Multichromophoric sugar for fluorescence photoswitching

Article abstract of DOI:10.3762/bjoc.10.151

A multichromophoric glucopyranoside 2 bearing three dicyanomethylenepyran (DCM) fluorophores and one diarylethene (DAE) photochrome has been prepared by Cu(I)-catalyzed alkyne-azide cycloaddition reaction. The fluorescence of 2 was switched off upon UV irradiation, in proportion with the open to closed form (OF to CF) conversion extent of the DAE moiety. A nearly 100% Foerster-type resonance energy transfer (FRET) from all three DCM moieties to a single DAE (in its CF) moiety was achieved. Upon visible irradiation, the initial fluorescence intensity was recovered. The observed photoswiching is reversible, with excellent photo resistance.

Full text of DOI:10.3762/bjoc.10.151

Multichromophoric sugar for
fluorescence photoswitching
Stéphane Maisonneuve1, Rémi Métivier*1, Pei Yu2, Keitaro Nakatani1
and Juan Xie*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 1471–1481.
1PPSM, ENS Cachan, CNRS, UMR8531, 61 avenue du Président
Wilson, 94235 Cachan cedex, France and 2LCI, ICMMO, CNRS,
Université Paris-Sud, 15 rue Georges Clémenceau, 91405 Orsay
Cedex, France
doi:10.3762/bjoc.10.151
Received: 07 March 2014
Accepted: 28 May 2014
Published: 30 June 2014
Email:
Rémi Métivier* - metivier@ppsm.ens-cachan.fr; Juan Xie* -
joanne.xie@ens-cachan.fr
This article is part of the Thematic Series "Multivalent glycosystems for
nanoscience".
* Corresponding author
Guest Editor: J.-L. Reymond
Keywords:
© 2014 Maisonneuve et al; licensee Beilstein-Institut.
License and terms: see end of document.
click chemistry; energy transfer; fluorophore; monosaccharide;
photochromism
Abstract
A multichromophoric glucopyranoside 2 bearing three dicyanomethylenepyran (DCM) fluorophores and one diarylethene (DAE)
photochrome has been prepared by Cu(I)-catalyzed alkyne–azide cycloaddition reaction. The fluorescence of 2 was switched off
upon UV irradiation, in proportion with the open to closed form (OF to CF) conversion extent of the DAE moiety. A nearly 100%
Förster-type resonance energy transfer (FRET) from all three DCM moieties to a single DAE (in its CF) moiety was achieved.
Upon visible irradiation, the initial fluorescence intensity was recovered. The observed photoswiching is reversible, with excellent
photo resistance.
Introduction
The development of functional nanomaterials is nowadays a unit, and constitute “platforms” on which multiple functional
very attractive field of fundamental and applied research. The moieties can be attached. Among many applications, the use of
chemical functions at the molecular level yield properties, photochemical devices based on sugar derivatives is particu-
which are translated in terms of specific electronic or optical larly appealing for the development of supramolecular systems
functions to the materials and device level. One of the chal- for optical data storage media. Photochromic molecules are
lenges is to synthesize organic nano-architectures with a high particularly efficient photo-driven switches, as they can
degree of structural order and well-defined properties yielding commute upon light excitation between two distinct molecular
high-performance functions, for both economic and environ- species (states A and B, Figure 1) with the possibility to cycle
mental saving reasons. Saccharides are polyfunctional mole- up to one million “round trips”, showing different physical and
cules with well-defined stereogenic centres in one molecular chemical properties, the most noticeable one being the absorp-
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Figure 1: Requirements on absorption and emission spectral features of the photochromic and fluorescent units of the platform to induce efficient
fluorescence photoswitching by energy transfer process (FRET).
tion change [1]. Indeed, they usually shuttle between a color- energy transfer (FRET) process from the former to the latter
less and a colored form. Combining them with fluorescent com- would occur, when the photochromic moiety is in the colored
pounds provides an added value to their photophysical function. form (state B, Figure 1). At the opposite, in the colorless form
Actually, fluorescence allows the possibility to reach high (state A), the absence of FRET would keep the fluorescence
sensitivity and very low detection levels, down to the single alive, showing that the combination of these two functional
molecule limit, whereas absorption spectroscopy requires a high molecules leads to a photon-driven fluorescence switch.
number of active molecules [2]. If structural and spectral
features of the fluorophore and the photochromic compound fit Previously, we have synthesized a fluorescent-photochromic
well together, the fluorescence can be switched ON and OFF: dyad (1, Figure 2) combining a DCM fluorophore
quenching of the fluorescence through a Förster-type resonance (4-dicyanomethylene-2-tert-butyl-6-(p-dialkylaminostyryl)-4H-
Figure 2: Bifunctional fluorescent-photochromic molecules 1 and 2.
