Concise synthesis of aryl-C-nucleosides by Friedel-Crafts alkylation

Article abstract of DOI:10.1039/b509846g

A fast and simplified synthesis of 1′,2′-dideoxy-1′- pyrenyl-riboside and several other C-nucleosides is shown. Shelf-stable 1-O-methyl-3,5-di-O-toluoyl-2-deoxyribose is demonstrated to serve as a versatile glycosyl donor in Lewis acid promoted Friedel-Cr

Full text of DOI:10.1039/b509846g

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A R T I C L E
Concise synthesis of aryl-C-nucleosides by Friedel–Crafts alkylation
Sven Hainke, Sebastian Arndt and Oliver Seitz*
Humboldt-Universit a¨ t zu Berlin, Institut f u¨ r Chemie, Brook-Taylor Str. 2, D-12489, Berlin,
Germany. E-mail: oliver.seitz@chemie.hu-berlin.de; Fax: +49 030 20937266;
Tel: +49 030 20937446
Received 12th July 2005, Accepted 23rd September 2005
First published as an Advance Article on the web 20th October 2005
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ꢀ
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A fast and simplified synthesis of 1 ,2 -dideoxy-1 -pyrenyl-riboside and several other C-nucleosides is shown.
Shelf-stable 1-O-methyl-3,5-di-O-toluoyl-2-deoxyribose is demonstrated to serve as a versatile glycosyl donor in
Lewis acid promoted Friedel–Crafts alkylations of unsubstituted pyrene and other inexpensive arenes such as
fluorene and methylnaphthalene. The reaction conditions favour the formation of b-configurated C-nucleosides
which renders additional epimerisation steps unnecessary. As a result, protected b-aryl-C-nucleosides are available
directly from non-substituted arenes in three steps overall.
Introduction
The introduction of non-natural nucleobases into DNA pro-
vides a powerful tool to study DNA–DNA and DNA–protein
1
interactions. Amongst the numerous base analogues investi-
gated, polycyclic aryl groups are of particular interest due
2
to their supreme base stacking abilities. Accordingly, aryl-C-
nucleosides have found an increasing number of applications.
After their incorporation into DNA-oligomers via phospho-
ramidite chemistry, the aryl-C-nucleosides have been used to
2
assess base stacking in DNA–DNA duplexes or to explore
3
the reaction mechanisms of DNA-polymerases or DNA repair
4
5
enzymes. Recently, Kool et al. used different C-nucleosides as
building blocks for the synthesis of oligomeric lightsensitive flu-
orophores in a combinatorial approach. We synthesized aryl-C-
nucleosides with an aim to probe the mechanism of base flipping
6
DNA-methyltransferases such as MTaqI. In these and other
4
studies the pyrene C-nucleotide proved particularly valuable
due to its ability to fill the abasic site formed upon enzyme
mediated flipping of the target base out of the DNA helix.
In the synthesis of aryl-C-nucleosides such as 3, the b-selective
formation of the C-glycosidic bond is a critical step. Various
ꢀ
ꢀ
routes to gain access to 1 -C-aryl-2 -deoxyribosides have been
7
developed. For example, the establishment of a C-glycosidic
bond in phenyl, naphthyl and bipyridyl nucleosides was achieved
by using the reaction of protected ribonolactones with aryl-
lithium reagents and subsequent removal of the anomeric
Scheme 1 Comparison of aryl C-nucleoside synthesis by organometal
reagents with Friedel–Crafts alkylation. (M = Cd or CuMgX, Tol =
toluoyl, X = halide).
8,9
hydroxyl group by triethylsilane reduction. C-nucleosides have
also been obtained by palladium-catalysed coupling of aryl
1
0
iodides with glycals and stannyl glycals. One of the most
widely used synthetic methods is based on the coupling of
necessary. It is also an advantage that unsubstituted arenes can
be employed instead of more expensive bromo- or iodoarenes.
Though simplicity, cost and conciseness argue for the Friedel–
Crafts glycosylation route, applications to the synthesis of
11
organocadmium compounds (Ar Cd) or, preferably, Normant-
12
2
6
cuprates (Ar
,5-di-O-toluoyl-D-ribofuranosyl chloride) 2 (Scheme 1). This
method yields the a-anomers 3a as major products which have
2
CuMgX) with Hoffer’s chlorosugar (2-deoxy-
ꢀ
16
3
2 -deoxy-aryl-C-nucleosides are scarce, presumably due to
envisaged limitations as far as the generality of the method is
concerned. In the following we present a systematic study of
11,13
to be subjected to acid-mediated epimerisation
in order to
ꢀ
obtain the often desired, naturally configured b-anomers 3b.
Most of the currently available procedures give relatively
low overall yields and require cumbersome and costly re-
action sequences to access suitable C-glycoside donors and
glycosyl acceptors. In comparison to organometal-mediated
coupling reactions of aryl halides with sophisticated glycosyl
donors, the direct alkylation of aryl compounds by glycosyl
cations is expected to provide significant advantages. In such
Friedel–Crafts alkylations, relatively simple glycosyl donors
such as chloro sugar 2 or methoxy sugar 1 may be employed
2 -deoxy-C-nucleoside synthesis by Friedel–Crafts alkylation.
It is shown that variation of the electronic properties of the
aryl aglycons demands careful optimisation of Lewis acid
promotors and glycosyl donors. Friedel–Crafts alkylation is
demonstrated to provide unparalleled rapid and cost-efficient
access to interesting b-aryl-C-nucleosides including pyrenyl,
ꢀ
fluorenyl and methylnaphthyl 2 -deoxy-C-ribosides.
14
Results
15
(
Scheme 1). Moreover, the Lewis-acid conditions in Friedel–
Crafts alkylation favour the formation of b-configurated C-
nucleosides, rendering additional epimerisation steps un-
In the previous syntheses of pyrenyl nucleoside 4ab(Ar = 1-
pyrenyl), 1-a-chloro-3,5-di-O-toluoyl-2-deoxyribose 2 was used
as glycosyl donor in coupling reactions with cadmium organyls
16
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 2 3 3 – 4 2 3 8
4 2 3 3

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ꢀ
Table 1 Results of the Friedel–Crafts alkylation of Hoffer s chlorosugar 2 with pyrene
a
Entry
Promoter (eq.)
