Synthesis of O-1- O-6 Substituted Positional Isomers of d -Glucose-Thioether Ligands and Their Ruthenium Polypyridyl Conjugates

Article abstract of DOI:10.1021/acs.joc.8b01342

A library of positional isomers of d-glucose (O-1-O-6) as ligands and their 11 light-active ruthenium conjugates has been synthesized. A protecting group strategy without the necessity of using palladium on carbon for the modification for the 2-O and 4-O position allows for the incorporation of sulfur donor atoms as ligands for transition metal complexes.

Full text of DOI:10.1021/acs.joc.8b01342

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Article
The synthesis of O-1 to O-6 substituted positional isomers of D-
glucose-thioether ligands and their ruthenium polypyridyl conjugates
Lucien Nathanaël Lameijer, Julien le Roy, Stefan van der Vorm, and Sylvestre Bonnet
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01342 • Publication Date (Web): 01 Oct 2018
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The synthesis of Oꢀ1 to Oꢀ6 substituted positional isomers of Dꢀglucoseꢀthioether ligands and
their ruthenium polypyridyl conjugates
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Lucien N. Lameijer, Julien le Roy, Stefan van der Vorm, Sylvestre Bonnet*
Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, P.O Box 9502, 2300 RA
Leiden, The Netherlands
*bonnet@chem.leidenuniv.nl
ABSTRACT: A library of positional isomers of Dꢀglucose (O1ꢀO6) as ligands and their eleven lightꢀ
active ruthenium conjugates have been synthesized. A protecting group strategy without the necessity
of using palladium on carbon for the modification for the 2ꢀO and 4ꢀO position allow for the
incorporation of sulfur donor atoms as ligands for transition metal complexes.
Introduction
Carbohydrates are
a class of biomolecules ubiquitously present in nature, comprising
monosaccharides, oligosaccharides and polysaccharides, of which monosaccharides cannot be
hydrolyzed further into smaller units. These molecules are recognized as important building blocks in
the cell wall of bacteria,1,2 in plants,3 in the exoskeleton of insects,4 in cell recognition processes,5 the
backbone of RNA and DNA6 and are associated with many different physiological and diseaseꢀrelated
processes.7,8 Among them,
Dꢀglucose is the most wellꢀknown monosaccharide as it serves as the
primary source of chemical energy in eukaryotic cells for the production of ATP.9 Otto Warburg found
that cancer cells have an increased glycolysis rate for the production of ATP compared to normal
cells.10 As a consequence, glucose transporters (GLUTs) 1 and 3 are overexpressed in cancer cells.11 In
recent years there has been a growing interest in using this effect to selectively deliver molecules of
interest to cancer cells. In the field of diagnostic imaging the wellꢀknown radiotracer 2ꢀdeoxyꢀ2ꢀ
[18F]fluoroglucose (2ꢀFDG) selectively accumulates in cancer cells since its metabolic breakdown is
hampered by the replacement of a hydroxyl group on the 2ꢀposition of D
ꢀglucose by fluoride.12 This
clinically approved agent allows PET imaging of tumors anywhere in the whole body. In the field of
medicinal chemistry, glufosfamide has shown some success as a safer alternative for ifosfamide, an
alkylating agent used in cancer treatment. The therapeutic efficiency of glufosfamide is thought to be
higher due to its increased water solubility and preferred uptake in malignant cells versus normal
cells.13 Recently Palay et. al. have demonstrated that a series of glucose conjugates of platinumꢀbased
medicines are taken up via GLUT1.14,15 This result is in contrast to the observation of Schubiger, who
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found that none of their radiodiagnostic glycoconjugates based on 99mTc were taken up via glucose
transporters.16
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For ruthenium(II) polypyridylꢀbased drugs this effect has not been thoroughly investigated. Our group
has been involved in a research program aimed at targeting rutheniumꢀbased lightꢀactivated anticancer
prodrugs to GLUT transporters by glucose conjugation.17,18 These photoactivated chemotherapeutic
prodrugs are typically protected from binding to biomolecules in the dark by thioether ligands, which
under visible light irradiation are photosubstituted by water, thereby activating the prodrug.19ꢀ21 En
route to functionalizing such complexes with glucose, it came out that all available synthetic routes
towards series of positional isomers of glucose were incompatible with the presence of thioether
groups, which deactivate Pd/C catalysts used to deprotect benzyl protecting groups. For that reason,
we developed and report here on a series of new synthetic routes towards all positional isomers of
glucose that are compatible with the presence of sulfurꢀbased ligands.22 As traces of palladium also
often interfere with the biological activity of pharmaceuticals,23 these new routes do not make use of
palladium catalysis. PEGylation of all positional isomers was also realized to vary the spacer between
the thioether ligands and the glucose moiety. The coordination of the thioetherꢀglucose ligands to
known photoactive ruthenium(II) polypyridyl precursors afford eleven rutheniumꢀglycoconjugates
(Figure 1) as a demonstration that such molecules can be obtained in synthetically useful scales.
Recent publications describe the more photophysical and/or biological properties of this type of
complexes.17,18
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Figure 1. Overview of Oꢀ1 to Oꢀ6 positional Dꢀglucose ruthenium(II) polypyridyl conjugates presented in this study.
Results & Discussion
Five hydroxyl groups are available for modification in
Dꢀglucose, of which the 1ꢀO position is
modified via chemical glycosylation.24 Recently Patra et. al. have demonstrated that the spacer length
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exerts influence over GLUT mediated uptake of platinum complexes in cells,14 however there is
currently no established understanding of this effect in cationic ruthenium(II) polypyridyl compounds.
Therefore oligoethyleneglycol spacers [OCH2CH2]n with varying length (n = 0 – 3) were introduced in
glycoconjugates [1](PF6)2 – [5](PF6)2 (Figure 1). The first complex in this series ([1](PF6)2) was
synthesized starting from precursor 12 (Scheme 1).25 This building block and NaSMe were used in a
SN2 reaction ensuring the installment of the thioether group, affording 13. This ligand was then reacted
with [Ru(tpy)(bpy)Cl]Cl, affording the orange (λmax = 450 nm) glycoconjugate [1](PF6)2.
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Scheme 1
Reaction conditions: a). i. NaSMe in DMF, rt, 16 h ii. NaOMe in MeOH, 66% over two steps; b). [Ru(tpy)(bpy)Cl]Cl in H2O,
80 °C, 16 h, 39%.
For complex [2](PF6)2, a threeꢀstep oneꢀpot synthesis starting from perꢀacetylated glucose 14 (Scheme
2) was adapted from Valerio et. al.,26 which afforded the trans glucopyranoside as the only
diastereoisomer. Treatment of this compound with sodium methoxide in methanol afforded fully
deprotected 15 in 55% overall yield. Subsequent reaction of this ligand with [Ru(tpy)(bpy)Cl]Cl then
gave the orange complex [2](PF6).
Scheme 2
Reaction conditions: a). i. I2, Et3SiH in DCM, rt., 10 min; ii. Thiourea in MeCN, 80 °C, 30 min; iii. MeI, Et3N, rt., 10 min.; iv.
cat. NaOMe in MeOH, rt., overnight. 57% over four steps; b). [Ru(tpy)(bpy)Cl]Cl in H2O, 80 °C, 48 h, 28%.
A different approach was employed for the instalment of the ethylene glycolꢀbased linkers (n = 1 – 3)
for complexes [3](PF6)2ꢀ[5](PF6)2 and [11]Cl2 (Figure 1). The disarmed Schmidt donor 20 (Scheme 3)
was chosen due to its straightforward synthesis and robustness. The benzoyl protecting group in this
building block was favored over the more common acetyl group, due to its lower reactivity.27
Furthermore, this donor was chosen to reduce the possible formation of orthoesters, a common side
reaction when using acetylꢀbearing donors.28 Commercially available 2ꢀ(methylthio)ethanol was used
as acceptor and condensed with donor 20 (Scheme 3), affording 21 which after deꢀOꢀbenzoylation
acquired deprotected 24. Compounds 25, 26 and 28 were acquired in a similar fashion using acceptor
18, 19 and 1,3ꢀbis(methylthio)propanꢀ2ꢀol respectively. The synthesis of the corresponding ruthenium
complexes was found to be straightforward, by reacting excess ligand with the ruthenium species
[Ru(tpy)(bpy)Cl]Cl or [Ru(bpy)2Cl2]. Their purification however, was found arduous due to the
increased waterꢀsolubility of these compounds. Common workup methods were not applicable, and
the lability of these compounds on Cꢀ18 columns prevented reverseꢀphase chromatographic
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purification. The most reproducible approach was by purification over silica using a mixture of
acetone, water and aqueous KPF6, followed by Sephadex LHꢀ20 size exclusion purification to remove
excess salt and minor impurities. This method afforded the orange (λmax = 450 nm) ruthenium
polypyridyl derivatives [3](PF6)2ꢀ[5](PF6)2 and [11]Cl2 in moderate to good yield (28 – 66%).
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Scheme 3
Reaction conditions: a). 2ꢀ(2ꢀchloroethoxy)ethanol, NaSMe in THF, reflux, 6 h, 94%; b). 2ꢀ(methylthio)ethanol, 1,3ꢀ
bis(methylthio)propanol, 18 or 19, cat. TMSOTf in DCM, 4Å molsieves, rt, 4 h, 81% for 21, 66% for 22, 85% for 23, 90%
for 27; c). NaOMe in MeOH, rt, 88% for 24, 86% for 25, 91% for 26, 70% for 28; d). [Ru(bpy)2Cl2] in H2O, 80 °C, 59% for
[11]Cl2; e). [Ru(tpy)(bpy)Cl]Cl in H2O, 80 °C, 39% for [3](PF6)2, 66% for [4](PF6)2, 65% for [5](PF6)2.
Park and coworkers have demonstrated that glucose bioprobes with a formal charge of +1 are taken up
preferentially over neutral and negatively charged probes.29 To allow future study of the effect on the
overall charge for ruthenium(II) polypyridyl drugs on uptake and toxicity, a derivative of
[Ru(tpy)(bpy)Cl]Cl bearing a negative charge on the spectator terpyridine ligand was also synthesized.
Compound 31 (Scheme 4) was prepared starting from thione 29,30 which was oxidized using in situ
generated perꢀacetic acid followed by hydrogenation using 10% palladium on carbon to reverse partial
overoxidation to its Nꢀoxide, affording ligand 30. A oneꢀpot synthesis using (pꢀcymene)ruthenium(II)
chloride dimer, 30 and bpy provided complex 31. Reaction of ligand 26 (Scheme 3) with this complex
then gave the ruthenium complex [10](PF6)2.
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Reaction conditions: a). i. H2O2 in AcOH, 70 °C, 6 hr.; ii. H2, Pd/C, 40 °C, overnight, 24% over two steps; b). bpy in MeOH,
60 °C, 72%; c). 25, in H2O, 80 °C, 16 h, 38%.
Demonstrations of the covalent modification of the 2ꢀO position of
linker have been given by Dumas et. al and Patray and coworkers.14,31 Both groups chose a similar
approach starting from methyl 3,5,6ꢀtriꢀOꢀbenzylꢀα/βꢀ ꢀglucofuranoside followed by installment of
Dꢀglucose with an alkylꢀbased
D
the linker and subsequent deprotection of the protection groups using dihydrogen and palladium on
carbon. Sulfur based linkers however, poisoned the palladium catalysts which made removal of the
benzyl protecting groups impossible following this approach.22,32 Other methods to remove benzyl
groups, such as Birch reductions, have been reported to cleave thioethers.33 Therefore all described
approaches for the functionalization of the Oꢀ2 position in Dꢀglucose with a metalꢀbinding moiety,
including the glucofuranoside approach described by Schubiger or Lippard, or the approach via a
benzylorthoacetate intermediate described by Miao et. al.34 were found unsuitable for thioetherꢀ
containing compounds. We therefore devised a new protecting group strategy improving the 10ꢀstep,
5% yield procedure published by Lippard et al,14 and employing the αꢀoxirane method developed by
the group of Danishefsky35,36 and attempted by Dumas et. al (Scheme 5).31 Using this method,
Dꢀglucal
was protected using the pꢀmethoxy benzyl (PMB) group, affording 34. Treatment of this compound
with freshly prepared dimethyldioxirane (DMDO) afforded its corresponding 1,2ꢀanhydrosugar which
was then condensed with pꢀmethoxy benzyl alcohol (PMBꢀOH) in the presence of anhydrous ZnCl2 in
THF, affording βꢀsubstituted 35 while simultaneously liberating the 2ꢀO position. This compound was
then treated with tosylate 32 (Scheme 5) for the installment of the thioether moiety. This conversion
proceeded smoothly, which is in contrast to the observation of Schubiger et al. who had to divert to the
furanoside approach due to difficulties encountered during the installment of their iminodiacetic acid
based spacer.31 With compound 36 in hand, a recently described method37 using 37% hydrochloric acid
in hexafluoroisopropanol (HFIP) was used to remove all four PMB groups simultaneously. After
quenching the reaction using Et3N an intermediate species was observed (m/z = 463.4 found, 463.2
calculated) corresponding to the desired product H37 and a PMB group. This same intermediate was
also observed in the presence of a mild reducing agent such as Et3SiH. However, when this
intermediate was treated with MeNH2 in MeOH,38 the methyl thioether could be liberated, acquiring
hemiacetal H37 in five steps (18% overall yield). After reaction of this compound with
[Ru(tpy)(bpy)(H2O)](PF6)2 glycoconjugate [Ru(tpy)(bpy)(37)]PF6, ([6]PF6) was acquired instead of
[Ru(tpy)(bpy)(H37)](PF6)2. This is most likely due to the relatively protic nature of the anomeric
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proton, resulting in deprotonation during purification on Sephadex and replacement of one of the PF6
counterions by the ‘charged’ deprotonated glucose species as interpreted by elemental analysis. On
mass however, only the 2+ species is observed, indicating that reprotonation occurs in solution. This
behavior was observed for all hemiacetal glucose derivatives.
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Reaction conditions: a). 19, TsCl, Et3N in DCM, 0 °C to rt, 16 h, 92%; b). PMBꢀCl, NaH in DMF, 0° C to rt, 16 h, 84%; c). i.
DMDO (0.088M in acetone) in DCM, 0 °C to rt, 3 h; ii. PMBꢀOH, ZnCl2 in THF, ꢀ78 °C to rt, 16 h, 39% over two steps; d).
32, NaH in DMF, 0 °C to rt, 6 h, 80%; e). i. cat. HCl in HFIP/DCM, 5 min; ii. MeNH2 in MeOH/H2O, 60 °C, 30 min, 67%;
f). [Ru(tpy)(bpy)(H2O)](PF6)2 in acetone/H2O, 80 °C, 24 h, 36%.
The most straightforward thioether functionalization in these series of ligands was the modification of
the 3ꢀO position of D
ꢀglucose. Starting from diacetone glucose 38 (Scheme 6),39ꢀ41 the thioether moiety
was installed using 32 (Scheme 5), affording compound 39, which was subsequently hydrolyzed using
Amberlite® IRꢀ120 H+, affording H40 in 42% overall yield. Glycoconjugation of H40 with
[Ru(tpy)(bpy)Cl]Cl gave the orange (λmax = 450 nm) complex [Ru(tpy)(bpy)(40)]PF6 ([7]PF6).
Scheme 6
Reaction conditions: a). 32, NaH in DMF, 0 °C to rt, 16 h, 91%; b). Amberlite IRꢀ120 H+ in H2O, 60 °C, 24 h, 46% ; c).
[Ru(tpy)(bpy)Cl]Cl in H2O, 80 °C, 16 h, 37%.
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The 4ꢀO position of
Dꢀglucose was modified starting from acetobromoꢀαꢀDꢀglucose 40 (Scheme 7).
Using a procedure first described by Kaji et. al., this building block was converted in situ to its
anomeric iodide, followed by a KoenigsꢀKnorr type glycosylation with pꢀmethoxy benzyl alcohol as
an acceptor and Ag2CO3 as a base.42 DeꢀOꢀacetylation furnished intermediate 41, followed by 4,6ꢀOꢀ
benzylidenation and installment of PMB groups affording fully protected 43. With this building block
in hand, a reductive opening using NaCNBH3 and TFA, liberated the 4ꢀO position, which could then
be alkylated via a Williamson etherification using 32 described in the previous sections, affording 45.