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pyran) [3] with a photochromic diarylethene (DAE) which the presence of copper sulfate and sodium ascorbate led to the
showed a photoreversible two-way FRET controlled by the state fluorescent glucoside 6. The trityl group was then removed by a
of the photochromic moiety, and 49% quenching of the fluores- catalytic amount of acetyl chloride in a mixture of MeOH and
cence upon UV irradiation [4]. Bifunctional molecules built on CH2Cl2. Subsequent activation as mesylated followed by
two distinct (photochrome and fluorophore) moieties have also “microwave-assisted” nucleophilic substitution with sodium
been reported by other groups [5-9]. The fluorophore vs azide afforded the corresponding 6-azido sugar 8 which was
photochrome ratio in reported bifunctional systems is 1:1 [4-7] treated with alkyne-functionalized photochromic diarylethene 9
or 2:1 [8,9]. Other strategies to assemble interacting fluoro- [26] to furnish the target compound 2 in 68% yield. The struc-
phores and photochromes (supramolecular systems, nanoparti- ture of this compound has been confirmed by NMR and HRMS
cles, polymer materials) are also reported [10-13]. FRET oper- spectra.
ates at distances of a few nanometers around the photochromic
moiety (in its state B, Figure 1), which is related to the Förster Photophysical studies
radius. It means that in a suitably designed molecular system, The fluorescent glucoside derivative 6, bearing three DCM
one single photochromic unit can quench several fluorophores fluorophores, is used as a model fluorescent compound. Its
present within this distance. In a situation where one photo- absorption spectrum in acetonitrile, plotted in Figure 3a, shows
chromic unit is surrounded by several fluorophores, we can take a main large band peaking at 455 nm. It exhibits a wide fluores-
advantage of this phenomenon both to increase the brightness of cence spectrum between 550 nm and 700 nm, with a maximum
the fluorescent molecular system and to turn “ON” and “OFF” located at 610 nm (Figure 3b), associated with a fluorescence
several fluorophores with one given photochromic molecule. quantum yield ΦF = 0.12. These spectroscopic characteristics
This is valuable in terms of photon (thus energy) saving, since are rather comparable to the absorption and fluorescence
“switching a few photochromes leads to quenching many features of the fluorophore 5 [4]. The photophysical properties
fluorophores”. In this perspective, we decided to design a multi- of the photochromic model compound 9 have been described in
chromophoric glycopyranoside bearing three DCM fluoro- a previous report [4]. Briefly, the diarylethene 9 is originally in
phores and one photochromic bis(dithiazole)ethane [14-16] its colorless open form (9-OF), with an absorption spectrum in
(compound 2, Figure 2) so as to take advantage of this sugar- acetonitrile located in the UV range (λmax = 317 nm, Figure 3c,
based “platform” to get a specific molecular architecture and to full black line). In this state, 9-OF is moderately fluorescent in
study the energy transfer and photo-switching efficiency. To the the blue region (λmax = 440 nm, ΦF = 0.016, Figure 3d). Under
best of our knowledge, readily available monosaccharides have irradiation at 335 nm, 9-OF undergoes a cyclisation photoreac-
been rarely used to develop multichromophoric supramolecular tion yielding the molecule in its colored and non-fluorescent
systems. Only one artificial light-harvesting antenna system closed form (9-CF), as revealed by the appearance of a large
grafted on the α-D-glucopyranoside has been reported [17].
absorption band peaking in the 500–700 nm range (Figure 3c,
full blue line). The photostationary state (PSS) reached under
335 nm illumination is composed of 91% of 9-CF and 9% of
9-OF (Figure 3c, dashed line). The target compound 2 can be
Results and Discussion
Synthesis of multichromophoric sugars
Synthesis of organic nano-architectures with a high degree of considered as the assembly of the fluorescent model derivative
structural order and defined properties is challenging because 6 and the photochromic model compound 9. Indeed, before any
sophisticated multistep experimental procedures are often impli- UV irradiation, the absorption spectrum of 2 in its open form
cated. Recently, the Cu(I)-catalyzed alkyne–azide cycloaddi- (2-OF) represents the overlay of the absorption feature of 6 and
tion reaction (CuAAC, an excellent example of click chemistry) 9-OF: as displayed in Figure 3e (full line), the absorption band
has been demonstrated as a robust and highly efficient ligation at 455 nm matches to the three fluorophores, whereas the
tool to conjugate various azido- and alkyne-functionalized absorption bands at 286 nm and 325 nm correspond mostly to
moieties [18-20]. Monosaccharides can be readily functional- the photochromic diarylethene moiety. The fluorescence spec-
ized with several propargyl groups to synthesize, using click trum of 2-OF shows a very weak blue emission band between
chemistry, multivalent neoglycoconjugates for recognition 400 nm and 500 nm from the diarylethene unit, and a rather
studies with carbohydrate-binding proteins (lectins) [21-24] or strong red emission band peaking at 610 nm from the three
to develop light-harvesting antenna systems [17]. In order to DCM dyes (Figure 3f). This dual emission will be discussed
introduce three DCM fluorophores and one photochromic further, by a careful analysis of excitation spectra (vide infra).
species into the glycopyranoside scaffold, methyl 6-O-trityl-α- Figure 4a and b show that upon increasing irradiation times at
D-glucopyranoside 3 was chosen as starting material 335 nm, an absorption band at 600 nm emerges, corresponding
(Scheme 1). O-Propargylation followed by microwave-assisted to the photochromic moiety in its thermally stable closed form,
CuAAC with azido-functionalized DCM fluorophore 5 [25] in and the fluorescence emission is concomitantly quenched by
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Scheme 1: Synthesis of multichromophoric glucopyranoside 2.