Time/min
Solvent
Yield of 3a (%)
Ratio 3ab : 3aa
1
2
3
4
BF
BF
AgBF
AgBF
3
3
·OEt
2
2
(1.3)
(1.7)
20
20
120
60
CH
ClCH
CH Cl
ClCH
2
Cl
2
54
52
57
9
70 : 30
70 : 30
75 : 25
76 : 24
·OEt
2
CH
2
2
Cl
Cl
4
4
(1.1)
(1.1)
2
2
2
CH
a
1
Selectivity determined by H-NMR-spectroscopy via comparison of the signal intensity of the anomeric protons.
Scheme 2 Coupling reaction of chlorosugar 2 with pyrene.
6
,11
ꢀ
ꢀ
and Normant cuprates prepared from bromopyrene.
We
Friedel–Crafts-alkylation with the desired (a,b)-1 ,2 -dideoxy-
1 -(1-pyrenyl)-3 ,5 -di-O-toluoyl-ribose 3aa/b.
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ꢀ
ꢀ
thought that the same donor could be employed in a Lewis-acid
promoted Friedel–Crafts reaction with non-substituted pyrene
Scheme 2). Indeed, it was found that the mild Lewis acid boron
trifluoride etherate in dichloromethane was able to induce the
formation of toluoyl protected C-nucleoside 3aa/b which was
isolated in 54% yield (Table 1, entry 1). The a/b-selectivity of
The 33% yield of pure b-pyrenyl C-nucleoside obtained by
Friedel–Crafts alkylation was considered as practically useful,
particularly when taking the cost and conciseness of the
synthesis into account. For that reason, we tested the scope of
the reaction by allowing chloro sugar 2 to react with anthracene
and fluorene as glycosyl acceptors. However, under the mildly
Lewis-acid conditions the reactivity of these arenes was too
low and the desired anthracenyl- and fluorenyl-C-nucleosides
were only formed in trace amounts. The use of stronger Lewis
(
1
the C-glycosylation was assessed by H-NMR and analytical
HPLC analysis. Under the Lewis acid conditions, product 3a was
formed as a mixture of anomers 3ab : 3aa of 7 : 3. The anomeric
mixture was separated by flash chromatography to afford the
pure b-anomer 3ab in 33% yield. Friedel–Crafts alkylations
in dichoroethane often proceed with higher yields than in
acids such as SnCl
2. Recently, methoxy sugars were demonstrated to serve as
suitable glycosyl donors in SnCl -promoted C-glycosylation
4
led to rapid decomposition of chloro sugar
dichloromethane. However, the BF
3
-promoted C-glycosylation
4
16
furnished almost identical yields in both solvents (Table 1,
entry 2). The milder Lewis acid silver tetrafluoroborate required
extension of the reaction time to 2 h in dichloromethane
reactions. In light of its ease of synthesis and long shelf life,
the application of 1-O-methyl-3,5-di-O-toluoyl-2-deoxyribose 1
appeared attractive (Scheme 3). Accordingly, the reaction of
(
Table 1, entry 3). In this case, C-glycosylation occurred in
methoxy sugar 1 with pyrene induced by addition of SnCl
studied. The desired pyrenyl-C-nucleoside 3aa/b was obtained
in yields and selectivities which compared well with the BF
4
was
almost identical 57% yield with a slightly more favourable
selectivity of 3ab : 3aa of 75 : 25. The reaction with silver
tetrafluoroborate in dichloroethane instead of dichloromethane
under otherwise unchanged conditions led to the formation
of a new product (2R,3S)-2-hydroxy-5,5-dipyrenylpentyl 1,3-di-
toluoate 5 in 22% yield, while the desired compounds 3aa/b
3
-
promoted reactions. The pure b-anomer 3ab was isolated in
39% yield (Table 2). For the reaction of the less reactive arenes
fluorene, 1-methylnaphthalene, phenanthrene, benzothiophene
and thioanisole, it was deemed important to further increase
1
13
1
17
were obtained in only 9% yield. NMR-analysis ( H-; C-, H-
the Lewis acidity by adding silver trifluoroacetate (AgOTfa).
1
H-COSY) and mass spectroscopy of the isolated new product
The reaction of fluorene with methoxysugar 1 in dichloroethane
suggested the bispyrenyl structure 5 as product of a second
proceeded smoothly under catalysis of tin tetrachloride/silver
Table 2 Results of the Friedel–Crafts alkylation of different arenes with methoxysugar 1 in dichloroethane
◦
Arene
Promoter (eq.)
Temperature/ C
Product
Yield (%)
b : a ratio
Pyrene
Pyrene
Fluorene
SnCl
SnCl
SnCl
4
4
4
(0.51)
(2.3)
(1.0),
0
−15
−15
3a
3a
3b
61
56
49
75 : 25
70 : 30
85 : 15
a
AgOTfa(1.5)
SnCl (1.0),
AgOTfa(1.5)
SnCl (1.0),
AgOTfa(1.5)
SnCl (2.0),
AgOTfa(1.5)
SnCl (2.0),
AgOTfa(1.5)
Benzothiophene
4
−15
−15
3c
45
51
33
—
76 : 24
73 : 27
63 : 37
—
1
-Methylnaphthalene
4
3d
◦
Thioanisole
4
20 C
3e
◦
Phenanthrene
4
0 C
No reaction
a
Reaction in dichloromethane as solvent.
4
2 3 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 2 3 3 – 4 2 3 8

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Scheme 3 Friedel–Crafts glycosylation with methoxysugar 1.
ꢀ
ꢀ
+
trifluoroacetate (SnCl
4
/AgOTfa) to yield 41% of b-1 ,2 -
given by parameters of r = − 0.39 and −0.35, respectively.
