Nucleotides. Part LXVIII. Acetals as New 2'-O-Protecting Functions for the Synthesis of Oligoribonucleotides: Synthesis of Monomeric Building Units and Oligoribonucleotides

Article abstract of DOI:10.1002/1522-2675(20010516)84:5<1066::AID-HLCA1066>3.0.CO;2-H

For the efficient synthesis of oligoribonucleotides by the 5'-O-(4,4'-dimethoxytrityl) phosphoramidite approach, the 2'-O-[1-(benzyloxy)ethyl]acetals 56-67 were investigated. Studies with the 2'-O-[1-(benzyloxy)ethyl]-5'-O-(dimethoxytrityl)ribonucleoside

Full text of DOI:10.1002/1522-2675(20010516)84:5<1066::AID-HLCA1066>3.0.CO;2-H

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Nucleotides
Part LXVIII1)
Acetals as New 2'-O-Protecting Functions for the Synthesis of Oligoribonucleotides:
Synthesis of Monomeric Building Units and Oligoribonucleotides
by Stefan Matysiak and Wolfgang Pfleiderer*
Fakultät für Chemie, Universität Konstanz, Postfach 5560, D-78434 Konstanz
For the efficient synthesis of oligoribonucleotides by the 5'-O-(4,4'-dimethoxytrityl) phosphoramidite
approach, the 2'-O-[1-(benzyloxy)ethyl]acetals 56 ± 67 were investigated. Studies with the 2'-O-[1-(benzyloxy)-
ethyl]-5'-O-(dimethoxytrityl)ribonucleoside 3'-phosphoramidites 56 ± 59 gave, however, only reasonable results.
The oligoribonucleotides obtained showed some impurities since the acid stabilities of the acetal and
dimethoxytrityl functions are too close to guarantee a high selectivity. A combination of new acid-labile
protected 2'-O-protecting groups with the 2-(4-nitrophenyl)ethyl/[2-(4-nitrophenyl)ethoxy]carbonyl (npe/
npeoc) strategy for base protection was more successful. The synthesis and physical properties of the
monomeric building units and their intermediates 8 ± 67 and the conditions for the automated generation of
homo- and mixed oligoribonucleotides is described. The new 2'-acetal protecting group could be cleaved off in a
two step procedure and was designed for levelling their stability with regard to the attached nucleobase as well.
Therefore, we used the 1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (fnebe) moiety
for the protection of 2'-OH of uridine, and for that of 2'-OH of A, C, and G, the 1-{{4-{{[2-(4-
nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (nebe) residue. After selective deprotection by b-elimina-
tion induced by a strong organic base like DBU, the remaining activated acetal was hydrolyzed under very mild
acidic protic conditions, which reduced 2'-3' isomerization and chain cleavage. Also storage, handling, and
purification of the chemically and enzymatically sensitive oligomers was simplified by this approach.
1. Introduction. ± The chemical synthesis of oligoribonucleotides is still a big
challenge due to the fact that a perfect combination of compatible protecting groups
for the nucleobase, the sugar moiety, and the phosphate function has not yet
been found. There are practical solutions of the problem leading to longer RNA
sequences [2 ± 6] since, for 2'-OH protection, the tbds ((tert-butyl)dimethylsilyl
group) [7 ± 9] or the fpmp (1-(2-fluorophenyl)-4-methoxypiperidin-4-yl) [6][10]
residue can be used. Still, some side reactions [10][11] have to be overcome,
especially when other blocking groups such as the 2-nitrobenzyl (nbn) [12], the
dianisoyltrichloroethyl (date) [13], the 4,4'-dinitrobenzhydryl (dnbh) [14], the
[2-(4-nitrophenyl)ethyl]sulfonyl (npes) [15], or the acetal functions tetrahydro-2H-
pyran-2-yl (thp) [16], tetrahydro-4-methoxy-2H-pyran-2-yl (mthp) [17], [(tri-
methylsilyl)ethoxy]ethyl (see) [18], 3-methoxy-1,5-bis(methoxycarbonyl)pentan-
3-yl (mdmp) [19 ± 21], 1-alkoxyethyl- and 1-(2-chloroethoxy)ethyl (cee) [22] are
applied.
1
)
Part LXVII: [1].

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In our previous publication [23], we reported about the synthesis of new 2'-acetal-
protected uridine building units and their relative acid stability. From the kinetic data,
we were able to select a set of benzyl acetals that possess the stabilities needed to
protect the 2'-OH function during synthesis and that can be cleaved off under very mild
acidic conditions thereafter. First synthetic tests towards the machine-aided assembly
of oligoribonucleotides by the well-established 4,4'-dimethoxytrityl/2-(4-nitrophenyl)-
ethyl/[2-(4-nitrophenyl)ethoxy]carbonyl ((MeO)2Tr/npe/npeoc) approach [24 ± 26]
were done with the uridine phosphoramidites 2'-O-protected by the 1-{{4-{{[2-(4-
nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl residue (nebe) and by the corre-
sponding 3-fluoro residue (fnebe ˆ 1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}-
oxy}benzyl}oxy}ethyl).
An overview of the synthesis steps and all monomeric building units is shown in the
Scheme. The advantage of this new type of protecting group is the two-step procedure
for the liberation of the 2'-OH function. The first step goes parallel with the cleavage of
the base-labile protecting groups at the P-atom (cyanoethoxy) and the nucleobase-
blocking groups (npe and npeoc) by a strong base like DBU (1,8-diazabicyclo[5.4.0]un-
dec-7-ene) in MeCN. In the presence of the 2'-acetal protecting group, DBU induces b-
elimination of the npeoc residue, the acetal protecting group itself remaining
untouched. Therefore, on the solid support, only oligonucleotides with the 1-[(4-
hydroxybenzyl)oxy]ethyl (hboe) residue still attached at the 2'-O-position are present
and covalently bound via a succinate bridge, while all deprotection products can be
washed away. Hydrolysis with aqueous ammonia leads to 2'-O-protected oligoribonu-
cleotides free of contamination and without other cleavage products. After standard
workup procedures, these partially protected oligomers can be stored for several
months at 208 and are fully deprotected just before their use with highly diluted
AcOH. A similar strategy was established by others involving the 2'-O-bis(2-
acetoxyethoxy)methyl (ace) orthoester function in combination with a 5'-O-alkoxy-
bis[(trimethylsilyl)oxy]silyl group [27] and the 2'-O-[(triisopropylsilyl)oxy]methyl
(tom) group [28][29], which is structurally related to the tbdms group and can also be
cleaved off by fluoride ions, but which is more stable towards 2' ! 3' phosphodiester
migration due to the acetal nature of the protecting group. Despite the mild cleavage
conditions, the use of fluoride salts still leads to additional workup procedures, which is
not necessary in the protocols we have developed in our strategy.
2. Synthesis of the Monomers. ± The monomeric building units were synthesized by
protocols more or less analogous to the procedures described before [23] (Scheme).
Starting from the corresponding 3',5'-O-silyl-protected uridine or 3',5'-O-silyl/npe and/
or npeoc-protected guanosine, cytidine, and adenosine derivatives 1 ± 4, the corre-
sponding acetal protecting groups derived from 5 ± 7 were introduced by an acid-
catalyzed reaction, giving 8 ± 19 in yields of 65 ± 95%. Fluoride-ion-induced desilylation
liberating the 3'-OH and 5'-OH groups ( ! 20 ± 31) was followed by selective reaction
of the primary OH function with 4,4'-dimethoxytrityl chloride in toluene/pyridine to
give 32 ± 43 in very good yields. Then, either the corresponding succinate derivatives
44 ± 55 or the phosphoramidites 56 ± 67 were synthesized by standard procedures in
expectedly satisfying yields. All the different derivatives were characterized by TLC,
HPLC, 1H- or 19F-NMR, and elementary analysis (see Exper. Part).