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Figure 3: Absorption and fluorescence spectra of compounds 6, 9, and 2 in CH3CN: (a) absorption spectrum of 6; (b) emission spectrum of 6
(λexc = 450 nm); (c) absorption spectra of 9-OF, 9 at the photostationary state (PSS) under 335 nm illumination, isolated 9-CF; (d) emission spectrum
of 9-OF (λexc = 325 nm); (e) absorption spectra of 2-OF, 2 at the photostationary state (PSS) under 335 nm illumination (no noticeable change has
been observed over 5 days, indicating the thermal stability of 2), 2-CF (obtained by extrapolation of the 1H NMR vs UV–visible absorption experiment,
see text for details); (f) emission spectra of 2-OF and 2 at the photostationary state (PSS) under 335 nm illumination (λexc = 325 nm).
51%. As displayed in Figure 3, the emission band of the fluoro- maximum conversion reached was about 39%. Such combined
phores in the 550–700 nm range overlaps well the absorption 1H NMR vs UV–visible absorption data allowed us to extrapo-
band of the photochromic derivative in its closed form, in the late the absorption spectrum of the dyad molecule in its pure
same spectral region. Therefore, the fluorescence quenching closed form 2-CF, as plotted in Figure 3e (dotted line). It
observed for the compound 2 under UV irradiation can be easily appears that the PSS obtained for the compound 2 with a light-
interpreted as the consequence of a FRET process from the irradiation at 335 nm corresponds to a mixture of 53% of 2-CF
DCM fluorophores (donors) to the diarylethene derivative in its and 47% of 2-OF. Such a conversion yield has to be compared
colored closed form (acceptor), which plays the role of the to the fluorescence quenching of 2 observed after irradiation at
quencher. The multichromophoric system 2 is completely re- 335 nm (51% fluorescence quenching, vide supra). Therefore,
versible: under irradiation at 575 nm, the cycloreversion reac- the incomplete fluorescence quenching is due to a limited
tion 2-CF → 2-OF occurs, the absorption band centered at photochromic conversion yield under UV light. Furthermore,
610 nm drops back to zero and the fluorescence of the sample is since the photochromic conversion yield (53%) corresponds
fully recovered (Figure 4c and d). As shown in Figure 4e and f, almost to the fluorescence quenching (51%), the FRET process
several UV–visible irradiation cycles were applied to the system appears to be extremely efficient: under irradiation at 335 nm,
without any degradation of its photophysical properties, half of the multichromophoric system is still in its initial open
revealing its excellent fatigue resistance.
form 2-OF, associated with a strong fluorescence emission, and
another half are promoted in their closed form 2-CF, whose
1H NMR spectra were recorded under increasing irradiation fluorescence is almost totally quenched by FRET.
times at 335 nm in order to follow the photoisomerisation of
compound 2 (Figure 5), and corresponding UV–visible absorp- This phenomenon is well-supported by time-resolved fluores-
tion spectra were measured, in order to correlate the absorption cence measurements. Fluorescence decay curves of 6, 2-OF,
changes with the OF → CF conversion yield. Under 335 nm and 2 after irradiation at 335 nm were recorded in acetonitrile
illumination, new signals appear near 5.2 ppm (for OCH2 by the time-correlated single photon counting method (TCSPC)
group) and 6.5 to 8.0 ppm which are induced by the photocycli- at λexc = 475 nm, and analyzed by a sum of three exponential
sation of the photochromic moiety from the open to the closed components (Table 1). The model fluorescent glucoside deriva-
form. Due to higher concentration of NMR sample, the tive 6 shows a main time-constant at τ1 = 1.00 ns, a second
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Figure 4: Absorption and fluorescence changes of compound 2 (1.0 μM in CH3CN) upon UV–visible irradiation: (a) absorption and (b) emission
spectra (λexc = 450 nm) under increasing irradiation times at 335 nm; (c) time-evolution profile of absorption and (d) emission upon irradiation at
335 nm and 575 nm; (e) fatigue resistance followed by the absorption band at 610 nm and (f) the emission band at 610 nm under alternate 355 nm/
575 nm irradiation cycles. Irradiation conditions at 335 nm: (a–d) 2.7 mW cm−2 and (e,f) 40 s at 7.2 mW cm−2. Irradiation conditions at 575 nm:
(a–d) 3.1 mW cm−2 and (e,f) 120 s at 9.5 mW cm−2.
