A route to oligosaccharide-appended salicylaldehydes: Useful building blocks for the synthesis of metal-salophen complexes

Article abstract of DOI:10.1021/jo401148f

A simple and general synthetic protocol to obtain oligosaccharide-appended salicylaldehydes, key intermediates for the synthesis of water-soluble metal-salophen complexes, is here reported. Six new aldehydes have been prepared and fully characterized as well as the corresponding zinc- and uranyl-salophen complexes. These new derivatives show very good solubility in water. Preliminary studies on the association of compound 19-U, that is, the uranyl maltotetraose derivative, with hydrogen phosphate and fluoride provide very encouraging results and open up the possibility of using such compounds for the efficient recognition of anions in pure water.

Full text of DOI:10.1021/jo401148f

Article
pubs.acs.org/joc
A Route to Oligosaccharide-Appended Salicylaldehydes: Useful
Building Blocks for the Synthesis of Metal−Salophen Complexes
Emiliano Bedini,*,† Gianpiero Forte,‡ Cristina De Castro,† Michelangelo Parrilli,†
and Antonella Dalla Cort*,‡
†Dipartimento di Scienze Chimiche, Universita
80126 Napoli, Italy
̀
di Napoli “Federico II”, Complesso Universitario Monte Sant’Angelo, Via Cintia, 4 −
‡Dipartimento di Chimica and IMC-CNR, Universita
̀
La Sapienza, Piazzale Aldo Moro 5, 00185 Roma, Italy
S
* Supporting Information
ABSTRACT: A simple and general synthetic protocol to
obtain oligosaccharide-appended salicylaldehydes, key inter-
mediates for the synthesis of water-soluble metal−salophen
complexes, is here reported. Six new aldehydes have been
prepared and fully characterized as well as the corresponding
zinc− and uranyl−salophen complexes. These new derivatives
show very good solubility in water. Preliminary studies on the association of compound 19-U, that is, the uranyl maltotetraose
derivative, with hydrogen phosphate and fluoride provide very encouraging results and open up the possibility of using such
compounds for the efficient recognition of anions in pure water.
Chart 1
INTRODUCTION
■
Lately, the development of synthetic receptors that work in water
has emerged as a central topic and a tricky challenge in
supramolecular chemistry,1 mostly nurtured by the potential
practical applications.2−4 The analytical detection of chemical
species present at low concentrations in aqueous media
represents a problem not only in environmental monitoring5−7
but also in medical diagnostics.8−13 The task is intrinsically
difficult; however, recent acquisitions do suggest that solutions
can be found through a supramolecular approach, which takes
inspiration from the natural world.14−17 Enzymes and antibodies
achieve extremely high selectivity and affinity toward their
substrates through the simultaneous establishment of multiple
weak interactions, and many biochemical transformations, which
take place in water, rely on these features.18 In this context, the
development of synthetic receptors or, in general, of building
blocks that can selectively interact in water with a given substrate
to yield highly responsive functional materials is a topic of
increasing importance.
synthetic routes to substituted salicylaldehydes and diamines
gives access to a large variety of structures with subtle variations
in the steric and electronic configuration. Thus, we decided to
follow this route, introducing, as a first attempt, glucose moieties
on the salicylaldehyde ring. The corresponding zinc and uranyl
complexes, 1b and 1c, although poorly soluble, preserve their
Lewis acidity even in water and behave as selective and efficient
supramolecular receptors toward anions, such as fluoride,
dihydrogen phosphate, nucleotides,21 and aminoacids, providing
also secondary stabilizing interactions ascribable to the presence
of the appended sugar.22
A common strategy is to suitably functionalize the backbone of
artificial receptors whose binding properties toward selected
substrates have been already successfully studied in lipophilic
media, to allow their solubilization in water.19
In recent years, we have extensively reported that metal−
sal(oph)en [salophen = N,N′-phenylenebis(salicylideneimine);
salen = N,N′-ethylenebis(salicylideneimine)] type complexes,
1a, behave as highly efficient receptors for anions and neutral
species through Lewis acid−base interactions in organic
solvents.20 A great advantage of this class of compounds is that
they are easily accessible through the reaction of the
corresponding tetradentate Schiff base derived from the
condensation of the diamine with 2 equiv of salicylaldehyde,
and the corresponding metal salt (Chart 1). The large number of
To improve the water solubility of these derivatives and to
obtain a library of potential artificial receptors able to work in
aqueous media, we developed a simple and general protocol to
Received: May 28, 2013
Published: July 15, 2013
© 2013 American Chemical Society
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Scheme 1. (a) NaOAc, Ac2O, 120 °C, 90 min; (b) I2, Et3SiH, CH2Cl2, reflux, 30 min; (c) thiourea, CH3CN, 60 °C, 60 min; (d) 5-
chloromethyl-salicylaldehyde, Et3N, rt, 60 min
obtain a series of salicylaldehydes functionalized with a variety of
oligosaccharides (up to a tetrasaccharide) via a stereospecific S-
glycosidic junction, that is, applying the method previously
described by Iadonisi and co-workers for the synthesis of
thioglycosides from glycosyl acetates and alkyl halides.23 As far as
we know, this is the first time that this procedure is used on
oligosaccharides higher than a disaccharide. The obtained
aldehydes 8−13 were then reacted with o-phenylenediamine in
the presence of zinc acetate and uranyl-acetate, respectively, to
obtain the corresponding metal−salophen complexes 14−19
(Scheme 2). The complete NMR characterization of the
aldehydes as well as that of the complexes is also reported.
treated with iodine and triethylsilane in CH2Cl2 under reflux to
give glycosyl iodides, after a simple extractive workup.
Subsequent reaction with thiourea in acetonitrile afforded S-
glycosyl isothiouronium salts, which were S-alkylated (one-pot)
with 5-chloromethyl-salicylaldehyde in the presence of triethyl-
amine (Scheme 1).27 Thioglycosides 2−7 were obtained with a
high 1,2-trans stereoselectivity as pure β-anomers after silica-gel
chromatography in acceptable yields (47−65% over four steps,
Table 1), demonstrating that both α and β as well as 1→4 and
Table 1. Conversion of per-O-Acetyl Di-, Tri-, and
Tetrasaccharides into the Corresponding Salicylaldehyde
Thioglycoside Derivatives
RESULTS AND DISCUSSION
■
Synthesis. The obtainment of some carbohydrate-function-
alized metal−salophen complexes has been recently reported
using two different approaches. The first was proposed by
MacLachlan and co-workers. It relies upon a Ag2O-mediated
glycosylation of 4,5-dinitrocatechol with per-O-acetyl-glucosyl or
galactosyl bromide, followed by deacetylation, reduction of the
nitro groups, and then complex formation by reacting the
glycosyl phenylenediamines with salicylaldehyde in the presence
of various metal ions.24 To avoid the involvement of air- and
light-sensitive intermediates, like the products obtained from the
reduction step, we recently proposed a base-promoted
conjugation of 5-chloromethyl-salicylaldehyde with a suitably
protected glucose derivative, followed by global deprotection of
the sugar-appended aldehyde and metal−template complex
formation in the presence of o-phenylenediamine.22 However, to
the best of our knowledge, the synthesis of complexes that bear
oligosaccharide moieties has not been reported to date. To
achieve this goal, a general method for oligosaccharide−
salicylaldehyde conjugation is necessary.
Alkyl and aryl-thioglycosides are very often prepared in
synthetic carbohydrate chemistry as useful glycosyl donors for
oligosaccharide and glycoconjugate synthesis.25 Several proto-
cols have been described for alkyl thioglycoside formation from
per-O-acetyl sugars.26 Among them, we focused our attention on
a rather fast and efficient procedure recently developed by
Iadonisi and co-workers, which generates the thioglycoside from
an alkyl halide and an S-glycosyl isothiouronium intermediate
obtained from the per-O-acetyl sugar through glycosyl iodide.23
It is worth noting that this thioglycosylation procedure avoids the
use of malodorous thiolic agents as well as harsh reagents, which
could not be tolerated by the O-glycosidic bonds of the sugars.
Thus, commercially available oligosaccharides (cellobiose,
lactose, gentiobiose, maltose, maltotriose, and maltotetraose)
were first per-O-acetylated under standard conditions, then
1→6 glycosidic linkages were stable under reaction conditions.
Noteworthy, although the thioglycosylation procedure devel-
oped by Iadonisi et al. has been already employed by other
groups as well as by us,28 we report now for the first time its use
on oligosaccharides with more than two units.
Thioglycosides 2−7 were then de-O-acetylated by reaction
with triethylamine in MeOH−CH2Cl2, affording water-soluble
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Scheme 2. (a) Et3N, CH2Cl2, MeOH, rt, 5 h, 97−99% yield; (b) Zn(CH3COO)2 or UO2(CH3COO)2·2H2O, o-phenylenediamine,
MeOH, rt, 16 h, 60−70% yield
glycoconjugates 8−13 in quantitative yields (Scheme 2). The
subsequent metal−template complex formation by condensation
with o-phenylenediamine in the presence of the corresponding
metal acetate afforded compounds 14−19 as yellow to orange
precipitates, depending on the coordinated cation.
Characterization of Compounds. The solubility in water
of the new metal derivatives, 14−19, resulted to be satisfactory.