Global deprotection was achieved by treatment with HFIP/HCl, which gave thioether ligand H46 in
11% overall yield. The subsequent reaction of H46 with [Ru(tpy)(bpy)(H2O)](PF6)2, afforded
glycoconjugate [Ru(tpy)(bpy)(46)]PF6 ([8]PF6). The synthesis of H46 was also attempted via an
alternative approach using αꢀmethyl glucose following a similar protecting group strategy. However,
this proved to be unsuccessful due to the inertness of the anomeric methyl acetal towards acid.
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Scheme 7
Reaction conditions: a). i. PMBꢀOH, I2, Ag2CO3 in Et2O, rt, 24 h,; ii. NaOMe in MeOH, rt, 4 h, 72% over two steps; b).
α,α,4ꢀTrimethoxytoluene, cat. pꢀTsOH.H2O in DMF, 60 °C, 16 h, 89%; c). PMBꢀCl, NaH in DMF, 0 °C to rt, 78%; d).
NaCNBH3, TFA in DMF, 0 °C to rt, 16 h, 95%; e). 32, NaH in DMF, 0 °C to rt, 6 h, 78%; f). cat. HCl in HFIP/DCM, 30 min,
29%; g). [Ru(tpy)(bpy)Cl]Cl in H2O, 80 °C, 64%.
Finally, the 6ꢀO position of Dꢀglucose was easily modified starting from dimethyl glucose 48 (Scheme
8),43 which could be converted to 49 using a Williamson etherification with tosylate 32, followed by
acid hydrolysis using dilute hydrochloric acid affording methyl thioether H50 in 55% over two steps.
Glycoconjugation with [Ru(tpy)(bpy)Cl]Cl afforded [Ru(tpy)(bpy)(50)]PF6 ([9]PF6).
Scheme 8
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a). 31, NaH in DMF, 0 °C to rt, 3 h, 78%; b). 2M HCl in H2O, 60 °C, 1 h, 70%; c). [Ru(tpy)(bpy)Cl]Cl in H2O, 80 °C, 16 h,
17%.
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Conclusion
In this work, we have presented efficient and robust routes to all positional isomers of
Dꢀglucose
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bearing a thioether ligand bound to a lightꢀcleavable ruthenium(II) polypyridyl complex. The general
protectingꢀdeprotecting group strategy presented in this work is compatible with compounds bearing
donor atoms such as sulfur, without the need of palladium catalysts until final coordination to the
functional ruthenium compound. These routes might possibly be extended to application with other
functionalized ligands, such as carboxylates, amines, or pyridines. The study of this library of
ruthenium(II) glycoconjugates might shed light on the influence of the stereochemistry of glucose
functionalization on GLUTꢀmediated uptake and the metabolism of the rutheniumꢀglucose conjugates
by enzymes such as hexokinase II.
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Experimental section
General
Reagents were purchased from SigmaꢀAldrich and used without further purification. 2,2′:6′,2′′ꢀ
Terpyridine (tpy) was ordered from ABCR GmbH & Co. Dry solvents were collected from a Pure
Solve MD5 solvent dispenser from Demaco. For all inorganic reactions solvents were deoxygenated
by bubbling dinitrogen through the solution for 30 minutes. All organic reactions were carried out
under a diniotrogen atmosphere at rt. Flash chromatography was performed on silica gel (Screening
devices B.V.) with a particle size of 40 ꢀ 64 µM and a pore size of 60 Å. TLC analysis was conducted
on TLC aluminium foils with silica gel matrix (Supelco, silica gel 60, 56524) with detection by UVꢀ
absorption (254 nm), by spraying with 10% H2SO4 in ethanol or with a solution of NH4Mo7O24.4H2O
25 g/L, NH4CeSO4.H2O 10 g/L, 10% H2SO4 in H2O, followed by charring at ~250 °C on a heating
plate. Optical rotation measurements were performed on a Propol automated polarimeter (sodium Dꢀ
line, λ = 589 nm) with a concentration of 10 mg/mL (c = 1) unless stated otherwise. Infrared spectra
were recorded on a Perkin Elmer UATR (Single Reflection Diamond) Spectrum Two device (4000ꢀ
1
700 cmꢀ1; resolution 4 cmꢀ1). H NMR and 13C NMR were recorded in CD3OD and CDCl3 with
chemical shift (δ) relative to the solvent peak on a Bruker AV 400 or AV 500. High resolution mass
spectra were recorded by direct injection (2 µl of 2 µM solution in water/acetonitrile; 50/50; v/v and
0.1% formic acid) in a mass spectrometer (Thermo Finnigan LTQ Orbitrap) equipped with an
electrospray 250 °C) with resolution R = 60,000 at m/z 400 (mass range m/z = 150 – 2000) and
dioctylphtalate (m/z = 391.28428) as a lock mass. The highꢀresolution mass spectrometer was
calibrated prior to measurements with a calibration mixture (Thermo Finnigan). Melting point ranges
were determined on a Stuart SMP30. Elemental analysis for glycoconjugates [1](PF6)2 ꢀ [5](PF6)2,
[6]PF6 ꢀ [10]PF6, and [11]Cl2 was performed at Mikrolab Kolbe Germany.
Synthesis
(2ꢀMethylthio)ethylꢀαꢀ
D
ꢀglucopyranoside,
13:
2,3,4,6ꢀTetraꢀOꢀacetylꢀ(2ꢀbromo)ethylꢀαꢀDꢀ
glucopyranoside25 (135 mg, 0.297 mmol) was dissolved in dry DMF (3 mL) and to this solution was
added fresh NaSMe (23 mg, 0.33 mmol). The reaction was stirred overnight after which it was diluted
with EtOAc (25 mL), washed with water (2x), aq. NaHCO3 (2x), and dried (Na2SO4). Concentration
in vacuo was followed by purification of the residue by silica column chromatography (10% MeOH in
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DCM), affording the title compound (50.0 mg, 0.197 mmol, 66% over two steps) as a colorless oil. Rf
= 0.84 (20% MeOH in DCM); IR (neat): 3350, 2918, 1639, 1426, 1018; 1H NMR (400 MHz, CD3OD)
δ = 4.80 (d, J = 3.8 Hz, 1H, Hꢀ1), 3.91 – 3.75 (m, 2H, CHH Hꢀ6, CHH OCH2), 3.69 – 3.58 (m, 4H, Hꢀ
4, Hꢀ5, CHH Hꢀ6, CHH OCH2), 3.37 (dd, J = 9.7, 3.8 Hz, 1H, Hꢀ2), 3.25 (d, J = 9.3 Hz, 1H, Hꢀ3),
2.73 (td, J = 6.9, 1.8 Hz, 2H, OCH2SMe), 2.12 (s, 3H, OCH2SMe). 13C NMR (101 MHz, CD3OD) δ =
100.3 (Cꢀ1), 75.1 (Cꢀ4), 73.9 (Cꢀ5), 73.5 (Cꢀ2), 71.8 (Cꢀ3), 68.4 (OCH2), 62.7 (Cꢀ6), 34.3
(OCH2SMe), 15.8 (OCH2SMe); HRMS (ESI) m/z: [M + Na]+ Calcd for C9H18O6SNa 277.0716; Found
277.0711.
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MethylthioꢀβꢀDꢀglucopyranoside, 15: α/βꢀDꢀGlucose pentaacetate (4.99 g, 12.4 mmol) was dissolved
in anhydrous DCM (20 mL) and to this solution was added I2 (4.84 g, 19.0 mmol) and Et3SiH (2.90
mL, 18.2 mmol) this mixture was allowed to stir for 10 minutes after which it was diluted with DCM
(100 mL) and washed with aqueous saturated Na2S2O3 (1x) and Na2CO3 (1x). Layers were separated,
the organic layer was dried (Na2SO4) and concentrated in vacuo. The crude was coevaporated with
toluene (3x) and redissolved in dry MeCN (20 mL), followed by the addition of thiourea (1.46 g, 19.2
mmol). The mixture was then heated for 30 minutes at 80 °C, concentrated in vacuo, followed by
purification of the residue over silica (0 to 50% Et2O in PE) yielding methyl 2,3,4,6ꢀtetraꢀOꢀacetylꢀ1ꢀ
thioꢀβꢀDꢀglucopyranoside as a yellow foam (2.71 g, 7.24 mmol). This compound was then dissolved in
dry MeOH (70 mL) followed by the addition of a catalytic amount of NaOMe, which after stirring
overnight was quenched upon the addition of Amberlite IRꢀ120 H+. Filtration was followed by
concentration in vacuo, yielding the title compound as a colorless oil (1.48 g, 7.04 mmol, 57% over
four steps). Rf = 0.63 (20% MeOH in DCM); IR (neat): 3336, 2923, 2881, 1425, 1017; 1H NMR (400
MHz, CD3OD) δ = 4.35 (d, J = 9.6 Hz, 1H, Hꢀ1), 3.93 (d, J = 11.8 Hz, 1H, CHH Hꢀ6), 3.77 – 3.68 (m,
1H, CHH Hꢀ6), 3.48 – 3.35 (m, 3H, Hꢀ3, Hꢀ4, Hꢀ5), 3.31 (t, J = 9.1 Hz, 1H, Hꢀ2), 2.26 (s, 3H, SMe).
13C NMR (101 MHz, CD3OD) δ = 87.1 (Cꢀ1), 81.8 (Cꢀ3), 79.3 (Cꢀ4), 73.5 (Cꢀ2), 71.3 (Cꢀ5), 62.7 (Cꢀ
6), 12.0 (SMe). HRMS (ESI) m/z: [M + Na]+ Calcd for C7H14O5SNa 233.0454; Found 233.0444.
2ꢀ(Methylthio)ethoxy)ethanol, 18: To a flameꢀdried roundꢀbottom flask was added freshly prepared
NaSMe44 (1.21 g, 15.5 mmol) under argon. Deoxygenated THF (50 mL) was added, followed by the
addition of 2ꢀ(2ꢀ(2ꢀchloroethoxy)ethanol (1.50 mL, 14.2 mmol). This solution was heated at 60 °C for
6 h, after which it was allowed to cool to room temperature. The mixture was diluted with EtOAc (100
mL) and washed with aqueous NaHCO3 (2x) and water (1x). Layers were separated, the organic layer
was dried (Na2SO4) and concentrated in vacuo affording a slightly yellowish oil (1.89 g, 13.9 mmol,
1
89%). IR (neat): 3480, 2907, 2866, 1611, 1512; H NMR (400 MHz, CDCl3) δ = 3.68 (m, 2H, CH2),
3.62 (t, J = 6.7 Hz, 2H, CH2), 3.54 (d, J = 5.1 Hz, 2H, CH2), 2.94 – 2.81 (s, 1H, OH), 2.66 (t, J = 6.6
Hz, 2H, ꢀSCH2), 2.10 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ = 72.1 (CH2), 69.9 (CH2), 61.5
(CH2), 33.6 (SCH2), 15.8 (SCH3); HRMS (ESI) m/z: [M + Na]+ Calcd for C5H12O2SNa 159.0450;
Found 159.0457.
2ꢀ[2ꢀ(2ꢀ(Methylthio)ethoxy)ethoxy]ethanol, 19: The procedure was followed as described for 18
using NaSMe44 (4.23 g, 60.4 mmol) and 2ꢀ(2ꢀ(2ꢀchloroethoxy)ethoxy)ethanol (10.0 g, 59.3 mmol). 19
was afforded as a colourless oil (9.25 g, 51.0 mmol, 85%). IR (neat): 3427, 2915, 2869, 1105, 1063;
1H NMR: (400 MHz, CDCl3) δ = 3.61 – 3.42 (m, 10H, 5 x CH2), 3.09 (s, 1H, ꢀOH), 2.60 – 2.50 (m,
2H, 1 x CH2), 2.03 – 1.94 (s, 3H, CH3). 13C NMR: (100 MHz, CDCl3) δ = 72.4 (ꢀCH2), 70.2 (CH2),
70.1 (CH2), 70.0 (CH2), 61.3 (CH2) 33.13 (ꢀSCH2), 15.7 (ꢀSCH3). HRMS (ESI) m/z: [M + Na]+ Calcd
for C7H16O3SNa 203.0712; Found 203.0713.
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(2ꢀMethylthio)ethyl 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
D
D
ꢀglucopyranoside, 21: 2,3,4,6ꢀTetraꢀOꢀbenzoylꢀβꢀ
ꢀglucopyranosyl trichloroacetimidate45 (370 mg, 0.364 mmol) and 2ꢀ(methylthio)ethanol (100 µL,
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1.15 mmol) were coevaporated three times with anhydrous toluene after which they were dissolved in
anhydrous DCM (36 mL). Freshly activated 4 Å molsieves were added, and the mixture was allowed
to stir for 15 minutes after which a catalytic amount of TMSOTf (20.0 µL, 111 µmol) was added.
After stirring for 4 h at room temperature, the reaction was quenched upon the addition of Et3N (100
µL, 0.714 mmol) and concentrated in vacuo followed by purification of the residue over silica (10% to
50% EtOAc in PE), affording the title compound as a clear oil (270 mg, 0.410 mmol, 81%). Rf = 0.74
(30% EtOAc in PE); IR (neat): 3064, 2922, 2853, 1720, 1258; 1H NMR (400 MHz, CDCl3) δ = 8.07 –
8.02 (m, 2H, Harom), 8.00 – 7.96 (m, 2H, Harom), 7.94 – 7.90 (m, 2H, Harom), 7.87 – 7.81 (m, 2H, Harom),
7.60 – 7.25 (m, 12H, Harom), 5.93 (t, J = 9.7 Hz, 1H, Hꢀ3), 5.70 (t, J = 9.7 Hz, 1H, Hꢀ4), 5.56 (dd, J =
9.8, 7.8 Hz, 1H, Hꢀ2), 4.93 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.67 (dd, J = 12.2, 3.2 Hz, 1H, CHH Hꢀ6), 4.52
(dd, J = 12.1, 5.4 Hz, 1H, CHH Hꢀ6), 4.19 (ddd, J = 8.6, 5.4, 3.2 Hz, 1H, Hꢀ5), 4.09 (dt, J = 10.2, 6.7
Hz, 1H, CHH OCH2), 3.78 (dt, J = 10.3, 7.3 Hz, 1H, CHH OCH2), 2.67 (t, J = 6.9 Hz, 2H, CH2SMe),
2.01 (s, 3H, CH2SMe). 13C NMR (101 MHz, CDCl3) δ = 166.2 (C=O Bz), 165.9 (C=O Bz), 165.3
(C=O Bz), 165.2 (C=O Bz), 133.6 (CH Arom), 133.4 (CH Arom), 133.3 (CH Arom), 129.9 (CH Arom),
129.9 (CH Arom), 129.9 (CH Arom), 129.8 (CH Arom), 129.7 (Cq Arom), 129.4 (Cq Arom), 128.9 (Cq
Arom), 128.8 (Cq Arom), 128.5 (CH Arom), 128.5 (CH Arom), 128.5 (CH Arom), 128.4 (CH Arom),
101.4 (Cꢀ1), 73.0 (Cꢀ3), 72.4 (Cꢀ5), 71.9 (Cꢀ2), 69.8 (Cꢀ4), 69.8 (OCH2) 63.2 (Cꢀ6), 33.4 (CH2SMe),
16.1 (CH2SMe); HRMS (ESI) m/z: [M + NH4]+ Calcd for C37H38O10SN 688.2211; Found: 688.2222.
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[2ꢀ(2ꢀ(Methylthio)ethoxy)]ethyl 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
procedure described for 21 was followed, with 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
D
ꢀglucopyranoside, 22: The general
ꢀglucopyranosyl
D
trichloroacetimidate (6.00 g, 8.14 mmol) and 2ꢀ(2ꢀ(methylthio)ethoxy)ethanol (1.24 g, 9.10 mmol).