component at τ2 = 0.35 ns, and a minor time-constant at with the fraction of the intensities comparable to 6. In a similar
τ3 = 0.04 ns. The latter one has been neglected in the following manner, the two significant contributions correspond to the E
discussion, since it is very close to the time-resolution of our and Z-isomers of the fluorophores, respectively. Interestingly,
instrument, and associated with a very low fraction of intensity the fluorescence decay curves of 2 before and after UV irradi-
(0.02). The two other time-constants are attributed to the ation are overlapping, and the results of the fitting are identical
E-isomer (τ1) and the Z-isomer (τ2) of the fluorophores, which in both cases, despite the fact that the fluorescence intensity is
is consistent with our previous studies [4]. The fluorescence decreased by a factor of two (51% fluorescence quenching, vide
decays of 2-OF and 2 after irradiation at 335 nm are plotted in supra). Such an observation is compatible with a static FRET
Figure 6a, and the result of a global three-exponential fitting quenching process. Indeed, when the PSS is reached under
procedure is displayed on Table 1. The three time-constants 335 nm irradiation, the population of 2-OF molecules repre-
obtained by this method are in the same range as the ones deter- sents 47% of the whole system, behaves as the initial non-irra-
mined for 6: τ1 = 1.26 ns, τ2 = 0.47 ns, τ3 = 0.05 ns, associated diated molecules and contributes to the fluorescence decay,
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Figure 5: Partial 1H NMR spectra of compound 2 (11 μM in CD3CN/DMSO-d6 4:1) before and after increasing irradiation times at 335 nm (from
bottom to top). The conversion yield at each irradiation time is deduced from the integration of signals around 5.2–5.3 and 7.0–7.1 ppm.
Table 1: Fluorescence decay parameters of compounds 6 and 2 in CH3CN.
τ1/ns (a1, f1a)
τ2/ns (a2, f2a)
τ3/ns (a3, f3a)
χ2R
6
1.00 (0.43, 0.79)
1.26 (0.40, 0.75)
1.26 (0.35, 0.74)
0.35 (0.29, 0.19)
0.47 (0.33, 0.23)
0.47 (0.30, 0.23)
0.04 (0.28, 0.02)
0.05 (0.27, 0.02)
0.05 (0.35, 0.03)
1.08
1.16
1.12
2-OFb
2 (PSS under irradiation at 335 nm)b
aThe fraction of intensities fi is defined as follows: fi = aiτi/Σajτj. bResults obtained by means of a global fitting procedure.
whereas the population of 2-CF molecules (53% of the system) shape of its absorption spectrum, with a large band centered at
is fully quenched through a very efficient FRET process, its 455 nm. However, the excitation spectrum of the molecule
contribution to the emission signal is negligible, and its decay- 2-OF recorded at λem = 620 nm (corresponding to the fluoro-
time is obviously below the time-resolution of our instrument. phore emission) shows an additional contribution in the
As a conclusion, the FRET process from the fluorophores to the 250–350 nm range, which corresponds to the open form of the
closed form of the photochromic diarylethene is close to 100% photochromic moiety, revealing a FRET process from the open
in the molecule 2.
form of the diarylethene unit (donor) to the DCM fluorophores
(acceptors). This energy transfer pathway is actually allowed by
Fluorescence excitation spectra provide another evidence of the favorable spectral overlap in the 400–500 nm range between
FRET intramolecular phenomenon within the compound 2. the blue emission of the photochromic moiety in its open form
Indeed, the excitation spectrum of the model fluorescent gluco- (see Figure 3d) and the absorption of the fluorophores (see
side 6, displayed in Figure 6b (red curve), resembles to the Figure 3a). As evidenced previously on 1 [4], this "reverse"
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Figure 6: (a) Fluorescence decays (λexc = 475 nm, λem = 610 nm) of compound 2-OF, and 2 after irradiation at 335 nm in CH3CN (7 mW cm−2).
(b) Normalized excitation spectra (λem = 620 nm) of 6 (red line) and 2-OF (green line) in CH3CN.
FRET explains why the emission of the photochromic moiety is moieties, by a FRET yield close to unity. This study is
almost absent in the fluorescence spectrum of the dyad 2-OF supported by time-resolved fluorescence experiments. This
(Figure 3f).
result represents a step forward, compared to our previous
report on the 1/1 system 1. The increase of the OF to CF
Finally, the limited conversion yield of the molecule 2 under ir- conversion extent of the photochromic unit is among our future
radiation in the UV (53%), compared to the model photo- perspectives, since this could lead to a better ON vs OFF fluo-
chromic compound 9 (conversion yield = 91%) can be rescence contrast. By a careful molecular engineering,
explained by this efficient double FRET effect: (i) the energy combining photophysical analysis and synthetic work, we are
transfer from the open form of the photochromic unit to the endeavoring to tune optimally the fluorophore/photochrome
fluorophores tends to deactivate the photochromic activity of ratio. Glycosides, and more generally sugar molecules, may
2-OF, and (ii) the energy transfer from the fluorophores to the further provide appropriate "platforms".
closed form of the photochromic unit contributes to favor the
Experimental
CF → OF cycloreversion reaction. Consequently, the PSS of 2
when irradiated at 335 nm is much lower than the photo- General details
chromic moiety 9 alone, because of the highly efficient FRET Commercially available solvents and reagents were used
processes.
