Chiroptical assignment of the anomeric configuration of 4-(α,β-D-lyxopyranosyl)- and 4-(α,β-D-lyxofuranosyl)-2- phenyl-2H-1,2,3-triazole C-nucleoside anomeric pairs: Extension of the CD triazole rule

Article abstract of DOI:10.1080/07328300903339996

The circular dichroism of the anomeric 4-(α,β-D-lyxopyranosyl)- and 4-(α,β-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs obtained by acid-catalyzed dehydrative cyclization of 4-(D-galacto-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole analog was studied. A correlation between the sign of the Cotton effect at the maximal UV absorption and the absolute configuration of the anomeric carbon atom was obtained and used for their anomeric configuration assignment. This correlation supports the CD triazole rule for anomeric assignment and is in accord with the assignment obtained by NMR spectral studies.

Full text of DOI:10.1080/07328300903339996

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Chiroptical Assignment of the Anomeric
Configuration of 4-(α,β-D-lyxopyranosyl)-
and 4-(α,β-D-lyxofuranosyl)-2-
phenyl-2H-1,2,3-Triazole C-Nucleoside
Anomeric Pairs: Extension of the CD
Triazole Rule
Mohammed A.E. Sallam a
a Chemistry Department, Faculty of Science , Alexandria University ,
Alexandria, Egypt
Published online: 17 Nov 2009.
To cite this article: Mohammed A.E. Sallam (2009) Chiroptical Assignment of the Anomeric
Configuration of 4-(α,β-D-lyxopyranosyl)- and 4-(α,β-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-Triazole C-
Nucleoside Anomeric Pairs: Extension of the CD Triazole Rule, Journal of Carbohydrate Chemistry,
28:9, 498-505
To link to this article: http://dx.doi.org/10.1080/07328300903339996
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Journal of Carbohydrate Chemistry, 28:498–505, 2009
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328300903339996
Chiroptical Assignment of the
Anomeric Configuration of
4-(α,β-D-lyxopyranosyl)- and
4-(α,β-D-lyxofuranosyl)-2-
phenyl-2H-1,2,3-Triazole
C-Nucleoside Anomeric Pairs:
Extension of the CD Triazole
Rule1
Mohammed A.E. Sallam
Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
The circular dichroism of the anomeric 4-(α,β-D-lyxopyranosyl)- and 4-(α,β-D-
lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs obtained by acid-
catalyzed dehydrative cyclization of 4-(D-galacto-pentitol-1-yl)-2-phenyl-2H-1,2,3-
triazole analog was studied. A correlation between the sign of the Cotton effect at the
maximal UV absorption and the absolute configuration of the anomeric carbon atom
was obtained and used for their anomeric configuration assignment. This correlation
supports the CD triazole rule for anomeric assignment and is in accord with the assign-
ment obtained by NMR spectral studies.
Keywords CD; C-Nucleosides; 1,2,3-Triazoles; D-Lyxopyranosyl; D-Lyxofuronosyl;
Anomeric configuration
Received September 13, 2008; accepted August 29, 2009.
1Part II. For part I, see reference 1.
Presented at the 11th International Conference on Circular Dichroism, 2007,
Groningen, The Netherlands.
Contract grant sponsor: The Ministry of Economic and International Cooperation,
Cairo, Egypt.
Address correspondence to Mohammed A.E. Sallam, Chemistry Department, Faculty of
Science, Alexandria University, Alexandria, Egypt. E-mail: maesallam@yahoo.com
498

