Natural phosphate doped with KI in HMDS: A mild and efficient reagent for alkylation and glycosylation of nucleobases

Article abstract of DOI:10.1081/NCN-200059179

Several D ribonucleosides are prepared from 1-O-acetyl-2,3,5-tri-O-benzoyl- β-D-ribofuranoside and trimethylsilylated nucleobases under mild conditions by using natural phosphate doped with KI as catalyst. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/NCN-200059179

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NATURAL PHOSPHATE DOPED WITH KI IN HMDS: A
MILD AND EFFICIENT REAGENT FOR ALKYLATION AND
GLYCOSYLATION OF NUCLEOBASES
H. B. Lazrek a , M. Taourirte b , A. Rochdi a , N. Redwane a , D. Ouzebla a , L. Baddi a , S.
Sebti c & J. J. Vasseur d
a Faculty of Sciences Semlalia, Marrakech, Morocco
b Faculty of Sciences and Techniques, Marrakech, Morocco
c Faculty of Sciences Ben Msik, Casablanca, Morocco
d Montpellier II University, Montpellier, France
Version of record first published: 15 Nov 2011.
To cite this article: H. B. Lazrek, M. Taourirte, A. Rochdi, N. Redwane, D. Ouzebla, L. Baddi, S. Sebti & J. J. Vasseur (2005):
NATURAL PHOSPHATE DOPED WITH KI IN HMDS: A MILD AND EFFICIENT REAGENT FOR ALKYLATION AND GLYCOSYLATION OF
NUCLEOBASES, Nucleosides, Nucleotides and Nucleic Acids, 24:5-7, 1093-1095
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Nucleosides, Nucleotides, and Nucleic Acids, 24 (5–7):1093–1095, (2005)
Copyright D Taylor & Francis, Inc.
ISSN: 1525-7770 print/ 1532-2335 online
DOI: 10.1081/NCN-200059179
NATURAL PHOSPHATE DOPED WITH KI IN HMDS: A MILD
AND EFFICIENT REAGENT FOR ALKYLATION AND
GLYCOSYLATION OF NUCLEOBASES
5
H. B. Lazrek
M. Taourirte
Faculty of Sciences Semlalia, Marrakech, Morocco
5
Faculty of Sciences and Techniques, Marrakech, Morocco
5
A. Rochdi, N. Redwane, D. Ouzebla, and L. Baddi
Faculty of Sciences Semlalia,
Marrakech, Morocco
5
S. Sebti
Faculty of Sciences Ben Msik, Casablanca, Morocco
5
J. J. Vasseur
Montpellier II University, Montpellier, France
5
Several D-ribonucleosides are prepared from 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranoside and
trimethylsilylated nucleobases under mild conditions by using natural phosphate doped with KI
as catalyst.
Keywords Natural Phosphate, Potassium Iodide, Nucleosides
INTRODUCTION
The Vorbruggen modification of the Hilbert-Johnson reaction has been widely
employed for the preparation of various nucleoside analogues by coupling different
silylated nucleobases with the appropriate sugars. Usually this reaction has been
carried out using a catalytic amount of TMSOTf or TMSClO4, under the as-
sumption that the stable counter ion (ÀOTf or ClOÀ4 ) is necessary to achieve the
catalytic glycosylation reaction. Iodotrimethylsilane has been also used for this pur-
pose even though this reagent is extremely sensitive to moisture and is expensive.
Recently, the use of solid acids such as clays, zeolites, and ion-exchange resins
has achieved importance in organic chemistry.[1] Heterogeneous solid acids are
The authors gratefully acknowledge Dr. J. A. Secrist, III (Southern Research Institute, Birmingham, Alabama,
USA) for providing facilities for this work.
Address correspondence to H. B. Lazrek, Faculty of Sciences Semlalia, Marrakech, Morocco.
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H. B. Lazrek et al.
SCHEME 1
advantageous over conventional homogeneous acid catalysts, since they can be
easily recovered from the reaction mixture by filtration and can be reused after
activation or without activation, thus making the processes economically viable.[2]
*
Of the many possible heterogeneous catalysts, natural phosphate is attractive
because of its low cost, reusability, flexibility in acid strength, ease of handling,
environmental compatibility, non-toxicity and experimental simplicity.[3]
In this respect, and in connection with our other work on the use of natural
phosphate as a catalyst,[4,5] we now report a new one pot novel method by using
an inexpensive natural phosphate catalyst doped with KI instead of TMSOTf,
TMSClO4, or iodotrimethylsilane to perform the glycosylation reaction (Scheme 1).
In order to assess the influence of natural phosphate (NP) doped with KI as
a catalyst on this reaction and to find the most effective conditions, a number
of experiments were performed. The results of these studies are summarized in
Table 1 and Table 2.
As shown in Table 1, when either NP and KI were used alone, the reaction of
1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranoside with bis-(trimethylsilyl)uracil gave
the ribonucleoside in only 5 and 28% yields, respectively. As can be seen in the
subsequent examples, the yield increased when NP doped with KI was used. For
example, in entry 4 the desired ribonucleoside was obtained as a major isomer and
in good yield by using NP/KI corresponding to 0.8 eq of KI in acetonitrile at 105°C
overnight. This procedure appears to be regioselective and gives only the N-1
isomer. Other nucleobases (entries 6–8) were then also subjected to N-glycosylation
and found to afford the corresponding nucleosides in 50% yield (Table 1). The same
conditions were also used to prepare some acyclonucleosides in 50% yield (entries
1–3, Table 2). All products were characterized by 1HNMR, and mass spectroscopy
and also by comparison with literature data.
In conclusion, the mild conditions, low cost, and easy work-up of this new
method offer some advantages over former procedures, and thus it should be of
*
Natural phosphate (NP) comes from an ore extracted in the region of Khouribga (it is available in raw form
or treated form from Cerphos, Casablanca, Morocco). Prior to use this material requires initial treatments such as
crushing and washing. For use in organic synthesis, the NP is treated by techniques involving attrition, sifting,
calcinations (900°C), washing, and recalcination. These treatments lead to a fraction between 100 and 400 lm,
which is rich in phosphate. The structure of NP is similar to that of fluorapatite (Ca10(PO4)6F2), as shown by X-ray
diffraction and chemical analysis. The surface area of NP was measured at 1 m2 gÀ1 (nitrogen adsorption) and the
total pore volume was 0.005 cm3 g-1.