without further purification. Compounds 3 [27], 5 [25] and 9
[26] were prepared according to the literature. Melting points
were measured on a Kofler bench. Optical rotations were
Conclusion
Through click chemistry, we have successfully introduced three measured using a JASCO P-2000 polarimeter. Column chroma-
DCM fluorophores and a DAE photochrome on the methyl α-D- tography was performed on Carlo Erba Silica Gel 60A
glucopyranoside in good yield. The multichromophoric com- (40–63 µm). Analytical thin-layer chromatography was
pound 2 can be reversibly switched upon UV and visible irradi- performed on E. Merck aluminum percolated plates of Silica
ation, and showed an excellent fatigue resistance. Under UV ir- Gel 60F-254 with detection by UV. 1H and 13C NMR spectra
radiation at 335 nm, the fluorescence was decreased by 51%. were recorded on a Jeol ECS-400 spectrometer. HRMS–ESI
This value corresponds to the photochromic conversion yield at spectra were recorded on a Bruker microTOF-Q II spectrom-
this photostationary state, with 53% of the DAE molecules eter or Bruker maXis using standard conditions.
promoted to their closed form. We therefore demonstrated that,
at the molecular level, one single DAE moiety in the closed Absorption spectra were recorded on a Cary-5000 spectropho-
form induces the full fluorescence quenching of all three DCM tometer from Agilent Technologies. Corrected emission spectra
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Beilstein J. Org. Chem. 2014, 10, 1471–1481.
were performed on a Fluorolog FL3-221 spectrofluorometer rated under vacuum to give the crude product which was puri-
from Horiba Jobin-Yvon. The fluorescence quantum yields fied by column chromatogrphy using a mixture of petroleum
were determined by using quinine sulfate dihydrate in sulfuric ether (PE):EtOAc (95:5, 9:1, 8:2) to give 87% of the desired
acid (0.5 N) as a standard at λexc = 325 nm (ΦF = 0.546) and compound (3.36 g, 6.10 mmol) as white solid, mp 96–97 °C;
coumarin 540A in ethanol as a standard at λexc = 450 nm Rf = 0.64 (PE/EtOAc = 4:1); [α]D +51 (c 0.5, CHCl3); 1H NMR
(ΦF = 0.544). Photochromic reactions were induced in situ by a (400 MHz, CDCl3) δ 2.23 (t, J = 2.3 Hz, 1H, CH≡), 2.45 (t, J =
continuous irradiation Hg–Xe lamp (Hamamatsu, LC6 Light- 2.3 Hz, 1H, CH≡), 2.50 (t, J = 2.3 Hz, 1H, CH≡), 3.12 (dd, J =
ningcure, 200 W) equipped with narrow band interference 5.0, 10.1 Hz, 1H, H-6), 3.46 (s, 3H, OMe), 3.45–3.49 (m, 1H,
filters of appropriate wavelengths (Semrock FF01-335/7-25 for H-6’), 3.53 (t, J = 9.2 Hz, 1H, H-4), 3.68 (dd, J = 3.7, 9.6 Hz,
λirr = 335 nm; FF01-575/25-25 for λirr = 575 nm). The irradi- 1H, H-2), 3.69–3.72 (m, 1H, H-5), 3.78 (t, J = 9.2 Hz, 1H, H-3),
ation power was measured using a photodiode from Ophir 4.08 (dd, J = 2.8, 15.1 Hz, 1H, OCH), 4.25 (dd, J = 2.8, 15.1
(PD300-UV). The photoconversion was followed by a combina- Hz, 1H, OCH), 4.40–4.45 (m, 4H, 2×OCH2), 4.97 (d,
tion of 1H NMR and UV–visible absorption spectra, realized by J = 3.7 Hz, 1H, H-1), 7.21–7.32 (m, 9H, HAr), 7.47–7.49 (m,
successive irradiation at 335 nm for a total time of 20 min. 6H, HAr) ppm; 13C NMR (100 MHz, CDCl3) δ 55.05 (OMe),
Fluorescence intensity decays were obtained by the time-corre- 58.83, 59.94, 60.59 (OCH2), 62.83 (C-6), 69.80 (C-5), 74.31,
lated single-photon counting (TCSPC) method with femto- 75.06 (Cq), 77.36 (C-4), 79.46 (C-2), 79.87, 79.99, 80.19
second laser excitation using a set-up composed of a Ti:Sa laser (CH≡), 81.75 (C-3), 86.49 (Cq), 97.79 (C-1), 127.11, 127.95,
(Tsunami, Spectra-Physics) pumped by a doubled Nd:YAG 128.86 (CHAr), 144.11 (Cq) ppm; HRMS–ESI (m/z): [M + Na]+
cw-laser (Millennia, Spectra-Physics), pumped itself by two calcd for 573.2253; found: 573.2244.