Purification of the residue by silica column purification (0 – 25% EtOAc in PE) afforded the title
compound as a clear oil (3.86 g, 5.40 mmol, 66%). Rf = 0.34 (33% EtOAc in PE); IR (neat): 3064,
2919, 1722, 1602, 1249; 1H NMR (400 MHz, CDCl3) δ = 8.05 – 8.01 (m, 2H, Harom), 8.00 – 7.96 (m,
2H, Harom), 7.93 – 7.88 (m, 2H, Harom), 7.86 – 7.81 (m, 2H, Harom), 7.58 – 7.24 (m, 12H, Harom), 5.92 (t,
J = 9.7 Hz, 1H, Hꢀ3), 5.69 (t, J = 9.7 Hz, 1H, Hꢀ4), 5.54 (dd, J = 9.9, 7.7 Hz, 1H, Hꢀ2), 4.99 (d, J = 7.8
Hz, 1H, Hꢀ1), 4.65 (dd, J = 12.1, 3.2 Hz, 1H, CHH Hꢀ6), 4.51 (dd, J = 12.1, 5.1 Hz, 1H, CHH Hꢀ6),
4.18 (ddd, J = 10.1, 5.2, 3.1 Hz, 1H, Hꢀ5), 4.00 (dt, J = 11.4, 4.1 Hz, 1H, CHH OCH2), 3.81 (ddd, J =
11.1, 6.9, 3.8 Hz, 1H, CHH OCH2), 3.58 (dt, J = 6.7, 3.7 Hz, 2H, OCH2), 3.48 (t, J = 6.7 Hz, 2H,
OCH2), 2.44 (t, J = 6.7 Hz, 2H, CH2SMe), 2.03 (s, 3H, CH2SMe). 13C NMR (101 MHz, CDCl3) δ =
166.3 (C=O Bz), 165.9 (C=O Bz), 165.3 (C=O Bz), 165.2 (C=O Bz), 133.6 (CH Arom), 133.4 (CH
Arom), 133.3 (CH Arom), 129.9 (CH Arom), 129.9 (CH Arom), 129.9 (CH Arom), 129.9 (CH Arom),
129.7 (Cq Arom), 129.4 (Cq Arom), 128.9 (Cq Arom), 128.9 (Cq Arom), 128.5 (CH Arom), 128.5 (CH
Arom), 128.4 (CH Arom), 101.4 (Cꢀ1), 73.0 (Cꢀ3), 72.3 (Cꢀ5), 72.0 (Cꢀ2), 70.6 (OCH2), 70.2 (OCH2) ,
69.8 (Cꢀ4), 69.4 (OCH2), 63.2 (Cꢀ6), 33.5 (CH2SMe), 16.1 (CH2SMe); HRMS (ESI) m/z: [M + NH4]+
Calcd for C39H42O11SN 732.2473; Found 732.2484.
2ꢀ[2ꢀ(2ꢀ(Methylthio)ethoxy)ethoxy]ethyl 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
Dꢀglucopyranoside, 23: The
general procedure described for 21 was followed, with 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
D
ꢀglucopyranosyl
trichloroacetimidate45 (2.65 g, 3.58 mmol) and 19 (792 mg, 4.39 mmol). Purification of the residue
over silica (10% to 50% EtOAc in PE) afforded the title compound as a clear oil (2.32 g, 3.06 mmol,
85%). Rf = 0.16 (20% EtOAc in PE); [α] 20 (CHCl3): +18.0 ; IR (neat): 3063, 2918, 2869, 1722, 1451;
D
1HꢀNMR: (400 MHz, CDCl3) δ = 8.03 (d, J = 8.6 Hz, 2H, Harom), 7.97 (d, J = 8.6 Hz, 2H, Harom), 7.90
(d, J = 8.7 Hz, 2H, 2H, Harom), 7.83 (d, J = 8.6 Hz, 2H, Harom), 7.58 – 7.43 (m, 3H, Harom), 7.43 – 7.29
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(m, 7H, Harom), 7.29 – 7.21 (m, 2H, Harom), 5.93 (t, J = 9.7 Hz, 1H, Hꢀ3), 5.70 (t, J = 9.7 Hz, 1H, Hꢀ4),
5.55 (dd, J = 9.7, 7.8 Hz, 1H, Hꢀ2), 5.01 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.66 (dd, J = 12.1, 3.1 Hz, 1H, CHH
Hꢀ6), 4.51 (dd, J = 12.1, 5.1 Hz, 1H, CHH Hꢀ6), 4.20 (ddd, J = 9.9, 5.1, 3.1 Hz, 1H, Hꢀ5), 4.03 – 3.95
(m, 1H, CHH –OCH2), 3.83 (m, 1H, CHH –OCH2), 3.69 – 3.56 (m, 2H, ꢀOCH2), 3.55 (t, J = 6.9 Hz,
2H, ꢀOCH2), 3.50 – 3.42 (m, 2H, ꢀOCH2), 3.37 (t, J = 4.6 Hz, 2H, ꢀOCH2), 2.64 (t, J = 6.9 Hz, 2H, ꢀ
CH2SMe), 2.11 (s, 3H, ꢀSCH3). 13C NMR: (101 MHz, CD3OD) δ = 166.1 (C=O Bz), 165.8 (C=O Bz),
165.2 (C=O Bz), 165.1 (C=O Bz), 133.5 (CH Arom), 133.3 (CH Arom), 133.2 (CH Arom), 129.8 (CH
Arom), 129.8 (CH Arom), 129.6 (Cq Arom), 129.4 (Cq Arom), 128.8 (Cq Arom), 128.4 (CH Arom),
128.4 (CH Arom), 101.3 (Cꢀ1), 73.0 (Cꢀ3), 72.2 (Cꢀ5) 72.0 (Cꢀ2), 70.7 (OCH2), 70.5 (OCH2), 70.2
(OCH2), 69.8 (Cꢀ4), 69.4 (OCH2), 63.2 (OCH2), 33.4 (CH2SMe), 16.0 (CH2SMe). HRMS (ESI) m/z:
[M + Na]+ Calcd for C41H42O12SNa 781.2289; Found 781.2280.
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(2ꢀMethylthio)ethylꢀβꢀDꢀglucopyranoside, 24: The protected glucoside 23 (240 mg, 0.410 mmol)
was dissolved in MeOH (6 mL) after which a catalytic amount of NaOMe was added. The solution
was allowed to stir for 16 h, after which Amberlite IRꢀ120 H+ was added, until neutral pH. The resin
was filtered off and the mixture was concentrated in vacuo. Purification of the residue over silica (0 to
10% MeOH in DCM) afforded the title compound as a colorless oil (80.0 mg, 0.315 mmol, 88%). Rf =
0.15 (5% MeOH in DCM); IR (neat): 3351, 2919, 2881, 1072, 1016; 1H NMR (400 MHz, CD3OD) δ =
4.30 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.03 (dt, J = 10.1, 7.1 Hz, 1H, CHH OCH2), 3.87 (dd, J = 11.9, 1.8 Hz,
1H, CHH Hꢀ6), 3.74 (dt, J = 10.1, 7.1 Hz, 1H, CHH OCH2), 3.69 – 3.64 (m, 1H, CHH Hꢀ6), 3.39 –
3.33 (m, 1H, Hꢀ4), 3.29 – 3.26 (m, 2H, Hꢀ3, Hꢀ5), 3.21 – 3.15 (m, 1H, Hꢀ2), 2.73 (t, J = 7.1 Hz, 2H,
CH2SMe), 2.13 (s, 3H, CH2SMe). 13C NMR (101 MHz, CD3OD) δ = 104.4 (Cꢀ1), 77.9 (Cꢀ3), 77.9 (Cꢀ
4), 75.0 (Cꢀ2), 71.6 (Cꢀ5), 70.0 (OCH2), 62.7 (Cꢀ6), 34.3 (CH2SMe), 15.7 (CH2SMe); HRMS (ESI)
m/z: [M + Na]+ Calcd for C9H18O6SNa 277.0714; Found 277.0716.
[2ꢀ(2ꢀ(Methylthio)ethoxy)]ꢀethylꢀβꢀDꢀglucopyranoside, 25: The procedure as described for 24 was
followed, using protected glycoside 22 (560 mg, 0.780 mmol) and THF/MeOH (10 mL, 1:1).
Purification of the crude over silica (0 to 20% acetone in DCM) afforded the title compound as a white
solid (200 mg, 0.670 mmol, 86%). Rf = 0.19 (10% acetone in DCM); IR (neat): 3304, 2919, 1075,
1354, 1028; 1H NMR (400 MHz, CD3OD) δ = 4.31 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.05 – 3.96 (m, 1H, CHH
OCH2), 3.87 (dd, J = 11.9, 1.8 Hz, 1H, CHH Hꢀ6), 3.78 – 3.62 (m, 6H, CHH Hꢀ6, CHH OCH2, 2 x
OCH2), 3.40 – 3.25 (m, 3H, Hꢀ3, Hꢀ4, Hꢀ5), 3.19 (dd, J = 9.3, 7.5 Hz, 1H, Hꢀ2), 2.68 (t, J = 6.8 Hz,
2H, CH2SMe), 2.13 (s, 3H, CH2SMe). 13C NMR (101 MHz, CD3OD) δ = 104.4 (Cꢀ1), 78.0 (Cꢀ3), 78.0
(Cꢀ4), 75.1 (Cꢀ2), 71.6 (Cꢀ5), 71.5 (OCH2), 71.2 (OCH2), 69.7 (OCH2), 62.8 (Cꢀ6), 34.2 (CH2SMe),
15.8 (CH2SMe); Mp = 89.9 – 90.8 °C; HRMS (ESI) m/z: [M + Na]+ Calcd for C11H22O7SNa 321.0978;
Found 321.0976.
2ꢀ[2ꢀ(2ꢀ(Methylthio)ethoxy)ethoxy]ethyl βꢀDꢀglucopyranoside, 26: The protected glucoside 23 (973
mg, 1.28 mmol) was dissolved in MeOH (10 mL) after which a catalytic amount of NaOMe was
added. The solution was allowed to stir for 16 h, after which Amberlite IRꢀ120 H+ was added, until
reaching neutral pH. The resin was filtered off and the mixture was concentrated in vacuo. Purification
of the residue over silica (0 ꢀ 10% MeOH in DCM) afforded the title compound as a colorless oil (400
mg, 1.17 mmol, 91%). Rf = 0.29 (10% MeOH in DCM): [α] 20 (MeOH): ꢀ10.0; IR: 3371, 2915, 2874,
D
1
1073, 1031; H NMR (400 MHz, CDCl3) δ = 4.35 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.06 (ddd, J = 10.2, 5.0,
3.0 Hz, 1H, CHH OCH2), 3.90 (dd, J = 11.9, 1.7 Hz, 1H, CHH OCH2), 3.82 – 3.65 (m, 10H, CHH
OCH2, Hꢀ5, Hꢀ6, 3 x CH2 OCH2), 3.45 – 3.37 (m, 1H, Hꢀ3), 3.37 – 3.28 (m, 1H, Hꢀ4), 3.24 (dd, J =
9.1, 7.8 Hz, 1H, Hꢀ2), 2.72 (t, J = 6.8 Hz, 2H, ꢀOCH2), 2.17 (s, 3H, ꢀSCH3). 13C NMR (101 MHz,
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CD3OD) δ = 104.4 (Cꢀ1), 77.9 (Cꢀ3), 75.0 (Cꢀ4), 71.6 (OCH2), 71.5 (Cꢀ5), 71.5 (2 x OCH2), 71.1
(OCH2), 69.6 (OCH2), 62.7 (Cꢀ6), 34.2 (CH2SMe), 15.9 (CH2SMe). HRMS (ESI) m/z: [M + Na]+
Calcd for C13H26O8SNa 365.1241; Found 365.1238
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[1,3ꢀBis(methylthio)]ꢀpropylꢀ2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
procedure described for 21 was followed, with 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
D
ꢀglucopyranoside, 27: The general
D
ꢀglucopyranosyl
trichloroacetimidate (5.00 g, 6.75 mmol) and 1,3ꢀbis(methylthio)propanol (830 µL, 6.09 mmol).
Purification of the residue by silica column purification (0 – 20% EtOAc in PE) afforded the title
compound as a clear oil (3.95 g, 5.40 mmol, 90%). Rf = 0.55 (20% EtOAc in PE); IR (neat): 2919,
2853, 1722, 1601, 1259; 1H NMR (400 MHz, CDCl3) δ = 8.07 – 8.00 (m, 2H, Harom), 7.99 – 7.94 (m,
2H, Harom), 7.91 (d, J = 7.8 Hz, 2H, Harom), 7.85 – 7.79 (m, 2H, Harom), 7.60 – 7.24 (m, 12H, Harom),
5.91 (t, J = 9.7 Hz, 1H, Hꢀ3), 5.65 (t, J = 9.7 Hz, 1H, Hꢀ4), 5.52 (dd, J = 10.1, 7.7 Hz, 1H, Hꢀ2), 5.09
(d, J = 7.9 Hz, 1H, Hꢀ1), 4.67 (dd, J = 12.1, 3.1 Hz, 1H, CHH Hꢀ6), 4.48 (dd, J = 12.2, 5.6 Hz, 1H,
CHH Hꢀ6), 4.18 (ddd, J = 9.3, 5.7, 3.0 Hz, 1H, Hꢀ5), 4.04 – 3.91 (m, 1H, CH(CH2SMe)2), 2.86 (dd, J
= 13.8, 4.4 Hz, 1H, CHH CH(CH2SMe)2), 2.81 – 2.71 (m, 2H, CH2 CH(CH2SMe)2), 2.61 (td, J = 13.5,
7.4 Hz, 1H, CHH CH(CH2SMe)2), 2.06 (s, 3H, SMe), 1.90 (s, 3H, SMe). 13C NMR (101 MHz, CDCl3)
δ = 166.2 (C=O Bz), 165.9 (C=O Bz), 165.4 (C=O Bz), 165.3 (C=O Bz), 133.6 (CH Arom), 133.4 (CH
Arom), 133.4 (CH Arom), 133.3 (CH Arom), 130.0 (CH Arom), 129.9 (CH Arom), 129.9 (CH Arom),
129.9 (CH Arom), 129.6 (Cq Arom), 129.5 (Cq Arom), 128.9 (Cq Arom), 128.8 (Cq Arom), 128.6 (CH
Arom), 128.4 (CH Arom), 101.7 (Cꢀ1), 80.2 (CH(CH2SMe)2), 73.0 (Cꢀ3), 72.4 (Cꢀ5), 72.1 (Cꢀ2), 69.9
(Cꢀ4), 63.2 (Cꢀ6), 38.4 (CH2 CH(CH2SMe)2), 37.8 (CH2 CH(CH2SMe)2), 16.7 (2 x SMe); HRMS
(ESI) m/z: [M + NH4]+ Calcd for C39H42O10S2N 748.2245; Found 748.2254.
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[1,3ꢀbis(methylthio)]ꢀpropylꢀβꢀDꢀglucopyranoside, 28: The procedure as described for 22 was
followed, using protected glycoside 27 (3.20 g, 4.38 mmol) and DCM/MeOH (50 mL, 1:50).
Purification of the residue over silica (0 to 10% MeOH in DCM) afforded 28 as a white foam (960 mg,
1
3.05 mmol, 70%). Rf = 0.24 (100% EtOAc); IR (neat): 3368, 2916, 1424, 1071, 1016; H NMR (400
MHz, CD3OD) δ = 4.45 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.06 (p, J = 5.8 Hz, 1H, CH(CH2SMe)2), 3.90 – 3.83
(m, 1H, CHH Hꢀ6), 3.70 – 3.63 (m, 1H, CHH Hꢀ6), 3.41 – 3.33 (m, 1H, Hꢀ3), 3.33 – 3.26 (m, 2H, Hꢀ
4, Hꢀ5), 3.24 – 3.14 (m, 1H, Hꢀ2), 2.94 – 2.83 (m, 3H, CHH, CH2 CH(CH2SMe)2), 2.79 (dd, J = 13.8,
5.6 Hz, 1H, CHH CH(CH2SMe)2), 2.15 (s, 6H, 2 x SMe). 13C NMR (101 MHz, CD3OD) δ = 104.1 (Cꢀ
1), 79.4 (CH(CH2SMe)2), 77.9 (Cꢀ3), 77.9 (Cꢀ4), 75.2 (Cꢀ2), 71.5 (Cꢀ5), 62.7 (Cꢀ6), 39.0 (CH2
CH(CH2SMe)2) 37.9 (CH2 CH(CH2SMe)2), 16.6 (SMe), 16.4 (SMe); HRMS (ESI) m/z: [M + Na]+
Calcd for C11H22O6S2Na 337.0750; Found 337.0752
[2,2':6',2''ꢀTerpyridine]ꢀ4'ꢀsulfonic acid, 30 (HSꢀtpy): [2,2':6',2''ꢀterpyridine]ꢀ4'(1'H)ꢀthione46 (534
mg, 2.01 mmol) was suspended in acetic acid (6 mL) and to this mixture was added 30% H2O2 (1 mL).
