentynoate), 3.45-3.65, 3.85-3.88 (2m, 10H, H-2”, 3”, 4”,
5”, 6”), 3.71 (dd, 2H, J = 5.4 Hz, J = 11.9 Hz, H-6”), 5.04-5.10
(m, 1H, H-3), 5.21-5.25 (m, 1H, H-3’), 5.55, 5.56 (2d, overlayed,
2H, J = 9.2 Hz, 2xH-1”), 6.15 (ps, 2H, H-7, H-8), 6.18 (d, 1H, J
= 11.8 Hz, H-10), 6.32 (d, 1H, J = 11.2 Hz, H-14), 6.40-6.44 (m,
2H, H-12, H-14’), 6.55 (d, 1H, J = 15.1 Hz, H-7’), 6.61-6.65 (m,
2H, H-10’, 12’), 6.68-6.81 (m, 4H, 11, 11’, 15, 15’), 7.31 (d, 1H,
J = 15.1 Hz, H-8’), 7.97, 7.98 (2s, 2H, triazoles). 13C-NMR (125
MHz, CD3OD): δ = 12.8, 12.8, 12.9 (19, 19’, 20, 20’-Me), 21.0,
21.8 (18, 18’-Me), 21.91 (2 CH2-C≡C), 25.3, 26.0 (17, 17’-Me),
29.0, 30.6 (16, 16’-Me), 34.7, 34.8 (2 CH2-CO), 37.8, 39.3, 43.5,
44.8, 45.2 (C-1, 1’, 2, 2’, 4, 4’), 62.5 (C-6”), 70.0 (C-3), 75.3 (C-
3’), 71.0, 74.1, 78.6, 81.2 (C-2”-C-5”), 89.6 (C-1”), 120.6, 124.1,
Acknowledgements
This study was financed by the Hungarian Scientific Research
Fund (Grant: OTKA 115931, OTKA 109450) and the PTE ÁOK
(Grant No: KA-2015-18). VN thanks the János Bolyai Research
Scholarship of the Hungarian Academy of Sciences for support.
The authors are grateful to Mrs. Judit Rigó, Mrs. Krisztina Sajti
and Mr. Roland Lukács for their skillful assistance. The authors
thank Dr. Zoltán Novák (Eötvös Loránd University, Budapest)
for his generous donation of the catalyst bis-triphenylphosphano-

8
Tetrahedron
ACCEPTED MANUSCRIPT
12. Bokor, É.; Koppány, C.; Gonda, Z.; Novák, Z.; Somsák, L.
copper(I)-butyrate, Mr. Gergely Gulyás-Fekete for the NMR
Carbohydr. Res. 2012, 351, 42–48.
measurements, and Dr. Cecília Sár for the elemental analysis
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the 650th anniversary of the foundation of the University of Pécs,
Hungary.
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Supplementary Material
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