laser diode arrays. Light pulses at 950 nm were selected by
DCM-functionalized methyl 6-O-trityl-α-D-
optoacoustic crystals at a repetition rate of 4 MHz, and then
doubled at 475 nm by non-linear crystals. Fluorescence photons glucopyranoside 6
were detected through a band-pass filter 370–500 nm (a mono- To a solution of 4 (1.01 g, 1.83 mmol) in distilled DMF
chromator set at 620 nm, respectively) by means of a Hama- (15 mL), were added the azido-DCM 5 (2.23 g, 5.57 mmol),
matsu MCP R3809U photomultiplier, connected to a constant- CuSO4 (110.9 mg, 0.44 mmol) and Na ascorbate (188 mg,
fraction discriminator. The time-to-amplitude converter was 0.95 mmol). The reaction mixture was stirred at 70 °C during
purchased from Tennelec. In the present investigation, the 5 min then at 130 °C during 30 to 45 min under microwave ir-
channel width was set to 3.1 ps. The instrumental response radiation (700 rpm, monitoring by TLC), and poured into
function was recorded before each decay measurement with a distilled water after cooling to room temperature. The precipi-
fwhm (full width at half-maximum) of ~25 ps. The fluores- tate was then filtred through a cellulose acetate filter (porosity
cence data were analyzed using the Globals software package 2 µm) under vacuum and washed with water, then purified
developed at the Laboratory for Fluorescence Dynamics at the by column chromatography using pure EtOAc, then
University of Illinois at Urbana-Champaign, which includes EtOAc/acetone (gradient 9:1, 8:2, 5:5) then EtOAc/EtOH (7:3)
reconvolution analysis and non-linear least-squares minimiza- to give 65% of the desired compound (2.09 g, 1.19 mol) as a red
tion method. The shortest fluorescence decay time accessible by solid; mp 164–166 °C; Rf = 0.29 (EtOAc/acetone = 9:1); [α]D
our instrumental set-up and our data analysis method was esti- +12 (c 0.5, CHCl3); 1H NMR (400 MHz, acetone-d6) δ 1.38 (s,
mated to be around 10 ps (time-resolution).
27H, Ht-Bu), 2.84 (s, 3H, NMe), 2.85 (s, 3H, NMe), 2.85 (s, 3H,
NMe), 3.10 (dd, J = 4.6, 10.1 Hz, 1H, H-6), 3.39–3.40 (m, 1H,
H-6’), 3.41 (s, 3H, OMe), 3.50 (t, J = 9.5 Hz, 1H, OCH), 3.55
(dd, J = 3.7, 9.6 Hz, H-2), 3.62–3.70 (m, 2H, 2×OCH),
Methyl 2,3,4-tri-O-propargyl-6-O-trityl-α-D-
glucopyranoside (4)
To a stirred solution of methyl 6-O-trityl-α-D-glucopyranoside 3.82–3.99 (m, 6H, 3×NCH2), 4.34 (d, J = 11.4 Hz, 1H, NCH),
(3, 3.08 g, 7.05 mmol) in distilled DMF (60 mL) under argon in 4.58–4.86 (m, 11H, NCH, 2×NCH2, 3×OCH2), 4.98 (d,
an ice bath, were added Bu4NI (3.07 g, 8.32 mmol) and J = 3.7 Hz, 1H, H-1), 6.45–6.46 (m, 3H, 3×CH=), 6.56–6.73
propargyl bromide (80% solution in toluene, 2.3 mL, (m, 9H, 9×CH=), 6.81 (d, J = 16.0 Hz, 1H, CH=), 6.86 (d,
20.65 mmol). The NaH (60% in mineral oil, 1.02 g, 25.5 mmol) J = 16.0 Hz, 1H, CH=), 6.87 (d, J = 16.0 Hz, 1H, CH=),
was then added slowly by portions. After 15 min, the mixture 7.21–7.33 (m, 10H, 10×CH=), 7.39 (s, 1H, HTriazole), 7.41–7.53
was heated at 50 °C over 2 to 3 h (brown to black color). After (m, 14H, 14×CH=), 8.15 (s, 1H, HTriazole), 8.17 (s, 1H,
evaporation under vacuum, the residue was partitioned in a mix- HTriazole) ppm; 13C NMR (100 MHz, acetone-d6) δ 28.14
ture of EtOAc/H2O (200:200 mL) and the aqueous layer was (Met-Bu), 37.26 (Cq), 38.63, 38.78 (NMe), 47.99, 48.12, 48.18,
extracted with EtOAc (2 × 100 mL). The organic layers were 52.89 (NCH2), 55.14 (OMe), 57.61 (Cq), 63.50 (C-6), 64.41,
combined, washed with brine, dried over MgSO4 and evapo- 66.39, 66.98 (OCH2), 69.68 (Cq), 70.96 (C-5), 78.46, 80.40,
1479

Beilstein J. Org. Chem. 2014, 10, 1471–1481.
81.91 (C-2,3,4), 87.03 (Cq), 98.37 (C-1), 102.62, 106.02, mesylate in DMF (3 mL) was added sodium azide (29.9 mg,
106.07, 112.67, 112.75, 114.21, 114.33 (CH=), 116.13, 116.18, 0.46 mmol) and the mixture was stirred at 110 °C during 15 min
123.98, 124.07 (Cq), 124.81, 125.29, 125.45 (CHTriazole), under microwave irradiation (700 rpm, monitoring by TLC).