The Zn2+ and UO2+ salophen complexes bearing disaccharide
subunits are indeed soluble in water up to the 10−4
M
concentration range, which is almost one order of magnitude
higher than that of the glucose-functionalized compounds.21,22
Even better is the solubility shown by complexes bearing tri- and
tetrasaccharide moieties, which we estimated to be greater than a
millimolar concentration.
Nevertheless, a detailed spectroscopic characterization of the
synthesized complexes in water was prevented by the fact that
their H NMR spectra in D2O feature very broad signals.
1
Figure 1. UV−vis absorption spectra of 19-U upon addition of
increasing amounts of disodium hydrogen phosphate. The inset shows
the titration plot at 340 nm of a 4.07 × 10−5 M solution of compound 19-
U with hydrogen phosphate at 25 °C in bidistilled water. The points are
experimental; the curve is calculated.
Temperature dependence of spectra resolution was observed,
consisting in a general sharpening of the signals on increasing the
temperature. Unfortunately, the hydrolysis of the imine bonds,
clearly detected by the appearance of new signals in the aldehydic
region of the spectrum, becomes already significant below 323 K.
We think that the low resolution at room temperature can be
likely attributed to the occurrence of dynamic exchange
phenomena on the NMR time scale comprising intermolecular
hydrogen bonding interactions between the carbohydrate
subunits and the metal center.
Well-resolved NMR spectra were instead obtained in DMSO-
d6. Complexes 14-Zn−19-Zn and 14-U−19-U were subjected to
a detailed 2D-NMR (COSY, TOCSY, HSQC-DEPT and
HMBC) analysis. The data are collected in the Experimental
Section.
Preliminary Binding Measurements. To check the anion
binding capabilities of these new water-soluble receptors, we
undertook some preliminary measurements. We report here, as
an example, the study performed on complex 19-U, that is, the
maltotetraose derivative. The association constant between this
receptor and the hydrogen phosphate anion was determined by
UV−vis spectroscopic titration experiments, by adding increas-
ing amounts of a standard solution of sodium hydrogen
phosphate to a solution of 19-U, in bidistilled water. The
titration data were analyzed using a 1:1 binding model and
applying a nonlinear least-squares regression method (Figure 1).
The receptor exhibited a quite strong interaction with the anion;
the value of the binding constant is 3500 70. M−1 Remarkably,
this value is almost 8 times higher than that previously reported
by us for the poorly water-soluble glucose derivative, 1c,21 and, as
far as we know, is one of the highest ever reported for a neutral
receptor in pure water. Furthermore, very preliminary titration
experiments performed with the same receptor and fluoride
anion indicate a good interaction and an association constant in
the order of 500 M−1, which is quite noteworthy considering the
extremely high hydration enthalpy of this anion. Complete
binding studies on the affinities of all the derivatives are currently
in progress and will be reported in due course.
CONCLUSIONS
■
Here, we have described a simple and general synthetic protocol
to obtain oligosaccharide-appended salicylaldehydes, key inter-
mediates for the synthesis of water-soluble metal−salophen
complexes starting from commercially available materials.
Remarkably, as far as we know, it is the first time that the
thioglycosylation procedure here applied is successfully
performed on tri- and tetrasaccharides. The particularly mild
conditions used to achieve the S-glycosidic junction are perfectly
tolerated by the sugar backbone as well as by the aldehyde moiety
of the aglycon, and we do not foresee any intrinsic limitation in
applying this procedure to differently substituted aryl halides or
to higher oligosaccharides.
We have also reported the synthesis and the NMR
characterization of the corresponding zinc− and uranyl−
salophen complexes obtained by using the oligosaccharide-
appended salicylaldehydes. The introduction of tri- and
tetrasaccharide units on the skeleton of the complexes increases
water solubility and allows the preparation of millimolar
solutions in such a medium.
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3B-H), 5.04 (1H, t, J4,3 = J4,5 9.5, 4B-H), 4.97 (1H, t, J2,3 = J2,1 9.5, 2A-H),
4.89 (1H, t, J2,3 = J2,1 9.5, 2B-H), 4.51 (2H, m, 1B-HI, 6aA-H), 4.34 (1H,
dd, Jgem 12.5, J6a,5 4.0, 6aB-H), 4.31 (1H, d, J1,2 9.5, 1A-H), 4.06 (1H, dd,
Jgem 12.0, J6b,5 5.0, 6bA-H), 4.02 (1H, dd, Jgem 12.5, J6b,5 1.5, 6bB-H), 3.87
(1H, d, Jgem 13.0, SCHHAr), 3.79 (1H, d, Jgem 13.0, SCHHAr), 3.75 (1H,
t, J4,3 = J4,5 9.5, 4A-H), 3.64 (1H, m, 5B-H), 3.54 (1H, m, 5A-H), 2.11 (3H,
s, CH3CO), 2.05 (3H, s, CH3CO), 2.02 (3H, s, CH3CO), 2.00 (3H, s,
CH3CO), 1.99 (3H, s, CH3CO), 1.98 (3H, s, CH3CO), 1.96 (3H, s,
CH3CO); 13C NMR (125 MHz, CDCl3) δ 196.2 (CHO), 170.3−168.9
(COCH3), 160.8 (C-OH Ar), 137.6, 133.7, 128.3, 120.4, 117.9 (C-Ar),
100.6 (1B-C), 81.8 (1A-C), 77.2, 76.2, 73.2, 72.8, 71.9, 71.5, 69.9, 67.7,
61.9, 61.4 (2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C),
32.5 (SCH2Ar), 20.7−20.4 (CH3CO); TOF-MS (MALDI TOF
positive) m/z 809.12 [M + Na]+; Anal. Calcd for C34H42O19S: C,
51.91; H, 5.38; S, 4.08. Found C, 51.80; H, 5.45; S, 4.00.
Preliminary studies on the binding affinity of the newly
synthesized complex 19-U toward the hydrogen phosphate
anion open up the possibilty of using such compounds for anion
recognition in pure water. Moreover, given the well-established
catalytic properties of uranyl−salophen complexes in organic
solvents,29 we will definitely investigate also the catalytic
potentialities of the new derivatives in an aqueous environment.
EXPERIMENTAL SECTION
■
General Methods. Commercial grade reagents and solvents were
1
used without further purification. H and 13C 1D-NMR spectra of the
synthetic intermediates were recorded at 298 K on 1H NMR, 200, 400,
and 500 MHz, and 13C NMR, 50, 100, and 125 MHz, instruments in
CDCl3 (internal standard, for 1H: CHCl3 at δ 7.26; for 13C: CDCl3 at δ
77.0) or in D2O (acetone as internal standard, for 1H: (CH3)2CO at δ
2.22; for 13C: (CH3)2CO at δ 30.9). J values are given in hertz. 2D-NMR
spectra of the complexes were recorded at 298 K on a DRX-600 (1H:
600 MHz, 13C: 150 MHz) instrument equipped with a cryoprobe, in
DMSO-d6 (internal standard, for 1H: CHD2SOCD3 at δ 2.49; for 13C:
CD3SOCD3 at δ 39.5). Double quantum-filtered phase-sensitive COSY
and TOCSY experiments were performed using spectral widths of either
6000 in both dimensions, using data sets of 4096 × 512 points.
Quadrature indirect dimensions were achieved through the States-TPPI
method. Spectra were processed applying an unshifted Qsine function to
both dimensions, and the data matrix was zero-filled by a factor of 2
before Fourier transformation. The TOCSY mixing time was set to 120
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-β-D-galacto-
pyranosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside (3).
22
336 mg (65%) as a white powder; [α]D −39.4 (c 2.0 in CH2Cl2);
1H NMR (500 MHz, CDCl3) δ 10.98 (1H, s, OH), 9.88 (1H, s, CHO),
7.50 (1H, d, Jmeta 2.0, 2′-H), 7.47 (1H, dd, Jortho 8.5, Jmeta 2.0, 6′-H), 6.95
(1H, d, Jortho 8.5, 5′-H),5.34 (1H, d, J4,3 3.0, 4B-H), 5.17 (1H, t, J3,4 = J3,2
9.5, 3A-H), 5.10 (1H, dd, J2,1 10.5, J2,3 8.0, 2B-H), 4.99 (1H, t, J2,1 = J2,3
10.0, 2A-H), 4.96 (1H, dd, J3,2 10.5, J3,4 3.5, 3B-H), 4.51 (1H, dd, Jgem
12.5, J6a,5 2.0, 6aA-H), 4.48 (1H, d, J1,2 8.0, 1B-H), 4.33 (1H, d, J1,2 10.5,
1A-H), 4.09 (3H, m, 6aB-H, 6bA-H, 6bB-H), 3.88 (2H, m, 5B-
H,SCHHAr), 3.81 (1H, d, Jgem 12.5, SCHHAr), 3.78 (1H, t, J4,3 = J4,5
9.5, 4A-H), 3.56 (1H, m, 5A-H), 2.15 (3H, s, CH3CO), 2.13 (3H, s,
CH3CO), 2.05 (3H, s, CH3CO), 2.04 (6H, s, 2 CH3CO), 2.03 (3H, s,
CH3CO), 1.96 (3H, s, CH3CO); 13C NMR (100 MHz, CDCl3) δ 196.2
(CHO), 170.3−169.0 (COCH3), 160.9 (C-OH Ar), 137.7, 133.7, 128.3,
120.4, 118.0 (C-Ar), 101.0 (1B-C), 81.8 (1A-C), 76.8, 76.1, 73.6, 70.9,
70.7, 70.1, 69.1, 66.5, 62.1, 60.7 (2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-
C, 5B-C, 6A-C, 6B-C), 32.6 (SCH2Ar), 20.8−20.5 (CH3CO); TOF-MS
(MALDI TOF positive) m/z 809.09 [M + Na]+; Anal. Calcd for
C34H42O19S: C, 51.91; H, 5.38; S, 4.08. Found C, 51.74; H, 5.50; S, 3.98.