ꢀ
ꢀ
ꢀ
+
+
dideoxy-1 -(2-fluorenyl)-3 ,5 -di-O-toluoyl-ribose 3bb and 9%
Fluorene (r = − 0.48), benzothiophene (r = − 0.54) and
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
+
of a-1 ,2 -dideoxy-1 -(2-fluorenyl)-3 ,5 -di-O-toluoyl-ribose 3ba
Table 2). Changing the reaction conditions by using only SnCl
as promoter or dichloromethane as solvent lead to significantly
1-methylnaphthalene (r = − 0.57) are more reactive arenes
(
4
and reacted successfully under promotion of SnCl /AgOTfa. It
4
is conceivable that the thioether structure of benzothiophene
offers a coordination site to soft metal electrophiles which
might explain the need for over-stoichiometric loads of Lewis
acid. A further increase of arene reactivity requires the use of
1
1
1
decreased yields. Structures were verified by H- and H- H-
NOESY-NMR-spectroscopy (Fig. 1). The NOESY-spectrum of
ꢀ
the b-anomer showed characteristic interactions between H1
ꢀ
ꢀ
ꢀ
+
and H2 a and also H3 and H2 b which proved the anomeric
configuration. The configuration at the fluorene was validated
by the cross peaks between the H9 protons of the fluorene and
the H1 proton which formed a singlet (Fig. 1).
The methoxy sugar 1 was allowed to react with benzothio-
phene and 1-methylnaphthalene. Promotion of C-glycosylation
milder reaction conditions. Therefore pyrene (r = − 0.68),
the most reactive arene examined in this study, was coupled
by using catalytic amounts of SnCl
and decomposition of the desired products. Even milder Lewis
acids like BF or AgBF can be employed when increasing
4
to avoid side reactions
3
4
the reactivity of the glycosyl donor such as in Friedel–Crafts
glycosylations with chloro sugar 2.
by addition of the SnCl /AgOTfa promotor combination re-
4
sulted in the formation of bis-toluoyl aryl-C-nucleosides 3ca/b
and 3da/b in 45% and 51% yield (Table 2). NMR-spectroscopy
Aryl-C-nucleosides such as pyrenyl nucleoside 4ab have
emerged as powerful designer nucleotides to probe DNA–DNA
and DNA–protein interactions. We presumed that research in
the field would benefit if synthetic access to the required C-
glycosides was facilitated. To the best of our knowledge, the
Friedel–Crafts glycosylation route shown in Scheme 1 and
Scheme 3 provides the shortest route to aryl-C-nucleotide build-
ing blocks suitable for automated DNA-synthesis. Starting from
2-deoxyribose only two steps are needed for the synthesis of key
1
13
1
1
(
H- C-HMBC, HMQC and H- H-NOESY) confirmed the
supposed structures. In the case of the benzothiophene nu-
cleoside 3cb, the H2-proton shows no correlation with other
benzothiophene ring protons in the NOESY-NMR spectrum.
Electrophilic attack at the aromatic ring systems occurred at
the expected 3- and 4-positions of benzothiophene and 1-
methylnaphthalene, respectively.
19
Next, the C-glycosylation of thioanisole was examined as the
only monocyclic arene in this study. This reaction proceeded
glycosyl donor 1. As a result of the b-selective Friedel–Crafts
glycosylation reaction, b-aryl-C-nucleosides 4b are available
+
sluggishly when performed with stoichiometric amounts of
directly from non-substituted arenes (r < −0.4) in four steps
◦
SnCl
4
at −15 C, which indicated that thioanisole is a less
overall.
powerful substrate than polycyclic arenes. However, through
increases of the SnCl
perature (20 C) C-nucleoside 3eb was afforded in a moderate
4
-promoter load (2 eq.) and reaction tem-
◦
Conclusion
2
1% yield. Furthermore, the Friedel–Crafts glycosylation of
In summary, we have developed a fast and simplified synthe-
sis of the known pyrene-C-nucleoside 4a and several other
new C-nucleosides via Friedel–Crafts alkylation using the
SnCl /AgOTfa-promoter system or SnCl and shelf-stable
phenanthrene and unsubstituted naphthalene was attempted.
The desired reaction products could not be detected.
ꢀ
Deprotection of the b-anomeric toluoylated 2 -desoxyribose-
4
4
C-nucleosides 3bb–3eb was carried out following standard pro-
cedures by treatment with sodium methoxide in dry methanol.
After column chromatography the corresponding unprotected
C-nucleosides 4bwere obtained in good to excellent yields (72%–
methoxysugar 1 as glycosyl donor. Importantly, the Friedel–
Crafts glycosylation is in favour of the formation of b-anomers.
According to this convenient protocol and in contrast to most
other methods of aryl-C-nucleoside synthesis, additional steps
such as arene metallation or acid catalysed anomerisation
reactions are not required.
9
5%).
Discussion
The reaction yields obtained in a given aryl-C-nucleoside
synthesis can be correlated with the reactivities of the arenes
Experimental
General
used. The reactivity of an arene in Friedel–Crafts alkylations is
+
commonly characterised by means of its r
parameters from
Reagents and chemicals were obtained from Acros and
Lancaster and were used without further purification. Hof-
fer’s chlorosugar 2 was synthesised according to literature
arene
18
the Hammett–Brown relationship. Phenanthrene and naph-
thalene, which proved unreactive in SnCl /AgOTfa-promoted
reactions with methoxy sugar 1, have the lowest reactivity,
4
19
procedures. Dichloromethane was freshly distilled from CaH ,
2
Fig. 1 Aryl-C-nucleosides and important correlations in 1H-1H-NOESY (dashed) and 1H-13C-HMBC (bold) NMR-spectra.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 2 3 3 – 4 2 3 8
4 2 3 5

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+
˚
dichloroethane was dried over molecular sieve MS 4 A. All
65.5, 38.7, 37.2, 21.7 (Ar–Me); HRMS(ESI): m/z C53
calcd. 779.2768(M + Na ), found 779.2768.
H
40
5
O Na
+
NMR spectra were recorded on a Bruker DPX-300 or a Bruker
AV 400 spectrometer. The signal of the residual protonated
solvent was used as a reference signal. Coupling constants
J are reported in Hz. Flash chromatography was performed
using Merck silica gel 60 (particle size 0.040–0.063 mm). TLC
was performed with aluminium-baked silica gel 60 F254 plates
Merck). Analytical reversed phase HPLC was performed with
an Agilent 1100 series system. A Macherey & Nagel RP-C18 CC
25/4 Nucleosil C18 gravity column was used. As the mobile
phase a binary mixture of A (98.9% H O/1% acetonitrile/0.1%
TFA) and B (98.9% acetonitrile/1% H O/0.1% TFA) was used.