127.86, 128.66, 129.56, 130.79, 130.84, 139.11, 139.22 (CH=), After cooling to room temperature, the reaction mixture was
145.00, 145.56, 145.91, 146.14, 151.13, 151.18, 157.49, 157.49, poured into 20 to 25 mL of distilled water. The precipitate was
161.50, 161.55, 173.02 (Cq) ppm; HRMS–ESI (m/z): [M + H]+ then filtred through cellulose acetate filter (porosity 2 µm)
calcd for 1751.8463; found: 1751.8397.
under vacuum and washed with water. The product was puri-
fied by column chromatography using EtOAc/acetone (gradient
1:0 to 9:1) to give 75% of the desired compound (328 mg,
0.21 mmol) as a red solid; mp 156–158 °C; Rf = 0.49
DCM-functionalized methyl α-D-glucopyrano-
side 7
To a stirred solution of compound 6 (940 mg, 0.54 mmol) in a (EtOAc/acetone = 4:1); [α]D +9 (c 0.5, CHCl3); 1H NMR
mixture of CH2Cl2/MeOH (10/10 mL) cooled in an ice bath, (400 MHz, CDCl3) δ 1.37 (s, 27H, Ht-Bu), 2.91 (s, 3H, NMe),
was added acetyl chloride (115 µL, 1.61 mmol). After 2.5 h, the 2.92 (s, 3H, NMe), 2.92 (s, 3H, NMe), 3.31–3.51 (m, 3H,
reaction was quenched by addition of a saturated NaHCO3 solu- H-4,6,6’), 3.39 (s, 3H, OMe), 3.49 (dd, J = 3.7, 9.6 Hz, 1H,
tion (5 mL). The mixture was extracted with CH2Cl2. The H-2), 3.64–3.69 (m, 1H, H-5), 3.79 (t, J = 9.6 Hz, 1H, H-3),
organic layers were combined, washed with brine, dried over 3.90–3.97 (m, 6H, 3×NCH2), 4.57–4.64 (m, 6H, 3×NCH2),
MgSO4 and evaporated under vacuum. The product was puri- 4.65–4.97 (m, 7H, 3×OCH2, H-1), 6.46–6.66 (m, 16H,
fied by column chromatography using pure EtOAc followed by 16×CH=), 7.26–7.42 (m, 8H, 8×CH=), 7.69 (s, 1H, HTriazole),
a mixture of EtOAc/acetone (gradient 9:1, 8:2, 7:3, 6:4) to give 7.89 (s, 1H, HTriazole), 8.00 (s, 1H, HTriazole) ppm; 13C NMR
74% of the desired compound (600 mg, 0.40 mmol) as a red (100 MHz, CDCl3) δ 28.16 (Met-Bu), 36.68 (Cq), 38.54, 38.65,
solid; mp 156–158 °C; Rf = 0.22 (EtOAc/acetone = 4:1); [α]D 38.71 (NMe), 47.51 (NCH2), 51.22 (C-6), 52.52 (NCH2), 55.39
+25 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.37 (s, (OMe), 57.84, 57.91, 57.91 (Cq), 64.26, 65.87, 66.28 (OCH2),
27H, Ht-Bu), 2.89 (s, 3H, NMe), 2.91 (s, 3H, NMe), 2.92 (s, 3H, 69.57 (Cq), 69.83 (C-5), 77.37 (Cq), 78.00 (C-4), 79.29 (C-2),
NMe), 3.37 (s, 3H, OMe), 3.47 (dd, J = 3.2, 9.6 Hz, 1H, H-2), 81.08 (C-3), 97.43 (C-1), 102.41, 105.80, 111.95, 112.01,
3.52–3.54 (m, 2H, H-3,4), 3.73 (s, 2H, H-6,6’), 3.80–3.83 (m, 113.73, 113.78 (CH=), 115.70, 115.83, 123.31, 123.37 (Cq),
1H, H-5), 3.92–3.94 (m, 6H, 3×NCH2), 4.58–4.60 (m, 6H, 124.13, 124.43, 124.77 (CHTriazole), 129.89 (Cq), 137.89,
3×NCH2), 4.74–4.97 (m, 7H, H-1, 3×OCH2), 6.45–6.65 (m, 137.93, 138.02 (CH=), 144.81, 144.86, 145.27, 149.86, 149.96,
16H, 16×CH=), 7.25–7.42 (m, 8H, 8×CH=), 7.63 (s, 1H, 149.96, 156.80, 159.97, 160.03, 172.02 (Cq) ppm; HRMS–ESI
HTriazole), 7.87 (s, 1H, HTriazole), 8.00 (s, 1H, HTriazole) ppm; (m/z): [M + H]+ calcd for 1534.7432; found: 1534.7381; [M +
13C NMR (100 MHz, CDCl3) δ 28.18 (Met-Bu), 36.70 (Cq), 2H]2+ calcd for 767.8753; found: 767.8746.
38.59, 38.66, 38.74 (NMe), 47.49, 47.57, 52.53 (NCH2), 55.22
DCM and DAE-functionalized methyl α-D-
(OMe), 57.89, 57.94 (Cq), 61.18 (C-6), 64.13, 65.75, 66.27
(OCH2), 69.60 (Cq), 70.71, 77.36 (C-3,4), 79.39 (C-2), 81.42 glucopyranoside 2
(C-5), 97.51 (C-1), 102.43, 105.81, 111.98, 112.03, 113.81 To a solution of compound 8 (51.1 mg, 0.033 mmol) in DMF
(CH=), 115.70, 115.81, 115.86, 123.30, 123.35, 123.41 (Cq), (2 mL) were added the photochromic compound 9 (62.0 mg,
123.86, 124.43, 124.74 (CHTriazole), 129.91, 137.95, 138.02 0.111 mmol), CuSO4 (2.5 mg, 0.010 mmol) and Na ascorbate
(CH=), 144.90, 145.32, 145.42, 149.84, 149.92, 149.98, 156.83, (6.8 mg, 0.034 mmol). The reaction mixture was stirred at
160.01, 160.01, 160.05, 172.04 (Cq) ppm. HRMS–ESI (m/z): 70 °C during 5 min then at 130 °C during 30 to 45 min under
[M + H]+ calcd for 1509.7367; found: 1509.7332; [M + 2H]2+ microwave irradiation (700 rpm, monitoring by TLC), and
calcd for 755.3720; found: 755.3715.
poured into distilled water after cooling to room temperature.
