632
EFIMOV et al.
give 80, 82, and 74% of dC (IIa), dA (IIb), and dG (1 H, m, Hβ2'). 31P NMR: 0.91. Mass (m/z): 944.38
(
IIc) derivatives, respectively.
[M
–]. Calc. for C46H43N9O12P– 944.28.
For the introduction of the 5'ꢀdimethoxytrityl resiꢀ
due, 2'ꢀdeoxy derivatives (IIa)–(IIc) were dissolved in a
minimal volume of dry pyridine and treated with 4,4'ꢀ
dimethoxytrityl chloride (1.2 equiv) for 2 h at room
temperature. The reaction was stopped by the addition
of the same volume of 0.5 M TEAB, and the target
product was extracted with chloroform. Organic fracꢀ
tions were evaporated to oil, and the residue was disꢀ
solved in chloroform and purified by column chromaꢀ
Monomeric Ribonucleoside Syntones (XI
)
Ribonucleosides bearing the AZMB protective
group at the heterocyclic bases were obtained similarly
to the procedure described above for deoxyribonucleꢀ
osides. The yield of compounds ((IIa)–(IIc), R =
OH) were 80, 85, and 83% for Cyt, Ade, and Gua
derivatives, respectively.
For the preparation of 2'ꢀOꢀazidomethyl ribonuꢀ
tography on silica gel in a gradient of methanol (0⎯5%)
cleoside derivatives, 3'ꢀ and 5'ꢀhydroxy groups of (VI
)
in chloroform containing 0.1% triethylamine to give
target compounds (IIIa)–(IIIc) in 84, 82, and 73%
yields, respectively. The phosphorylation of deoxyriboꢀ
were blocked by treatment with TIPDSꢀCl in pyriꢀ
dine, and the AZMB derivative (II, R = OH)
(1 mmol) was treated with 1,3ꢀdichloroꢀ1,1,3,3ꢀtetꢀ
raisopropyldisiloxane (1.2 mmol) in dry pyridine
(5 ml). The reaction mixture was stirred at room temꢀ
perature for 16 h, and 1 M TEAB (5 ml) and water
(10 ml) was added. The product was isolated by
nucleosides (III) and the removal of the pꢀchlorophenyl
protective group from the phosphate residue of exhausꢀ
tively blocked nucleotides (IVa)–(IVc) was performed
as described in [9] to give (Va )–(Vc).
N
4ꢀ[(2ꢀAzidomethyl)benzoyl]ꢀ5'ꢀ
trityl)deoxycytidineꢀ3'ꢀ ꢀ(1ꢀoxidoꢀ4ꢀmethoxyꢀ2ꢀpicolyl)
phosphate (Va). Yield 83%. H NMR: 8.17 (1 H, d,
7.5, H6 Cyt), 8.05 (1 H, d, 7.2, H6 picolyl), 7.67–
Oꢀ(4,4'ꢀdimethoxyꢀ
extraction with chloroform (2
× 15 ml). The organic
O
fractions were evaporated to oil, dried in a vacuum to
remove pyridine traces, and the residue was dissolved
in chloroform. Target (VI) was isolated by column
chromatography on silica gel in a gradient of methanol
1
J
J
7.16 (15 H, m, H Ar, AZMB, H Ar, DMTr, H5 Cyt,
H3 picolyl), 6.86–6.80 (4 H, m, H Ar, DMTr), 6.71
(0
VIa)–(VIb) were united and evaporated to dryness to
give 89, 85, and 83% Cyt, Ade, and Gua derivatives,
respectively. The 2'ꢀ ꢀAZM group was introduced in
compounds (VI) as described in [8]. ꢀmethylthiomeꢀ
⎯5%) in chloroform. The fractions containing
(1 H, dd,
J 7.2, 3.6, H5 picolyl), 6.28 (1 H, t, J 6.3,
(
H1'), 5.13 (2 H, m, PꢀOCH2), 5.07 (1 H, m, H3'), 4.66
(2 H, s, CH2ꢀN AZMB), 4.45 (1 H, m, H4'), 3.81
(3 H, s, OCH3 picolyl), 3.78 (6 H, s, OCH3, DMTr),
3.48–3.39 (2 H, m, H5'), 2.92–2.87 (1 H, m, Hα2'),
2.36–2.31 (1 H, m, Hβ2'). 31P NMR: 0.41. Mass
O
O
thyl group was introduced into the nucleoside 2'ꢀposiꢀ
tion of (VIa)–(VIc) using dimethylsulfoxide and aceꢀ
tic anhydride in the presence of acetic acid. The
removal of the 3'ꢀ and 5'ꢀTIPDS protective groups from
(
m/z): 904.36 [
6ꢀ[(2ꢀAzidomethyl)benzoyl]ꢀ5'ꢀ
trityl)deoxyadenosineꢀ3'ꢀ
M
–]. Calc. for C45H43N7O12P– 904.27.