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Scheme

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1069
3. Simulated Synthesis on Solid Support. ± First, we synthesized a series of
oligoribonucleotides (Table 1) starting with the 2'-O-[1-(benzyloxy)ethyl]nucleoside
3'-phosphoramidites 56 ± 59, and noticed, after deprotection and HPLC analysis, that
the oligomers are not pure enough to meet our standards. To investigate the stability of
the 2'-acetal protecting groups, in general, under standard synthesis conditions, we
simulated the condensation cycle with the 2'-O-protected uridine monomer 37 attached
to the resin LCAMA-CPG via a 3'-succinate linker. Thus, 0.2 mmol of the correspond-
ing loaded solid support was first treated several times under the detritylation
conditions shown in Table 2, and second, optionally, a DBU cleavage step was
implemented to remove the npeoc residue from the 2'-protecting group. After standard
ammonia cleavage and workup the resulting reaction products were analyzed by
reversed-phase HPLC. The results shown in Fig. 1,a and b, establish the detritylation of
25 (attached at the solid support) on CHCl2COOH treatment, and subsequent cleavage
of 25 from the support and concomitant breaking of the 2-(4-nitrophenyl)ethyl
carbonate bridge with formation of 2'-O-{1-[(3-fluoro-4-hydroxybenzyl)oxy]ethyl}ur-
idine (68) and 2-(4-nitrophenyl)ethyl carbamate on DBU and NH3 treatment. Thus,
Table 1. Synthesis of Oligoribonucleotides Carrying Various 2'-O-Protecting Groups
2'-O-Protected Sequence
Number of monomers
2'-O-Blocking groupa)
5'-UUU-3'
5'-UUU U-3'
3
4
fnebe
fnebe
5'-UUU UUU-3'
6
fnebe
5'-UUU UUU-3'
6
npee
5'-CCC CCC-3'
6
boe
5'-CCC CCC-3'
6
fnebe
5'-CCC CCC CCC C-3'
5'-CCC CCC CCC C-3'
5'-CCC CCC CCC C-3'
5'-AAA AAA AAA A-3'
5'-AAA AAA AAA A-3'
5'-AAA AAA AAA A-3'
5'-GGG GGG GGG G-3'
5'-GGG GGG GGG G-3'
5'-GGG GGG GGG G-3'
5'-GGA GA-3'
10
10
10
10
10
10
10
10
10
5
boe
nebe
fnebe
boe
nebe
fnebe
boe
nebe
fnebe
fnebe
5'-CGC GCG-3'
6
boe
5'-UAC CUA-3'
5'-UAA UUU U-3'
6
7
nebe ‡ fnebe
nebe ‡ fnebe
boe
5'-CCU GCG AUG A-3'
5'-AAA AAU UUU U-3'
5'-UGC AUG CAU GCA-3'
5'-UAA UCC UAA UUA UAA-3'
5'-AGG GUA CAG GUG GCC GGC-3'
5'-GCG GGG GUC CAU GGG GGU CG-3'
5'-GGA GAG GUC UCC GGU UCG UCG
AUU CCG GAC UCG ACC A-3'
10
10
12
15
18
20
37
boe
nebe ‡ fnebe
nebe ‡ fnebe
nebe ‡ fnebe
boe
boe
nebe ‡ fnebe
a
)
npee ˆ 1-[2-(4-nitrophenyl)ethoxy]ethyl; boe ˆ 1-(benzyloxy)ethyl; fnebe ˆ 1-{{3-fluoro-4-{{[2-(4-nitro-
phenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl; nebe ˆ 1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}-
ethyl.

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Table 2. Timetable of the Synthesis Cycle Applied
Synthesis step
Reagents
Time/s
Detritylation
Washing
1.3% CHCl2COOH in CH2Cl2
MeCN
75 (2 Â 20, 2 Â 10, 3 Â 5)
45
Activation and condensation 0.075 ± 0.1m phosphoramidite solution
700 ± 1200
30
Capping
Ac2O,
2,6-lutidine (ˆ 2,6-dimethylpyridine) in THF, and
1-methyl-1H-imidazole in THF
0.05m I2 solution in
Oxidation
30
THF/H2O/pyridine
Washing
MeCN
40
Total cycle time
inclusive all waiting steps
1020 ± 1500 (ˆ 17 ± 25 min)
detritylation with CHCl2COOH and subsequent treatment with DBU and NH3 led to
very pure 68 (Fig. 1,c).
Two conclusions could be drawn from these experiments. First, there is no
significant loss of the fnebe moiety, even after 10 repeats of the detritylation step.
Second, when the stabilizing npeoc residue was cleaved off with DBU after the first
CHCl2COOH treatment and then the CHCl2COOH treatment was repeated 9 further
times, only little uridine (2 ± 5%) was detectable (Fig. 1,d). This effect was expected
and verified our results from kinetic studies in diluted protic acids, which established
that the electron-donating effect of the aromatic 4-hydroxy function reduces the acid
stability of the ketal significantly.
4. Synthesis of Oligoribonucleotides. ± To optimize the reaction conditions in the
synthesizer, the more easily accessible uridine phosphoramidite 61 was applied first. In
Fig. 1. HPLC Traces of the crude reaction products from 37 after the following treatments: a) 1 Â CHCl2COOH/
NH3, b) 10 Â CHCl2COOH/NH3, c) 1 Â CHCl2COOH/DBU/NH3, and d) 1 Â CHCl2COOH/DBU, then 9 Â
CHCl2COOH/NH3. Column: LiChrospher 100 RP-18, 4 Â 125 mm) (Merck): gradient: 0% MeCN (0 ± 2 min)
0 ± 50% MeCN (2 ± 32 min), 50% MeCN (32 ± 40 min) in 0.1m (Et3NH)OAc (pH 7.0); flow rate: 1 ml/min.

Helvetica Chimica Acta ± Vol. 84 (2001)
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comparison to a DNA-oligomer synthesis, the condensation time had to be increased
significantly because of the steric hindrance by the bulky acetal moiety in the
phosphoramidates. We compared the quality of hexameric and decameric homouri-
dylates with regard to the condensation times, 600 s vs. 1200 s, and found no significant
difference in purity by measuring the concentration of the dimethoxytrityl cation at
498 nm and by HPLC analysis of the 2'-acetal-protected oligomers.
Additional experiments showed that the same reaction conditions also worked well
with the C, A, and G phosphoramidites 62 ± 67, leading to high average condensation
yields of 97.8 ± 99.1% with the pyrimidine, of 97.1 ± 97.7% with the adenosine, and of
95.3 ± 97.1% with the guanine building blocks, respectively. A large variety of homo-
and mixed oligoribonucleotides (Table 1) were synthesized by the npe/npeoc approach,
which turned out, after partial deprotection to the corresponding 2'-acetal derivatives,
to be of very good quality.
Another very important outcome was the orthogonality of the 5'-O-(dimethoxy-
trityl) and the new 2'-acetal protecting groups. Therefore, the detritylation step was
investigated thoroughly and in great detail. We found that 1.3 ± 2% CHCl2COOH in
CH2Cl2 worked best for fast and selective deprotection of the 5'-(MeO)2Tr group
without harming the nebe and the fnebe groups at all. However, to minimize undesired
loss of the 2'-protecting group, it is absolutely necessary to use anhydrous reagents.
From these and other investigations (data not shown), we could also see that, in the
case of the C, A, and G nucleosides, the nebe protecting group was more stable in acidic
environment than in the case of the corresponding uridine. A similar observation was
already made by Reese et al. [30] for the mthp blocking group. Such differences can be
explained by the different nature of the nucleobases and their electronic influence,
which is also the reason for the different stabilities of substituted acetals under acidic
conditions, as demonstrated earlier [23].
In general, after workup and isolation of the crude 2'-acetal-protected oligomers, it
was noticed that these products are rather lipophilic, which makes the usually applied
ꢀtrityl-onꢁ adsorption-purification procedure to get rid of failure sequences less efficient
compared to the DNA series. Another characteristic of these racemic acetal protecting
groups is peak broadening, observed mainly for poly(G) strands when reversed-phase
HPLC was applied for analysis. We isolated, therefore, pure diastereoisomeric
monomers, repeated the synthesis, and found the expected sharp peaks, thus confirming
the conclusion that broad product signals are caused by the various diastereoisomeric
units of the synthesized 2'-O-protected RNA sequence.
5. Isolation of Partially and Fully Deprotected Oligoribonucleotides. ± Partial
deprotection of the oligoribonucleotides still bound to the solid support was achieved
by acid treatment to remove the dimethoxytrityl group, followed by DBU treatment to
eliminate the 2-cyanoethyl groups from the phosphotriester function and the npe/npeoc
groups from the nucleobases and the acetal functions. Final acidic deprotection of the
acetal groups was achieved with dilute AcOH (0.3 ± 3%) at room temperature.
Normally, the reaction was complete within 2 h. The progress of the cleavage was easily
monitored by HPLC analysis of aliquots.
The quality of crude homouridylate still carrying ± after ammonia treatment ± the
(MeO)2Tr group at the 5'-O and the fnebe group at the 2'-O position is demonstrated