The precipitate was then filtred through a cellulose acetate filter
(porosity 2 µm) under vacuum and washed with water, then
purified by column chromatogrphy using EtOAc:ethanol (9:1)
DCM-functionalized methyl 6-azido-6-deoxy-
α-D-glucopyranoside 8
To a stirred solution of compound 7 (414 mg, 0.27 mmol) in to give 66% of the desired compound (45.8 mg, 0.022 mmol) as
CH2Cl2 (2 mL) were added Et3N (125 µL, 0.90 mmol) and a red solid; mp 181–183 °C; Rf = 0.53 (EtOAc/acetone = 4:1);
MsCl (52 µL, 0.67 mmol). After stirring 3.5 h, the mixture was [α]D +45 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.36 (s,
treated with 10 mL of water and the aqueous layer was 27H, Ht-Bu), 2.09 (s, 3H, Me), 2.54 (s, 3H, Me), 2.88 (s, 3H,
extracted with CH2Cl2 (3 × 20 mL). The organic layers were NMe), 2.90 (s, 3H, NMe), 2.92 (s, 3H, NMe), 2.97 (t,
combined, washed with brine, dried over MgSO4 and evapo- J = 9.6 Hz, 1H, H-4), 3.21 (s, 3H, OMe), 3.35 (dd, J = 3.2,
rated under vacuum to a crude mesylate which was used 9.6 Hz, 1H, H-2), 3.79–3.93 (m, 8H, H-3,5, 3×NCH2),
without purification for the next step. To a solution of crude 4.45–4.81 (m, 13H, H-1,6,6’, 3×NCH2, 2×OCH2), 4.93 (d,
1480

Beilstein J. Org. Chem. 2014, 10, 1471–1481.
15.Nakashima, T.; Kajiki, Y.; Fukumoto, S.; Taguchi, M.; Nagao, S.;
Hirota, S.; Kawai, T. J. Am. Chem. Soc. 2012, 134, 19877–19883.
doi:10.1021/ja309275q
J = 11.4 Hz, 1H, OCH), 4.97 (d, J = 11.5 Hz, 1H, OCH), 5.26
(s, 2H, OCH2), 6.45–6.64 (m, 15H, 15×CH=), 7.02 (d,
J = 8.7 Hz, 2H, 2×CH=), 7.26–7.49 (m, 15H, 15×CH=),
7.77–7.79 (m, 4H, 4×CH=), 7.88 (d, 2H, J = 8.7 Hz, 2×CH=),
7.97 (s, 1H, HTriazole), 8.03–8.09 (m, 3H, 3×CH=) ppm;
13C NMR (100 MHz, CDCl3) δ 12.46, 12.94 (Me), 28.25
(Met-Bu), 36.77 (Cq), 38.79, 38.88 (NMe), 47.56, 47.68
(NCH2), 50.54 (C-6), 52.56, 52.62, 52.72 (NCH2), 55.56
(OMe), 58.20, 58.28 (Cq), 62.07, 64.23, 65.96, 66.27 (OCH2),
68.89 (CH), 69.65 (Cq), 77.36, 79.31, 81.05 (OCH), 97.56
(C-1), 102.54, 112.21, 113.95, 114.05, 114.09, 115.29 (CH=),
115.71, 115.87, 123.51, 123.55, 123.60, 123.66 (Cq), 124.57,
124.68, 124.94, 126.41, 126.72, 128.20, 128.89, 129.08, 129.95,
130.40 (CH=), 133.59, 133.68 (Cq), 137.89, 137.95, 138.02
(CH=), 143.90, 144.78, 144.99, 145.06, 149.85, 156.89, 160.02,
163.93, 164.13, 167.30, 172.08 (Cq) ppm; HRMS–ESI (m/z):
[M + 2H]2+ calcd for 1048.4254; found: 1048.4247; [M +
3H]3+ calcd for 699.2860; found: 699.2845.
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doi:10.1002/anie.200701396
11.Del Guerzo, A.; Olive, A. G. L.; Reichwagen, J.; Hopf, H.;
Desvergne, J.-P. J. Am. Chem. Soc. 2005, 127, 17984–17985.
doi:10.1021/ja0566228
12.Fölling, J.; Polyakova, S.; Belov, V.; van Blaaderen, A.; Bossi, M. L.;
Hell, S. W. Small 2008, 4, 134–142. doi:10.1002/smll.200700440
13.Métivier, R.; Badré, S.; Méallet-Renault, R.; Yu, P.; Pansu, R. B.;
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The definitive version of this article is the electronic one
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