H. B. Lazrek et al.
1095
TABLE 1 Synthesis of 2’,3,5’-Tri-O-Benzoyl-a/b-D-Ribonucleosides
Entry
Nucleobase
Uracil (1 mmol)
Uracil (1 mmol)
Uracil (1 mmol)
(0.9 eq)
NP/KI
325/0 mg
Yielda (%)
a/b
1
2
3
4
5
6
7
8
453 mg
453 mg
453 mg
453 mg
453 mg
453 mg
453 mg
335 mg
5
28
48
55
52
45
51
54
–
0/129 mg (0.8 eq)
37/63
34/66
13/87
28/72
50/50
50/50
50/50
581 mg (1 eq of KI)
473 mg (0.8 eq of KI)
473 mg (0.8 eq of KI)
473 mg (0.8 eq of KI)
473 mg (0.8 eq of KI)
350 mg (0.8 eq of KI)
Uracil (1 mmol)
Thymine (1 mmol)
Cytosine (1 mmol)
Adenine (1 mmol)
N-R-guanine
R = Dimethylaminomethylene
(0.74 mmol)
aThe yield was calculated after purification on column chromatography.
TABLE 2 Synthesis of Acyclonucleosides
Entry
1
Nucleobase
Alkylating Agent
NP/KI
Yielda (%)
50
Uracil (1 mmol)
470 mg (0.8 eq of KI)
470 mg (0.8 eq of KI)
470 mg (0.8 eq of KI)
200 mg
200 mg
200 mg
45
50
2
3
Thymine (1 mmol)
Adenine (1 mmol)
aThe yield was calculated after purification on column chromatography.
further interest in synthetic nucleoside chemistry. Other examples are under
investigation and will be reported elsewhere.
REFERENCES
1. Clark, J.H. Solid acids for green chemistry. Acc. Chem. Res. 2002, 35, 791–797.
2. Sen, S.E.; Smith, S.M.; Sullivan, K.A. Organic transformations using zeolites and zeotype materials.
Tetrahedron 1999, 55, 12657–12698 and references cited therein.
3. Zahouily, M.; Bahlaouan, B.; Rayadha, A.; Sebti, S. Natural phosphate and potassium fluoride doped natural
phosphate: efficient catalyst for the construction of a carbon-nitrogen bond. Tetrahedron Lett. 2004, 45,
4135–4138 and references cited therein.
4. Alahiane, A.; Rochdi, A.; Taourirte, M.; Redwane, N.; Sebti, S.; Engels, J.W.; Lazrek, H.B. Building blocks for
polyamide nucleic acids: facile synthesis using potassium fluoride doped natural phosphate as basic catalyst.
Nucleosides Nucleotides Nucleic Acids 2003, 22, 109–114.
5. Rochdi, A.; Taourirte, M.; Redwane, N.; Sebti, S.; Engels, J.W.; Lazrek, H.B. Doped natural phosphate: a new
and environmental friendly catalyst in nucleoside synthesis. Nucleosides Nucleotides Nucleic Acids 2003, 22,
679–681.