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyr-
anosyl-(1→6)-2,3,4-tri-O-acetyl-1-thio-β-D-glucopyranoside (4). 274
mg (53%) as a white powder; [α]D22 −29.3 (c 1.0 in CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 11.04 (1H, s, OH), 9.90 (1H, s, CHO), 7.52 (1H,
d, Jmeta 2.0, 2′-H), 7.49 (1H, dd, Jortho 8.5, Jmeta 2.0, 6′-H), 6.98 (1H, d,
Jortho 8.5, 5′-H),5.21 (1H, t, J3,4 = J3,2 9.5, 3B-H), 5.13 (1H, t, J3,4 = J3,2 9.5,
3A-H), 5.09 (1H, t, J4,3 = J4,5 9.5, 4B-H), 5.04 (2H, m, 2A-H, 2B-H), 4.89
(1H, t, J4,3 = J4,5 9.5, 4A-H), 4.54 (1H, d, J1,2 7.5, 1B-H), 4.30 (1H, dd, Jgem
12.0, J6a,5 4.5, 6aB-H), 4.22 (1H, d, J1,2 10.0, 1A-H), 4.14 (1H, dd, Jgem
12.0, J6b,5 2.0, 6bB-H), 3.95 (1H, d, Jgem 13.0, SCHHAr), 3.89 (1H, d, Jgem
8.5, 6aA-H), 3.78 (1H, d, Jgem 13.0, SCHHAr), 3.70 (1H, m, 5B-H), 3.58
(2H, m, 5A-H, 6bA-H), 2.11 (3H, s, CH3CO), 2.03 (9H, s, 3 CH3CO),
1
ms. HSQC experiments were measured in the H-detected mode via
single quantum coherence with proton decoupling in the 13C domain,
using data sets of 2048 × 512 points. HMBC spectra were measured
using a data set of 2048 × 512 points; 64 scans were acquired for each t1
value.
For the MALDI-MS spectra, compounds were dissolved in CH3CN
or in D2O at a concentration of 0.1 mg/mL, and 1 μL of these solutions
were mixed with 1 μL of a 20 mg/mL solution of 2,5-dihydroxybenzoic
acid in 7:3 CH3CN/H2O. Analytical thin-layer chromatographies
(TLCs) were performed on aluminum plates. The plates were treated
with a 10% H2SO4 ethanolic solution and then heated to 130 °C.
Column chromatographies were performed on silica (63−200 mesh).
General Procedure for Thioglycosylation. To a suspension of
anhydrous sodium acetate (150 mg, 1.83 mmol) in acetic anhydride (3.3
mL, 34.9 mmol) heated at 120 °C was added the commercially available
oligosaccharide (660 μmol). After a few minutes stirring at 120 °C, the
suspension turned to a clear colorless solution. After 90 min, the
solution was cooled to rt and then added to water (60 mL). After 2 h
standing at 4 °C, the mixture was extracted with CH2Cl2 (60 mL). The
organic layer was collected, dried over anhydrous sodium sulfate,
filtered, and concentrated. The obtained per-O-acetylated oligosacchar-
ide (660 μmol) was dissolved in anhydrous CH2Cl2 (3.2 mL) and
treated with I2 (226 mg, 890 μmol) and then Et3SiH (142 μL, 890
μmol). The solution was stirred at reflux with a water-cooled condenser
fitted with a drying tube (anhydrous CaCl2). After 30 min, the solution
was cooled to rt, diluted with CH2Cl2 (80 mL), and washed with a 1:1 v/
v 1 M NaHCO3/10% Na2S2O3 mixture (80 mL). The organic layer was
collected, dried over anhydrous sodium sulfate, filtered, and
concentrated. The residue was dissolved in acetonitrile (3.2 mL) and
treated with thiourea (55.2 mg, 725 μmol). After a few minutes, the
mixture turned to a clear yellowish solution, and stirring was continued
at 60 °C for 1 h. After cooling to rt, 5-chloromethyl-salicylaldehyde (191
mg, 1.12 mmol) was added, followed by triethylamine (367 μL, 2.64
mmol). The stirring was continued while a white precipitate was
gradually formed. After 1 h, the mixture was concentrated, and the
residue was subjected to column chromatography (hexane−ethyl
acetate mixtures).
2.01 (3H, s, CH3CO), 1.99 (3H, s, CH3CO), 1.98 (3H, s, CH3CO); 13
C
NMR (125 MHz, CDCl3) δ 196.0 (CHO), 170.6−169.4 (COCH3),
160.9 (C-OH Ar), 137.9, 134.1, 128.1, 120.4, 118.2 (C-Ar), 100.7 (1B-
C), 81.2 (1A-C), 73.6, 72.7, 72.0, 71.1, 71.0, 69.7, 68.9, 68.5, 68.3, 61.7
(2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C), 32.2
(SCH2Ar), 20.8−20.5 (CH3CO); TOF-MS (MALDI TOF positive) m/
z 809.00 [M + Na]+. Anal. Calcd for C34H42O19S: C, 51.91; H, 5.38; S,
4.08. Found C, 51.81; H, 5.45; S, 3.99.
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-α-D-glucopyr-
anosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside (5). 246
mg (47%) as a white powder; [α]D22 +1.6 (c 1.0 in CH2Cl2); 1H NMR
(400 MHz, CDCl3): δ 11.01 (1H, s, OH), 9.91 (1H, s, CHO), 7.50 (2H,
m, 2′-H, 6′-H), 6.98 (1H, d, Jortho 8.5, 5′-H), 5.40 (1H, d, J1,2 4.0 Hz, 1B-
H), 5.35 (1H, t, J3,4 = J3,2 9.7, 3B-H), 5.23 (1H, t, J3,4 = J3,2 9.0, 3A-H), 5.05
(1H, t, J4,5 = J4,3 9.9 Hz, 4B-H), 4.92 (1H, t, J2,1 = J2,3 9.7, 2A-H), 4.85 (1H,
dd, J2,1 10.5, J2,3 4.0, 2B-H), 4.48 (1H, dd, Jgem 12.1, J6a,5 2.8, 6aA-H), 4.38
(1H, d, J1,2 10.0, 1A-H), 4.25 (2H, m, 6aB-H, 6bA-H), 4.07 (1H, dd, Jgem
12.4, J6b,5 2.2, 6bB-H), 4.00 (2H, m, 4A-H, 5B-H), 3.92 (1H, d, Jgem 13.1,
SCHHAr), 3.80 (1H, d, Jgem 13.1, SCHHAr), 3.60 (1H, ddd, J5,4 9.7, J5,6a
4.4, J5,6b 3.1, 5A-H), 2.16 (3H, s, CH3CO), 2.11 (3H, s, CH3CO), 2.04
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyr-
anosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside (2). 330
mg (64%) as a white powder; [α]D22 −36 (c 0.5 in CH2Cl2); 1H NMR
(500 MHz, CDCl3) δ 10.95 (1H, bs, OH), 9.85 (1H, s, CHO), 7.48 (1H,
d, Jmeta 1.5, 2′-H), 7.44 (1H, dd, Jortho 8.5, Jmeta 1.5, 6′-H), 6.92 (1H, d,
Jortho 8.5, 5′-H),5.13 (1H, t, J3,4 = J3,2 9.5, 3A-H), 5.12 (1H, t, J3,4 = J3,2 9.5,
(6H, s, 2 CH3CO), 2.01 (3H, s, CH3CO), 2.00 (6H, s, 2 CH3CO); 13
C
NMR (100 MHz, CDCl3) δ 196.3 (CHO), 170.5−169.4 (COCH3),
160.9 (C-OH Ar), 137.7, 133.7, 128.3, 120.5, 118.1 (C-Ar), 95.6 (1B-C),
7965
dx.doi.org/10.1021/jo401148f | J. Org. Chem. 2013, 78, 7962−7969

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Article
81.4 (1A-C), 76.2, 76.1, 72.8, 70.6, 69.9, 69.2, 68.5, 68.1, 63.0, 61.5 (2A-C,
2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C), 32.6 (SCH2Ar),
20.8−20.4 (CH3CO); TOF-MS (MALDI TOF positive) m/z 809.28
[M + Na]+; Anal. Calcd for C34H42O19S: C, 51.91; H, 5.38; S, 4.08.
Found C, 51.77; H, 5.51; S, 4.00.
4.03−3.27 (14H, m); 13C NMR (50 MHz, CDCl3) δ 197.7 (CHO),
159.5 (C-OH Ar), 138.7, 134.1, 130.6, 121.4, 118.1 (C-Ar), 103.1 (1B-
C), 84.6 (1A-C), 79.2, 76.6, 76.3, 76.2, 73.8, 72.6, 70.1, 70.0, 61.2, 60.8
(2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C), 33.4
(SCH2Ar); TOF-MS (MALDI TOF positive) m/z 515.21 [M + Na]+;
Anal. Calcd for C20H28O12S: C, 48.77; H, 5.73; S, 6.51. Found C, 48.54;
H, 5.83; S, 6.40.