The resulting purple mixture was heated at 70 °C for 12 h, and concentrated in vacuo. The crude was
then redissolved in H2O, followed by the addition of 10% Pd/C (32 mg) and purged with H2 (5 min).
After stirring overnight at 40 °C under a H2 atmosphere, the reaction was filtered over Celite®,
concentrated and purified over silica (0 to 10% MeOH in DCM), affording the title compound as a
bright yellow powder (151 mg, 0.428 mmol, 24%). Rf = 0.37 (20% MeOH in DCM); IR (neat): 3391,
3064, 1622, 1398, 1189; 1H NMR (400 MHz, D2O) δ = 8.09 (dd, J = 4.9, 1.9 Hz, 2H, T3, T3”), 7.84 (s,
2H, T3’, T5’), 7.61 (d, J = 7.4 Hz, 2H, T6, T6”), 7.54 (td, J = 7.7, 1.9 Hz, 2H, T4, T4”), 7.15 (ddd, J =
7.4, 5.0, 1.4 Hz, 2H, T5, T5”). 13C NMR (101 MHz, D2O) δ = 154.9 (Cq Arom), 152.7 (Cq Arom),
152.7 (Cq Arom), 148.1 (T3, T3”) , 138.1 (T4, T4”), 124.9 (T5, T5”) , 121.8 (T6, T6”), 116.5 (T3, T3”);
HRMS (ESI) m/z: [M + H]+ Calcd for C15H12N3O3S 314.0594; Found 314.0600.
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[Ru(Sꢀtpy)(bpy)(Cl)], 31: Compound 30 (134 mg, 0.428 mmol) was dissolved in MeOH (10 mL) and
to this solution was added 100 mg washed Amberlite® Na+. After stirring for 5 minutes at rt, the ion
exchange resin was filtered off and the filtrate was concentrated in vacuo, affording a pinkish solid.
This compound was then together with dichloro(pꢀcymene)ruthenium(II) dimer (130 mg, 0.213
mmol), redissolved in deoxygenated MeOH (5 mL) and heated to 60 °C. A solution of bpy (69.0 mg,
0.440 mmol) in MeOH (2.3 mL) was then added dropwise over 10 minutes from which the color of
the solution changed from purple to red. After stirring for 2 h under nitrogen, the solution was allowed
to cool to rt, after which Et2O (20 mL) was added. The resulting precipitate was filtered and washed
with Et2O (3x) affording a brown powder (185 mg, 0.306 mmol, 72%). Rf = 0.29 (10% MeOH in
DCM); Mp > 350 °C; HRMS (ESI) m/z: [M+H]+ Calcd for C25H19ClN5O3RuS: 605.9935; Found:
605.9946.
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2ꢀ(2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy)ethyl 4ꢀmethylbenzenesulfonate, 32: Compound 19 (715 mg,
3.97 mmol) was dissolved in dry DCM (40 mL) and cooled to 0 °C. To this solution were added Et3N
(850 ul, 6.09 mmol) and TsꢀCl (1.12 g, 5.87 mmol). The reaction was allowed to stir overnight after
which it was diluted with DCM (100 mL) and transferred to a separatory funnel. After washing with
water (1x) and brine (1x), layers were separated, the organic layer was dried (Na2SO4) and
concentrated in vacuo. Purification of the residue by silica column chromatography (0 to 50% EtOAc
in PE) afforded the title compound as a colorless oil (1.22 g, 3.64 mmol, 92%). Rf = 0.78 (50% EtOAc
in PE); IR (neat): 2917, 2868, 1598, 1353, 1174; 1H NMR (400 MHz, CDCl3) δ = 7.73 (d, J = 8.3 Hz,
2H, Harom), 7.30 (d, J = 8.1 Hz, 2H, Harom), 4.18 – 4.02 (m, 2H, CH2), 3.65 – 3.61 (m, 2H, CH2), 3.57
(t, J = 6.8 Hz, 2H, CH2), 3.51 (m, 4H, 2 x CH2), 2.60 (t, J = 6.8 Hz, 2H, CH2), 2.39 (s, 3H, CH3 Tosyl),
2.07 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ = 144.7 (Cq Arom), 132.7 (Cq Arom), 129.7 (CH
Arom), 127.7 (CH Arom), 70.5 (CH2), 70.4 (CH2), 70.0 (CH2), 69.2 (CH2), 68.5 (CH2), 33.2 (SCH2),
21.5 (CH3 Tosyl), 15.8 (SCH3); HRMS (ESI) m/z: [M + Na]+ Calcd for C14H22O5S2Na 357.0801;
Found 357.0800.
3,4,6ꢀTriꢀOꢀ(4ꢀmethoxybenzyl)ꢀDꢀglucal, 34: To a cooled solution (0 °C) of Dꢀglucal in dry DMF
(230 mL) was slowly added NaH (60% dispersion in mineral oil, 3.10 g, 77.5 mmol) followed by the
addition of 4ꢀmethoxybenzyl chloride (10.1 mL, 74.5 mmol). After stirring overnight under a
dinitrogen atmosphere, H2O (10 mL) was added and the mixture was allowed to stir for another 10
minutes. The mixture was further diluted with EtOAc (200 mL) and transferred to a separatory funnel,
washed with water (3x) and brine (3x). The organic layer was dried over Na2SO4 and concentrated in
vacuo. Purification by silica column chromatography (0 to 15% EtOAc in PE) afforded 34 (9.82 g,
19.4 mmol, 84%) as a clear oil that solidified upon standing over a longer time. Rf = 0.66 (10% EtOAc
in PE); IR (neat): 2999, 2863, 2907, 1647, 1512; 1H NMR (400 MHz, CDCl3) δ = 7.16 (d, J = 8.3 Hz,
4H, Harom), 7.04 (d, J = 8.5 Hz, 2H, Harom), 6.75 (dd, J = 11.9, 8.1 Hz, 6H, Harom), 6.31 (d, J = 6.2 Hz,
1H, Hꢀ1), 4.74 (dd, J = 6.2, 3.2 Hz, 1H, Hꢀ2), 4.64 (d, J = 10.9 Hz, 1H, CHH PMB), 4.52 – 4.35 (m,
5H, CHH PMB, 2 x CH2 PMB), 4.07 (dd, J = 6.5, 2.2 Hz, 1H, Hꢀ3), 3.92 (dt, J = 8.6, 4.1 Hz, 1H, Hꢀ
5), 3.70 (s, 3H, CH3 PMB), 3.69 (s, 4H, CH3 PMB, Hꢀ4), 3.69 (s, 3H, CH3 PMB), 3.66 – 3.58 (m, 2H,
CH2 Hꢀ6). 13C NMR (101 MHz, CDCl3) δ = 159.3 (CH Arom), 159.3 (CH Arom), 159.3 (CH Arom),
144.7 (Cꢀ1), 130.6 (Cq Arom), 130.4 (Cq Arom), 130.1 (Cq Arom), 129.7 (CH Arom), 129.6 (CH
Arom), 129.5 (CH Arom), 113.9 (CH Arom), 113.9 (CH Arom), 100.2 (Cꢀ2), 76.9 (Cꢀ5), 75.6 (Cꢀ2),
74.2 (Cꢀ4), 73.5 (CH2 PMB), 73.2 (CH2 PMB), 70.3 (CH2 PMB), 68.3 (Cꢀ6), 55.4 (3 x CH3 PMB);
HRMS (ESI) m/z: [M + NH4]+ Calcd for C30H38O7N 524.2643; Found 524.2655.
(4ꢀMethoxybenzyl)ꢀ3,4,6ꢀTriꢀOꢀ(4ꢀmethoxybenzyl)ꢀβꢀdꢀglucopyranoside, 35: To a solution of
protected glycoside 35 (821 mg, 1.62 mmol) in dry DCM (8 mL) under a dinitrogen atmosphere, were
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added freshly activated 4Å molsieves. After stirring for 15 minutes, the mixture was allowed to cool to
0 °C and freshly prepared dimethyldioxirane in acetone (20 mL, 88 mM) was slowly added. The
mixture was stirred for 3 h and allowed to reach rt, after which it was filtered over Celite® and
concentrated in vacuo. The crude was then, together with 4ꢀmethoxyl benzyl alcohol (335 mg, 2.42
mmol) redissolved in dry THF under a dinitrogen atmosphere, followed by the addition of freshly
activated 4Å molsieves. After stirring for 15 minutes, the mixture was cooled down to ꢀ78 °C and a
cooled solution (10 °C) of ZnCl2 in dry THF (2.43 mL, 1M) was added dropwise over ten minutes.
The mixture was allowed to stir overnight at rt after which it was filtered over Celite®, concentrated in
vacuo and purified by silica column chromatography (0 to 20% EtOAc in PE) to afford 35 (413 mg,
0.625 mmol, 39% over two steps) as a colorless oil. Rf = 0.48 (40% EtOAc in PE); IR (neat): 3480,
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3000, 2907, 1611, 1511; H NMR (400 MHz, CDCl3) δ = 7.30 (dd, J = 8.5, 4.8 Hz, 6H, Harom), 7.08
(d, J = 8.6 Hz, 2H, Harom), 6.98 – 6.77 (m, 8H, Harom), 4.87 (dd, J = 15.4, 11.2 Hz, 2H, CH2 PMB), 4.76
(dd, J = 10.7, 6.4 Hz, 2H, CH2 PMB), 4.63 – 4.42 (m, 4H, 2 x CH2 PMB), 4.32 (d, J = 7.3 Hz, 1H, Hꢀ
1), 3.80 (s, 6H, 2 x CH3 PMB), 3.79 (s, 3H, CH3 PMB), 3.79 (s, 3H, CH3 PMB), 3.70 (m, 2H, Hꢀ6),
3.62 – 3.50 (m, 3H, Hꢀ2, Hꢀ3, Hꢀ4), 3.45 (dd, J = 9.9, 4.1 Hz, 1H, Hꢀ5), 2.41 (s, 1H, OH). 13C NMR
(101 MHz, CDCl3) δ = 159.5 (Cq Arom), 159.3 (Cq Arom), 159.3 (Cq Arom), 130.9 (Cq Arom), 130.4
(Cq Arom), 130.3 (Cq Arom), 130.0 (CH Arom), 129.7 (CH Arom), 129.7 (CH Arom), 129.6 (CH Arom),
129.3 (Cq Arom), 114.0 (CH Arom), 113.9 (CH Arom), 113.9 (CH Arom), 101.5 (Cꢀ1), 84.3 (Cꢀ2), 77.4
(Cꢀ3), 75.3 (Cꢀ4), 74.9 (CH2 PMB), 74.7 (Cꢀ5), 73.2 (CH2 PMB), 70.8 (CH2 PMB), 68.5 (Cꢀ6), 55.4 (4
x CH3 PMB); HRMS (ESI) m/z: [M + NH4]+ Calcd for C38H48O10N 678.3273; Found 678.3302.
(4ꢀMethoxybenzyl)ꢀ2ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀ3,4,6ꢀTetraꢀOꢀ(4ꢀ
methoxybenzyl)ꢀβꢀDꢀglucopyranoside, 36: Glycoside 35 (333 mg, 0.504 mmol) was dissolved in dry
DMF (5 mL) and cooled to 0 °C. To this solution was added NaH (60% dispersion in mineral oil, 26
mg, 0.65 mmol) portionwise followed by the addition of tosylate 31 (185 mg, 0.554 mmol). After
stirring for 6 h at rt under a dry atmosphere, MeOH was added (1 mL). The mixture was then diluted
with EtOAc (50 mL), transferred to a separatory funnel and washed with water (3x) and brine (3x).
The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by
column chromatography (0 to 30% EtOAc in PE) afforded the title compound 36 as milky oil (334
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mg, 0.405 mmol, 80%). Rf = 0.39 (40% EtOAc in PE); IR (neat): 2999, 2864, 2835, 1612, 1512; H
NMR (400 MHz, CDCl3) δ = 7.39 – 7.18 (m, 6H, Harom), 7.07 (dd, J = 8.7, 4.8 Hz, 2H, Harom), 6.92 –
6.75 (m, 8H, Harom), 4.96 – 4.80 (m, 2H, CH2 PMB), 4.78 – 4.66 (m, 2H, CH2 PMB), 4.62 – 4.37 (m,
5H, CH2 PMB, Hꢀ1), 4.06 (dt, J = 9.9, 4.6 Hz, 1H, CHH OCH2), 3.85 (q, J = 5.2 Hz, 1H, CHH OCH2),
3.81 (s, 3H, CH3 PMB), 3.80 (s, 3H, CH3 PMB), 3.79 (s, 3H, CH3 PMB), 3.79 (s, 3H, CH3 PMB), 3.74
– 3.66 (m, 2H, Hꢀ6), 3.66 – 3.53 (m, 9H, Hꢀ3, 4 x OCH2), 3.49 (t, J = 9.2 Hz, 1H, Hꢀ4), 3.40 (ddd, J =
9.7, 5.1, 2.2 Hz, 1H, Hꢀ5), 3.29 (t, J = 8.3 Hz, 1H, Hꢀ2), 2.62 (t, J = 7.0 Hz, 2H, CH2SMe), 2.10 (s,
3H, CH2SMe). 13C NMR (101 MHz, CDCl3) δ = 159.3 (Cq arom), 159.3 (Cq arom), 159.3 (Cq arom),
159.3 (Cq arom), 131.1 (Cq arom), 130.5 (Cq arom), 130.4 (Cq arom), 129.8 (CH arom), 129.7 (CH
arom), 129.7 (CH arom), 129.6 (CH arom), 113.8 (CH arom), 102.1 (Cꢀ1), 84.4 (Cꢀ4), 83.3 (Cꢀ2), 77.6
(Cꢀ4), 75.3 (CH2 PMB), 74.9 (Cꢀ5), 74.7 (CH2 PMB), 73.2 (CH2 PMB), 72.1 (OCH2), 70.9 (OCH2),
70.9 (CH2 PMB), 70.6 (OCH2), 70.5 (OCH2), 70.4 (OCH2), 68.7 (Cꢀ6), 55.4 (4 x CH3 PMB), 33.4
(CH2SMe), 16.1 (CH2SMe); HRMS (ESI) m/z: [M + NH4]+ Calcd for C45H62O12SN 840.3987; Found
840.4002.
2ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀα/βꢀDꢀglucopyranoside, H37: Compound 36 (241
mg, 0.293 mmol) was dissolved in a mixture of DCM/HFIP (3 mL) and to this solution were added 5
drops of 37% HCl in H2O. The color immediately changed to dark red, and after stirring for 5 minutes
the mixture was quenched upon the addition of Et3N (500 µL, 3.57 mmol). The mixture was then
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concentrated in vacuo and redissolved in H2O (5.8 mL), followed by the addition of a solution of
MeNH2 in MeOH (145 µL, 2M). After heating the reaction mixture for 30 minutes at 60 °C, solvents
were removed under reduced pressure and the resulting residue was purified by silica column
chromatography (0 to 20% MeOH in DCM) to afford fully deprotected hemiacetal H37 (67 mg, 0.196
mmol, 67%) as a clear oil. Rf = 0.54 (25% MeOH in DCM); IR (neat): 3411, 2917, 2865, 1115, 1042;
1H NMR (400 MHz, CD3OD) δ = 5.29 (d, J = 3.5 Hz, 1H, Hꢀ1α), 4.53 (d, J = 7.8 Hz, 1H, Hꢀ1β), 4.04
(dt, J = 11.3, 4.4 Hz, 1H, CHH Hꢀ6), 3.89 – 3.70 (m, 8H), 3.70 – 3.59 (m, 19H), 3.42 – 3.32 (m, 1H,
Hꢀ3β), 3.30 – 3.20 (m, 2H), 3.03 – 2.86 (m, 1H, Hꢀ2β), 2.68 (t, J = 6.8 Hz, 4H, 2 x CH2SMe), 2.13 (s,
6H, 2 x CH2SMe). 13C NMR (101 MHz, CD3OD) δ = 98.1 (Cꢀ1β), 91.8 (Cꢀ1α), 85.1 (Cꢀ1β), 82.4,
77.9, 77.5, 73.9, 72.8, 72.6, 71.9, 71.9, 71.6, 71.6, 71.5, 71.5, 71.4, 71.2, 71.1, 71.0, 62.8 (Cꢀ6α), 62.7
(Cꢀ6β), 34.2 (2 x CH2SMe), 15.9 (2 x CH2SMe); HRMS (ESI) m/z: [M + Na]+ Calcd for C13H26O8SNa
365.1241; Found 365.1251.
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1,2:5,6ꢀdiꢀOꢀisopropylideneꢀ3ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀαꢀDꢀglucofuranose,
38: To a cooled solution of diacetone glucose (200 mg, 0.768 mmol) in dry DMF (8 mL) was added
60% NaH in mineral oil (80.0 mg, 2.00 mmol). After stirring for 5 min, tosylate 32 was added and the
mixture was overnight. After quenching the reaction with MeOH (1 mL), Et2O (50 mL) was added and
the reaction was transferred to a separatory funnel. After washing with water (1x), aq. NaHCO3 (1x)
and brine (1x), layers were separated and the organic layer was dried (Na2SO4) and concentrated in
vacuo. Purification of the residue over silica (0 ꢀ50% EtOAc in PE) gave 38 as a clear oil. (294 mg,
0.700 mmol, 91%). Rf = 0.73 (50% EtOAc in PE); IR (neat): 2985, 2871, 1456, 1371, 1058; 1H NMR
(400 MHz, CDCl3) δ = 5.87 (d, J = 3.8 Hz, 1H, Hꢀ1), 4.57 (d, J = 3.6 Hz, 1H, Hꢀ2), 4.31 (dt, J = 7.8,
5.9 Hz, 1H, Hꢀ5), 4.14 – 4.10 (m, 1H, Hꢀ3), 4.09 – 4.05 (m, 1H, CHH Hꢀ6), 3.99 (dd, J = 8.6, 5.8 Hz,
1H, CHH Hꢀ6), 3.92 (d, J = 3.1 Hz, 1H, Hꢀ4), 3.79 – 3.71 (m, 2H, OCH2), 3.68 – 3.60 (m, 8H, 4 x
OCH2), 2.69 (t, J = 6.9 Hz, 2H, CH2SMe), 2.14 (s, 3H, CH2SMe), 1.49 (d, J = 2.7 Hz, 3H, CH3
isopropylidene), 1.42 (s, 3H, CH3 isopropylidene), 1.34 (s, 3H, CH3 isopropylidene), 1.31 (d, J = 3.6
Hz, 3H, CH3 isopropylidene). 13C NMR (101 MHz, CDCl3) δ = 111.9 (Cq isopropylidene), 109.0 (Cq
isopropylidene), 105.4 (Cꢀ1), 82.8 (Cꢀ2), 82.7 (Cꢀ4) , 81.2 (Cꢀ3), 72.7 (Cꢀ5), 70.8 (OCH2), 70.7
(OCH2), 70.6 (OCH2), 70.5 (OCH2), 70.28, 67.3 (Cꢀ6), 33.5 (CH2SMe), 27.0 (CH3 isopropylidene),
27.0 (CH3 isopropylidene), 26.4 (CH3 isopropylidene), 25.6 (CH3 isopropylidene), 16.2 (CH2SMe);
HRMS (ESI) m/z: [M + NH4]+ Calcd for C19H38O8SN 440.2313; Found 440.2320.
3ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀα/βꢀDꢀglucopyranoside, H40: To a suspension of
compound 38 in H2O, was added Amberlite® IRꢀ120 H+ and this mixture was stirred for 24 h at 60 °C
after which it was filtered and concentrated in vacuo. Purification of the residue over silica (0 to 10%
MeOH in DCM) afforded the title compound H40 as a clear oil (α/β = 1:1, 81 mg, 0.24 mmol, 46%).
1
Rf = 0.32 (10% MeOH in DCM); IR (neat): 3369, 2918, 2873, 1104, 1077; H NMR (400 MHz,
CD3OD) δ = 5.08 (d, J = 3.6 Hz, 1H, Hꢀ1α), 4.47 (d, J = 7.7 Hz, 1H, Hꢀ1β), 4.24 – 3.13 (m, 40H),
2.67 (t, J = 6.9 Hz, 4H, 2 x CH2SMe), 2.11 (s, 6H, 2 x CH2SMe). 13C NMR (101 MHz, CD3OD) δ =
98.1 (Cꢀ1β), 94.0 (Cꢀ1α), 87.6, 84.5, 77.8, 76.1, 73.7, 73.1, 73.0, 72.2, 72.1, 71.6, 71.4, 71.4, 71.3,
71.1, 62.8 (Cꢀ6β), 62.6 (Cꢀ6α), 34.2 (2x OCH2SMe), 15.9 (2x OCH2SMe); HRMS (ESI) m/z: [M +
Na]+ Calcd for C13H26O8SNa 365.1241; Found 365.1243.
(4ꢀMethoxybenzyl)ꢀβꢀ
Dꢀglucopyranoside, 41: To
a
solution of 2,3,4,6ꢀtetraꢀOꢀacetylꢀαꢀDꢀ
glucopyranosyl bromide (3.00 g, 7.30 mmol) and 4ꢀmethoxybenzyl alcohol (5.04 g, 36.5 mmol) in dry
Et2O (75 mL) were added freshly activated 4Å molsieves. The resulting mixture was allowed to stir
for ten minutes, after which Ag2CO3 (6.00 g, 21.8 mmol) and I2 (1.85 g, 7.30 mmol) were added. After
stirring an additional 24 h under a dinitrogen atmosphere at rt in the dark, the reaction mixture was
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filtered over Celite®, diluted with EtOAc (200 mL), washed with 1M Na2S2O3 (3x), aq. NaHCO3 (3x)
and brine (3x). The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the
residue by silica column chromatography (20% EtOAc in DCM) afforded (4ꢀmethoxybenzyl)ꢀ2,3,4,6ꢀ
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tetraꢀOꢀacetylꢀβꢀDꢀglucopyranoside (2.39 g), which was then redissolved in dry MeOH (70 mL)
followed by the addition of a catalytic amount of NaOMe. The resulting mixture was allowed to stir
for 4 h, after which Amberlite® IRꢀ120 H+ was added until neutral pH, filtered and concentrated in
vacuo, affording the title compound 41 as a clear oil (1.57 g, 5.23 mmol, 72% over two steps). Rf =
0.57 (20% MeOH in DCM); IR (neat): 3335, 2924, 1612, 1027, 819; 1H NMR (400 MHz, CD3OD) δ =
7.32 (d, J = 8.6 Hz, 2H, Harom), 6.95 – 6.71 (m, 2H, Harom), 4.85 (d, J = 18.0 Hz, 1H, CHH PMB), 4.58
(d, J = 11.3 Hz, 1H, CHH PMB), 4.31 (d, J = 7.8 Hz, 1H, Hꢀ1), 3.89 (dd, J = 12.0, 2.2 Hz, 1H, CHH
Hꢀ6), 3.68 (dd, J = 12.0, 5.5 Hz, 1H, CHH Hꢀ6), 3.42 – 3.14 (m, 4H, Hꢀ2, Hꢀ3, Hꢀ4, Hꢀ5). 13C NMR
(101 MHz, CD3OD) δ = 160.8 (Cq Arom), 130.9 (CH Arom), 130.9 (Cq Arom), 114.6 (CH Arom),
102.9 (Cꢀ1), 78.0 (Cꢀ3), 78.0 (Cꢀ4), 75.1 (Cꢀ2), 71.7 (Cꢀ5), 71.4 (CH2 PMB), 62.8 (Cꢀ6), 55.7 (CH3
PMB). HRMS (ESI) m/z: [M + Na]+ Calcd for C14H20O7Na 323.1107; Found 323.1088.
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(4ꢀMethoxybenzyl)ꢀ4,6ꢀOꢀ(4ꢀmethoxybenzylidene)ꢀβꢀDꢀglucopyranoside, 42: To a solution of 41
(309 mg, 1.03 mmol) in dry DMF (5 mL) were added 4ꢀmethoxybenzaldehyde dimethyl acetal (135
µL, 0.793 mmol) and pꢀTsOH.H2O (10 mg, 0.05 mmol). The resulting reaction mixture was heated at
60 °C for 16, after which it was concentrated in vacuo. Saturated aqueous NaHCO3 (50 mL) was
added, and the mixture was further diluted with EtOAc (200 mL) and transferred to a separatory
funnel. After washing with aq. NaHCO3 (3x), water (3x) and brine (3x), layers were separated, the
organic layer was dried (Na2SO4) and concentrated in vacuo. Compound 43 (382 mg, 0.910 mmol,
89%) was obtained after silica column chromatography (0 to 10% MeOH in DCM) as a white powder.
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Rf = 0.48 (10% MeOH in DCM); IR (neat): 3480, 2869, 1612, 1516, 1244; H NMR (400 MHz,
CD3CN) δ = 7.39 (d, J = 8.8 Hz, 2H, Harom), 7.31 (d, J = 8.7 Hz, 2H, Harom), 7.00 – 6.86 (m, 4H, Harom),
5.50 (s, 1H, CH PMB acetal), 4.76 (d, J = 11.5 Hz, 1H, CHH PMB), 4.55 (d, J = 11.5 Hz, 1H, CHH
PMB), 4.43 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.24 (dd, J = 10.3, 4.6 Hz, 1H, CHH Hꢀ6), 3.78 (s, 6H, 2 x CH3
OMe) 3.72 (t, J = 9.9 Hz, 1H, CHH Hꢀ6), 3.62 – 3.50 (m, 1H, Hꢀ3), 3.49 – 3.33 (m, 2H, Hꢀ4, Hꢀ5),
3.26 (td, J = 8.1, 3.7 Hz, 1H, Hꢀ2). 13C NMR (101 MHz, CD3CN) δ = 161.1 (Cq Arom), 160.4 (Cq
Arom), 131.3 (Cq Arom), 130.7 (CH Arom), 128.6 (CH Arom), 114.6 (CH Arom), 114.4 (CH Arom),
103.4 (Cꢀ1), 102.1 (CH PMB acetal), 81.6 (Cꢀ4), 75.6 (Cꢀ2), 74.3 (Cꢀ3), 71.4 (CH2 PMB), 69.3 (Cꢀ6),
67.2 (Cꢀ5), 55.9 (2 x CH3 PMB). HRMS (ESI) m/z: [M + H]+ Calcd for C22H27O8 419.1700; Found
419.1710.
(4ꢀMethoxybenzyl)ꢀ2,3ꢀdiꢀOꢀ(4ꢀmethoxybenzyl)ꢀ4,6ꢀOꢀ(4ꢀmethoxybenzylidene)ꢀβꢀDꢀ
glucopyranoside, 43: To a cooled solution (0 °C) of pꢀmethoxy benzylidene protected 42 (377 mg,
0.900 mmol) in dry DMF (9 mL) was slowly added NaH (60% dispersion in mineral oil, 80.0 mg, 2.00
mmol) followed by the addition of 4ꢀmethoxybenzyl chloride (255 µL, 1.89 mmol). After stirring for 5
h under a dinitrogen atmosphere, the reaction was quenched upon the addition of MeOH (3 mL). The
mixture was further diluted with Et2O (200 mL) and transferred to a separatory funnel, washed with
water (1x), aq. NaHCO3 (1x) and brine (1x). The organic layer was dried over Na2SO4 and
concentrated in vacuo. Purification by silica column chromatography (0 to 20% EtOAc in PE) yielded
the title compound 43 as a clear oil (447 mg, 0.680 mmol, 76%). Rf = 0.74 (40% EtOAc in PE); IR
(neat): 3480, 2869, 1612, 1516, 1244; 1H NMR (400 MHz, CDCl3) δ = 7.43 (d, J = 8.9 Hz, 2H, Harom),
7.36 – 7.18 (m, 5H, Harom), 7.00 – 6.78 (m, 6H, Harom), 5.54 (s, 1H, CH benzylidene), 4.89 (d, J = 11.4
Hz, 1H, CHH PMB), 4.82 (dd, J = 10.8, 5.6 Hz, 2H, CH2 PMB), 4.71 (dd, J = 16.0, 10.7 Hz, 2H, CH2
PMB), 4.65 – 4.57 (m, 2H, CHH PMB, Hꢀ1), 4.37 (dd, J = 10.5, 5.0 Hz, 1H, CHH Hꢀ6), 3.82 (s, 6H, 2
x CH3 PMB), 3.82 (s, 3H, CH3 PMB), 3.80 (s, 3H, CH3 PMB), 3.69 (p, J = 9.1 Hz, 2H, Hꢀ3, Hꢀ4),
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3.49 (t, J = 7.9 Hz, 1H, Hꢀ2), 3.40 (td, J = 9.5, 5.0 Hz, 1H, Hꢀ5). 13C NMR (101 MHz, CDCl3) δ =
160.1 (Cq Arom), 159.5 (Cq Arom), 159.3 (Cq Arom), 159.3 (Cq Arom), 130.8 (Cq Arom), 130.6 (Cq
Arom), 129.9 (CH Arom), 129.8 (CH Arom), 129.8 (CH Arom), 129.3 (Cq Arom), 127.4 (CH Arom),
113.9 (CH Arom), 113.8 (CH Arom), 113.7 (CH Arom), 103.0 (Cꢀ1), 101.2 (CH PMB acetal), 81.9 (Cꢀ
2), 81.5 (Cꢀ3), 80.7 (Cꢀ4), 75.1 (CH2 PMB), 74.9 (CH2 PMB), 71.4 (CH2 PMB), 68.9 (Cꢀ6), 66.2 (Cꢀ
5), 55.4 (3 x CH3 PMB), 55.3 (CH3 PMB acetal); HRMS (ESI) m/z: [M + Na]+ Calcd for C38H42O10Na
681.2670; Found: 681.2671.
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(4ꢀMethoxybenzyl)ꢀ2,3,6ꢀtriꢀOꢀ(4ꢀmethoxybenzyl)ꢀβꢀDꢀglucopyranoside, 44: Fully protected
glycoside 43 (400 mg, 0.610 mmol) was dissolved in DMF (12 mL) and to this solution were added
freshly activated 4Å molsieves and fresh NaCNBH3 (385 mg, 6.13 mmol). After stirring for 15
minutes the solution was cooled to 0 °C and a precooled solution (0 °C) of trifluoroacetic acid (1.2
mL) in dry DMF (3 mL) on 4Å molsieves was then added dropwise over 15 minutes. The reaction
mixture was maintained at rt for 48 h at rt and filtered over Celite®, diluted with EtOAc (100 mL) and
transferred to a separatory funnel. After washing with water (1x), aq. NaHCO3 (1x) and brine (1x), the
organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column
chromatography over silica (0 to 30% EtOAc in PE) afforded 44 (385 mg, 0.580 mmol, 95%) as a
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clear oil. Rf = 0.48 (40% EtOAc in PE); IR (neat): 3480, 3000, 2907, 1612, 1512; H NMR (400 MHz,
CD3Cl3) δ = 7.42 – 7.16 (m, 8H, Harom), 6.87 (tdd, J = 8.9, 4.7, 2.6 Hz, 8H, Harom), 4.92 – 4.82 (m, 3H,
CHH PMB, CH2 PMB), 4.67 – 4.53 (m, 5H, CHH PMB, 2 x CH2 PMB), 4.49 (d, J = 7.2 Hz, 1H, Hꢀ1),
3.82 (s, 3H, CH3 PMB), 3.81 (s, 3H, CH3 PMB), 3.81 (s, 3H, CH3 PMB), 3.80 (s, 3H, CH3 PMB), 3.79
– 3.66 (m, 2H, Hꢀ6), 3.59 – 3.51 (m, 1H, Hꢀ5), 3.48 – 3.36 (m, 3H, Hꢀ2, Hꢀ3, Hꢀ4). 13C NMR (101
MHz, CDCl3) δ = 159.4 (Cq Arom), 152.7 (Cq Arom), 152.5 (Cq Arom), 130.7 (CH Arom), 130.0 (CH
Arom), 129.9 (CH Arom), 129.8 (CH Arom), 129.5 (CH Arom), 114.1 (CH Arom), 113.9 (CH Arom),
102.5 (Cꢀ1), 83.8 (Cꢀ4), 81.6 (Cꢀ2), 75.0 (CH2 PMB), 74.5 (CH2 PMB), 74.2 (Cꢀ3), 73.4 (CH2 PMB),
71.7 (Cꢀ5), 71.1 (CH2 PMB), 70.2 (Cꢀ6), 55.4 (4 x CH3 PMB); HRMS (ESI) m/z: [M + NH4]+ Calcd
for C38H48O10N 678.3273; Found 678.3321.