Products were eluted with the following gradient: 0–6 min (20%
B); 6–7 min (20–75% B); 7–27 min (75%B) and detected by
UV absorbance at 254 nm, where the relationship between the
extinction coefficients of 3ab : 3aa is 1.14 as calibrated by a
mixture of known decomposition of 3aa/b.
Friedel–Crafts-alkylation with the methoxysugar 1; Typical
procedure. To a solution of 200 mg of 1-O-methyl-3,5-di-O-
toluoyl-2-deoxyribose 1 (0.52 mmol), 172.3 mg silver triflu-
oroacetate (0.78 mmol) and 218 ll of 1-methylnaphthalene
(
6
1.56 mmol; 3 eq.) in dry dichloroethane (3 ml) was added
(
◦
1 ll SnCl
4
(0.52 mmol; 1.0 eq.) at −15 C. After stirring
for 10 min the reaction mixture was treated with 10 ml
saturated aqueous sodium bicarbonate and extracted with 20 ml
dichloromethane(×3). The combined organic layer was washed
1
2
2
with saturated NaHCO
3
solution (×3) and brine (×1), dried over
anhydrous MgSO
4
and concentrated. Flash chromatography
(
cyclohexane–ethyl acetate 19:1) yielded 96 mg (0.19 mmol; 37%)
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
of b-1 ,2 -dideoxy-1 -(1-(4-methyl)naphthyl)-3 ,5 -di-O-toluoyl-
ꢀ
ꢀ
ꢀ
ribose 3db and 35 mg (0.07 mmol; 14%) of a-1 ,2 -dideoxy-1 -
ꢀ
ꢀ
(
1-(4-methyl)naphthyl)-3 ,5 -di-O-toluoyl-ribose 3da.
Friedel–Crafts-alkylation with Hoffer’s chlorosugar 2; typical
procedure
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(1-(4-methyl)naphthyl)-3 ,5 -di-O-toluoyl-
ribose 3db. : 0.40 (cyclohexane–ethyl acetate 4.5 : 1); d
300 MHz, CDCl ) 8.06–8.02 (4H, m, Ar–H), 7.93 (2H, d,
R
f
H
(
3
To a solution of 81 mg of chlorosugar 2 (0.21 mmol) and 93 mg
of pyrene (0.47 mmol; 2 eq.) in dry dichloromethane (3 ml) was
J 8.2, Ar–H), 7.66 (1H, d, J 7.3, Ar–H), 7.56–7.46 (2H,
m, Ar–H), 7.32–7.27 (3H, m, Ar–H), 7.19 (2H, d, J 8.0,
Ar–H), 5.96 (1H, dd, J
d, J 6.3, H3 ), 4.72 (2H, d, J 3.9, H5 ), 4.67–4.62 (1H, m,
H4 ), 2.78 (1H, ddd, JH2ꢀa,H2ꢀb 13.8, JH1ꢀ,H2ꢀa 5.1, JH3ꢀ,H2ꢀa 1.1,
H2 a), 2.68 (s, 3H, Ar–Me), 2.45 (s, 3H, Ar–Me), 2.39 (s, 3H,
Ar–Me), 2.32 (1H, ddd, JH2ꢀa,H2ꢀb 13.8, JH1ꢀ,H2ꢀb 10.8, JH3ꢀ,H2ꢀb 6.2,
added 45 mg silver tetrafluoroborate (0.23 mmol; 1.1 eq.) at
ꢀ
◦
ꢀ
ꢀ
10.7, J
ꢀ
ꢀ
5.0, H1 ), 5.67 (1H,
H1 ,H2 a
H1 ,H2 b
0
C. After stirring at that temperature for 2 h the reaction
ꢀ
ꢀ
mixture was treated with 10 ml saturated aquous sodium
ꢀ
bicarbonate and extracted with 10 ml dichloromethane(×3). The
ꢀ
combined organic layer was washed with saturated NaHCO
3
solution (×3) and brine (×1), dried over anhydrous MgSO
4
and
ꢀ
H2 b); d
c
(75 MHz, CDCl
, Ar), 143.8 (C
82.6, 78.0, 77.5, 64.7, 40.9, 21.8 (Ar–Me), 21.7 (Ar–Me), 19.6
3
) 166.5 (C
q
, -COOR), 166.2 (C ,
, Ar), 134.6–122.1(Ar–C),
q
concentrated in vacuo. Flash chromatography (cyclohexane–
-
COOR),144.2 (C
q
q
ethyl acetate 19:1) yielded 65 mg (0.12 mmol; 57%) of the de-
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
sired (a,b)-1 ,2 -dideoxy-1 -(1-pyrenyl)-3 ,5 -di-O-toluoyl-ribose
+
+
(
8
(
Ar–Me); MS(EI): m/z 494(M , 10%), 358(M –C
7
H
7
COOH,
3aa/b.
+
), 222(M –2C
7
H
7
COOH, 35), 169(1-(4-methyl)-naphthyl-
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
11
b-1 ,2 -Dideoxy-1 -(1-pyrenyl)-3 ,5 -di-O-toluoyl-ribose 3ab .
+
+
CO) ,100); HRMS(EI): m/z C32
H
30
O
5
calcd. 494.2093(M),
R
f
: 0.25 (cyclohexane–ethyl acetate 6 : 1); d
H
(300 MHz, CDCl )
3
found 494.2094.