Extension of the CD Triazole Rule
499
INTRODUCTION
Circular dichroism is a reliable tool for determining the stereochemistry of
the asymmetric carbon atoms of saccharides.[2,3] The chromophoric base moi-
ety of C-nucleosides makes them target compounds for CD measurements and
anomeric assignment. We have been interested lately in the synthesis of C-
nucleoside analogs by acid-catalyzed dehydrative cyclization of polyhydrox-
yalkyl heterocyclic analogs.[4–9] This reaction gives an anomeric mixture of
C-nucleosides, whose anomeric configuration is of importance. The anomeric
configuration of the products may be assigned by NMR spectroscopy that re-
quires the presence of the two anomers on hand and applying different NMR
criteria such as comparing the chemical shift values of the anomeric proton
for the anomeric pair or the coupling constant values (J1’,2’) of their anomeric
protons. These techniques are sometimes not reliable and cannot give unequiv-
ocal proof for the anomeric configuration. The NOE measurements are a more
reliable tool for assigning the anomeric configuration by NMR spectroscopy.
The CD chiroptical studies[10–12] are more simple and can be used
for anomeric assignment from the sign of the Cotton effect at the max-
imal UV absorption. In this work the anomeric configuration of the C-
nucleoside anomeric pairs 4-(α,β-D-lyxopyranosyl)-2-phenyl-2H-1,2,3-triazole
2,3 and 4-(α,β-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole 4,5, obtained from
acid-catalyzed dehydrative cyclization of 4-(D-galacto-pentitol-1-yl)-2-phenyl-
2H-1,2,3-triazole 1, was investigated by CD chiroptical measurements.
RESULTS AND DISCUSSION
The anomeric mixture 4-(α,β-D-lyxopyranosyl)-2-phenyl-2H-1,2,3-triazole
analogs 2 and 3, and 4-(α,β-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole 4 and
5 were obtained by acid-catalyzed dehydrative cyclization of 4-(D-galacto-
pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole 1 (Scheme 1). The four isomeric C-
nucleosides were separated by chromatography. The anomeric configuration
of compounds 2–5 was assigned by NMR spectroscopy. In a recent publica-
tion,[1] the anomeric configuration was subjected to CD measurements, which
reversed the anomeric assignment obtained by NMR measurements.
In or-
der to confirm the anomeric configuration of compounds 2–5, chiroptical meth-
ods were applied. As expected, the sign of rotation of the cyclic nucleosides
2–5 did not follow the sign of the specific rotation at the D-line, as it does in
the El-Khadem triazole rule.[13,14] The latter deals specifically with the rota-
tion of the chiral centers in acyclic polyhydroxyalkyl chains attached to aro-
matic or heterocyclicrings. In addition, these compounds did not obey Hudson
isorotation rules[15,16] for glycosides. The α anomers 2 and 4 were not more
dextrorotatory than the corresponding β anomers 3 and 5 (Table 1). Other
examples in the literature[17] showed opposition to Hudson isorotation rules.

M.A.E. Sallam
500
Scheme 1: Acid catalyzed dehydrative cyclyzation of 4-(D-galacto-pentitol-1-yl)-2-phenyl-
2H-1,2,3-triazol 1
The β anomer was more dextrorotatory than the corresponding α anomer.
These results did not allow anomeric assignment for compounds 2–5 from
their specific rotation at the D-line. The CD chiroptical properties of these com-
pounds showed a correlation similar to that obtained for the D-arabinoglycosyl
Table 1: Specific rotation, observed CD, and UV spectra of compounds 1–5
Compound
[α]D
Obs CD λ(ꢀε)
266.4 (+2.7)
258.6 (–0.4)
λmax
266.6
266.4
256.2
266.4
256.8
Log ε
4.31
4.28
4.32
4.41
4.31
1
2
3
4
5
+80.3◦ (c 0.84,
pyridine)[20]
+4.3◦ (c 2.4,
methanol)[8]
+52.3◦ (c 0.52,
methanol)[8]
+39.3◦ (c 1.08,
methanol)[8]
+72.7◦ (c 1.08,
methanol)[8]
256.4 (+2.0)
253–225 (–0.1)
266.4 (+3.3)

Extension of the CD Triazole Rule
501
Figure 1: CD Spectrum of 4-(D-galacto-pentitol-l-yl)-2-phenyl-2H-1,2,3-triazole 1, in
methanol.
stereoisomeric C-nucleoside analogs.[1] The CD spectrum of the acyclic analog
1, having the hydroxyl group α- to the triazole base moiety to the right D-
glycero-(S) configuration, showed a positive Cotton effect at the maximal UV
absorption (Fig. 1). The CD spectra of the D-lyxorpyranosyl anomeric pair 2
and 3 showed a single Cotton effect of the opposite sign at the maximal UV ab-
sorption (Fig. 2). Compound 3 showed a positive Cotton effect of the same sign
of the acyclic analog 1, in accord with the right configuration of the ring oxygen
of the Fischer projection formula (i.e., the β-D-lyxopyranosyl configuration of
the glycosyl group formed). Compound 2 showed a negative Cotton effect at the
same region, manifested by the left configuration of the ring oxygen at the Fis-
cher projection formula (i.e., the α-D-lyopyranosyl configuration of the glycosyl
group formed). The CD spectra of the D-lyxofuranosyl anomeric pair 4 and 5
showed a single Cotton effect at the maximal UV absorption (Fig. 3). Com-
pound 5 showed a positive Cotton effect, manifested by the right configuration
of the ring oxygen of the Fischer projection formula (i.e., the β-D-lyxofuranosyl