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by the HPLC analysis of Fig. 2, and that of the completely deprotected crude
homouridylate by the HPLC trace of Fig. 3.
Fig. 2. HPLC Trace of crude undecameric homouridylate after ammonia treatment, having the 2'-O-function
blocked by the fnebe moiety and the 5'-O-function by the ((MeO)2Tr) group. Column: LiChrospher 100 RP-18,
4 Â 125 mm (Merck); gradient: 2.5% MeCN (0 ± 2 min), 0 ± 20% MeCN (2 ± 32 min), 20 ± 50% MeCN
(32 ± 37 min), 50% MeCN (37 ± 45 min) in 0.1m (Et3NH)OAc buffer (pH 7.0); flow rate: 1 ml/min.
Fig. 3. HPLC Trace of undecameric homouridylate, after deprotection of {2'-O-{1-[(3-fluoro-4-hydroxybenzyl)-
oxy]ethyl}}10U11 by treatment with 3% AcOH for 180 min. Gradient: 0% MeCN (0 ± 2 min), 0 ± 50% MeCN
(2 ± 32 min), 50% MeCN (32 ± 37 min), 50% MeCN (37 ± 45 min).
There is obviously a big difference in acetal stability under aprotic and protic acidic
conditions, which is the main reason for the orthogonality of the two acid-sensitive
protecting groups ((MeO)2Tr and 2'-acetal). In the case of longer (>12) homouridylate
oligomers, it was quite surprising that treatment with very dilute acids led to significant
side reactions involving cleavage and isomerization of the RNA strand, whereas the
same conditions applied to homomers of C, A, or G did not show any degradation at all,
even after several hours or days. This instability of adjacent uridine units may be due to
a special sugar puckering, which could enhance the nucleophilic attack of the 2'-OH
group at the central P-atom and would lead to an increased 2' ! 3'isomerization and
strand cleavage.
To obtain protecting groups that allow efficient deprotection and have similar
kinetics for all four nucleoside units, we decided to combine the fnebe group for uridine

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with the nebe group for the three other building blocks. After studies of various
preliminary oligomer syntheses, we then started the assembly of longer mixed
sequences. The results are shown by the HPLC traces in Fig. 4, which demonstrate the
quality of crude products after full deprotection.
Fig. 4. HPLC Traces of crude mixed oligoribonucleotide sequences, obtained after final acetal deprotection by
treatment with 3% AcOH at room temperature. Column: Nucleopak Pa-100 (Dionex), 25 mm, 4 Â 250 mm;
gradient: 0% B (0 ± 2 min), 0 ± 40% B (2 ± 32 min), 40 ± 100% B (32 ± 37 min), 100% B (37 ± 47 min); A 25 mm
Tris/0.5% MeCN (pH 8; low salt conc.), B ˆ 25 mm Tris/800 mm NH4Cl/0.5% MeCN (pH 8, hight salt conc.),
flow rate: 1 ml/min.
Because of the equalized stabilities of the acetal protecting groups after DBU
treatment, the complete deprotection with 1 ± 3% AcOH/H2O could be achieved in a
few hours at room temperature. After lyophilization, the oligoribonucleotides were
obtained in very good quality and nearly free of salt contamination. The final test for
the applicability of the new approach based on protected protecting groups was the
synthesis of a 37-mer (exchanging rT and Y against U), found as the 3'-terminus of t-
RNAAla from Saccharomyces cerevisae. The result was, however, disappointing since a
denaturating 20% PAGE electropherogram showed distinctive signals of the expected
failure sequences around a major product band, but we failed to get reliable ion-
exchange HPLCs of the fully deprotected RNA sequence. This may be due to strong
intramolecular base pairing, which leads to stable secondary structures, as expected for
an intact RNA single strand.

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Conclusion and Discussion. ± We have developed a new type of protecting group for
the 2'-OH function of oligoribonucleotides following automated standard synthesis
protocols. These acetal protecting groups were stable enough under standard solid-
phase conditions applied for 5'-O-(MeO)2Tr- and npe/npeoc-protected phosphorami-
dites. After the final synthesis cycle, detritylation was performed first, followed by
cleavage of the 2-cyanoethyl and all npe/npeoc protecting groups by DBU-induced b-
elimination. Simultaneously, the 2'-acetal protecting group was converted to a more
acid-labile form, which was still stable under basic or neutral conditions, but was
cleaved off under very mild acidic conditions. Synthesis and physical properties of all of
the monomeric building units are described, and solid-phase built-up of homomeric and
mixed oligoribonucleotides was successfully achieved. We determined the average
condensation yields with the trityl-cation assay and controlled the quality of the
oligomers with reversed-phase ion-exchange HPLC and PAGE.
There are still analytical problems for longer sequences, but the quality of the
oligoribonucleotides generated and analyzed so far is excellent. It will be an exciting
challenge for the future to synthesize longer RNA fragments of high quality using these
new ꢀprotected protecting groupsꢁ, approach and the corresponding easy workup
procedures.
Experimental Part
1. General. Org. solvents were purchased from Fluka, Buchs, Switzerland. Oligomer synthesis was done on a
ABI-392-DNA synthesizer and with standard reagents. Products were dried under high vacuum or in a
desiccator over CaCl2. TLC: Precoated silica gel thin-layer sheets F1500 LS 254 from Schleicher & Schüll. Flash
column chromatography (FC): silica gel, Baker (30 ± 60 mm), 0.3 ± 0.5 bar. HPLC: L-6200-Intelligent pump, UV
integrator L4000, autosampler AS 4000, software HPLC-Manager/Merck-Hitachi; UV detector Uvikon 820
(Fa. Kontron), detection at 260 nm. M.p.: Gallenkamp or Büchi. Melting-point apparatus, model Dr. Tottoli; no
corrections. UV/VIS: Perkin-Elmer Lambda 5; lmax in nm (log e). 1H-NMR: Bruker WM-250; d in ppm rel. to
SiMe4. 31P-NMR: Bruker AC-250, Jeol JM GX 400; in ppm rel. to 85% phosphoric acid; CDCl3 or (D6)DMSO
as internal standard.
2. Acetalization of 1 ± 4 to 8 ± 19. 2.1. General Procedure. See [23].
2.2. 2'-O-[1-(Benzyloxy)ethyl]-3',5'-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)uridine (8) [23].
2.3. 2'-O-[1-(Benzyloxy)ethyl]-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]-3',5'-
O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)guanosine (9). According to 2.1, from 2. Yield 91%. Colorless
foam. TLC (hexane/AcOEt 1:1): Rf 0.67, 0.69. UV (MeOH): 203 (4.71), 216 (4.67), 268 (4.57), 276 (sh, 4.46).
1H-NMR (CDCl3): 8.22 ± 8.07 (m, H C(8), 2 H o to NO2 (npeoc), 2 H o to NO2 (npe)); 7.50 (m, 2 H m to NO2
(npeoc); 7.40 ± 7.31 (m, 2 H m to NO2 (npe)); 7.28 ± 7.02 (m, 2 arom. H, H N(2)); 6.03 (d, H C(1')); 5.28, 5.13
(2q, MeCH(O)2); 4.94 ± 3.97 (m, 11 H, H C(2'), H C(3'), H C(4'), 3 CH2CH2O, ArCH2, 2 H C(5')); 3.30
(t, CH2CH2O (npeoc)); 3.13 ± 3.00 (m, CH2CH2O (npeoc)); 1.50 (2d, MeCH(O)2); 1.14 ± 0.88 (m, 28 h,
4 Me2CH). Anal. calc. for C48H63N7O13Si2 (1002.1): C 57.52, H 6.34, N 9.78; found: C 57.64, H 6.39, N 9.75.
2.4. 2'-O-[1-(Benzyloxy)ethyl]-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldi-
siloxane-1,3-diyl)cytidine (10). According to 2.1, from 3. Yield 84%. Colorless foam. TLC (toluene/AcOEt
1:2): Rf 0.48, 0.52. UV (MeOH): 212 (4.49), 225 (sh, 4.32), 244 (4.26), 278 (4.19). 1H-NMR (CDCl3): 8.40 ± 8.28
(m, H C(6)); 8.18 (d, 2 H o to NO2 (npeoc)); 8.08 (br. s, H N(4)); 7.45 ± 7.11 (m, 2 H m to NO2 (npeoc),
H
C(5), 5 arom. H); 5.80 (m, H C(1')); 5.27, 5.09 (2q, MeCH(O)2); 4.93 ± 4.57 (m, PhCH2); 4.40
(t, CH2CH2O); 4.33 ± 3.92 (m, H C(2'), H C(3'), H C(4'), 2 H C(5')); 3.09 (t, CH2CH2O (npeoc)); 1.49
(2d, MeCH(O)2); 1.17 ± 0.85 (m, 4 Me2CH). Anal. calc. for C39H56N4O11Si2 (813.1): C 57.61, H 6.94, N 6.89;
found: C 57.42, H 6.97, N 6.84.
2.5. 2'-O-[1-(Benzyloxy)ethyl]-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldi-
siloxane-1,3-diyl)adenosine (11). According to 2.1, from 4. Yield 63%. Colorless foam. TLC (toluene/AcOEt
1:2): Rf 0.48, 0.53. 1H-NMR (CDCl3): 8.66, 8.62 (2s, H C(2)); 8.28, 8.19 (2s, H C(8)); 8.17 (d, 2 H o to NO2