8
.31–7.95 (13H, m, Ar–H), 7.32 (2H, d, J 8.0, Ar–H), 7.17 (2H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
a-1 ,2 -Dideoxy-1 -(1-(4-methyl)naphthyl)-3 ,5 -di-O-toluoyl-
ribose 3da. R : 0.34 (cyclohexane–ethyl acetate 4.5 : 1); dH
d, J 8.3, Ar–H), 6.29 (1H, dd, JH1ꢀ,H2ꢀa 10.7, JH1ꢀ,H2ꢀb 4.9, H1 ),
ꢀ
ꢀ
5
4
J
.74 (1H, dd, J 5.1, JH3ꢀ,H4ꢀ 1.9, H3 ), 4.84–4.80 (2H, m, H5 ),
f
ꢀ
(300 MHz, CDCl ) 8.06–7.13 (14H, m, Ar–H), 6.05 (1H, t, J
6.7, H1 ), 5.67 (1H, ddd, J
.75–4.71 (1H, td, JH4ꢀ,H5ꢀ 3.5, JH3ꢀ,H4ꢀ 2.3, H4 ), 2.89 (1H, ddd,
3
ꢀ
ꢀ
ꢀ
ꢀ
6.6, J
ꢀ
ꢀ
3.4, J
ꢀ
ꢀ
3.4,
H2ꢀa,H2ꢀb 13.9, JH1ꢀ,H2ꢀa 5.1, JH3ꢀ,H2ꢀa 0.8, H2 a), 2.43–2.36 (1H, m,
H3 ,H2 b
H3 ,H2 a
H3 ,H4
ꢀ
ꢀ
ꢀ
H3 ), 4.83 (1H, td, J
ꢀ
H4 ,H5ꢀ 4.7, JH3ꢀ,H4ꢀ 2.9, H4 ), 4.66 (2H, m,
H2 b), 2.45 (s, 3H, Ar–Me), 2.36 (s, 3H, Ar–Me); d
c
(75 MHz,
, -COOR),144.3 (C , Ar),
, Ar), 134.1–122.3(Ar–C), 83.4, 78.2, 77.4, 64.8, 41.6,
1.8 (Ar–Me), 21.7 (Ar–Me); HPLC: R : 26.3 min; HRMS(EI):
calcd. 554.2093(M), found 554.2093.
ꢀ
H5 ), 3.17 (1H, ddd, JH2ꢀa,H2ꢀb 14.2, JH1ꢀ,H2ꢀb 7.3, JH3ꢀ,H2ꢀb 7.3,
CDCl
3
) 166.5 (C
q
, -COOR), 166.3 (C
q
q
ꢀ
H2 b), 2.70 (3H, s, Ar–Me), 2.56 (1H, ddd, JH2ꢀa,H2ꢀb 13.9,
143.9 (C
q
ꢀ
J
H1ꢀ,H2ꢀa 7.1, JH3ꢀ,H2ꢀa 2.0, H2 a), 2.41 (3H, s, Ar–Me); 2.37 (3H, s,
2
t
+
Ar–Me); d (75 MHz, CDCl ) 166.5 (C , -COOR), 166.1 (C ,
COOR),144.1 (C
2.3, 78.1, 76.5, 65.2, 39.8, 21.8 (Ar–Me), 21.7 (Ar–Me), 19.6
Ar–Me); HRMS(EI): m/z C32
m/z C37
H
30
O
5
c
3
q
q
-
q
, Ar), 143.9 (C , Ar), 136.1–122.1(Ar–C),
q
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
11
a-1 ,2 -Dideoxy-1 -(1-pyrenyl)-3 ,5 -di-O-toluoyl-ribose 3aa .
8
(
R
f
: 0.17 (cyclohexane–ethyl acetate 6 : 1); d
H
(300 MHz, CDCl
3
)
+
H
30
O
5
calcd. 494.2093(M),
8
.34 (1H, d, J = 7.8, Ar–H), 8.22–7.86 (10H, m, Ar–H), 7.60
found 494.2093.
(
2H, d, J 8.2, Ar–H), 7.27 (2H, d, J 8.1, Ar–H), 7.08 (2H, d,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J 7.9, Ar–H); 6.39 (1H, dd, JH1ꢀ,H2ꢀb 7.6, JH1ꢀ,H2ꢀa 5.8, H1 ), 5.77–
5
b-1 ,2 -Dideoxy-1 -(2-fluorenyl)-3 ,5 -di-O-toluoyl-ribose 3bb.
ꢀ
.71 (1H, ddd, JH3ꢀ,H2ꢀb 7.0, JH3ꢀ,H2ꢀa 3.7, JH3ꢀ,H4ꢀ 2.8, H3 ), 4.97
1H, td, JH4ꢀ,H5ꢀ 4.7, JH3ꢀ,H4ꢀ 2.8, H4 ), 4.73 (2H, m, H5 ), 3.31
R
f
:0.42(cyclohexane–ethylacetate 4.5:1); d
H
(400MHz, CDCl )
3
ꢀ
ꢀ
(
(
8.06–8.02 (4H, m, Ar–H), 7.93 (2H, d, J 8.2, Ar–H), 7.66 (1H,
d, J 7.3, Ar–H), 7.56–7.46 (2H, m, Ar–H), 7.32–7.27 (3H, m,
ꢀ ꢀ
Ar–H), 7.19 (2H, d, J 8.0, Ar–H), 5.64 (1H, dd, J 5.1, JH3 ,H4
1.2, H3 ), 5.33 (1H, dd, JH1 ,H2 a
4.64 (2H, m, H5 ), 4.67–4.62 (1H, td, J
H4 ), 3.79 (d, 2H, CH
5.0, JH3 ,H2 a
Me), 2.29 (1H, ddd, JH2 a,H2 b
H2 b); d
ꢀ
1H, ddd, JH2ꢀa,H2ꢀb 13.5, JH1ꢀ,H2ꢀb 7.6, JH3ꢀ,H2ꢀb 7.0, H2 b), 2.50 (1H,
ꢀ
ddd, JH2ꢀa,H2ꢀb 13.5, JH1ꢀ,H2ꢀa 5.8, JH3ꢀ,H2ꢀa 3.7, H2 a), 2.43 (3H, s,
ꢀ
ꢀ
ꢀ
ꢀ
10.9, J
ꢀ ꢀ
5.0, H1 ), 4.74–
Ar–Me), 2.34 (3H, s, Ar–Me); d
COOR), 166.1 (C , -COOR), 144.0 (C
31.4–122.4 ((Ar–C)), 82.6, 78.4, 76.5, 64.8, 40.6, 21.8 (Ar–
Me), 21.7 (Ar–Me); HPLC: R : 25.0 min; HRMS(ESI): m/z
c
(75 MHz, CDCl
3
) 166.5 (C
q
,
H1 ,H2 b
ꢀ
H4 ,H5ꢀ 3.9, J
), 2.56 (1H, ddd, JH2 a,H2 b
ꢀ
ꢀ
ꢀ
2.0,
-
q
q
, Ar), 136.0 (C
q
, Ar),
H3 ,H4
ꢀ
ꢀ
ꢀ
13.7, J
ꢀ ꢀ
H1 ,H2 a
1
2
ꢀ
ꢀ
ꢀ
0.7, H2 a), 2.43 (s, 3H, Ar–Me), 2.38 (s, 3H, Ar–
t
+
+
ꢀ
ꢀ
13.8, J
ꢀ
ꢀ
11.0, J
, -COOR), 166.2 (C , -
ꢀ ꢀ
6.0,
q
C
37
H
30
O
5
Na calcd. 577.1985(M + Na ), found 577.1999.