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-α-D-glucopyr-
anosyl-(1→4)-2,3,6-tri-O-acetyl-α-D-glucopyranosyl-(1→4)-2,3,6-
tri-O-acetyl-1-thio-β-D-glucopyranoside (6). 395 mg (56%) as a white
powder; [α]D22 +53 (c 0.7 in CH2Cl2); 1H NMR (500 MHz, CDCl3) δ
11.03 (1H, s, OH), 9.92 (1H, s, CHO), 7.53 (1H, d, Jmeta 1.5, 2′-H), 7.49
(1H, dd, Jortho 8.5, Jmeta 1.5, 6′-H), 6.98 (1H, d, Jortho 8.5, 5′-H), 5.38 (3H,
m, 1B-H, 3B-H, 3C-H),5.27 (1H, d, J1,2 4.0, 1C-H), 5.23 (1H, t, J3,4 = J3,2
9.5, 3A-H), 5.07 (1H, t, J4,3 = J4,5 10.0, 4C-H), 4.90 (1H, t, J2,3 = J2,1 9.5, 2A-
H), 4.86 (1H, dd, J2,3 10.0, J2,1 4.0, 2C-H), 4.72 (1H, dd, J2,3 10.0, J2,1 3.5,
2B-H), 4.46 (2H, m, 6aA-H, 6aB-H), 4.34 (2H, m, 1A-H, 6bA-H), 4.25
(1H, dd, Jgem 12.5, J6a,5 3.5, 6aC-H), 4.19 (1H, dd, Jgem 12.0, J6b,5 3.5, 6bB-
H), 4.06 (1H, dd, Jgem 12.5, J6b,5 1.5, 6bC-H), 4.05−3.92 (m, 5H, 4A-H,
4B-H, 5B-H, 5C-H, SCHHAr), 3.80 (1H, d, Jgem 13.0, SCHHAr), 3.64
(1H, m, 5A-H), 2.20 (3H, s, CH3CO), 2.16 (3H, s, CH3CO), 2.10 (3H,
s, CH3CO), 2.05 (6H, s, 2 CH3CO), 2.04 (3H, s, CH3CO), 2.00 (9H, s,
3 CH3CO), 1.98 (3H, s, CH3CO); 13C NMR (125 MHz, CDCl3) δ
196.0 (CHO), 170.1−169.0 (COCH3), 160.5 (C-OH Ar), 137.3, 133.5,
128.0, 120.1, 117.7 (C-Ar), 95.4, 95.2 (1B-C, 1C-C), 80.8 (1A-C), 75.8,
73.5, 72.1, 71.2, 70.3, 70.0, 69.8, 68.9, 68.6, 68.1, 67.5, 62.8, 62.0, 61.0,
59.9 (2A-C, 2B-C, 2C-C, 3A-C, 3B-C, 3C-C, 4A-C, 4B-C, 4C-C, 5A-C, 5B-C,
5C-C, 6A-C, 6B-C, 6C-C), 32.1 (SCH2Ar), 20.6−20.1 (CH3CO); TOF-
MS (MALDI TOF positive) m/z 1096.99 [M + Na]+; Anal. Calcd for
C46H58O27S: C, 51.39; H, 5.44; S, 2.98. Found C, 51.51; H, 5.55; S, 3.06.
m-Formyl-p-hydroxy-benzyl-2,3,4,6-tetra-O-acetyl-α-D-glucopyr-
anosyl-(1→4)-2,3,6-tri-O-acetyl-α-D-glucopyranosyl-(1→4)-2,3,6-
tri-O-acetyl-α-D-glucopyranosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-
D-glucopyranoside (7). 424 mg (47%) as a white powder; [α]D22 +82.1
(c 5.0 in CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 11.04 (1H, s, OH),
9.93 (1H, s, CHO), 7.53 (1H, bs, 2′-H), 7.49 (1H, d, Jortho 8.5, 6′-H),
6.98 (1H, d, Jortho 8.5, 5′-H), 5.42−5.33 (4H, m, 1B-H, 3B-H, 3C-H, 3D-
H), 5.28 (2H, m, 1C-H, 1D-H), 5.23 (1H, t, J3,4 = J3,2 9.6, 3A-H), 5.08 (1H,
t, J4,3 = J4,5 10.0, 4D-H), 4.90 (1H, t, J2,3 = J2,1 9.6, 2A-H), 4.87 (1H, dd, J2,3
10.0, J2,1 4.0, 2D-H), 4.73 (2H, m, 2B-H, 2C-H), 4.49−4.40 (4H, m, 6aA-
H, 6aB-H, 6aC-H, 6bA-H), 4.35 (1H, d, J1,2 10.0, 1A-H), 4.27−4.15 (3H,
m, 6aD-H, 6bB-H, 6bC-H), 4.07−3.86 (8H, m, 4A-H, 4B-H, 4C-H, 5B-H,
5C-H, 5D-H, 6bD-H, SCHHAr), 3.79 (1H, d, Jgem 13.1, SCHHAr), 3.65
(1H, m, 5A-H), 2.21 (3H, s, CH3CO), 2.19 (3H, s, CH3CO), 2.15 (3H,
s, CH3CO), 2.10 (3H, s, CH3CO), 2.06 (3H, s, CH3CO), 2.04 (6H, s, 2
CH3CO), 2.03 (3H, s, CH3CO), 2.01 (3H, s, CH3CO), 2.00 (3H, s,
CH3CO), 1.99 (6H, s, CH3CO), 1.98 (3H, s, CH3CO); 13C NMR (100
MHz, CDCl3) δ 196.4 (CHO), 170.5−169.4 (COCH3), 160.9 (C-OH
Ar), 137.7, 133.7, 128.2, 120.4, 118.1 (C-Ar), 95.8, 95.6, 95.5 (1B-C, 1C-
C, 1D-C), 81.1 (1A-C), 76.1, 75.9, 73.8, 73.5, 72.3, 71.6, 71.3, 70.6, 70.4,
70.3, 70.0, 69.2, 68.9, 68.4, 67.8, 63.2, 62.5, 62.1, 61.3, 60.3 (2A-C, 2B-C,
2C-C, 2D-C, 3A-C, 3B-C, 3C-C, 3D-C, 4A-C, 4B-C, 4C-C, 4D-C, 5A-C, 5B-C,
5C-C, 5D-C, 6A-C, 6B-C, 6C-C, 6D-C), 32.5 (SCH2Ar), 20.8−20.4
(CH3CO); TOF-MS (MALDI TOF positive) m/z 1385.11 [M + Na]+;
Anal. Calcd for C56H72O34S: C, 50.91; H, 5.49; S, 2.43. Found C, 50.80;
H, 5.57; S, 2.38.
m-Formyl-p-hydroxy-benzyl-β-D-galactopyranosyl-(1→4)-1-thio-
β-D-glucopyranoside, (9). 48 mg (98%) as a white powder; [α]D22 −54
(c 0.6 in H2O); 1H NMR (500 MHz, D2O) δ 9.92 (1H, s, CHO), 7.71
(1H, d, Jmeta 2.0, 2′-H), 7.62 (1H, dd, Jortho 9.0, Jmeta 2.0, 6′-H), 7.00 (1H,
d, Jortho 9.0, 5′-H), 4.42 (1H, d, J1,2 7.0, 1B-H), 4.31 (1H, d, J1,2 10.0, 1A-
H), 4.02 (1H, d, Jgem14.0, SCHHAr), 3.94−3.36 (13H, m); 13C NMR
(50 MHz, CDCl3) δ 198.1 (CHO), 159.7 (C-OH Ar), 138.9, 134.4,
130.8, 121.5, 118.2 (C-Ar), 103.5 (1B-C), 84.6 (1A-C), 79.3, 78.8, 76.4,
76.0, 73.2, 72.5, 71.6, 69.2, 61.7, 60.8 (2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-
C, 5A-C, 5B-C, 6A-C, 6B-C), 33.5 (SCH2Ar); TOF-MS (MALDI TOF
positive) m/z 515.08 [M + Na]+; Anal. Calcd for C20H28O12S: C, 48.77;
H, 5.73; S, 6.51. Found C, 48.49; H, 5.81; S, 6.33.
m-Formyl-p-hydroxy-benzyl-β-D-glucopyranosyl-(1→6)-1-thio-β-
D-glucopyranoside, (10). 48 mg (98%) as a white powder; [α]D22 −62
(c 0.5 in H2O); 1H NMR (500 MHz, D2O) δ 9.94 (1H, s, CHO), 7.75
(1H, d, Jmeta 2.0, 2′-H), 7.64 (1H, dd, Jortho 8.5, Jmeta 2.0, 6′-H), 7.01 (1H,
d, Jortho 8.5, 5′-H), 4.45 (1H, d, J1,2 8.0, 1B-H), 4.32 (1H, d, J1,2 10.0, 1A-
H), 4.11−3.29 (14H, m); 13C NMR (50 MHz, D2O) δ 197.8 (CHO),
159.6 (C-OH Ar), 138.9, 134.1, 130.7, 121.4, 118.1 (C-Ar), 103.4 (1B-
C), 85.1 (1A-C), 79.3, 77.8, 76.6, 76.4, 73.8, 72.6, 70.3, 69.9, 69.2, 61.4
(2A-C, 2B-C, 3A-C, 3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C), 33.5
(SCH2Ar); TOF-MS (MALDI TOF positive) m/z 515.07 [M + Na]+;
Anal. Calcd for C20H28O12S: C, 48.77; H, 5.73; S, 6.51. Found C, 48.48;
H, 5.85; S, 6.35.