Helvetica Chimica Acta ± Vol. 84 (2001)
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(npeoc)); 8.10 (br. s, H N(6)); 7.43 (d, 2 H m to NO2 (npeoc)); 7.32 ± 7.18 (m, 5 arom. H); 6.03 (m, H C(1'));
5.20, 5.14 (2q, MeCH(O)2); 4.99 ± 4.46 (m, PhCH2, CH2CH2O, H C(2')); 4.30 ± 3.97 (m, H C(3'), H C(4'),
2 H C(5')); 3.13 (t, CH2CH2O (npeoc)); 1.51 (2d, MeCH(O)2); 1.13 ± 0.88 (m, 4 Me2CH). Anal. calc. for
C40H56N6O10Si2 (837.1): C 57.39, H 6.74, N 10.04; found: C 57.19, H 6.62, N 9.86.
2.6. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-3',5'-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)uridine (12) [23].
2.7. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-3',5'-O-(1,1,3,3-tetra-
isopropyldisiloxane-1,3-diyl)uridine (13) [23].
2.8. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}-O6-[2-(4-nitrophenyl)ethyl]-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)guanosine (14). Accord-
ing to 2.1, from 2 with 6. Yield 87%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.53, 0.55. UV (MeOH): 203
(4.68), 214 (4.67), 268 (4.65), 284 (sh, 4.42). 1H-NMR (CDCl3): 8.22 ± 8.10 (m, 4 H o to NO2 (npeoc), 2 H o to
NO2 (npe), H C(8)); 7.48 (d, 2 H m to NO2 (npeoc)); 7.45 ± 7.20 (m, 4 H m to NO2 (npe, npeoc), 2 arom. H,
H
H
N(2)); 7.70 ± 6.93 (m, 2 arom. H); 6.03 (d, H C(1')); 5.22 (2q, MeCH(O)2); 4.93 ± 3.88 (m, H C(2'),
C(3'), H C(4'), 3 CH2CH2O, ArCH2, 2 H C(5')); 3.29 (t, CH2CH2O (npeoc)); 3.18 ± 2.98 (m, CH2CH2O
(npeoc), CH2CH2O (npe)); 1.50 (2d, MeCH(O)2); 1.14 ± 0.83 (m, 4 Me2CH). Anal. calc. for C57H70N8O18Si2
(1211.4): C 56.52, H 5.82, N 9.25; found: C 56.43, H 5.85, N 8.99.
2.9. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N2-{[2-(4-nitrophen-
yl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)guanosine
(15). According to 2.1, from 2 with 7. Yield 81%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.55, 0.57. UV
(MeOH): 203 (4.72), 216 (4.71), 268 (4.68), 275 (sh, 4.64). 1H-NMR (CDCl3): 8.22 ± 8.08 (m, 4 H o to
NO2(npeoc), 2 H o to NO2(npe), H C(8)); 7.48 (d, 4 H m to NO2 (npeoc)); 7.46 ± 6.96 (m, 2 H m to NO2(npe),
3 arom. H, H N(2)); 6.04 (d, H C(1')); 5.32, 5.19 (2q, MeCH(O)2); 4.94 ± 3.97 (m, H C(2'), H C(3'),
H
C(4'), 3 CH2CH2O (npeoc, npe), ArCH2 , 2 H C(5')); 3.29 (t, CH2CH2O (npeoc)); 3.20 ± 2.98
(m, CH2CH2O (npeoc), CH2CH2O (npe)); 1.50 (2d, MeCH(O)2); 1.17 ± 0.89 (m, 4 Me2CH). Anal. calc. for
C57H69FN8O18Si2 (1229.4): C 55.69, H 5.66, N 9.11; found: C 55.83, H 5.72, N 9.06.
2.10. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)cytidine (16). According to 2.1, from 3 with 6. Yield
70%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.40, 0.43. UV (MeOH): 203 (4.64), 212 (4.63), 246 (sh,
4.42), 271 (4.43). 1H-NMR (CDCl3): 8.37 ± 8.29 (m, H C(6)); 8.21 ± 8.11 (m, 4 H o to NO2 (npeoc)); 7.98 ± 7.64
(br. s, H N(4)); 7.48 ± 7.27 (m, 4 H m to NO2 (npeoc), 2 arom. H); 7.14 ± 7.02 (m, H C(5), 3 arom. H); 5.85,
5.73 (2s, H C(1')); 5.27, 5.08 (2q, MeCH(O)2); 4.92 ± 3.93 (m, H C(2'), H C(3'), H C(4'), 2 CH2CH2O
(npeoc), ArCH2 , 2 H C(5')); 3.18 ± 3.05 (m, 2 CH2CH2O (npeoc)); 1.50 (2d, MeCH(O)2); 1.13 ± 0.80
(m, 4 Me2CH). Anal. calc. for C48H63N5O16Si2 (1022.2): C 56.40, H 6.21, N 6.85; found: C 55.88, H 6.22, N 6.80.
2.11. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N4-{[2-(4-nitrophen-
yl)ethoxy]carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)cytidine (17). According to 2.1, from 3
with 7. Yield 75%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.42, 0.45. UV (MeOH): 204 (4.67), 211
(4.65), 248 (sh, 4.40), 269 (4.35), 274 (sh, 3.37). 1H-NMR (CDCl3): 8.38 ± 8.27 (m, H C(6)); 8.21 ± 8.12 (m, 2 H
o to NO2 (npeoc)); 8.04 ± 7.80 (br. s, H N(4)); 7.49 ± 7.01 (m, 2 H m to NO2 (npeoc), H C(5), 3 arom. H); 5.87,
5.73 (2s, H C(1')); 5.27, 5.09 (2m, MeCH(O)2); 4.92 ± 3.92 (2d, m, H C(2'), H C(3'), H C(4'), 2 CH2CH2O
(npeoc), ArCH2), 2 H C(5')); 3.19 ± 3.05 (m, 2 CH2CH2O (npeoc)); 1.50 (2d, MeCH(O)2); 1.13 ± 0.80
(m, Me2CH). Anal. calc. for C48H62FN5O16Si2 (1040.2): C 55.42, H 6.01, N 6.73; found: C 55.18, H 6.02, N 6.71.
2.12. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)adenosine (18). According to 2.1, from 4 with 6.
Yield 52%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.46, 0.48. UV (MeOH): 205 (4.70), 267 (4.58), 272
(sh, 4.54). 1H-NMR (CDCl3): 8.67, 8.62 (2s, H C(2)); 8.31, 8.24 (2s, H C(8)); 8.18 (m, 4 H o to NO2 (npeoc));
7.96 (s, H N(6)); 7.46 ± 7.38 (m, 4 H m to NO2 (npeoc)); 7.36 ± 7.27 (m, 2 arom. H); 7.08 ± 6.98 (m, 2 arom. H);
6.08, 6.06 (2s, H C(1')); 5.18 (m, MeCH(O)2); 4.98 ± 4.43 (2m, H C(2'), H C(3'), H C(4'), 2 CH2CH2O
(npeoc), ArCH2); 4.32 ± 3.97 (m, 2 H C(5')); 3.14 (2t, 2 CH2CH2O (npeoc)); 1.52 (2d, MeCH(O)2); 1.15 ± 0.89
(m, Me2CH). Anal. calc. for C49H63N7O15Si2 (1046.3): C 56.25, H 6.07, N 9.37; found: C 56.31, H 6.04, N 9.19.
2.13. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N6-{[2-(4-nitrophen-
yl)ethoxy]carbonyl}-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)adenosine (19). According to 2.1, from 4
with 7. Yield 66%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.46, 0.48. UV (MeOH): 209 (4.61), 267
(4.56), 272 (sh, 4.52). 1H-NMR (CDCl3): 8.68, 8.62 (2s, H C(2)); 8.32, 8.28 (2s, H C(8)); 8.18 (m, 4 H o to NO2
(npeoc)); 8.04 (br. s, H N(6)); 7.46 ± 7.37 (m, 4 H m to NO2 (npeoc)); 7.21 ± 7.11 (m, H C(2) (Ar)); 7.10 ± 7.02
(m, 2 arom. H); 6.08 (d, H C(1')); 5.19 (m, MeCH(O)2); 4.98 ± 4.43 (2m, H C(2'), H C(3'), H C(4'),