(4ꢀMethoxybenzyl)ꢀ2ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀ3,6ꢀtriꢀOꢀ(4ꢀmethoxybenzyl)ꢀ
βꢀDꢀglucopyranoside, 45: Compound 44 (300 mg, 0.454 mmol) was dissolved in dry DMF (5 mL)
and cooled to (0 °C) after which 60% NaH in mineral oil (31 mg, 0.77 mmol) was added. This mixture
was allowed to stir for 5 min, after which tosylate 32 (177 mg, 0.530 mmol) was added dropwise. The
reaction was allowed to stir for 6 h, after which it was quenched upon the addition of MeOH (2 mL),
diluted with Et2O (20 mL) and transferred to a separatory funnel. After washing with aq. NaHCO3
(1x), water (1x) and brine (1x), layers were separated, the organic layer dried (Na2SO4) and
concentrated in vacuo. Purification of the residue by column chromatography (0 to 40% EtOAc in PE)
afforded the title compound 45 as a clear oil (291 mg, 0.354 mmol, 78%). Rf = 0.38 (40% EtOAc in
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PE); IR (neat): 2998, 2907, 2836, 1612, 1513; H NMR (400 MHz, CDCl3) δ = 7.36 – 7.18 (m, 8H,
Harom), 6.94 – 6.79 (m, 8H, Harom), 4.97 – 4.50 (m, 8H, 4 x CH2 PMB), 4.46 (d, J = 7.8 Hz, 1H, Hꢀ1),
3.95 (dt, J = 9.8, 4.5 Hz, 1H, CHH OCH2), 3.81 – 3.74 (m, 1H, CHH Hꢀ6), 3.76 – 3.63 (m, 3H, CHH
Hꢀ6, 2 x CHH OCH2), 3.65 – 3.50 (m, 8H, Hꢀ5, CHH OCH2, 3 x OCH2), 3.46 – 3.38 (m, 3H, Hꢀ2, Hꢀ
3, Hꢀ4), 2.66 (t, J = 6.9 Hz, 2H, CH2SMe), 2.12 (s, 3H, CH2SMe). 13C NMR (101 MHz, CDCl3) δ =
159.7 (Cq Arom), 159.4 (Cq Arom), 131.1 (Cq Arom), 130.8 (Cq Arom), 130.6 (Cq Arom), 130.0 (CH
Arom), 129.8 (CH Arom), 129.5 (CH Arom), 113.9 (CH Arom), 113.8 (CH Arom), 102.5 (Cꢀ1), 84.3 (Cꢀ
5), 82.0 (Cꢀ2), 78.7 (Cꢀ3), 75.4 (CH2 PMB), 75.0 (Cꢀ4), 74.6 (CH2 PMB), 73.2 (CH2 PMB), 72.2
(OCH2), 71.0 (CH2 PMB), 70.9 (OCH2), 70.7 (OCH2), 70.6 (OCH2), 70.4 (CH2SMe), 68.8 (Cꢀ6), 33.5
(4 x CH3 PMB), 16.2 (CH2SMe). HRMS (ESI) m/z: [M + NH4]+ Calcd for C45H62O12SN 840.3987;
Found 840.4028.
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4ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀα/βꢀ
Dꢀglucopyranoside, H46: Compound 45 (108
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mg, 0.131 mmol) was dissolved in a mixture of DCM/HFIP (1:1, 2 mL) and to this solution were
added 4 drops of 37% HCl. The mixture slowly turned red to deep purple in 30 minutes, after which it
was quenched with Et3N (0.5 mL) and concentrated in vacuo. The crude was redissolved in MeOH (5
mL), Amberlite IRꢀ120 H+ was added and the mixture was stirred for 5 minutes, filtered and
concentrated. Purification of the resulting residue over silica (0 to 15% MeOH in DCM) afforded the
title compound H46 as a clear oil (13 mg, 0.038 mmol, 29%). Rf = 0.57 (20% MeOH in DCM); IR
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(neat): 3370, 2918, 2873, 1104, 1077; H NMR (400 MHz, CD3OD) δ = 5.09 (d, J = 3.7 Hz, 1H, Hꢀ
1α), 4.45 (d, J = 7.7 Hz, 1H, Hꢀ1β), 4.02 – 3.58 (m, 28H), 3.47 (t, J = 8.9 Hz, 1H, Hꢀ3β), 3.29 – 3.19
(m, 2H), 3.13 (dd, J = 9.2, 7.9 Hz, 1H, Hꢀ2β), 2.68 (t, J = 6.8 Hz, 4H, 2 x OCH2SMe), 2.13 (s, 6H, 2 x
OCH2SMe). 13C NMR (100 MHz, CD3OD) δ = 98.2 (Cꢀ1β), 93.9 (Cꢀ1α), 80.5, 80.3, 78.2, 77.0, 76.3,
75.0, 73.9, 72.9, 72.0, 71.7, 71.5, 71.2, 62.5 (Cꢀ1β), 62.4 (Cꢀ1α), 34.3 (2x OCH2SMe), 15.9
(OCH2SMe); HRMS (ESI) m/z: [M + Na]+ Calcd for C13H26O8SNa 365.1241; Found 365.1251.
1,2:3,5ꢀbis(Oꢀmethylidene)ꢀ6ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)αꢀDꢀglucofuranose, 49:
To a cooled (0 °C) solution of 1,2:3,5ꢀbis(Oꢀmethylidene)ꢀαꢀDꢀglucofuranose (206 mg, 1.00 mmol) in
dry DMF (10 mL) was added 60% NaH in mineral oil (57 mg, 1.42 mmol). After 10 minutes, 19 (385
mg, 1.15 mmol) was added dropwise and the resulting mixture was stirred for 3 hr at rt, after which it
was quenched upon the addition of MeOH (2 mL). The reaction mixture was extracted with Et2O (50
mL), washed with aq. NaHCO3 (2x), water (2x) and brine (2x). Layers were separated, the organic
layer was dried (Na2SO4) and concentrated in vacuo. The resulting residue was then purified by silica
column chromatography (0 to 60% EtOAc in PE) affording 49 as a colorless oil. Rf = 0.57 (50%
EtOAc in PE); IR (neat): 2867, 1455, 1082, 1184, 1058; 1H NMR (400 MHz, CDCl3) δ = 6.03 (d, J =
3.8 Hz, 1H, Hꢀ1), 5.12 (d, J = 5.9 Hz, 1H, CHH methylene), 5.08 (s, 1H, CH2 methylene), 5.03 (s, 1H,
CH2 methylene), 4.78 (d, J = 6.0 Hz, 1H, CHH methylene), 4.46 (d, J = 3.9 Hz, 1H, Hꢀ2), 4.37 (d, J =
3.0 Hz, 1H, Hꢀ3), 4.14 (t, J = 4.4 Hz, 1H, Hꢀ5), 4.03 (d, J = 2.7 Hz, 1H, Hꢀ4), 3.85 (dd, J = 10.5, 3.9
Hz, 1H, CHH Hꢀ6), 3.75 (dd, J = 10.5, 4.8 Hz, 1H, CHH Hꢀ6), 3.64 (dd, J = 11.8, 5.6 Hz, 10H, 4 x
OCH2), 2.69 (t, J = 6.9 Hz, 2H, CH2SMe), 2.14 (s, 3H, CH2SMe). 13C NMR (101 MHz, CDCl3) δ =
104.4 (Cꢀ1), 96.6 (CH2 methylene), 88.2 (CH2 methylene), 83.9 (Cꢀ2), 76.8 (Cꢀ3), 76.1 (Cꢀ4), 72.5 (Cꢀ
6), 71.6 (Cꢀ5), 71.0 (OCH2), 70.7(OCH2), 70.7 (OCH2), 70.7 (OCH2), 70.4 (OCH2), 33.5 (OCH2SMe),
16.2 (OCH2SMe). HRMS (ESI) m/z: [M + H]+ Calcd for C15H27O8S 367.1421; Found 367.1430.
6ꢀOꢀ(2ꢀ[2ꢀ(2ꢀ(methylthio)ethoxy)ethoxy]ethyl)ꢀα/βꢀDꢀglucopyranoside, H50: Compound 49 was
dissolved in 2M HCl (5 mL) and this mixture was heated at 100 °C for 1 h after which the reaction
was neutralized with 1M NaOH (10 mL) and concentrated in vacuo. Purification of the residu by silica
column chromatography (0 to 20% MeOH in DCM) afforded H50 as a colorless oil (101 mg, 0.295
mmol, 70%). Rf = 0.50 (20% MeOH in DCM); IR (neat): 3368, 2917, 2874, 1427, 1078; 1H NMR
(500 MHz, CD3OD) δ = 5.13 (d, J = 3.7 Hz, 1H, Hꢀ1α), 4.52 (d, J = 7.7 Hz, 1H, Hꢀ1β), 4.06 – 3.94 (m,
4H), 3.91 – 3.87 (m, 1H, CHH Hꢀ6α/β), 3.86 – 3.77 (m, 2H), 3.75 – 3.64 (m, 20H, 10 x OCH2), 3.49 –
3.38 (m, 3H), 3.41 (ddd, J = 9.8, 8.8, 6.0 Hz, 2H), 3.34 – 3.30 (m, 1H), 3.25 – 3.22 (m, 2H), 2.72 (t, J
= 6.8 Hz, 4H, 2 x CH2SMe), 2.16 (s, 6H, 2 x CH2SMe). 13C NMR (126 MHz, CD3OD) δ = 98.1 (Cꢀ
1β), 94.0 (Cꢀ1α), 87.6, 84.4, 77.8, 76.1, 73.6, 73.0 (OCH2), 73.0 (OCH2), 73.0, 72.1 (OCH2), 72.1
(OCH2), 71.6 (OCH2), 71.6 (OCH2), 71.4 (OCH2), 71.4 (OCH2), 71.3, 71.1 (OCH2), 71.1 (OCH2), 62.8
(Cꢀ6α/β), 62.7 (Cꢀ6α/β), 34.2 (2 x CH2SMe), 15.9 (2 x CH2SMe). HRMS (ESI) m/z: [M + Na]+ Calcd
for C13H26O8SNa 365.1241; Found: 365.1252.
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[Ru(tpy)(bpy)(13)](PF6)2, [1](PF6)2: [Ru(tpy)(bpy)Cl]Cl (63 mg, 0.112 mmol) and 13 (93 mg, 0.366
mmol) were dissolved in deoxygenated H2O (18 mL) and this mixture was heated at 80 °C for 16 h,
after which it was concentrated in vacuo. Purification of the residue by silica column chromatography
(100/0/0 to 100/80/20 aceton/water/aq. KPF6), followed by purification over Sephadex LHꢀ20
(MeOH), afforded the title compound as a red solid (44 mg, 42.4 umol, 39%). Rf = 0.69 (100/80/20
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aceton/water/aq. KPF6); H NMR (400 MHz, CD3OD) δ = 9.85 (d, J = 5.7 Hz, 1H, 1), 8.81 (d, J = 8.0
Hz, 1H, 4), 8.77 (d, J = 8.2 Hz, 2H, T3’, T5’), 8.62 (d, J = 8.1 Hz, 2H, T6, T6”), 8.58 (d, J = 7.8 Hz, 1H,
10), 8.44 – 8.34 (m, 2H, T4’, 3), 8.18 – 8.04 (m, 3H, T5, T5”, 2), 7.92 (td, J = 7.8, 1.6 Hz, 1H, 9), 7.79
(d, J = 5.6 Hz, 2H, T3, T3”), 7.45 (ddd, J = 7.3, 5.6, 1.4 Hz, 2H, T4, T4”), 7.34 – 7.26 (m, 1H, 7), 7.23
(ddd, J = 7.3, 5.7, 1.3 Hz, 1H, 8), 4.69 (d, J = 3.7 Hz, 1H, Hꢀ1), 3.79 – 3.68 (m, 2H, CHH Hꢀ6, CHH
OCH2), 3.64 – 3.34 (m, 5H, CHH Hꢀ6, CHH OCH2, Hꢀ2, Hꢀ3, Hꢀ5), 3.29 – 3.20 (m, 1H, Hꢀ4), 2.12 –
1.91 (m, 2H, CH2SMe), 1.39 (s, 3H, CH2SMe). 13C NMR (101 MHz, CD3OD) δ = 159.3 (Cq Arom),
158.7 (Cq Arom), 158.1 (Cq Arom), 157.9 (Cq Arom), 154.3 (CH T3, T3”), 153.5 (CH 1), 150.8 (CH 7),
140.1 (CH T5, T5”), 139.4 (CH T4’), 139.3 (CH 9), 138.3 (CH 3), 129.8 (CH T4, T4”), 129.4 (CH 2), 128.4
(CH 8), 126.2 (CH T6), 126.2 (CH T6”), 125.9 (CH 4), 125.5 (CH T3’, T5’), 125.1 (CH 10), 100.2 (Cꢀ1),
75.1 (Cꢀ5), 74.3 (Cꢀ3), 73.1 (Cꢀ2), 71.7 (Cꢀ4), 64.8 (OCH2), 62.8 (Cꢀ6), 35.9 (CH2SMe), 14.8
(CH2SMe); HRMS (ESI) m/z: [M]2+ Calcd for C34H37N5O6RuS 372.5749; Found 372.5756; Elemental
analysis calcd (%) for [1](PF6)2.2MeOH: C, 39.35; H, 4.13; N, 6.37; found: 41.45; H, 4.18; N, 6.35.