ꢀ(4,4'ꢀdimethoxyꢀ
ꢀ(1ꢀoxidoꢀ4ꢀmethoxyꢀ2ꢀ
N
O
O
(
VIIa)–(VIIb) was performed with 0.5 M TBAF in tetꢀ
1
picolyl) phosphate (Vb). Yield 77%. H NMR: 9.09
(1 H, br s, NH Ade), 8.69 (1 H, s, H8 Ade), 8.14 (1 H, s,
rahydrofurane to give (VIIIa)–(VIIIb), which were
treated with NBSꢀCl in DMF followed by the reaction
with lithium azide to give 38, 31, and 32% Cyt, Ade,
and Gua derivatives (IXa)–(IXc).
H2 Ade), 8.08 (1 H, d, J 7.2, H6 picolyl), 7.79–7.13
(14 H, m, H Ar, AZMB, H Ar, DMTr; H3 picolyl),
6.78–6.69 (5 H, m, H Ar, DMTr; H5 picolyl), 6.56
In case of purine deriatives (VIIIb) and (VIIIc
)
(1 H, t,
J 6.8, H1'), 5.24–5.08 (3 H, m, PꢀOCH2,
transformation of methylthiomethyl group into aziꢀ
domethyl groip was conducted in the presence of triꢀ
fluoromethanesulfonic acid.
H3'), 4.76 (2 H, s, CH2ꢀN AZMB), 4.50 (1 H, m,
H4'), 3.79 (3 H, s, OCH3 picolyl), 3.75 (6 H, s,
OCH3DMTr), 3.49–3.35 (2 H, m, H5'), 2.94–2.80
(2 H, m, H2'). 31P NMR: 0.27. Mass (m/z): 928.37
5'ꢀDimethoxytritylation of nucleosides (IX) was
carried out as described above for deoxyribonucleoside
derivatives (II, R = H). The yields of Cyt, Ade, and
Gua derivatives (Xa)–(Xc) achieved 82, 80, and 85%,
respectively. A phosphate residue containing an
ꢀnucleophilic catalytic group was introduced at the
3'ꢀhydroxyl as described in [9] to give ribonucleotide
[M
–]. Calc. for C46H43N9O11P– 928.28.
N
2ꢀ[(2ꢀAzidomethyl)benzoyl]ꢀ5'ꢀ
O
ꢀ(4,4'ꢀdimethoxyꢀ
trityl)deoxyguanosineꢀ3'ꢀ
O
ꢀ(1ꢀoxidoꢀ4ꢀmethoxyꢀ2ꢀ
1
O
picolyl) phosphate (Vc). Yield 79%. H NMR: 12.35
(1 H, br s, NH Gua), 7.82 (1 H, C, H8 Gua), 7.77
syntones (XIa)–(XIc).
(1 H, d,
AZMB, HꢀAr DMTr, H3 picolyl), 6.84–6.79 (4 H, m,
H Ar, DMTr), 6.50 (1 H, dd, 7.4, 3.5, H5 picolyl), trityl)ꢀ2'ꢀ
6.34 (1 H, m, H1’), 5.45 (1 H, dd,
17.3, 5.2, PꢀOCHα), methoxyꢀ2ꢀpicolyl) phosphate (XIa). Yield 82%.
5.28 (1 H, dd, 7.2,
17.3, 7.8, PꢀOCHβ), 5.09 (1 H, m, 1H NMR: 8.77 (1 H, br s, NH Cyt), 8.35 (1 H, d,
H3'), 4.83 (1 H, d, 7.2, H6 picolyl), 7.70–7.43
14, CHαꢀN AZMB), 4.61 (1 H, d, H6 Cyt), 8.06 (1 H, d,
14, CHβꢀN AZMB), 4.39 (1 H, m, H4'), 3.79 (3 H, s, (4 H, m, H Ar, AZMB), 7.46–6.82 (15 H, m, H Ar,
OCH3 picolyl), 3.78 (6 H, s, OCH3 DMTr), 3.47–3.20 DMTr; H5 Cyt; H3 picolyl), 6.71 (1 H, dd, 7.2, 3.6,
(2 H, m, H5'), 2.88–2.82 (1 H, m, Hα2'), 2.24–2.17 H5 picolyl), 6.13 (1 H, d,
3.0, H1'), 5.17 (1 H, d,
J 7.4, H6 picolyl), 7.61–7.16 (14 H, m, H Ar,
N
4ꢀ[2ꢀ(Azidomethyl)benzoyl]ꢀ5'ꢀ
O
ꢀ(4,4'ꢀdimethoxyꢀ
J
O
ꢀ(azidomethyl)cytidine 3'ꢀ ꢀ(1ꢀoxidoꢀ4ꢀ
O
J
J
J
J
J
J
J
J
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 5
2010