m-Formyl-p-hydroxy-benzyl-α-D-glucopyranosyl-(1→4)-1-thio-β-
D-glucopyranoside, (11). 49 mg (99%) as a white powder; [α]D22 −1.7
(c 1.1 in H2O); 1H NMR (400 MHz, D2O) δ 9.89 (1H, s, CHO), 7.67
(1H, bs, 2′-H), 7.59 (1H, d, Jortho 8.6, 6′-H), 6.97 (1H, d, Jortho 8.6, 5′-
H),5.36 (1H, d, J1,2 3.7, 1B-H), 4.31 (1H, d, J1,2 9.9, 1A-H), 4.00 (1H, d,
Jgem 13.5 Hz, SCHHAr), 3.91 (1H, d, Jgem 13.5 Hz, SCHHAr), 3.86−3.36
(12H, m); 13C NMR (100 MHz, D2O): δ 197.9 (CHO), 159.6 (C-OH
Ar), 138.8, 134.2, 130.7, 121.5, 118.1 (C-Ar), 100.3 (1B-C), 84.6 (1A-C),
79.1, 78.3, 77.4, 73.5, 73.4, 72.7, 72.3, 70.0, 61.5, 61.2 (2A-C, 2B-C, 3A-C,
3B-C, 4A-C, 4B-C, 5A-C, 5B-C, 6A-C, 6B-C), 33.4 (SCH2Ar); TOF-MS
(MALDI TOF positive) m/z 515.29 [M + Na]+; Anal. Calcd for
C20H28O12S: C, 48.77; H, 5.73; S, 6.51. Found C, 48.59; H, 5.79; S, 6.46.
m-Formyl-p-hydroxy-benzyl-α-D-glucopyranosyl-(1→4)-α-D-glu-
copyranosyl-(1→4)-1-thio-β-D-glucopyranoside, (12). 65 mg (99%)
as a white powder; [α]D22 −4.8 (c 0.4 in H2O); H NMR (500 MHz,
1
D2O) δ 9.92 (1H, s, CHO), 7.71 (1H, d, Jmeta 2.0, 2′-H), 7.62 (1H, dd,
Jortho 8.5, Jmeta 2.0, 6′-H), 6.99 (1H, d, Jortho 8.5, 5′-H), 5.39 (1H, d, J1,2
3.5, 1B-H), 5.36 (1H, d, J1,2 3.5 Hz, 1C-H), 4.31 (1H, d, J1,2 10.0, 1A-H),
4.02 (1H, d, Jgem 13.5, SCHHAr), 3.94−3.35 (19H, m); 13C NMR (100
MHz, D2O) δ 198.0 (CHO), 159.7 (C-OH Ar), 138.9, 134.4, 130.8,
121.5, 118.1 (C-Ar), 100.4, 100.1 (1B-CI,1C‑C), 84.6 (1A-C), 79.0, 78.3,
77.4, 77.3, 74.0, 73.5, 73.4, 72.6, 72.4, 72.1, 71.8, 70.0, 61.4, 61.1, 61.0
(2A-C, 2B-C, 2C-C, 3A-C, 3B-C, 3C-C, 4A-C, 4B-C, 4C-C, 5A-C, 5B-C, 5C-C,
6A-C, 6B-C, 6C-C), 33.4 (SCH2Ar); TOF-MS (MALDI TOF positive)
m/z 677.00 [M + Na]+; Anal. Calcd for C26H38O17S: C, 47.70; H, 5.85;
S, 4.90. Found C, 47.45; H, 5.99; S, 4.70.
General Procedure for Transesterification. Thioglycoside (100
μmol) was dissolved in 4:1 v/v MeOH/CH2Cl2 (7.5 mL), cooled to 0
°C, and treated with freshly prepared 0.15 M methanolic NaOMe (1.3
mL). The yellow solution was then stirred at rt. The deprotection of
trisaccharide 6 required, after ∼4 h, further addition of 5.0 mL of MeOH
to dissolve the partially deprotected species, and complete deacetylation.
Analogously, deprotection of tetrasaccharide 7 required addition of
MeOH (two 5.0 mL aliquots) after 1 and 4 h, respectively. After 5 h, the
solutions were treated with Amberlyst 15 (H+ form) until colorless, then
filtered and concentrated to dryness. The residue was dissolved in a
small amount of water and freeze-dried.
m-Formyl-p-hydroxy-benzyl-β-D-glucopyranosyl-(1→4)-1-thio-β-
D-glucopyranoside (8). 48 mg (98%) as a white powder; [α]D22 −50 (c
0.5 in H2O); 1H NMR (500 MHz, D2O: δ 9.91 (1H, s, CHO), 7.72 (1H,
d, Jmeta 2.0, 2′-H), 7.63 (1H, dd, Jortho 9.0, Jmeta 2.0, 6′-H), 7.00 (1H, d,
Jortho 9.0, 5′-H), 4.48 (1H, d, J1,2 8.0, 1B-H), 4.31 (1H, d, J1,2 10.0, 1A-H),
m-Formyl-p-hydroxy-benzyl-α-D-glucopyranosyl-(1→4)-α-D-glu-
copyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-1-thio-β-D-glucopyr-
22
anoside, (13). 81 mg (99%) as a white powder; [α]D +41 (c 0.4 in
H2O); 1H NMR (500 MHz, D2O) δ 9.93 (1H, s, CHO), 7.73 (1H, d,
Jmeta 2.0, 2′-H), 7.63 (1H, dd, Jortho 8.5, Jmeta 2.0, 6′-H), 7.00 (1H, d, Jortho
8.5, 5′-H), 5.38 (3H, m, 1B-H, 1C-H, 1D-H), 4.30 (1H, d, J1,2 10.0, 1A-H),
4.03 (1H, d, Jgem 14.0, SCHHAr), 3.98−3.35 (25H, m); 13C NMR (100
MHz, D2O) δ 198.0 (CHO), 160.1 (C-OH Ar), 138.9, 134.2, 130.5,
121.6, 118.4 (C-Ar), 100.4, 100.3, 100.1 (1B-C, 1C-C, 1D-C), 84.6 (1A-
C), 79.0, 78.3, 77.5, 77.3, 74.0, 73.9, 73.5, 73.4, 72.7, 72.6, 72.4, 72.2,
72.1, 71.9, 70.0, 61.4, 61.3, 61.1 (2A-C, 2B-C, 2C-C, 2D-C, 3A-C, 3B-C, 3C-
C, 3D-C, 4A-C, 4B-C, 4C-C, 4D-C, 5A-C, 5B-C, 5C-C, 5D-C, 6A-C, 6B-C, 6C-
C, 6D-C), 33.5 (SCH2Ar); TOF-MS (MALDI TOF positive) m/z
7966
dx.doi.org/10.1021/jo401148f | J. Org. Chem. 2013, 78, 7962−7969

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Article
839.09 [M + Na]+; Anal. Calcd for C32H48O22S: C, 47.06; H, 5.92; S,
3.93. Found C, 46.89; H, 6.03; S, 3.79.
(2B′-C), 103.8 (1B-C), 82.8 (1A-C), 80.7 (4A-C), 78.9 (5A-C), 76.3 (3A-
C), 75.3 (5B-C), 73.0 (2A-C, 3B-C), 70.3 (2B-C), 68.1 (4B-C), 60.5 (6A-
C), 60.2 (6B-C), 31.6 (CH2S); MS (ESI-TOF) m/z 1348.09 [M + Na]+.
General Procedure for the Synthesis of the Complexes 14−
19. The aldehyde, 8−13 (100 μmol), was added to a solution of zinc or
uranyl acetate (60 μmol) in MeOH (4 mL), followed by the addition of
o-phenylenediamine (50 μmol). The solution was kept overnight at
room temperature, under constant stirring. The volume was reduced to
about half, and the precipitate was collected, washed three times with
cold diethyl ether, and dried under vacuum.