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[Ru(tpy)(bpy)(15)](PF6)2, [2](PF6)2: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (200 mg, 0.357 mmol) and 15 (100 mg,
0.476 mmol) in H2O (60 mL) affording [2](PF6)2, as an orange powder (98.4 mg, 99.3 µmol, 28%). Rf
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= 0.15 (100/80/20 acetone/water/aq. KPF6); H NMR (400 MHz, CD3OD) δ = 10.01 (d, J = 4.1 Hz,
1H, 1), 8.82 (dt, J = 8.2, 1.1 Hz, 1H, 4), 8.76 (ddd, J = 8.2, 4.3, 0.9 Hz, 2H, T3’, T5’), 8.66 – 8.56 (m,
3H, T6, T6”, 10), 8.43 – 8.36 (m, 2H, T4’, 3), 8.13 – 8.02 (m, 3H, T5, T5”, 2), 7.93 (ddd, J = 8.2, 7.0,
2.1 Hz, 1H, 9), 7.86 (ddd, J = 5.5, 1.5, 0.7 Hz, 1H, T3), 7.80 (ddd, J = 5.5, 1.5, 0.7 Hz, 1H, T3”), 7.44
(ddt, J = 7.8, 5.5, 1.3 Hz, 2H, T4, T4”), 7.27 – 7.18 (m, 2H, 7, 8), 3.52 (d, J = 9.1 Hz, 1H, Hꢀ1), 3.43 (t,
J = 3.6 Hz, 2H, Hꢀ6), 3.02 – 2.90 (m, 3H, Hꢀ2, Hꢀ3, Hꢀ4), 2.48 (d, J = 8.7 Hz, 1H, Hꢀ5), 1.39 (s, 3H,
SMe). 13C NMR (101 MHz, CD3OD) δ = 163.4 (Cq Arom), 160.7 (Cq Arom), 160.0 (Cq Arom), 159.8
(Cq Arom), 158.9 (Cq Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.5 (CH T3), 154.3 (CH T3”), 153.8
(CH 1), 150.4 (CH 7), 140.2 (CH T5), 140.1 (CH T5”), 139.6 (CH T4’), 139.5 (CH 9), 138.2 (CH 3), 129.7
(CH T4), 129.6 (CH T4”), 129.0 (CH 2), 128.5 (CH 8), 126.1 (CH 4), 126.0 (CH T6), 125.9 (CH T6”)
125.3 (CH T3’, T5’), 125.1 (CH 10), 85.7 (Cꢀ1), 82.7 (Cꢀ5), 78.6 (Cꢀ2), 71.3 (Cꢀ3), 70.0 (Cꢀ4), 61.8 (Cꢀ
6), 9.0 (SMe). HRMS (ESI) m/z: [M]2+ Calcd for C32H33N5O5RuS 350.5618; Found: 350.5629.
Elemental analysis calcd (%) for [2](PF6)2: C, 38.18; H, 3.30; N, 6.96; found: 38.93; H, 3.39; N, 7.19.
[Ru(tpy)(bpy)(24)](PF6)2, [3](PF6)2: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (101 mg, 0.180 mmol) and 24 (75.7 mg,
0.298 mmol) in H2O (30 mL) affording the title compound as a hygroscopic orange powder (73.3 mg,
70.7 µmol, 39%). Rf = 0.36 (100/10/20 aceton/water/aq. KPF6); 1H NMR (500 MHz, CD3OD) δ = 9.85
(dd, J = 5.6, 0.7 Hz, 1H, 1), 8.81 (dd, J = 17.9, 8.2 Hz, 3H, 4, T3’, T5’), 8.63 (d, J = 8.1 Hz, 2H, T6,
T6”), 8.59 (d, J = 8.2 Hz, 1H, 10), 8.45 – 8.36 (m, 2H, T4’, 3), 8.14 – 8.04 (m, 3H, T5, T5”, 2), 7.93 (td,
J = 7.8, 1.5 Hz, 1H, 9), 7.80 (td, J = 5.4, 0.8 Hz, 2H, T3, T3”), 7.45 (ddd, J = 7.6, 5.5, 1.3 Hz, 2H, T4,
T4”), 7.30 (ddd, J = 5.7, 1.5, 0.7 Hz, 1H, 7), 7.23 (ddd, J = 7.2, 5.7, 1.3 Hz, 1H, 8), 4.15 (d, J = 7.8 Hz,
1H, Hꢀ1), 3.88 – 3.76 (m, 2H, CHH Hꢀ6, CHH OCH2), 3.57 (ddd, J = 12.7, 11.5, 5.6 Hz, 2H, CHH Hꢀ
6, CHH OCH2), 3.26 (m, 1H, Hꢀ3), 3.23 – 3.17 (m, 2H, Hꢀ2, Hꢀ4), 3.09 (dd, J = 9.2, 7.8 Hz, 1H, Hꢀ5),
1.98 (t, J = 5.6 Hz, 2H, CH2SMe), 1.39 (s, 3H, CH2SMe). 13C NMR (126 MHz, CD3OD) δ = 159.3 (Cq
Arom), = 159.3 (Cq Arom), 158.8 (Cq Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.4 (CH T3), 154.4
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(CH T3”), 153.6 (CH 1), 150.8 (CH 7), 140.1 (CH T5, T5”), 139.5 (T4’), 139.4 (CH 9), 138.3 (CH 3), 129.8
(CH T4, T4”), 129.2 (CH 2), 128.4 (CH 8), 126.2 (T6, T6”), 125.9 (CH 4), 125.5 (T3’, T5’), 125.1 (CH 10),
104.2 (Cꢀ1), 78.2 (Cꢀ3), 78.1 (Cꢀ4), 74.9 (Cꢀ2), 71.5 (Cꢀ5), 66.6 (OCH2), 62.6 (Cꢀ6), 35.8 (CH2SMe),
14.8 (CH2SMe). HRMS (ESI) m/z: [M]2+ Calcd for C34H37N5O6RuS 372.5749; Found 372.5758;
Elemental analysis calcd (%) for [3](PF6)2: C, 39.47; H, 3.60; N, 6.77; found: 40.57; H, 3.53; N, 7.00.
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[Ru(tpy)(bpy)(25)](PF6)2, [4](PF6)2: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (94.2 mg, 0.168 mmol) and 25 (71.0 mg,
0.238 mmol) in H2O (28 mL) affording the title compound as a hygroscopic orange powder (120 mg,
111 µmol, 66%). Rf = 0.56 (50/30/20 acetone/water/aq. KPF6); 1H NMR (400 MHz, CD3OD) δ = 9.83
(d, J = 5.7 Hz, 1H, 1), 8.79 (dd, J = 14.9, 8.1 Hz, 3H, 4, T3’, T5’), 8.60 (dd, J = 16.6, 8.1 Hz, 2H, T6,
T6”), 8.43 – 8.34 (m, 2H, T4’, 3), 8.10 (m, 3H, T5, T5”, 2), 7.91 (td, J = 7.8, 1.5 Hz, 1H, 9), 7.80 (d, J =
4.7 Hz, 1H, T3, T3”), 7.51 – 7.41 (m, 2H, T4, T4”), 7.32 – 7.27 (m, 1H, 7), 7.23 (ddd, J = 7.2, 5.7, 1.3
Hz, 1H, 8), 4.27 (d, J = 7.8 Hz, 1H, Hꢀ1), 3.97 – 3.89 (m, 1H, CHH OCH2), 3.85 (dd, J = 11.8, 1.7 Hz,
1H, CHH Hꢀ6), 3.71 – 3.58 (m, 2H, CHH Hꢀ6, CHH OCH2), 3.54 (dd, J = 5.4, 3.8 Hz, 2H, OCH2),
3.46 (t, J = 5.5 Hz, 2H, OCH2), 3.35 (m, J = 2.4 Hz, 1H, Hꢀ3), 3.28 – 3.22 (m, 3H, Hꢀ4, Hꢀ5), 3.12
(dd, J = 9.0, 7.8 Hz, 1H, ), 1.96 – 1.88 (m, 2H, CH2SMe), 1.40 (s, 3H, CH2SMe). 13C NMR (101 MHz,
CD3OD) δ = 159.3 (Cq Arom), 158.7 (Cq Arom), 158.1 (Cq Arom), 157.9 (Cq Arom), 154.4 (CH T3,
T3”), 153.4 (CH 1), 150.8 (CH 7), 140.1 (T5, T5”), 139.5 (CH T4’), 139.3 (CH 9), 138.3 (CH 3), 129.8 (CH
T4, T4”), 129.3 (CH 2), 128.4 (CH 8), 126.2 (CH T6), 125.9 (CH T6”), 125.5 (CH 4), 125.1 (CH T3’, T5’),
104.4 (Cꢀ1), 78.1 (Cꢀ3), 78.0 (Cꢀ4), 75.1 (Cꢀ2), 71.6 (Cꢀ5), 71.4 (OCH2), 69.7 (OCH2), 68.2 (OCH2),
62.7 (Cꢀ6), 35.6 (CH2SMe), 15.2 (CH2SMe). HRMS (ESI) m/z: [M]2+ Calcd for C36H41N5O7RuS
394.5880; Found 394.5887; Elemental analysis calcd (%) for [4](PF6)2: C, 40.08; H, 3.83; N, 6.49;
found: 40.78; H, 3.97; N, 6.34.
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[Ru(tpy)(bpy)(26)](PF6)2, [5](PF6)2: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (102 mg, 0.182 mmol) and 26 (100 mg,
0.292 mmol) in H2O (30 mL) affording the title compound as a red solid (130 mg, 116 µmol, 65%). Rf
= 0.35 (100/80/20 acetone/water/aq. KPF6); 1H NMR (400 MHz, CD3OD) δ = 9.83 (d, J = 5.8 Hz, 1H,
1), 8.81 (dd, J = 12.6, 7.9 Hz, 3H, 4, T3’, T5’), 8.62 (dd, J = 17.9, 8.1 Hz, 3H, T6, T6”, 10), 8.46 – 8.35
(m, 2H, T4’, 3), 8.10 (t, J = 8.3 Hz, 3H, T5, T5”, 2), 7.93 (t, J = 7.9 Hz, 1H, 9), 7.80 (d, J = 5.8 Hz, 2H,
T3, T3”), 7.47 (t, J = 6.6 Hz, 2H, T4, T4”), 7.30 (d, J = 5.8 Hz, 1H, 7), 7.23 (t, J = 6.6 Hz, 1H, 8), 4.26
(d, J = 7.8 Hz, 1H, Hꢀ1), 4.06 – 3.91 (m, 1H, CHH OCH2), 3.86 (d, J = 11.8 Hz, 1H, CHH Hꢀ6), 3.73
– 3.39 (m, 10H, CHH Hꢀ6, CHH OCH2, 4 x OCH2), 3.35 (m, 1H, Hꢀ5), 3.26 (d, J = 6.3 Hz, 2H, Hꢀ3,
H4), 3.10 (t, J = 8.5 Hz, 1H, Hꢀ2), 1.90 (d, J = 5.6 Hz, 2H, OCH2SMe), 1.41 (s, 3H, OCH2SMe). 13
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NMR (101 MHz, CD3OD) δ = 157.9 (Cq Arom), 157.4 (Cq Arom), 156.8 (Cq Arom), 156.6 (Cq Arom),
153.1 (CH T3, T3”), 152.1 (CH 1), 149.5 (CH 7), 138.8 (CH T5,T5”), 138.2 (CH 9), 138.0 (CH T4’), 136.9
(CH 3), 128.5 (CH T4, T4”), 127.9 (CH 8), 127.1 (CH 2), 124.9 (CH T6, T6”), 124.6 (CH 4), 124.1 (CH T3,
T5’), 123.8 (CH 10), 103.1 (Cꢀ1), 76.6 (Cꢀ3, Cꢀ5), 73.7 (Cꢀ2), 70.3 (Cꢀ4), 70.0 (OCH2), 69.9 (OCH2),
69.8 (OCH2), 68.3 (OCH2), 67.0 (OCH2), 61.3 (Cꢀ6), 34.1 (OCH2SMe), 14.00 (OCH2SMe). HRMS
(ESI) m/z: [M]2+ Calcd for C38H45N5O8RuS 416.6011 Found; 416.6025; Elemental analysis calcd (%)
for [5](PF6)2.3H2O: C, 38.78; H, 4.37; N, 5.95; found: 39.27; H, 4.68; N, 5.95.
[Ru(tpy)(bpy)(37)]PF6, [6]PF6: [Ru(tpy)(bpy)(H2O)](PF6)2 (35.9 mg, 45.0 µmol) and H37 (30.3 mg,
44.7 µmol) were dissolved in a deoxygenated mixture of acetone/H2O (4:1, 8 mL) and heated at 50 °C
for 16 h, after which the reaction mixture was concentrated in vacuo and purified over Sephadex LHꢀ
20 (MeOH), affording the title compound as a red solid (18 mg, 18.4 µmol, 41%). Rf = 0.52
(acetone/water/aq. KPF6 100/80/20); 1H NMR (500 MHz, CD3OD) δ = 9.84 (d, J = 5.6 Hz, 1H, 1),
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8.88 – 8.80 (m, 3H, 4, T3’, T5’), 8.67 (d, J = 7.1 Hz, 2H, T6, T6”), 8.62 (d, J = 7.5 Hz, 1H, 10), 8.43 (q,
J = 7.9 Hz, 2H, T4’, 3), 8.17 – 8.08 (m, 3H, T5, T5”, 2), 7.95 (td, J = 7.8, 1.5 Hz, 1H, 9), 7.81 (d, J =
5.5 Hz, 2H, T3, T3”), 7.48 (ddd, J = 7.2, 5.5, 1.3 Hz, 2H, T4, T4”), 7.36 – 7.28 (m, 1H, 7), 7.24 (ddd, J
= 7.2, 5.7, 1.3 Hz, 1H, 8), 5.23 (d, J = 3.5 Hz, 0.5H, Hꢀ1α), 4.45 (d, J = 7.8 Hz, 0.5H, Hꢀ1β), 3.99 (dt,
J = 11.1, 4.6 Hz, 0.5H CHH OCH2 α/β), 3.86 (dd, J = 11.8, 2.3 Hz, 0.5H, CHH Hꢀ6α), 3.81 – 3.55 (m,
7.5H, CHH Hꢀ6α, CH2 Hꢀ6β, Hꢀ3α, Hꢀ5α, Hꢀ5β, CHH OCH2 α/β, 1 x OCH2 α/β, 2 x OCH2 α+β), 3.51
– 3.47 (m, 2H, OCH2), 3.45 (ddd, J = 6.4, 5.2, 1.6 Hz, 2H, OCH2), 3.30 – 3.20 (m, 1.5H, Hꢀ3β, Hꢀ4β,
Hꢀ4α), 3.16 (dd, J = 9.6, 3.5 Hz, 0.5H, Hꢀ2α), 2.91 (dd, J = 8.9, 7.8 Hz, 0.5H, Hꢀ2β), 1.97 – 1.89 (m,
2H, CH2SMe), 1.43 (s, 1.5H, CH2SMe α), 1.42 (s, 1.5H, CH2SMe β). 13C NMR (126 MHz, CD3OD) δ
= 159.3 (Cq Arom), 158.8 (Cq Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.4 (CH T3, T3”), 153.4
(CH 1), 150.8 (CH 7), 140.2 (CH T5, T5”), 139.6 (CH T5, T5”), 139.4 (CH T4’, 9), 138.4 (CH 3), 129.9 (CH
T4, T4”), 129.3 (CH 2), 128.4 (CH 8), 126.3 (CH T6, T6”), 126.0 (CH 4), 125.5 (CH T3’, T5’), 125.2 (CH
10), 98.1 (Cꢀ1β), 91.8 (Cꢀ1α), 85.2 (Cꢀ2β), 82.5 (Cꢀ2α), 78.0, 77.6, 73.9, 72.9, 72.6, 71.8, 71.8, 71.6,
71.3, 71.3, 71.2, 70.9, 68.4, 68.3, 62.8 (Cꢀ6α/β), 62.7 (Cꢀ6α/β), 35.7 (CH2SMe), 35.6 (CH2SMe), 15.4
(CH2SMe), 15.4 (CH2SMe). HRMS (ESI) m/z: [M+H]2+ Calcd for C38H45N5O8RuS 416.6011; found:
416.6028; Elemental analysis calcd (%) for [6]PF6.3H2O: C, 44.27; H, 4.89; N, 6.79; found: 44.70; H,
4.73; N, 6.49.