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2 CH2CH2O (npeoc), ArCH2)); 4.32 ± 3.98 (m, 2 H C(5')); 3.17 (2t, 2 CH2CH2O (npeoc)); 1.53 (2d,
MeCH(O)2); 1.15 ± 0.89 (m, 4 Me2CH). Anal. calc. for C49H62FN7O15Si2 (1064.2): C 55.30, H 5.87, N 9.21;
found: C 55.36, H 5.93, N 9.18.
3. Desilylation of 8 ± 19. 3.1. General Procedure [23].
3.2. 2'-O-[1-(Benzyloxy)ethyl]uridine (20) [23].
3.3. 2'-O-[1-(Benzyloxy)ethyl]-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guano-
sine (21). According to 3.1, from 9. Yield 84%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.27,
0.30. UV (MeOH): 212 (4.88), 268 (4.55), 278 (sh, 4.48). 1H-NMR ((D6)DMSO): 10.35 (br. s, H N(2)); 8.45
(m, H C(8)); 8.20 ± 8.05 (m, 4 H o to NO2); 7.60 (m, 4 H m to NO2); 7.25 ± 7.08 (m, 5 arom. H); 6.04
(d, H C(1')); 5.27 (m, OH C(3')); 5.06 (m,OH C(5')); 5.03 (m, MeCH(O)2); 4.87 ± 4.72 (m, MeCH(O)2,
CH2CH2OCO, H C(2')); 4.43 ± 3.92 (2m, ArCH2, CH2CHO2, H C(3'), H C(4')); 3.64 (m, 2 H C(5')); 3.29
(t, CH2CH2OCO); 3.10 (t, CH2CH2O); 1.20 (m, MeCH(O)2). Anal. calc. for C36H37N7O12 (759.7): C 56.91,
H 4.91, N 12.91; found: C 56.59, H 4.93, N 12.66.
3.4. 2'-O-[1-(Benzyloxy)ethyl]-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine (22). According to 3.1, from
10. Yield 68%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.46, 0.50. UV (MeOH): 212 (4.49),
225 (4.32), 244 (4.26), 278 (4.15). 1H-NMR ((D6)DMSO): 10.79 (br. s, H N(4)); 8.41 (m, H C(6)); 8.18
(d, 2 H o to NO2); 7.50 (d, 2 H m to NO2); 7.33 ± 7.17 (m, 5 arom. H)); 6.94 (d, H C(5)); 5.97, 5.89 (2d,
H
C(1')); 5.30 ± 5.14 (m, OH C(3'), OH C(5')); 5.03 (m, MeCH(O)2); 4.72 ± 4.28 (m, ArCH2, CH2CH2O);
4.20 (m, H C(2')); 4.07 (m, H C(3')); 3.93 (m, H C(4')); 3.81 ± 3.56 (m, 2 H C(5')); 3.07 (t, CH2CH2O);
1.32 (m, MeCH(O)2). Anal. calc. for C27H30N4O10 (570.6): C 56.84, H 5.30, N 9.82; found: C 56.56, H 5.46,
N 9.65.
3.5. 2'-O-[1-(Benzyloxy)ethyl]-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine (23). According to 3.1,
from 11. Yield 97%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.39, 0.42. UV (MeOH): 208
(4.59), 267 (4.42), 272 (sh, 4.39). 1H-NMR ((D6)DMSO): 10.63 (s, H N(6)); 8.72, 8.60 (2d, H C(2),
H
C(8)); 8.17 (d, 2 H o to NO2); 7.62 (d, 2 H m to NO2); 7.28 ± 7.10 (m, 3 arom. H); 6.98 (m, 2 arom. H); 6.18
(d, H C(1')); 5.41 ± 5.19 (m, OH C(3'), OH C(5')); 4.95 ± 4.80 (m, MeCH(O)2, H C(2')); 4.48 ± 3.95
(m, ArCH2, CH2CH2O, H C(3'), H C(4')); 3.80 ± 3.53 (m, 2 H C(5')); 3.13 (t, CH2CH2O); 1.26 (m,
MeCH(O)2). Anal. calc. for C28H30N6O9 ´0.5 H2O (603.6): C 55.72, H 5.18, N 13.92; found: C 54.48, H 5.12, N 13.85.
3.6. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}uridine (24). According to 3.1,
from 12. Yield 76%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.38, 0.40. UV (MeOH): 204
1
(4.42), 209 (sh, 4.22), 264 (4.29). H-NMR ((D6)DMSO): 11.36 (br. s, H N(3)); 8.19 (d, 2 H o to NO2); 7.95
(d, H C(6)); 7.59 (d, 2 H m to NO2); 7.26 (d, 2 H o to OCO); 7.11 (d, 2 H m to OCO); 5.92 (m, H C(1')); 5.62
(dd, H C(5)); 5.28 ± 5.12 (m, OH C(3'), OH C(5')); 4.92 (m, MeCH(O)2); 4.69 ± 4.35 (m, ArCH2 ,
CH2CH2O); 4.24 (m, H C(2)); 4.09 (m, H C(3')); 3.88 (m, H C(4')); 3.60 (m, 2 H C(5')); 3.15
(t, CH2CH2O); 1.30 (m, MeCH(O)2). Anal. calc. for C27H29N3O12 (587.5): C 55.20, H 4.97, N 7.15; found:
C 54.91, H 5.02, N 7.13.
3.7. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}uridine (25). Accord-
ing to 3.1, from 13. Yield 89%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.45, 0.47. UV
(MeOH): 205 (4.38), 212 (sh, 4.28), 264 (4.31). 1H-NMR ((D6)DMSO): 11.28 (br. s, H N(3)); 8.18 (m, 2 H o to
NO2); 7.95 ± 7.80 (m, H C(6)); 7.63 ± 7.09 (m, 2 H m to NO2, H C(2) (Ar), H C(6) (Ar), H C(5) (Ar)); 5.91
(m, H C(1')); 5.53 (m, H C(5)); 5.29 ± 5.09 (m, OH C(3'), OH C(5')); 4.95 (m, MeCH(O)2); 4.70 ± 4.36
(m, ArCH2, CH2CH2O); 4.26 (t, H C(2')); 4.06 (m, H C(3')); 3.87 (m, H C(4')); 3.78 ± 3.48 (m, 2 H C(5'));
3.12 (t, CH2CH2O); 1.46, 1.38 (2d, MeCH(O)2). Anal. calc. for C27H28FN3O12 ´ 0.5 H2O (614.5): C 53.56, H 4.66,
N 6.94; found: C 52.86, H 4.83, N 6.91.
3.8. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine (26). According to 3.1, from 14. Yield 96%. Colorless foam.
TLC (toluene/AcOEt/MeOH 5 :5 :2): Rf 0.58, 0.60. UV (MeOH): 205 (4.73), 214 (sh, 4.73), 269 (4.63), 284 (sh,
4.46). 1H-NMR ((D6)DMSO): 10.34 (br. s, H N(2)); 8.48, 8.44 (2s, H C(8)); 8.20 ± 8.08 (m, 4 H o to NO2
(npeoc), 2 H o to NO2 (npe)); 7.66 ± 7.52 (m, 4 H m to NO2 (npeoc), 2 H m to NO2 (npe)); 7.09 ± 6.96
(m, 4 arom. H); 6.06 ± 5.98 (m, H C(1')); 5.31, 5.27 (2d, OH C(5')); 5.04 (m, OH C(3')); 4.94 ± 4.79
(m, MeCH(O)2 ,
H C(2')); 4.77 ± 4.64 (m, CH2CH2O (npeoc)); 4.51 ± 4.03 (m, CH2CH2O (npeoc),
CH2CH2O(npe), ArCH2, H C(3')); 3.97 (m, H C(4')); 3.77 ± 3.64, 3.63 ± 3.51 (2m, 2 H C(5')); 3.27
(t, CH2CH2O (npeoc)); 3.18 ± 3.04 (m, CH2CH2O (npeoc), CH2CH2O (npe)); 1.26, 1.18 (2d, Me(CH(O)2).
Anal. calc. for C45H44N8O17 (968.9): C 55.79, H 4.58, N 11.57; found: C 55.38, H 4.61, N 11.39.
3.9. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N2-{[2-(4-nitrophen-
yl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine (27). According to 3.1, from 15. Yield 86%. Colorless