2R,3S)-2-Hydroxy-5,5-dipyrenylpentyl 1,3-ditoluoate 5.
(300 MHz, CDCl
H1 ,H2 b
H3 ,H2 b
ꢀ
c
(75 MHz, CDCl
3
) 166.4 (C
q
(
R
3
f
:
COOR), 144.2, 143.9, 143.7, 143.4, 141.6, 141.4, 139.3, 129.8,
29.7, 129.2, 127.1, 127.0,126.7, 125.0, 124.8, 122.5, 119.9, 119.8,
3.0, 81.2, 77.4, 64.9, 42.1, 36.8, 21.8 (Ar–Me), 21.7 (Ar–Me);
0
8
.10 (cyclohexane–ethyl acetate 4.5 : 1); d
.57 (1H, d, J 9.3, Ar–H), 8.34 (1H, d, J 9.3, Ar–H), 8.32–7.93
H
)
1
8
(
7
15H, m, Ar–H), 7.85 (1H, d, J 9.3, Ar–H), 7.74 (4H, m, Ar–H),
.03 (4H, m, Ar–H), 6.44 (1H, t, JH5,H4 7.2, H5), 5.56 (1H, m,
+
+
+
MS(EI): m/z 518(M , 14%), 382(M –C
7
+
H
7
COOH, 4), 246(M –
2C
7
H
H
7
COOH, 18), 169 (fluorenyl-(CO) ,100); HRMS(EI): m/z
H3), 4.53 (1H, dd, Jvic. 11.4, JH1,H2 4.2, H1), 4.45–4.33 (2H, m,
H1, H2), 3.16 (2H, t, J 6.6, H4), 3.03 (1H, br, -OH), 2.35 (s,
+
C
34
30
O
5
calcd. 518.2093(M), found 518.2092.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
1
H, Ar–Me), 2.30 (s, 3H, Ar–Me); d
66.5 (C , -COOR), 166.1 (C , -COOR), 144.0 (C
, Ar), 138.7 (Cq, Ar), 137.0 (C , Ar), 131.4–122.4, 74.9, 72.2,
c
(75 MHz, CDCl
3
) 166.8,
a-1 ,2 -Dideoxy-1 -(2-fluorenyl)-3 ,5 -di-O-toluoyl-ribose 3ba.
q
q
q
, Ar), 143.8
R
f
:0.37(cyclohexane–ethylacetate 4.5:1); d
8.97–7.06 (15H, m, Ar–H), 5.61 (1H, ddd, JH3ꢀ,H2ꢀ b 6.8, JH3ꢀ,H2ꢀ a
H
(300MHz, CDCl )
3
(
C
q
q
4
2 3 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 2 3 3 – 4 2 3 8

View Article Online
ꢀ
ꢀ
3
J
2
2
.8, JH3ꢀ,H4ꢀ 3.0, H3 ), 5.43 (1H, t, J 6.7, H1 ), 4.73 (1H, td,
CH
2
Cl
2
–CH
3
OH 100:3) yielded 164 mg (0.63 mmol; 95%) of
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H4ꢀ,H5ꢀ 4.8, JH3ꢀ,H4ꢀ 3.0, H4 ), 4.58 (2H, m, H5 ), 3.84 (s, 2H, CH
.96 (1H, ddd, JH2ꢀa,H2ꢀb 14.0, JH1ꢀ,H2ꢀb 7.1, JH3ꢀ,H2ꢀb 7.1, H2 b),
.40 (3H, s, Ar–Me), 2.32 (3H, s, Ar–Me); HRMS(EI): m/z
),
b-1 ,2 -dideoxy-1 -(1-(4-methyl)naphthyl)-ribose 3db.
2
ꢀ
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(1-(4-methyl)naphthyl)-ribose
0.37 (ethyl acetate); dH (300 MHz, CDCl ) 8.08–8.02 (2H, m,
Ar–H), 7.56–7.51 (3H, m, Ar–H), 7.30 (1H, d, J 7.2, Ar–H),
5.88 (1H, dd, JH1ꢀ,H2ꢀa 10.1, JH1ꢀ,H2ꢀb 5.6, H1 ), 4.88 (1H, m, H3 ),
4db.
f
R :
+
3
C
34
H
30
O
5
calcd. 518.2093(M), found 518.2093.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(3-benzothiophenyl)-3 ,5 -di-O-toluoyl-
ꢀ
ribose 3cb.
R
f
: 0.38 (cyclohexane–ethyl acetate 4.5 : 1); d
) 8.00 (2H, d, J 8.2, Ar–H), 7.93 (2H, d, J 8.2,
Ar–H), 7.86 (2H, m, Ar–H), 7.46 (1H, s, Ar–H), 7.35–7.19 (6H,
H
4.11 (1H, td, JH4ꢀ,H5ꢀ = 3.8, JH3ꢀ,H4ꢀ = 4.1, H4 ), 3.85 (2H, m,
ꢀ
(
400 MHz, CDCl
3
H5 ), 2.68 (s, 3H, Ar–Me), 2.47 (1H, ddd, JH2ꢀa,H2ꢀb 13.2, JH1ꢀ,H2ꢀa
5.7, JH3ꢀ,H2ꢀa 2.2, H2
9.8, JH3ꢀ,H2ꢀb 6.5, H2 b), 2.00 (br, 2H, OH); d
ꢀ
a), 2.32 (1H, ddd, JH2ꢀa,H2ꢀb 13.2, JH1ꢀ,H2ꢀb
ꢀ
ꢀ
m, Ar–H), 5.67 (1H, d, J 5.7, H3 ), 5.59 (1H, dd, JH1ꢀ,H2ꢀa 10.6,
c
(75 MHz, CDCl )
3
ꢀ
ꢀ
J
3
J
2
H1ꢀ,H2ꢀb 5.2, H1 ), 4.74–4.64 (2H, m, H5 ), 4.58 (1H, td, JH4ꢀ,H5ꢀ
135.0, 134.3, 132.8, 130.8, 126.2, 125.8, 125.5, 124.9, 123.9,
121.7, 86.9, 77.2, 73.8, 63.4, 43.0(C-2 ), 19.6 (Ar–Me); MS(EI):
m/z C16
ꢀ
ꢀ
.8, JH3ꢀ,H4ꢀ 2.3, H4 ), 2.68 (1H, ddd, JH2ꢀa,H2ꢀb 13.6, JH1ꢀ,H2ꢀa 5.2,
ꢀ
+
H3ꢀ,H2ꢀa 0.9, H2 a), 2.44 (s, 3H, Ar–Me), 2.39 (s, 3H, Ar–Me),
H
18
O
3
calcd. 258.1(M), found 258.1.