1
Complex 16-Zn. Yellow powder, 34 mg, yield 61%. H NMR (600
MHz, DMSO-d6) δ 8.94 (1H, s, CHN), 7.83 (1H, bs, 2B′-H), 7.44 (1H,
s, 2A′-H), 7.38 (1H, bs, 3B′-H), 7.24 (1H, d, Jortho 8.0, 6A′-H), 6.67 (1H, d,
Jortho 8.0, 5A′-H), 5.10 (1H, bs, 2A-OH), 5.05 (1H, bs, 3A-OH), 5.02 (2H,
bs, 2B-OH, 3A-OH), 4.97 (1H, d, JH,OH 2.0, 3B-OH), 4.94 (1H, d, JH,OH
2.0, 4B-OH), 4.57 (1H, t, JH,OH 1.6 Hz, 6B-OH), 4.38 (1H, d, J1,2 7.6, 1B-
H), 4.11 (1H, d, Jgem 10.9 Hz, 6aA-H), 4.00 (1H, d, J1,2 2.8 Hz, 1A-H),
3.84 (1H, d, Jgem 12.7 Hz, SCHHPh), 3.72 (1H, m, 6aB-H), 3.67 (1H, d,
Jgem 12.7 Hz, SCHHPh), 3.56 (1H, m, 6bA-H), 3.48 (1H, m, 6bB-H),
3.23 (1H, m, 5A-H), 3.17 (1H, m, 3B-H), 3.13−3.04 (6H, m, 2A-H, 3A-H,
4A-H, 2B-H, 4B-H, 5B-H); 13C NMR (125 MHz, DMSO-d6) δ 171.2 (4A′-
C), 162.2 (CN), 139.2 (1B′-C), 136.4 (2A′-C), 135.4 (6A′-C), 127.0 (3B′-
C), 123.0 (5A′-C), 121.4 (1A′-C), 118.3 (3A′-C), 115.9 (2B′-C), 102.9
(1B-C), 82.5 (1A-C), 79.6 (5A-C), 77.9 (3A-C), 76.7 (5B-C), 76.6 (3B-C),
73.4 (2B-C), 72.6 (2A-C), 70.0 (4A-C), 69.8 (4B-C), 68.5 (6A-C), 60.7
(6B-C), 31.7 (CH2S); MS (ESI-TOF) m/z 1143.49 [M + Na]+.
1
Complex 14-Zn. Yellow powder, 35 mg, yield 62%. H NMR (600
MHz, DMSO-d6) δ 8.94 (1H, s, CHN), 7.85 (1H, bs, 2B′-H), 7.36 (2H,
m, 2A′-H, 3B′-H), 7.22 (1H, d, Jortho 7.1, 6A′-H), 6.66 (1H, d, Jortho 7.1, 5A′-
H), 5.27 (1H, d, JH,OH 5.9, 2A-OH), 5.23 (1H, d, JH,OH 4.8, 2B-OH), 5.01
(1H, d, JH,OH 4.9, 3B-OH), 4.99 (1H, d, JH,OH 5.4, 4B-OH), 4.77 (1H, t,
JH,OH 5.9, 6A-OH), 4.72 (1H, bs, 3A-OH), 4.59 (1H, t, JH,OH 5.2, 6B-OH),
4.24 (1H, d, J1,2 7.8, 1B-H), 4.13 (1H, d, J1,2 9.7, 1A-H), 3.84 (2H, m, 6aA-
H, SCHHPh), 3.69 (2H, m, 6aB-H, SCHHPh), 3.62 (1H, m, 6bA-H),
3.38 (1H, m, 6bB-H), 3.31 (1H, m, 4A-H), 3.26−3.12 (5H, m, 2A-H, 3A-
H, 3B-H, 5A-H, 5B-H), 3.03 (1H, m, 4B-H), 2.97 (1H, m, 2B-H); 13C
NMR (125 MHz, DMSO-d6) δ 171.3 (4A′-C), 162.1 (CN), 139.1 (1B′-
C), 135.9 (2A′-C), 135.3 (6A′-C), 127.0 (3B′-C), 122.9 (5A′-C), 121.6
(1A′-C), 118.5 (3A′-C), 116.3 (2B′-C), 102.9 (1B-C), 82.8 (1A-C), 80.4
(4A-C), 78.9 (5A-C), 76.6 (5B-C), 76.3 (3A-C), 76.2 (3B-C), 73.0 (2B-C),
72.6 (2A-C), 69.8 (4B-C), 60.7 (6B-C), 60.4 (6A-C), 31.7 (CH2S); MS
(ESI-TOF) m/z 1143.57 [M + Na]+.
1
Complex 16-U. Orange powder, 40 mg, yield 60%. H NMR (600
MHz, DMSO-d6) δ 9.56 (1H, s, CHN), 7.81 (1H, s, 2A′-H), 7.76 (1H,
bs, 2B′-H), 7.63 (1H, d, Jortho 8.6, 6A′-H), 7.54 (1H, bs, 3B′-H), 6.95 (1H,
d, Jortho 8.6, 5A′-H), 5.11 (1H, d, JH,OH 5.3, 2A-OH), 5.08 (1H, d, JH,OH 4.8,
2B-OH), 5.05 (1H, bs, 3A-OH), 5.01 (1H, d, JH,OH 5.4, 4A-OH), 4.98
(1H, d, JH,OH 4.4, 3B-OH), 4.93 (1H, d, JH,OH 5.1, 4B-OH), 4.55 (1H, t,
JH,OH 5.9, 6B-OH), 4.37 (1H, d, J1,2 7.7, 1B-H), 4.10 (1H, d, Jgem 11.2, 6aA-
H), 4.04 (1H, d, J1,2 8.3, 1A-H), 3.93 (1H, d, Jgem 13.0, SCHHPh), 3.78
(1H, d, Jgem 13.0, SCHHPh), 3.70 (1H, m, 6aB-H), 3.56 (1H, m, 6bA-H),
3.45 (1H, m, 6bB-H), 3.28 (1H, m, 5A-H), 3.16 (1H, m, 3B-H), 3.12 (1H,
m, 5B-H), 3.07−3.02 (5H, m, 2A-H, 2B-H, 3A-H, 4A-H, 4B-H); 13C NMR
(125 MHz, DMSO-d6) δ 168.6 (4A′-C), 166.4 (CN), 146.4 (1B′-C),
137.1 (6A′-C), 136.6 (2A′-C), 128.5 (3B′-C), 125.8 (1A′-C), 123.5 (3A′-
C), 120.6 (5A′-C), 120.0 (2B′-C), 103.1 (1B-C), 82.5 (1A-C), 79.7 (5A-
C), 77.8 (3A-C), 76.7 (3B-C, 5B-C), 73.4 (2B-C), 72.8 (2A-C), 70.2 (4A-
C), 69.8 (4B-C), 68.6 (6A-C), 60.8 (6B-C), 31.4 (CH2S); MS (ESI-TOF)
m/z 1348.17 [M + Na]+.
1
Complex 14-U. Orange powder, 43 mg, yield 65%. H NMR (600
MHz, DMSO-d6) δ 9.55 (1H, s, CHN), 7.77 (1H, bs, 2B′-H), 7.73 (1H,
s, 2A′-H), 7.59 (1H, d, Jortho 8.2, 6A′-H), 7.53 (1H, bs, 3B′-H), 6.94 (1H, d,
Jortho 8.2, 5A′-H), 5.28 (1H, d, JH,OH 5.8, 2A-OH), 5.22 (1H, d, JH,OH 4.6,
2B-OH), 5.02 (1H, d, JH,OH 4.7, 3B-OH), 4.99 (1H, d, JH,OH 5.3, 4B-OH),
4.77 (1H, t, JH,OH 5.7, 6A-OH), 4.71 (1H, bs, 3A-OH), 4.58 (1H, t, JH,OH
5.0, 6B-OH), 4.24 (1H, d, J1,2 7.8, 1B-H), 4.18 (1H, d, J1,2 9.7, 1A-H), 3.95
(1H, d, Jgem 12.9, SCHHPh), 3.86 (1H, m, 6aA-H), 3.82 (1H, d, Jgem 12.9,
SCHHPh), 3.67 (1H, m, 6aB-H), 3.61 (1H, m, 6bA-H), 3.38 (1H, m,
6bB-H), 3.32−3.24 (3H, m, 3A-H, 4A-H, 5A-H), 3.18−3.12 (3H, m, 2A-H,
3B-H, 5B-H), 3.02 (1H, m, 4B-H), 2.97 (1H, m, 2B-H); 13C NMR (125
MHz, DMSO-d6) δ 168.8 (4A′-C), 166.1 (CN), 146.5 (1B′-C), 136.9
(6A′-C), 135.5 (2A′-C), 128.6 (3B′-C), 125.7 (1A′-C), 123.6 (3A′-C),
120.4 (5A′-C), 120.0 (2B′-C), 102.9 (1B-C), 82.6 (1A-C), 80.4 (4A-C),
78.9 (5A-C), 76.5 (5B-C), 76.2 (3A-C, 3B-C), 73.0 (2B-C), 72.7 (2A-C),
69.7 (4B-C), 60.6 (6B-C), 60.2 (6A-C), 31.4 (CH2S); MS (ESI-TOF) m/
z 1348.12 [M + Na]+.
1
Complex 17-Zn. Yellow powder, 36 mg, yield 64%. H NMR (600
MHz, DMSO-d6) δ 8.95 (1H, s, CHN), 7.84 (1H, bs, 2B′-H), 7.37 (2H,
bs, 2A′-H, 3B′-H), 7.22 (1H, d, Jortho 8.5, 6A′-H), 6.66 (1H, d, Jortho 8.0, 5A′-
H), 5.56 (1H, bs, 3A-OH), 5.42 (1H, d, JH,OH 6.0, 2B-OH), 5.20 (1H, d,
JH,OH 7.0, 2A-OH), 5.02 (1H, d, J1,2 3.0, 1B-H), 4.88 (2H, m, 3B-OH, 4B-
OH), 4.70 (1H, t, JH,OH 5.5, 6A-OH), 4.53 (1H, t, JH,OH 4.5, 6B-OH), 4.12
(1H, d, J1,2 9.5, 1A-H), 3.83 (2H, m, 6aA-H, SCHHPh), 3.71 (1H, d, Jgem
13.0, SCHHPh), 3.61 (2H, m, 6aB-H, 6bA-H), 3.45 (2H, m, 5B-H, 6bB-
H), 3.34 (3H, m, 3A-H, 3B-H, 4A-H), 3.20 (2H, m, 2B-H, 5A-H), 3.11
(1H, q, J2,3 = J2,1 = JH,OH 7.0 Hz, 2A-H), 3.05 (1H, m, 4B-H); 13C NMR
(125 MHz, DMSO-d6) δ 171.2 (4A′-C), 162.1 (CN), 139.2 (1B′-C),
135.7 (2A′-C), 135.5 (6A′-C), 127.1 (3B′-C), 122.9 (5A′-C), 121.5 (1A′-
C), 118.8 (3A′-C), 116.0 (2B′-C), 100.4 (1B-C), 83.1 (1A-C), 79.4 (4A-
C), 79.1 (5A-C), 77.7 (3A-C), 73.3 (5B-C), 72.9 (3B-C), 72.2 (2A-C),
72.0 (2B-C), 69.6 (4B-C), 60.5 (6A-C), 60.3 (6B-C), 31.7 (CH2S); MS
(ESI-TOF) m/z 1143.54 [M + Na]+.