Helvetica Chimica Acta ± Vol. 84 (2001)
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foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.38, 0.41. UV (MeOH): 203 (4.68), 214 (4.67), 268 (4.65), 274
(sh, 4.55). 1H-NMR ((D6)DMSO): 10.53, 10.35 (2 br. s, H N(2)); 8.46, 8.43 (2s, H C(8)); 8.20 ± 8.08 (m, 4 H o
to NO2 (npeoc), 2 H o to NO2 (npe)); 7.66 ± 7.51 (m, 4 H m to NO2 (npeoc), 2 H m to NO2 (npe)); 7.23 ± 7.10
(m, H C(2) (Ar)); 7.06 ± 6.94 (m, H C(5)); 6.90 ± 6.82 (m, H C(6)); 6.06 ± 5.98 (m, H C(1')); 5.31, 5.28 (2d,
OH C(5')); 5.04 (m, OH C(3')); 4.94 ± 4.80 (m, MeCH(O)2, H C(2')); 4.77 ± 4.65 (m, CH2CH2O (npeoc));
4.55 ± 4.05 (m, CH2CH2O (npeoc), CH2CH2O (npe), ArCH2, H C(3')); 3.96 (m, H C(4')); 3.78 ± 3.63, 3.63 ±
3.51 (2m, 2 H C(5')); 3.25 (m, CH2CH2O (npeoc)); 3.18 ± 3.05 (m, CH2CH2O (npeoc), CH2CH2O (npe)); 1.26,
1.19 (2d, MeCH(O)2). Anal. calc. for C45H43FN8O17 ´ 0.5 H2O (995.9): C 54.27, H 4.45, N 11.25; found: C 54.09,
H 4.48, N 11.16.
3.10. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}cytidine (28). According to 3.1, from 16. Yield 92%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.41, 0.44. UV (MeOH): 204 (4.63), 210 (4.61), 269 (4.37). 1H-NMR ((D6)DMSO): 10.78 (br. s,
H
N(4)); 8.46 ± 8.38 (m, H C(6)); 8.24 ± 8.09 (m, 4 H o to NO2 (npeoc)); 7.65 ± 7.53 (m, 4 H m to NO2
(npeoc)); 7.35 ± 7.22 (m, H C(3) (Ar), H C(5) (Ar)); 7.15 ± 7.04 (m, H C(2) (Ar), H C(6) (Ar)); 6.94
(d, H C(5)); 5.93, 5.86 (2d, H C(1')); 5.28 ± 5.14 (m, OH C(5'), OH C(3')); 5.08, 4.98 (2q, MeCH(O)2);
4.71 ± 4.41 (m, 2 CH2CH2O (npeoc), ArCH2); 4.33 (t, 2 CH2CH2O (npeoc)); 4.18 (m, H C(2')); 4.05
(m, H C(3')); 3.94 (m, H C(4')); 3.82 ± 3.69, 3.68 ± 3.54 (2 m, 2 H C(5')); 3.19, 3.02 (2t, 2 CH2CH2O
(npeoc)); 1.35, 1.29 (2d, MeCH(O)2). Anal. calc. for C36H35N5O15 ´ H2O (786.7): C 54.96, H 4.61, N 8.90; found:
C 55.04, H 4.85, N 8.88.
3.11. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)-
ethoxy]carbonyl}cytidine (29). According to 3.1, from 17. Yield 90%. Colorless foam. TLC (toluene/AcOEt
1:1): Rf 0.40, 0.44. UV (MeOH): 203 (4.61), 210 (sh, 4.67), 268 (4.41), 274 (sh, 4.39). 1H-NMR ((D6)DMSO):
10.77 (br. d, H N(4)); 8.42 (m, H C(6)); 8.22 ± 8.12 (m, 4 H o to NO2 (npeoc)); 7.65 ± 7.51 (m, 4 H m to NO2
(npeoc)); 7.32 ± 7.19 (m, H C(2) (Ar), H C(5) (Ar)); 7.12 (t, H C(6) (Ar)); 6.94 (d, H C(5)); 5.91, 5.86 (2d,
H
C(1')); 5.29, 5.18 (2m, OH C(5'), OH C(3')); 5.11, 5.00 (2q, MeCH(O)2); 4.72 ± 4.40 (m, CH2CH2O
(npeoc), ArCH2); 4.35 (t, CH2CH2O (npeoc)); 4.18 (m, H C(2')); 4.07 (m, H C(3')); 3.93 (m, H C(4'));
3.82 ± 3.70, 3.69 ± 3.55 (2m, 2 H C(5')); 3.17, 3.07 (2t, 2 CH2CH2O (npeoc)); 1.36, 1.30 (2d, MeCH(O)2). Anal.
calc. for C36H34FN5O15 ´ H2O (813.7): C 53.14, H 4.46, N 8.61; found: C 53.32, H 4.56, N 8.59.
3.12. 2'-O-{1-{{4-{{[2-(4-Nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]-
carbonyl}adenosine (30). According to 3.1, from 18. Yield 87%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.50, 0.52. UV (MeOH): 207 (4.64), 267 (4.56), 273 (sh, 4.52). 1H-NMR ((D6)DMSO): 10.59 (br. d,
H
N(6)); 8.71 (2s, H C(2')); 8.60 (2s, H C(8)); 8.22 ± 8.11 (m, 4 H o to NO2 (npeoc)); 7.64 ± 7.52 (m, 4 H m to
NO2 (npeoc)); 7.04 ± 6.98 (m, 4 arom. H); 6.15 (d, H C(1')); 5.39, 5.32 (2d, OH C(5')); 5.31 ± 5.18
(m, OH C(3')); 4.95 ± 4.83 (m, MeCH(O)2), H C(2)); 4.46 (t, CH2CH2O (npeoc)); 4.38 (t, CH2CH2O
(npeoc)); 4.40 ± 3.98 (m, ArCH2, H C(3'), H C(4')); 3.79 ± 3.67, 3.66 ± 3.54 (2m, 2 H C(5')); 3.18 ± 3.04
(m, 2 CH2CH2O (npeoc)); 1.25, 1.19 (2d, MeCH(O)2). Anal. calc. for C37H37N7O14 (803.7): C 55.29, H 4.64,
N 12.20; found: C 55.32, H 4.68, N 12.00.
3.13. 2'-O-{1-{{3-Fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl}-N6-{[2-(4-nitrophen-
yl)ethoxy]carbonyl}adenosine (31). Not isolated. TLC (toluene/AcOEt/MeOH 5 :4 :2): Rf 0.60, 0.62.
4. Tritylation to 32 ± 43. 4.1. General Procedure. Predried 2'-acetal-protected monomer 20 ± 31 (2.0 mmol, ca.
1.2 ± 2.0 g) was co-evaporated with abs. toluene (2 Â 100 ml) and taken up in abs. pyridine (30 ml). Then,
(MeO)2TrCl (850 mg, 2.51 mmol) was added, the soln. stirred at r.t. overnight, and then the reaction stopped by
adding MeOH (1 ml). After 5 min, the soln. was evaporated in vacuo, the oil taken up in AcOEt (200 ml) and
extracted with NaHCO3 soln. (50 ml) and sat. NaCl soln. (50 ml), the aq. phase back-extracted with AcOEt
(150 ml), and the combined org. phase dried (Na2SO4) and evaporated. The crude oil was purified by FC (silica
gel, toluene/AcOEt). The product fractions were evaporated and co-evaporated several times with MeOH
(10 ml) and CH2Cl2. The resulting colorless foam was dried in a desiccator under high vacuum.
4.2. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)uridine (32). According to 4.1, from
20. Yield 88%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.86, 0.88. UV (MeOH): 209 (4.73),
233 (4.36), 265 (4.04). 1H-NMR (CDCl3): 8.50 (br. s, H N(3)); 7.92, 7.83 (2d, H C(6)); 7.40 ± 7.18 (m, 4 H m to
MeO, 5 arom. H); 6.82 (m, 4 H o to MeO); 6.07, 5.97 (2d, H C(1')); 5.24 (d, H C(5)); 5.06 (m, MeCH(O)2);
4.78 ± 4.31 (m, ArCH2, H C(2'), H C(3')); 4.08 (m, H C(4')); 3.79 (s, 2 MeO); 3.48 (m, 2 H C(5')); 2.91,
2.73 (2d, OH C(3')); 1.45, 1.38 (2m, MeCH(O)2). Anal. calc. for C39H40N2O9 (680.8): C 68.81, H 5.92, N 4.12;
found: C 68.55, H 6.07, N 4.07.
4.3. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N2-{[2-(4-nitrophenyl)ethoxy]car-
bonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine (33). According to 4.1, from 21. Yield 89%. Colorless foam.