M.A.E. Sallam
502
Figure 2: CD Spectra of 4-(α-D-lyxopyranosyl)-2-phenyl-2H-1,2,3-triazole 2(– – – – –), and
4-(β-D-lyxopyranosyl)-2-phenyl-2H-1,2,3-triazole 3 (—————-), in methanol.
configuration of the glycosyl group formed). Compound 4 showed a weak neg-
ative Cotton effect at the same region, in accord with the left configuration of
the ring oxygen of the Fischer projection formula (i.e., the α-D-lyxofuranosyl
configuration of the glycosyl group formed). The anomeric configuration of
compound 4 was supported by X-ray crystallography measurements.[8] The
β-D-lyxopyxopyranosyl and β-D-lyxofuranosyl anomers 3 and 5, respectively,
showed higher spectrum amplitude than the corresponding α-D-lyxopyranosyl
and α-D-lyxofuranosyl anomers 2 and 4, respectively. The difference in the
CD spectrum amplitude is attributed to the different conformational popula-
tion of the glycosyl part. The chiroptical assignment of compounds 2–5 is in
accord with the anomeric assignment obtained from NMR spectroscopy. Com-
pounds 2 and 4 are obtained from 1 with inversion at the configuration of the
carbon atom α- to the triazole base moiety (C-1ꢀ). Compounds 3 and 5 are ob-
tained from 1, without inversion at C-1ꢀ, during the dehydrative cyclization
process.
These CD results are an additional example supporting the CD triazole
rule for anomeric configuration assignment of 4-glycosyl-2-phenyl-2H-1,2,3-
triazole C-nucleoside analogs. C-Nucleosides having the β-D-configuration
show a positive Cotton effect at the maximal UV absorption, and the cor-
responding α-D-anomers show a negative Cotton effect at the same region.
In addition, the CD triazole rule is applicable for acyclic polyhydroxyalkyl-
2-phenyl-2H-1,2,3-triazole analogs, supporting the El-Khadem triazole rule
for specific rotation at the D-line. It is also applicable for C-nucleosides hav-
ing different cyclic glycosyl parts: D-glycopyranosyl,[1] D-glycofuranosyl,[18] 5ꢀ-
hydroxymethyl-D-glycofuranosyl,[1] and L-glycofuranosyl[19] analogs.

Extension of the CD Triazole Rule
503
Figure 3: CD Spectra of 4-(α-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole 4(– – – – –), and
4-(β-D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole 5 (—————), in methanol.
MATERIALS AND METHODS
Compounds 2–5 have been prepared by standard methods and separated by
column chromatography.[8] Their structure and anomeric configuration were
assigned using NMR spectroscopy. The CD measurements were recorded for
solutions in methanol on Jasco 500 H and Jasco 720 WI spectrometers at con-
centrations 0.25 to 0.30 mg/mL methanol using 0.2-mL micro-cell.
CONCLUSION
The chiroptical properties of the anomeric 4-(α,β-D-lyxopyranosyl) and 4-(α,β-
D-lyxofuranosyl)-2-phenyl-2H-1,2,3-triazole analogs were studied. These com-
pounds are obtained by the dehydrative cyclization of 4-(D-galacto-pentitol-1-
yl)-2-phenyl-2H-1,2,3-triazole with inversion or retention of the configuration
at C-1ꢀ. The anomeric configuration of these compounds obtained by CD studies
is in accord with NMR spectral assignment. The chiroptical anomeric assign-
ment of these compounds reports an additional example supporting the CD
triazole rule for anomeric assignment of glycosyl-2-phenyl-2H-1,2,3-triazole
analogs.
ACKNOWLEDGEMENTS
The author thanks Dr. Chifon Chang for J 500 CD measurements. Thanks also
to Prof. N. Harada, Prof. M. Watanabe, and Dr. S. Kuwahara, Tohoku Univer-
sity, Japan, for the J 720 CD measurements.

M.A.E. Sallam
504
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