1
Complex 15-Zn. Yellow powder, 39 mg, yield 70%. H NMR (600
MHz, DMSO-d6) δ 8.94 (1H, s, CHN), 7.86 (1H, bs, 2B′-H), 7.36 (2H,
m, 2A′-H, 3B′-H), 7.22 (1H, d, Jortho 8.5, 6A′-H), 6.66 (1H, d, Jortho 8.5, 5A′-
H), 5.27 (1H, d, JH,OH 5.9, 2A-OH), 5.09 (1H, d, JH,OH 3.0, 2B-OH), 4.78
(1H, d, JH,OH 3.6, 3B-OH), 4.74 (2H, m, 3A-OH, 6A-OH), 4.64 (1H, t,
JH,OH 4.9, 6B-OH), 4.50 (1H, d, JH,OH 3.0, 4B-OH), 4.19 (1H, d, J1,2 6.3,
1B-H), 4.14 (1H, d, J1,2 9.7, 1A-H), 3.85 (2H, m, 6aA-H, SCHHPh), 3.71
(1H, d, Jgem 12.9, SCHHPh), 3.60 (2H, m, 4B-H, 6bA-H), 3.51−3.45
(3H, m, 5B-H, 6aB-H, 6bB-H), 3.31−3.22 (5H, m, 2B-H, 3A-H, 3B-H, 4A-
H, 5A-H), 3.12 (1H, q, J2,3 = J2,1 = JH,OH 5.9 Hz, 2A-H); 13C NMR (125
MHz, DMSO-d6) δ 171.4 (4A′-C), 162.2 (CN), 139.2 (1B′-C), 135.9
(2A′-C), 135.4 (6A′-C), 127.1 (3B′-C), 123.2 (5A′-C), 121.6 (1A′-C),
118.5 (3A′-C), 116.4 (2B′-C), 103.7 (1B-C), 82.9 (1A-C), 80.5 (4A-C),
78.9 (5A-C), 76.3 (3A-C), 75.1 (5B-C), 72.9 (3B-C), 72.6 (2A-C), 70.1
(2B-C), 68.0 (4B-C), 60.5 (6A-C), 60.1 (6B-C), 31.7 (CH2S); MS (ESI-
TOF) m/z 1143.51 [M + Na]+.
1
Complex 17-U. Orange powder, 42 mg, yield 63%. H NMR (600
MHz, DMSO-d6) δ 9.57 (1H, s, CHN), 7.75 (2H, bs, 2A′-H, 2B′-H), 7.60
(1H, d, Jortho 8.1, 6A′-H), 7.54 (1H, bs, 3B′-H), 6.94 (1H, d, Jortho 8.1, 5A′-
H), 5.55 (1H, d, JH,OH 3.1, 3A-OH), 5.41 (1H, d, JH,OH 6.2, 2B-OH), 5.23
(1H, d, JH,OH 6.2, 2A-OH), 5.02 (1H, d, J1,2 3.8, 1B-H), 4.90 (1H, d, JH,OH
5.6, 4B-OH), 4.87 (1H, d, JH,OH 4.9, 3B-OH), 4.71 (1H, t, JH,OH 5.8, 6A-
OH), 4.54 (1H, t, JH,OH 5.7, 6B-OH), 4.16 (1H, d, J1,2 9.6, 1A-H), 3.95
(1H, d, Jgem 13.2, SCHHPh), 3.82 (2H, m, 6aA-H, SCHHPh), 3.60 (2H,
m, 6aB-H, 6bA-H), 3.48 (2H, m, 5B-H, 6bB-H), 3.36−3.31 (3H, m, 3A-H,
1
Complex 15-U. Orange powder, 46 mg, yield 69%. H NMR (600
MHz, DMSO-d6) δ 9.56 (1H, s, CHN), 7.77 (1H, bs, 2B′-H), 7.74 (1H,
s, 2A′-H), 7.59 (1H, d, Jortho 8.3, 6A′-H), 7.54 (1H, bs, 3B′-H), 6.94 (1H, d,
Jortho 8.3, 5A′-H), 5.29 (1H, d, JH,OH 5.9, 2A-OH), 5.09 (1H, bs, 2B-OH),
4.78 (1H, bs, 3B-OH), 4.74 (2H, m, 3A-OH, 6A-OH), 4.63 (1H, t, JH,OH
5.0, 6B-OH), 4.50 (1H, d, JH,OH 4.5, 4B-OH), 4.19 (2H, m, 1A-H, 1B-H),
3.95 (1H, d, Jgem 12.9, SCHHPh), 3.87 (1H, m, 6aA-H), 3.82 (1H, d, Jgem
12.9, SCHHPh), 3.59 (2H, m, 4B-H, 6bA-H), 3.51−3.44 (3H, m, 5B-H,
6aB-H, 6bB-H), 3.30−3.25 (5H, m, 2B-H, 3A-H, 3B-H, 4A-H, 5A-H), 3.12
(1H, q, J2,3 = J2,1 = JH,OH 5.9 Hz, 2A-H); 13C NMR (125 MHz, DMSO-d6)
δ 168.8 (4A′-C), 166.3 (CN), 146.6 (1B′-C), 137.2 (6A′-C), 135.8 (2A′-
C), 128.6 (3B′-C), 126.0 (1A′-C), 123.6 (3A′-C), 120.6 (5A′-C), 120.3
3B-H, 4A-H), 3.25 (1H, m, 5A-H), 3.21 (1H, m, 2B-H), 3.12 (1H, q, J2,3
=
J2,1 = JH,OH 6.2 Hz, 2A-H), 3.06 (1H, m, 4B-H); 13C NMR (125 MHz,
DMSO-d6) δ 169.2 (4A′-C), 166.7 (CN), 146.5 (1B′-C), 136.9 (6A′-C),
135.5 (2A′-C), 126.7 (3B′-C), 126.2 (1A′-C), 123.8 (3A′-C), 120.6 (5A′-
C), 120.1 (2B′-C), 100.6 (1B-C), 82.9 (1A-C), 79.5 (4A-C), 79.1 (5A-C),
77.8 (3A-C), 73.4 (5B-C), 73.2 (3B-C), 72.6 (2A-C), 72.2 (2B-C), 69.7
(4B-C), 60.6 (6A-C), 60.5 (6B-C), 31.5 (CH2S); MS (ESI-TOF) m/z
1348.01 [M + Na]+.
7967
dx.doi.org/10.1021/jo401148f | J. Org. Chem. 2013, 78, 7962−7969

The Journal of Organic Chemistry
Article
1
Complex 18-Zn. Yellow powder, 48 mg, yield 66%. H NMR (600
MHz, DMSO-d6): δ 8.94 (1H, s, CHN), 7.85 (1H, bs, 2B′-H), 7.36 (2H,
bs, 2A′-H, 3B′-H), 7.23 (1H, d, Jortho 8.7, 6A′-H), 6.66 (1H, d, Jortho 8.7, 5A′-
H), 5.59 (1H, bs, 3A-OH), 5.54 (1H, d, JH,OH 6.1, 2B-OH), 5.46 (2H, m,
2C-OH, 3B-OH), 5.23 (1H, d, JH,OH 5.6, 2A-OH), 5.03 (1H, d, J1,2 3.5, 1B-
H), 4.98 (1H, d, J1,2 3.6, 1C-H), 4.89 (2H, m, 3C-OH, 4C-OH), 4.73 (1H,
t, JH,OH 5.9, 6A-OH), 4.53 (2H, m, 6B-OH, 6C-OH), 4.14 (1H, d, J1,2 9.6,
1A-H), 3.84 (1H, d, Jgem 12.9, SCHHPh), 3.79 (1H, m, 6aA-H), 3.71 (1H,
d, Jgem 12.9, SCHHPh), 3.66−3.55 (6H, m, 3B-H, 5B-H, 6aB-H, 6aC-H,
6bA-H, 6bB-H), 3.46 (2H, m, 5C-H, 6bC-H), 3.39−3.27 (5H, m, 2B-H,
6bD-H), 3.40 (2H, m, 3A-H, 3D-H), 3.36−3.24 (7H, m, 2B-H, 2C-H, 2D-
H, 4A-H, 4B-H, 4C-H, 5A-H), 3.13 (1H, q, J2,3 = J2,1 = JH,OH 6.2 Hz, 2A-H),
3.08 (1H, q, J4,5 = J4,3 = JH,OH 5.6 Hz, 4D-H); 13C NMR (125 MHz,
DMSO-d6) δ 168.3 (4A′-C), 165.8 (CN), 146.3 (1B′-C), 136.9 (6A′-C),
135.5 (2A′-C), 128.3 (3B′-C), 125.5 (1A′-C), 123.2 (3A′-C), 120.3 (5A′-
C), 120.0 (2B′-C), 100.4 (1B-C, 1D-C), 100.0 (1C-C), 82.7 (1A-C), 79.4
(4B-C, 4C-C), 79.1 (4A-C), 79.0 (5A-C), 77.5 (3A-C), 73.1 (5D-C), 73.0
(3D-C), 72.7 (3B-C, 3C-C), 72.3 (2A-C), 72.2 (2D-C), 71.7 (2B-C), 71.6
(2C-C), 71.3 (5B-C, 5C-C), 69.6 (4D-C), 60.7 (6A-C), 60.3 (6D-C), 59.9
(6B-C, 6C-C), 31.3 (CH2S); MS (ESI-TOF) m/z 1996.75 [M + Na]+.