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Helvetica Chimica Acta ± Vol. 84 (2001)
TLC (toluene/AcOEt 1 :3): Rf 0.56, 0.59. UV (MeOH): 203 (4.99), 214 (4.80), 236 (4.48), 269 (4.57). 1H-NMR
(CDCl3): 8.13 (m, 4 H o to NO2 (npe)); 7.92, 7.82 (2s, H C(8)); 7.55 ± 7.45 (m, 2 H m to NO2 (npeoc)); 7.40
(m, 2 H m to NO2 (npe)); 7.35 ± 7.07 (m, H N(2), 10 arom. H, 4 H m to MeO); 6.74 (m, 4 H o to MeO); 6.03
(d, H C(1')); 5.05 (m, acetal-H,
H C(2')); 4.78 (t, CH2CH2OCO); 4.70 ± 4.13 (m, CH2CH2O, ArCH2 ,
H
C(3')); 4.20 (m, H C(4')); 3.73 (2s, 2 MeO); 3.49 ± 3.24 (m, 2 H C(5'), CH2CH2OCO); 3.03
(t, CH2CH2O); 2.85, 2.65 (2d, OH C(3')); 1.39, 1.25 (2d, MeCH(O)2). Anal. calc. for C57H55N7O14 (1062.1):
C 64.46, H 5.21, N 9.23; found: C 64.39, H 5.30, N 9.18.
4.4. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N4-{[2-(4-nitrophenyl)ethoxy]carbon-
yl}cytidine (34). According to 4.1, from 22. Yield 97%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1):
Rf 0.58, 0.60. UV (MeOH): 204 (4.96), 235 (4.54), 275 (4.23). 1H-NMR (CDCl3): 8.45 (m, H C(6)); 8.17
(m, 2 H o to NO2); 7.92, 7.82 (2s, H N(4)); 7.55 ± 7.45 (m, 2 H m to NO2 (npeoc)); 7.40 (m, 2 H m to NO2 (npe));
7.51 (br. s, H N(4)); 7.44 ± 7.18 (m, 10 arom. H, 4 H m to MeO, 2 H o to NO2); 6.82 (m, 4 H o to MeO,
H
H
C(5)); 6.00 (d, H C(1')); 5.34 (m, acetal-H); 4.88 ± 4.53 (m, ArCH2); 4.46 ± 4.03 (m, CH2CH2O, H C(2'),
C(3'), H C(4')); 3.79 (s, 2 MeO); 3.62 ± 3.47 (m, 2 H C(5)); 3.08 (m, CH2CH2O); 2.97, 2.67 (2d,
OH C(3')); 1.43, 1.38 (2d, MeCH(O)2). Anal. calc. for C48H49N4O13 (889.9): C 66.05, H 5.54, N 6.42; found:
C 66.20, H 5.60, N 6.23.
4.5. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N6-{[2-(4-nitrophenyl)ethoxy]carbon-
yl}adenosine (35). According to 4.1, from 23. Yield 90%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.66, 0.68. UV (MeOH): 204 (4.93), 235 (4.54), 275 (4.25), 288 (sh, 4.15). 1H-NMR (CDCl3): 8.64,
8.62 (2d, H C(2)); 8.20 ± 8.11 (m, H N(6), H C(8), 2 H o to NO2); 7.48 ± 7.03 (m, 2 H m to NO2, 4 H m to
MeO, 10 arom. H); 6.82 ± 6.71 (m, 4 H o to MeO); 6.16 (2d, H C(1')); 4.98 (m, MeCH(O)2, H C(2')); 4.60 ±
4.19 (m, H C(3'),
H C(4'), CH2CH2O, ArCH2); 3.75 (s, 2 MeO); 3.56 ± 3.32 (m, 2 H C(5')); 3.15
(t, CH2CH2O); 2.93, 2.72 (2d, OH C(3')); 1.39, 1.21 (2d, MeCH(O)2). Anal. calc. for C48H48N6O11 (897.0):
C 65.62, H 5.39, N 9.37; found: C 66.00, H 5.54, N 9.10.
4.6. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}uridine (36). According to 4.1, from 24. Yield 84%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.86, 0.88. UV (MeOH): 207 (4.78), 235 (4.42), 265 (4.32). 1H-NMR (CDCl3): 8.46, 8.39 (2 br. s,
H
N(3)); 8.18 (m, 2 H o to NO2 (npeoc)); 7.93, 7.83 (2d, H C(6)); 7.48 ± 7.18 (m, 4 H m to MeO, 5 arom. H,
2 H m to NO2 (npeoc), H C(2) (Ar), H C(6) (Ar)); 7.08 (m, C(3) (Ar), H C(5) (Ar)); 6.80 (m, 4 H o to
MeO); 6.04, 5.91 (2d, H C(1')); 5.24 (d, H C(5)); 5.10 (m, MeCH(O)2); 4.80 ± 4.27 (m, CH2CH2O (npeoc),
ArCH2, H C(2'), H C(3')); 4.06 (m, H C(4')); 3.79 (s, 2 MeO); 3.50 (m, 2 H C(5')); 3.17 (m, CH2CH2O
(npeoc)); 2.81, 2.67 (2d, OH C(3')); 1.45, 1.40 (2d, MeCH(O)2). Anal. calc. for C48H47N3O14 ´ 0.5 H2O (898.9):
C 64.14, H 5.38, N 4.68; found: C 64.15, H 5.39, N 4.68.
4.7. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}uridine (37). According to 4.1, from 25. Yield 98%. Colorless foam. TLC (toluene/AcOEt/
MeOH 5 :4 :1): Rf 0.78, 0.80. UV (MeOH): 205 (4.90), 235 (4.40), 265 (4.31), 279 (sh, 3.90). 1H-NMR (CDCl3):
8.50 (br. s, H N(3)); 8.18 (m, 2 H o to NO2 (npeoc)); 7.96, 7.87 (2d, H C(6)); 7.42 ± 7.02 (m, 5 arom. H, 4 H m
to MeO, 2 H m to NO2 (npeoc), H C(2) (Ar), H C(5) (Ar), H C(6) (Ar)); 6.88 ± 6.79 (m, 4 H o to MeO);
6.04, 5.90 (2d, H C(1')); 5.27 (m, H C(5)); 5.13 (m, MeCH(O)2); 4.78 ± 4.29 (m, ArCH2, CH2CH2O (npeoc),
H
C(2'), H C(3')); 4.07 (m, H C(4')); 3.78 (s, 2 MeO); 3.51 (m, 2 H C(5')); 3.15 (m, CH2CH2O (npeoc));
2.72, 2.58 (2d, OH C(3')); 1.46, 1.40 (2d, MeC(O)2). Anal. calc. for C48H46FN3O14 (907.9): C 63.50, H 5.11,
N 4.63; found: C 63.83, H 5.20, N 4.54.
4.8. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine (38). According to
4.1, from 26. Yield 96%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.67, 0.69. UV (MeOH):
204 (5.01), 211 (4.90), 236 (4.51), 269 (4.66), 289 (sh, 4.31). 1H-NMR (CDCl3): 8.18 ± 8.06 (m, 4 H o to NO2
(npeoc), 2 H o to NO2 (npe)); 7.98, 7.86 (2s, H C(8)); 7.53 ± 7.44 (m, 2 H m to NO2 (npeoc)); 7.43 ± 7.08 (m, 2 H
m to NO2 (npeoc), H N(2), 5 arom. H, 4 H m to MeO, 2 H m to NO2 (npe), H C(2) (Ar), H C(6) (Ar));
7.03 ± 6.96 (m, H C(3) (Ar), H C(5) (Ar)); 6.78 ± 6.69 (m, 4 H o to MeO); 6.03 (m, H C(1')); 5.13, 5.06 ± 4.97
(2m, MeCH(O)2), H C(2')); 4.77 (t, CH2CH2O (npeoc)); 4.63 ± 4.28 (m, CH2CH2O (npeoc), CH2CH2O (npe),
ArCH2, H C(3')); 4.23 ± 4.12 (m, H C(4')); 3.73 (s, 2 MeO); 3.50 ± 3.24 (m, 2 H C(5')), CH2CH2O (npeoc));
3.14 (t, CH2CH2O (npeoc)); 3.03 (t, CH2CH2O (npeoc)); 2.78, 2.62 (2d, OH C(3')); 1.39, 1.26 (2d,
MeCH(O)2). Anal. calc. for C66H62N8O19 (1271.3): C 62.36, H 4.92, N 8.81; found: C 62.01, H 4.93, N 8.56.
4.9. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine (39). Accord-
ing to 4.1, from 27. Yield 94%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.68, 0.70. UV