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[Ru(tpy)(bpy)(40)]PF6, [7]PF6: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (59.1 mg, 0.105 mmol) and H40 (40.0
mg, 0.117 mmol) in H2O (18 mL) affording the title compound as a red solid (44.2 mg, 39.3 µmol,
37%); Rf = 0.55 (100/80/20 acetone/water/aq. KPF6); 1H NMR (500 MHz, CD3OD) δ = 9.86 (d, J =
5.9 Hz, 1H, 1), 8.96 – 8.80 (m, 3H, 4, T3’, T5’), 8.74 – 8.69 (m, 2H, T6, T6”), 8.67 – 8.62 (m, 1H, 10),
8.51 – 8.40 (m, 2H, T4’, 3), 8.15 (dtd, J = 9.6, 4.4, 2.4 Hz, 3H, T5, T5”, 2), 8.01 – 7.93 (m, 1H, 9), 7.87
– 7.79 (m, 2H, T3, T3”), 7.55 – 7.46 (m, 2H, T4, T4”), 7.36 – 7.32 (m, 1H, 7), 7.27 (ddt, J = 7.3, 5.7, 1.5
Hz, 1H, 8), 5.10 (d, J = 3.6 Hz, 0.5H, Hꢀ1α), 4.51 (d, J = 7.6 Hz, 0.5H, Hꢀ1β), 4.29 – 3.08 (m, 15H),
1.96 (t, J = 5.4 Hz, 2H, 2 x CH2SMe), 1.45 (s, 3H, 2 x CH2SMe). 13C NMR (126 MHz, CD3OD) δ =
159.3 (Cq Arom), 158.8 (Cq Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.4 (CH T3, T3”), 153.4 (CH
1), 150.8 (CH 7), 140.2 (CH T5, T5”), 139.6 (CH T4’), 139.4 (CH 9), 138.3 (CH 3), 129.9 (CH T4, T4”),
129.3 (CH 2), 128.4 (CH 8), 126.3 (CH T6, T6”), 126.0 (CH 4), 125.5 (CH T3’, T5’), 125.2 (CH 10), 98.2
(Cꢀ1β), 94.0 (Cꢀ1α), 87.6, 84.4, 77.8, 76.1, 73.7, 73.0, 73.0, 72.0, 72.0, 71.6, 71.4, 71.3, 71.2, 71.2,
71.1, 71.1, 68.4, 68.3, 62.6 (Cꢀ6α/β), 62.5 (Cꢀ6α/β), 35.7 (2 x CH2SMe), 15.4 (2 x CH2SMe); HRMS
(ESI) m/z: [M+H]2+ Calcd for C38H45N5O8RuS 416.6011; Found 416.6024; Elemental analysis calcd
(%) for [7]PF6.2H2O: C, 45.02; H, 4.87; N, 6.91; found: C, 44.82; H, 4.61; N, 6.79.
[Ru(tpy)(bpy)(46)]PF6, [8]PF6: [Ru(tpy)(bpy)(H2O)](PF6)2 (25.8 mg, 32.0 µmol) and H46 (11.0 mg,
32.1 µmol) were dissolved in a deoxygenated mixture of acetone/H2O (4:1, 6 mL) and heated at 50 °C
for 48 h, after which the reaction mixture was concentrated in vacuo and purified over Sephadex LHꢀ
20 (MeOH), affording the title compound as a red solid (23 mg, 23.5 µmol, 73%). Rf = 0.61
(100/80/20 acetone/water/aq. KPF6); 1H NMR (500 MHz, CD3OD) δ = 9.85 (dd, J = 5.5, 1.1 Hz, 1H,
1), 8.86 (d, J = 8.3 Hz, 1H, 4), 8.83 (d, J = 8.1 Hz, 2H, T3’, T5’), 8.69 – 8.66 (m, 2H, T6, T6”), 8.63 (dt,
J = 8.2, 1.1 Hz, 1H, 10), 8.47 – 8.41 (m, 2H, T4’, 3), 8.13 (td, J = 7.8, 1.5 Hz, 3H, T5, T5”, 2), 7.96 (td,
J = 7.9, 1.5 Hz, 1H, 9), 7.82 (dd, J = 5.7, 1.6 Hz, 2H, T3, T3”), 7.49 (ddt, J = 7.3, 5.4, 1.8 Hz, 2H, T4,
T4”), 7.31 (ddd, J = 5.7, 1.6, 0.8 Hz, 1H, 7), 7.25 (ddd, J = 7.2, 5.7, 1.3 Hz, 1H, 8), 5.11 (d, J = 3.7 Hz,
0.5H, Hꢀ1α), 4.44 (d, J = 7.8 Hz, 0.5H, Hꢀ1β), 3.98 – 3.05 (m, 15H), 1.95 (t, J = 5.5 Hz, 2H, 2 x
CH2SMe), 1.43 (s, 1.5H, CH2SMe), 1.43 (s, 1.5H, CH2SMe). 13C NMR (126 MHz, CD3OD) δ = 159.3
(Cq Arom), 158.8 (Cq Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.4 (CH T3), 154.4 (CH T3’), 153.4
(CH 1), 150.8 (CH 7), 140.2 (CH T5, T5”), 139.6 (CH T4’), 139.4 (CH 9), 138.3 (CH 3), 129.9 (CH T4,
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T4”), 129.3 (CH 2), 128.4 (CH 8), 126.3 (CH T6, T6”), 125.9 (CH 4), 125.5 (CH T3’, T5’), 125.2 (CH 10),
98.3 (Cꢀ1β), 93.9 (Cꢀ1α), 80.6, 80.4, 78.1, 77.0, 76.3, 74.9, 73.8, 72.8, 72.0, 71.9, 71.3, 71.2, 71.2,
68.4, 68.4, 62.5 (Cꢀ6 α/β), 62.4 (Cꢀ6α/β), 35.7 (CH2SMe), 35.6 (CH2SMe), 15.3 (2x CH2SMe); HRMS
(ESI) m/z: [M+H]2+ Calcd for C38H45N5O8RuS 416.6011 Found; 416.6026; Elemental analysis calcd
(%) for [8]PF6.2.5H2O: C, 44.62; H, 4.93; N, 6.85; found: 45.17; H, 5.16; N, 6.55.
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[Ru(tpy)(bpy)(50)]PF6, [9]PF6: The title compound was synthesized analogous according to the
procedure described for [1](PF6)2 using [Ru(tpy)(bpy)Cl)]Cl (58.8 mg, 0.105 mmol) and H50 (42.0
mg, 123 µmol) in H2O (18 mL) affording the title compound as a red solid (23.5 mg, 24.1 µmol, 23%).
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Rf = 0.36 (16/4/1 acetone/water/1M HCl); H NMR (500 MHz, CD3OD) δ = 9.86 (ddd, J = 5.6, 1.5,
0.7 Hz, 1H, 1), 8.89 – 8.87 (m, 1H, 4), 8.85 (d, J = 8.2 Hz, 2H, T3’, T5’), 8.69 (dd, J = 8.2, 1.2 Hz, 2H,
T6, T6”), 8.67 – 8.62 (m, 1H, 10), 8.50 – 8.41 (m, 2H, T4’, 3), 8.16 – 8.10 (m, 3H, T5, T5”, 2), 7.97 (td,
J = 7.8, 1.5 Hz, 1H, 9), 7.84 (ddd, J = 5.6, 1.5, 0.7 Hz, 2H, T3, T3”), 7.50 (ddd, J = 7.2, 5.6, 1.4 Hz,
2H, T4, T4”), 7.33 (dq, J = 5.9, 0.9 Hz, 1H, 7), 7.26 (ddd, J = 7.2, 5.7, 1.3 Hz, 1H, 8), 5.10 (d, J = 3.6
Hz, 0.5H, Hꢀ1α), 4.50 (d, J = 7.6 Hz, 0.5H, Hꢀ1β), 3.99 – 3.08 (m, 15H), 1.96 (t, J = 5.5 Hz, 2H, 2 x
CH2SMe), 1.44 (s, 3H, 2 x CH2SMe). 13C NMR (126 MHz, CD3OD) δ = 159.3 (Cq Arom), 158.8 (Cq
Arom), 158.2 (Cq Arom), 158.0 (Cq Arom), 154.4 (CH T3’), 153.4 (CH 1), 150.8 (CH 7), 140.2 (CH T5,
T5”), 139.6 (CH T4’), 139.4 (CH 9), 138.3 (CH 3), 129.9 (CH T4, T4”), 129.3 (CH 2), 128.4 (CH 8), 126.3
(CH T6, T6”), 126.0 (CH 4), 125.6 (CH T3’), 125.5 (CH T5’), 125.1 (CH 10), 98.2 (Cꢀ1β), 94.0 (Cꢀ1α),
87.6, 84.4, 77.8, 76.1, 73.7, 73.0, 73.0, 73.0, 72.0, 72.0, 71.3, 71.3, 71.2, 71.2, 71.1, 68.4, 68.3, 62.6
(Cꢀ6α/β), 62.5 (Cꢀ6α/β), 35.7 (2 x CH2SMe), 15.4 (2 x CH2SMe); HRMS (ESI) m/z: [M+H]2+ Calcd
for C38H45N5O8RuS 416.6011; Found 416.6026; Elemental analysis calcd (%) for [9]PF6.2H2O: C,
45.02; H, 4.87; N, 6.91; found: C, 44.88; H, 4.59; N, 6.78.
[Ru(Sꢀtpy)(bpy)(26)]PF6, [10]PF6: A deoxygenated solution of 31 (40.0 mg, 0.0661 mmol) and 26
(48.0 mg, 0.140 mmol) in H2O (11 mL) was heated at 80 °C for 16 h after which it was concentrated
in vacuo. The resulting residue was then purified over silica (100/0/0 to 100/95/5 in acetone/water/aq.
KPF6), followed by purification over Sephadex LHꢀ20 (MeOH) to afford the title compound as a red
microcrystalline solid (18 mg, 24.4 µmol, 37%). Rf = 0.46 (100/80/20 acetone/water/aq. KPF6); 1H
NMR (500 MHz, CD3OD) δ = 9.84 (d, J = 5.9 Hz, 1H, 1), 9.03 (s, 2H, T3’, T5’), 8.81 (d, J = 8.2 Hz,
1H, 4), 8.73 (d, J = 8.1 Hz, 2H, T6, T6”), 8.58 (d, J = 8.2 Hz, 1H, 10), 8.43 (t, J = 7.9 Hz, 1H, 3), 8.13
(dt, J = 13.2, 7.4 Hz, 3H, 2, T4, T4”), 7.95 (t, J = 7.7 Hz, 1H, 9), 7.81 (d, J = 5.9 Hz, 2H, T3, T3”), 7.60
– 7.43 (m, 2H, T5, T5”), 7.25 (dt, J = 12.7, 6.0 Hz, 2H, 8, 7), 4.30 (d, J = 7.8 Hz, 1H, Hꢀ1), 4.00 (dd, J
= 10.6, 5.3 Hz, 1H, CHH OCH2), 3.86 (d, J = 12.0 Hz, 1H, CHH Hꢀ6), 3.67 (m, 4H, CHH Hꢀ6, CHH
OCH2, 2 x OCH2), 3.57 (dd, J = 5.7, 3.4 Hz, 2H, OCH2), 3.48 (dd, J = 5.8, 3.4 Hz, 2H, OCH2), 3.44 (t,
J = 5.5 Hz, 2H, OCH2), 3.41 – 3.36 (m, 1H, Hꢀ3), 3.29 (m, 2H, Hꢀ4, Hꢀ5), 3.14 (t, J = 8.5 Hz, 1H, Hꢀ
2), 1.91 (t, J = 5.5 Hz, 2H, CH2SMe), 1.41 (s, 3H, CH2SMe). 13C NMR (126 MHz, CD3OD) δ = 159.2
(Cq Arom), 158.7 (Cq Arom), 157.9 (Cq Arom), 157.7 (Cq Arom), 154.8 (Cq Arom), 154.2 (CH T3,
T3”), 153.2 (CH 1), 150.6 (CH 7), 140.4 (CH T4, T4”), 139.8 (CH 3), 139.6 (CH 9), 130.2 (CH T5, T5”),
129.3 (CH 8) 128.5 (CH 2), 126.7 (CH T6, T6”), 125.9 (CH 4), 125.1 (CH 10), 121.7 (CH T3’, T5’), 104.2
(Cꢀ1), 77.8 (Cꢀ3, Cꢀ5), 74.9 (Cꢀ2), 71.4 (Cꢀ5), 71.1 (OCH2), 71.0 (OCH2), 69.7 (OCH2), 68.0 (OCH2),
62.5 (Cꢀ6), 35.2 (CH2SMe), 15.2 (CH2SMe). HRMS (ESI) m/z: [M]+ Calcd for C38H44N5O11RuS2
912.1517 Found; 912.1543; Elemental analysis calcd (%) for [10]PF6.0.5KPF6.5H2O: C, 36.84; H,
4.39; N, 5.65; found: 36.83; H, 4.40; N, 5.36.
ꢁ/Λꢀ[Ru(tpy)(bpy)(28)](PF6)2, [11]Cl2: [Ru(bpy2)Cl2] (73.0 mg, 0.151 mmol) and 28 (46.0 mg, 0.146
mmol) were dissolved in deoxygenated H2O (10 mL) and this mixture was heated at 80 °C for 16 h,
after which the mixture was concentrated in vacuo. Purification by Sephadex LHꢀ20 (MeOH) afforded
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the title compound as an inseparable mixture of diastereomers (69.0 mg, 0.0864 mmol, 59%). Rf =
0.28 (16/4/1 acetone/water/1M HCl); H NMR (500 MHz, CD3OD) δ = 10.02 (dd, J = 5.7, 1.4 Hz,
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7
8
1H), 9.86 (dd, J = 5.7, 1.4 Hz, 1H), 9.50 (dd, J = 5.7, 1.4 Hz, 1H), 9.42 (dd, J = 5.7, 1.3 Hz, 1H), 8.81
(d, J = 8.2 Hz, 2H), 8.79 – 8.76 (m, 2H), 8.69 – 8.62 (m, 4H), 8.45 – 8.36 (m, 4H), 8.12 (tt, J = 8.0, 1.8
Hz, 4H), 8.06 (dddd, J = 13.5, 7.3, 5.6, 1.4 Hz, 5H), 7.63 (td, J = 5.7, 1.4 Hz, 2H), 7.57 (ddd, J = 7.5,
5.7, 1.4 Hz, 2H), 7.49 – 7.42 (m, 4H), 4.65 (d, J = 7.8 Hz, 1H), 4.58 (d, J = 7.8 Hz, 1H), 3.92 (ddd, J =
19.8, 11.8, 1.9 Hz, 2H), 3.78 – 3.70 (m, 1H), 3.62 (dd, J = 11.9, 6.4 Hz, 1H), 3.50 – 3.35 (m, 10H),
3.30 (t, J = 8.2 Hz, 1H), 3.27 – 3.20 (m, 2H), 3.13 (dd, J = 14.0, 6.4 Hz, 1H), 3.02 (dd, J = 13.9, 7.1
Hz, 1H), 2.92 (dd, J = 13.1, 2.1 Hz, 1H), 2.80 (dd, J = 13.1, 1.7 Hz, 1H), 1.53 (s, 3H), 1.50 (s, 3H),
1.25 (s, 3H), 1.23 (s, 3H). 13C NMR (126 MHz, CD3OD) δ = 159.1, 159.1, 159.0, 158.9, 158.1, 158.0,
157.9, 155.4, 155.0, 154.9, 154.8, 152.0, 152.0, 151.9, 151.9, 140.3, 140.2, 130.8, 130.0, 129.9, 129.5,
129.3, 129.0, 129.0, 128.9, 126.2, 126.1, 126.0, 125.6, 125.6, 125.5, 125.4, 104.2, 103.6, 78.4, 78.3,
78.3, 78.2, 75.3, 75.3, 75.2, 71.6, 71.6, 62.7, 40.5, 38.6, 38.4, 37.4, 18.5, 18. 1, 16.1, 16.0; HRMS
(ESI) m/z: [M]2+ Calcd for C31H38N4O6RuS2 364.0633; Found 364.0646; Elemental analysis calcd (%)
for [11]Cl2.3H2O: C, 43.66; H, 5.20; N, 6.57; found: 43.34; H, 5.35; N, 6.29.
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Supporting Information
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1H and 13C spectra for 13, 15, 18, 19, 21 – 28, 30 – 32, 34 – 36, H37, 38, H40, 41 – 45, H46, 49, H50,
[1](PF6)2 ꢀ [5](PF6)2, [6]PF6 ꢀ [10]PF6 and [11]Cl2 can be found in the Supporting Information.
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This work was supported by the Dutch Organization for Scientific Research (NWOꢀCW) via a VIDI
grant to S.B. The European Research Council is kindly acknowledged for a Starting Grant to S.B. Dr.
Wouter F.J. Hogendorf is greatly acknowledged for providing scientific input. Prof. Dr. Lies Bouwman
& AnneꢀGeert Volbeda are kindly acknowledged for scientific discussion. Corjan van de Griend is
kindly acknowledged for melting point measurements.
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