ꢀ
.50–2.40 (1H, m, H2 b); d
COOR), 166.2 (C , -COOR), 144.2, 143.9, 141.0, 137.1, 135.6,
29.8, 129.7, 129.3, 129.2, 127.1, 127.0, 124.5, 124.1, 123.0,
22.6, 122.2, 82.8, 77.0, 76.9, 64.6, 39.7, 21.8 (Ar–Me), 21.7
Ar–Me); HRMS(ESI): m/z C34
Na ), found 509.1392.
c
(75 MHz, CDCl
3
) 166.4 (C ,
q
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(1-pyrenyl)-ribose 4ab. 185 mg (85%),
NMR- and MS-analysis confirmed the identity with previously
synthesized material.
-
q
1
1
+
(
H
30
O
5
Na calcd. 509.1393(M +
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(2-fluorenyl)-ribose 4bb. 141 mg (72%);
: 0.37 (ethyl acetate); d (300 MHz, methanol-d ) 7.77–7.72
+
R
f
H
4
(
2H, m, Ar–H), 7.59 (1H, s, H1), 7.52 (1H, d, J 7.5, Ar–H), 7.39–
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
a-1 ,2 -Dideoxy-1 -(3-benzothiophenyl)-3 ,5 -di-O-toluoyl-
ribose 3ca. : 0.33 (cyclohexane–ethyl acetate 4.5 : 1); d
300 MHz, CDCl ) 7.91 (2H, d, J 8.2, Ar–H), 7.85–7.77 (2H,
m, Ar–H), 7.70 (2H, d, J 8.3, Ar–H), 7.39 (1H, d, J 1.0,Ar–H),
.31–7.27 (2H, m, Ar–H), 7.19–7.10 (4H, m, Ar–H), 5.64–5.57
ꢀ
7
4
3
1
J
1
1
.23 (3H, m, Ar–H), 5.19 (1H, dd, JH1ꢀ,H2ꢀ a 10.5, JH1ꢀ,H2ꢀ b 5.6, H1 ),
R
f
H
ꢀ
ꢀ
.34 (1H, m, H3 ), 3.97 (1H, td, JH4ꢀ,H5ꢀ = 5.2, JH3ꢀ,H4ꢀ = 2.4, H4 ),
(
3
ꢀ
.86 (s, 2H, CH
2
), 3.70 (2H, m, H5 ), 2.23 (1H, ddd, JH2ꢀa,H2ꢀb
ꢀ
3.2, JH1ꢀ,H2ꢀa 5.4, JH3ꢀ,H2ꢀa 1.7, H2 a), 2.00 (1H, ddd, JH2ꢀa,H2ꢀb 13.2,
H1ꢀ,H2ꢀb 10.5, JH3ꢀ,H2ꢀb 6.1, H2 b); d
7
ꢀ
(75 MHz, methanol-d ) 144.6,
4
ꢀ
ꢀ
ꢀ
c
(
2H, m, H1 ,H3 ), 4.64 (1H, td, JH4ꢀ,H5ꢀ 4.6, JH3ꢀ,H4ꢀ 3.0, H4 ),
44.6, 142.5, 141.6, 127.7, 127.7, 126.0, 126.0, 123.8, 120.7,
ꢀ
4
7
J
.61–4.50 (2H, m, H5 ), 2.97 (1H, ddd, JH2ꢀa,H2ꢀb 13.8, JH1ꢀ,H2ꢀ b
+
20.5, 89.1, 81.9, 74.4, 64.1, 45.1, 37.6; MS(EI): m/z C18
H
18
O
3
ꢀ
.1, JH3ꢀ,H2ꢀb 7.1, H2 b), 2.43 (1H, ddd, JH2ꢀa,H2ꢀb 13.8, JH1ꢀ,H2ꢀa 5.9,
calcd. 282.1(M), found 282.1.
ꢀ
H3ꢀ,H2ꢀa 3.7, H2 a), 2.34 (s, 3H, Ar–Me), 2.32 (s, 3H, Ar–Me);
d
c
(75 MHz, CDCl
44.1, 143.9, 141.0, 137.2, 136.9, 129.8, 129.7, 129.2, 129.1,
27.1, 126.8,124.5, 124.2, 123.0, 122.3, 122.2, 82.0, 77.3, 76.4,
4.6, 38.3, 21.7 (Ar–Me); HRMS(EI): m/z C34
3
) 166.4 (C
q
, -COOR), 166.2 (C
q
, -COOR),
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(3-benzothiophenyl)-ribose 4cb. 112 mg
82%); R : 0.35 (ethyl acetate); d (300 MHz, CDCl -methanol-
6 : 1) 7.87–7.80 (2H, m, Ar–H), 7.41 (1H, s, Ar–H), 7.39–7.32
1
1
6
4
(
d
f
H
3
4
+
H
30
O
5
calcd.
ꢀ
(
(
(
5
J
1
7
2
2H, m, Ar–H), 5.52 (1H, dd, JH1ꢀ,H2ꢀa 9.6, JH1ꢀ,H2ꢀb 5.7, H1 ), 4.42
86.1501(M), found 486.1501.