3A-H, 3C-H, 4B-H, 5A-H), 3.22 (2H, m, 2C-H, 4A-H), 3.11 (1H, q, J2,3
=
J2,1 = JH,OH 5.6 Hz, 2A-H), 3.05 (1H, m, 4C-H); 13C NMR (125 MHz,
DMSO-d6) δ 171.1 (4A′-C), 162.1 (CN), 139.1 (1B′-C), 136.0 (2A′-C),
135.5 (6A′-C), 127.1 (3B′-C), 123.1 (5A′-C), 121.6 (1A′-C), 118.5 (3A′-
C), 116.3 (2B′-C), 100.6 (1B-C, 1C-C), 83.1 (1A-C), 79.8 (4B-C), 79.2
(5A-C), 79.0 (4A-C), 77.7 (3A-C), 73.1 (3C-C, 5C-C), 72.9 (3B-C), 72.5
(2A-C), 72.4 (2C-C), 72.0 (2B-C), 71.3 (5B-C), 69.7 (4C-C), 60.6 (6A-C),
60.4 (6C-C), 59.9 (6B-C), 31.8 (CH2S); MS (ESI-TOF) m/z 1467.84
[M + Na]+.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for compounds 2−13 and H and
1
heteronuclear single quantum coherence (HSQC) 2D-NMR
spectra for compounds 14−19 are provided. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
Complex 18-U. Orange powder, 57 mg, yield 69%. H NMR (600
AUTHOR INFORMATION
Corresponding Author
*E-mail: ebedini@unina.it (E.B.), antonella.dallacort@
uniroma1.it (A.D.C.).
Notes
■
MHz, DMSO-d6) δ 9.57 (1H, s, CHN), 7.75 (2H, bs, 2A′-H, 2B′-H), 7.59
(1H, d, Jortho 8.6, 6A′-H), 7.55 (1H, bs, 3B′-H), 6.95 (1H, d, Jortho 8.6, 5A′-
H), 5.57 (1H, bs, 3A-OH), 5.50 (1H, d, JH,OH 6.5, 2B-OH), 5.48 (2H, m,
2C-OH, 3B-OH), 5.25 (1H, d, JH,OH 6.1, 2A-OH), 5.05 (1H, d, J1,2 3.7, 1B-
H), 4.99 (1H, d, J1,2 3.1, 1C-H), 4.92 (1H, d, JH,OH 5.6, 4C-OH), 4.90
(1H, d, JH,OH 4.7, 3C-OH), 4.76 (1H, t, JH,OH 5.8, 6A-OH), 4.54 (2H, m,
6B-OH, 6C-OH), 4.18 (1H, d, J1,2 9.5, 1A-H), 3.95 (1H, d, Jgem 12.9,
SCHHPh), 3.81 (2H, m, 6aA-H, SCHHPh), 3.66−3.56 (6H, m, 3B-H,
5B-H, 6aB-H, 6aC-H, 6bA-H, 6bB-H), 3.46 (2H, m, 5C-H, 6bC-H), 3.39−
3.28 (6H, m, 2B-H, 3A-H, 3C-H, 4A-H, 4B-H, 5A-H), 3.23 (1H, bs, 2C-H),
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
A.D.C and G.F. acknowledge the European Cooperation in
Science and Technology (COST Action CM1005, Supra-
molecular Chemistry in Water). E.B., C.D.C., and M.P. thank
the NMR facilities of CIMCF (Centro Interdipartimentale di
3.12 (1H, q, J2,3 = J2,1 = JH,OH 6.1 Hz, 2A-H), 3.06 (1H, m, 4C-H); 13
C
NMR (125 MHz, DMSO-d6) δ 168.8 (4A′-C), 166.4 (CN), 146.7 (1B′-
C), 136.9 (6A′-C), 135.5 (2A′-C), 128.4 (3B′-C), 126.0 (1A′-C), 123.6
(3A′-C), 120.3 (5A′-C), 119.9 (2B′-C), 100.6 (1C-C), 100.2 (1B-C), 82.8
(1A-C), 79.6 (4A-C), 79.4 (4B-C), 79.1 (5A-C), 77.6 (3A-C), 73.2 (5C-C),
73.1 (3C-C), 72.9 (3B-C), 72.4 (2A-C), 72.3 (2C-C), 71.7 (2B-C), 71.5
(5B-C), 69.7 (4C-C), 60.8 (6A-C), 60.5 (6C-C), 60.1 (6B-C), 31.6
(CH2S); MS (ESI-TOF) m/z 1672.27 [M + Na]+.
̀
Metodologie Chimico Fisiche) of Universita di Napoli “Federico
II”. A.D.C. and G.F. would also like to thank Ms. Monica
Costantini for her valuable help in the synthesis of metal−
salophen complexes.
1
Complex 19-Zn. Yellow powder, 60 mg, yield 68%. H NMR (600
REFERENCES
■
MHz, DMSO-d6) δ 8.95 (1H, s, CHN), 7.84 (1H, bs, 2B′-H), 7.38 (2H,
bs, 2A′-H, 3B′-H), 7.21 (1H, d, Jortho 8.6, 6A′-H), 6.65 (1H, d, Jortho 8.6, 5A′-
H), 5.58 (2H, m, 2B-OH, 3A-OH), 5.54 (1H, d, JH,OH 6.2, 2C-OH), 5.48
(3H, m, 2D-OH, 3B-OH, 3C-OH), 5.24 (1H, d, JH,OH 6.0, 2A-OH), 5.05
(1H, d, J1,2 3.4, 1C-H), 5.00 (2H, m, 1B-H, 1D-H), 4.93 (2H, m, 3D-OH,
4D-OH), 4.73 (1H, t, JH,OH 5.6, 6A-OH), 4.58 (1H, t, JH,OH 5.1, 6C-OH),
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Jgem 12.8, SCHHPh), 3.80 (1H, m, 6aA-H), 3.71 (1H, d, Jgem 12.8,
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6aD-H, 6bA-H, 6bB-H, 6bC-H), 3.47 (2H, m, 5D-H, 6bD-H), 3.39−3.22
(9H, m, 2B-H, 2C-H, 2D-H, 3A-H, 3D-H, 4A-H, 4B-H, 4C-H, 5A-H), 3.12
(1H, q, J2,3 = J2,1 = JH,OH 6.0 Hz, 2A-H), 3.06 (1H, q, J4,5 = J4,3 = JH,OH 5.8
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72.3 (2D-C), 71.9 (2B-C, 2C-C), 71.6 (5B-C, 5C-C), 69.8 (4D-C), 60.9
(6D-C), 60.8 (6A-C), 60.1 (6B-C, 6C-C), 31.8 (CH2S); MS (ESI-TOF)
m/z 1792.11 [M + Na]+.
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Complex 19-U. Orange powder, 69 mg, yield 70%. H NMR (600
MHz, DMSO-d6) δ 9.57 (1H, s, CHN), 7.75 (2H, bs, 2A′-H, 2B′-H), 7.59
(1H, d, Jortho 8.5, 6A′-H), 7.57 (1H, bs, 3B′-H), 6.95 (1H, d, Jortho 8.5, 5A′-
H), 5.60 (1H, d, JH,OH 6.2, 2B-OH), 5.55 (1H, d, JH,OH 3.0, 3A-OH),
5.52−5.48 (4H, m, 2C-OH, 2D-OH, 3B-OH, 3C-OH), 5.26 (1H, d, JH,OH
6.2, 2A-OH), 5.07 (1H, d, J1,2 3.4, 1C-H), 5.01 (2H, m, 1B-H, 1D-H), 4.96
(1H, d, JH,OH 5.6, 4D-OH), 4.94 (1H, d, JH,OH 4.9, 3D-OH), 4.77 (1H, t,
JH,OH 5.6, 6A-OH), 4.58 (1H, t, JH,OH 4.5, 6C-OH), 4.53 (2H, m, 6B-OH,
6D-OH), 4.17 (1H, d, J1,2 9.5, 1A-H), 3.96 (1H, d, Jgem 12.9, SCHHPh),
3.82 (2H, m, 6aA-H, SCHHPh), 3.66−3.56 (10H, m, 3B-H, 3C-H, 5B-H,
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