ꢀ
ꢀ
1H, m, H3 ), 4.02 (1H, td, JH4ꢀ,H5ꢀ = 4.9, JH3ꢀ,H4ꢀ = 3.4, H4 ), 3.75
ꢀ
2H, d, JH4ꢀ,H5ꢀ = 5.0, H5 ), 2.39 (1H, ddd, JH2ꢀa,H2ꢀb 13.3, JH1ꢀ,H2ꢀa
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(4-(methylthio)phenyl)-3 ,5 -di-O-toluoyl-
ribose 3eb. : 0.41 (cyclohexane–ethyl acetate 4.5 : 1); d
400 MHz, CDCl ) 7.98 (2H, d, J 8.2, Ar–H), 7.94 (2H, d,
J 8.2, Ar–H), 7.33–7.19 (6H, m, Ar–H), 5.60 (1H, dd, J 5.2,
ꢀ
.9, JH3ꢀ,H2ꢀa 2.4, H2 a), 2.22 (1H, ddd, JH2ꢀa,H2ꢀb 13.3, JH1ꢀ,H2ꢀb 9.9,
R
f
H
ꢀ
H3ꢀ,H2ꢀb 6.5, H2 b); d
(75 MHz, CDCl
-methanol-d 6:1) 140.9,
c
3
4
(
3
37.5, 136.5, 124.6, 124.2, 123.0, 122.3, 122.1, 87.3; 76.7, 75.7;
+
3.0, 63.0, 41.4; MS(EI): m/z C13
H
14
O S calcd. 250.1(M), found
3
ꢀ
ꢀ
J
4
J
H3ꢀ,H4ꢀ 1.1, H3 ), 5.21 (1H, dd, JH1ꢀ,H2ꢀa 10.9, JH1ꢀ,H2ꢀb 5.1, H1 ),
.69–4.59 (2H, m, H5 ), 4.55–4.50 (1H, m, H4 ), 2.51 (1H, dd,
H2ꢀa,H2ꢀb 14.0, JH1ꢀ,H2ꢀa 5.0, H2 a), 2.46 (s, 3H, -SMe), 2.43 (s, 3H,
Ar–Me), 2.40 (s, 3H, Ar–Me), 2.21 (1H, ddd, JH2ꢀa,H2ꢀb 13.8,
H1ꢀ,H2ꢀb 11.0, JH3ꢀ,H2ꢀb 6.1, H2 b); d
COOR), 166.1 (C
29.7, 129.2, 129.2, 126.7, 126.5, 83.0; 80.5, 77.3, 64.8, 41.7,
1.8 (Ar–Me), 21.7 (Ar–Me), 15.9 (-SMe); HRMS(ESI): m/z
50.1.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
b-1 ,2 -Dideoxy-1 -(4-(methylthio)phenyl)-ribose 4eb. 17 mg
(quant.); R : 0.42 (ethyl acetate); dH (300 MHz, CDCl3-
methanol-d 6 : 1) 7.27–7.15 (4H, m, Ar–H), 5.04 (1H, dd, J
10.3, J
5.1, J
(1H, ddd, J
ddd, J
CDCl
f
ꢀ
J
c
(75 MHz, CDCl
3
) 166.4 (C
q
,
ꢀ ꢀ
4
H1 ,H2 a
ꢀ
ꢀ
-
q
, -COOR), 144.2, 143.9, 138.0, 137.6, 129.7,
ꢀ
ꢀ
5.6, H1 ), 4.26 (1H, m, H3 ), 3.88 (1H, td, J
ꢀ ꢀ
=
H1 ,H2 b
H4 ,H5
ꢀ
ꢀ
1
2
C
ꢀ
H3 ,H4ꢀ = 2.8, H4 ), 3.63 (2H, m, H5 ), 2.41 (s, 3H, SMe), 2.15
ꢀ
ꢀ
ꢀ
13.2, J
H1 ,H2 b
ꢀ
ꢀ
5.6, J
ꢀ ꢀ
H3 ,H2 a
1.9, H2 a), 1.90 (1H,
H2 a,H2 b
H1 ,H2 a
+
+
ꢀ
34
H
30
O
5
Na calcd. 499.1550(M + Na ), found 499.1550.
H2 a,H2 b
ꢀ
ꢀ
13.2, J
ꢀ
ꢀ
10.3, J
H3 ,H2 b
ꢀ
ꢀ
6.3, H2 b); d (75 MHz,
c
3
-methanol-d 6:1) 138.1, 137.8, 126.6, 87.5, 79.8, 73.0,
+
4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
a-1 ,2 -Dideoxy-1 -(4-(methylthio)phenyl)-3 ,5 -di-O-toluoyl-
6
3.0, 43.3, 15.8; MS(ESI): m/z C13
H
14
O
3
SNa calcd. 263.1(M +
ribose 3ea.
300 MHz, CDCl
H3 ), 5.33 (1H, t, J 6.6, H1 ), 4.67 (1H, m, H4 ), 2.91 (1H, ddd,
H2ꢀa,H2ꢀb 14.0, JH1ꢀ,H2ꢀb 7.1, JH3ꢀ,H2ꢀb 7.1, H2 b), 2.48 (3H, s, -SMe),
.43 (3H, s, Ar–Me), 2.39 (3H, s, Ar–Me); d
66.1 (C , -COOR), 166.1 (C , -COOR),144.0 (C
, Ar), 139.4, 137.5, 129.7, 129.7, 129.2, 129.1, 126.8, 126.2,
2.1, 79.9, 76.4, 64.6, 40.4, 21.7 (Ar–Me), 21.7 (Ar–Me), 16.1
Ar–Me)); HRMS(EI): m/z C34
found 476.1658.
R
f
: 0.35 (cyclohexane–ethyl acetate 4.5 : 1); d
) 8.06–7.13 (12H, m, Ar–H), 5.59 (1H, m,
H
+
Na ), found 263.2.
(
3
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References
J
2
1
c
(75 MHz, CDCl
3
)
1 For reviews: (a) A. A. Henry and F. E. Romesberg, Curr. Opin. Chem.
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q
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(
C
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8
(
+
6, 775–793.
H
30
O
5
calcd. 476.1657(M),
2
3
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(
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Sodium methoxide (107 mg, 3 eq.) was added to a solution of
3
30 mg of compund 3db (0.66 mmol) in 5 ml of dry methanol.
After 6 h of stirring the solution was neutralised with solid
NH Cl until a pH of 8 is reached and water was added. The
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4
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4
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9
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4
2 3 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 2 3 3 – 4 2 3 8