Helvetica Chimica Acta ± Vol. 84 (2001)
1079
(MeOH): 204 (5.14), 211 (4.92), 236 (4.54), 269 (4.67), 287 (sh, 4.36). 1H-NMR (CDCl3): 8.18 ± 8.06 (m, 4 H o
to NO2 (npeoc), 2 H o to NO2 (npe)); 7.98, 7.90 (2s, H C(8)); 7.52 ± 7.44 (m, 2 H m to NO2 (npeoc)); 7.43 ± 7.11
(m, 2 H m to NO2 (npeoc), H N(2), 5 arom. H, 4 H m to MeO, 2 H m to NO2 (npe), H C(2) (Ar), H C(6)
(Ar)); 7.03 ± 6.93 (m, H C(5) (Ar)); 6.79 ± 6.69 (m, 4 H o to MeO); 6.03 (m, H C(1')); 5.15, 5.04 (2m,
MeCH(O)2), H C(2')); 4.75 (t, CH2CH2O (npeoc)); 4.63 ± 4.24 (m, CH2CH2O (npeoc), CH2CH2O (npe),
ArCH2, H C(3')); 4.23 ± 4.12 (m, H C(4')); 3.74 (s, 2 MeO); 3.51 ± 3.32 (m, 2 H C(5')); 3.28 (t, CH2CH2O
(npeoc)); 3.17 (t, CH2CH2O (npeoc)); 3.03 (t, CH2CH2O (npe)); 2.74, 2.59 (2d, OH C(3')); 1.41, 1.28 (2d,
MeCH(O)2). Anal. calc. for C66H61FN8O19 (1289.3): C 61.49, H 4.77, N 8.69; found: C 61.45, H 4.86, N 8.59.
4.10. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine (40). According to 4.1, from 28. Yield 88%. Colorless
foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.58, 0.61. UV (MeOH): 205 (4.92), 236 (4.59), 271 (4.46), 282
(sh, 4.42). 1H-NMR (CDCl3): 8.52 ± 8.42 (m, H C(6)); 8.21 ± 8.13 (m, 4 H o to NO2 (npeoc)); 7.45 ± 7.13
(m, H N(4), 5 arom. H, 4 H m to NO2 (npeoc), 4 H m to MeO, H C(2) (Ar), H C(6) (Ar)); 6.88 ± 6.78
(m, 4 H o to MeO, H C(3) (Ar), H C(5)); 6.03, 5.90 (2s, H C(1')); 5.41 ± 5.30 (m, MeCH(O)2); 4.87 ± 4.27
(m, ArCH2, H C(2'), H C(3'), 2 CH2CH2O (npeoc)); 4.14 ± 4.03 (m, H C(4')); 3.78 (s, 2 MeO); 3.63 ± 3.47
(m, 2 H C(5')); 3.18 ± 3.04 (m, 2 CH2CH2O (npeoc)); 2.83, 2.58 (2d, OH C(3')); 1.46 ± 1.37 (2d, MeCH(O)2).
Anal. calc. for C57H53N5O17 (1080.1): C 63.39, H 4.95, N 6.48; found: C 63.01, H 5.19, N 6.32.
4.11. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine (41). According to 4.1, from 29. Yield 88%.
Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.58, 0.61. UV (MeOH): 205 (4.90), 236 (4.56), 270
(4.42), 287 (sh, 4.31). 1H-NMR (CDCl3): 8.52 ± 8.41 (m, H C(6)); 8.21 ± 8.13 (m, 4 H o to NO2 (npeoc)); 7.45 ±
7.03 (m, H N(4), 5 arom. H, 4 H m to NO2 (npeoc), 4 H m to MeO, H C(2) (Ar), H C(5) (Ar), H C(6)
(Ar)); 6.88 ± 6.77 (m, 4 H o to MeO); 6.02, 5.90 (2s, H C(1')); 5.41, 5.32 (2q, MeCH(O)2); 4.87 ± 4.28
(m, ArCH2, H C(2'), H C(3'), 2 CH2CH2O (npeoc)); 4.14 ± 4.01 (m, H C(4')); 3.78 (s, 2 MeO); 3.64 ± 3.45
(m, 2 H C(5')); 3.18 ± 3.04 (m, 2 CH2CH2O (npeoc)); 2.70, 2.49 (2d, OH C(3')); 1.48 ± 1.39 (2d, MeCH(O)2).
Anal. calc. for C57H52FN5O17 (1098.1): C 62.35, H 4.77, N 6.38; found: C 62.18, H 5.07, N 6.42.
4.12. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine (42). According to 4.1, from 30. Yield 98%.
Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.58, 0.60. UV (MeOH): 205 (4.94), 236 (4.46), 267
(4.58), 272 (sh, 4.55). 1H-NMR (CDCl3): 8.63 (d, H C(2)); 8.22 ± 8.14 (m, 4 H o to NO2 (npeoc)); 8.06, 7.97 (2s,
H
C(8)); 7.97 (br. s, H N(6)); 7.46 ± 7.35 (m, 4 H m to NO2 (npeoc), H C(2) (Ar), H C(6) (Ar)); 7.34 ± 6.94
(m, 5 arom. H, 4 H m to MeO, H C(3) (Ar), H C(5) (Ar)); 6.83 ± 6.74 (m, 4 H o to MeO)); 6.17 (2d,
C(1')); 5.12 ± 4.93 (m, MeCH(O)2, H C(2')); 4.57 ± 4.38 (m, H C(3'), 2 CH2CH2O (npeoc)); 4.35 ± 4.21
H
(m, ArCH2, H C(4')); 3.75 (s, 2 MeO); 3.56 ± 3.45, 3.44 ± 3.33 (2m, 2 H C(5')); 3.14 (t, 2 CH2CH2O (npeoc));
2.84, 2.67 (2d, OH C(3')); 1.40, 1.26 (2d, MeCH(O)2). Anal. calc. for C58H55N7O16 (1106.1): C 62.98, H 5.01,
N 8.86; found: C 62.91, H 5.09, N 8.65.
4.13. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine (43). According to 4.1, from 31. Yield
92%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.59, 0.62. UV (MeOH): 206 (4.92), 236 (4.49),
267 (4.60), 275 (sh, 4.53). 1H-NMR (CDCl3): 8.62 (d, H C(2)); 8.22 ± 8.10 (m, 4 H o to NO2 (npeoc)); 8.07, 7.98
(2s, H C(8)); 7.46 ± 7.33, 7.32 ± 7.17 (m, 5 arom. H, 4 H m to NO2 (npeoc), 4 H m to MeO, H C(2) (Ar),
H
N(6)); 7.06 ± 6.95 (m, H C(5) (Ar)); 6.94 ± 6.84 (m, H C(6) (Ar)); 6.83 ± 6.72 (m, 4 H o to MeO); 6.17
(m, H C(1')); 5.13 ± 4.93 (m, MeCH(O)2, H C(2')); 4.58 ± 4.38 (m, H C(3'), 2 CH2CH2O (npeoc)); 4.35 ±
4.17 (m, ArCH2, H C(4')); 3.74 (s, 2 MeO); 3.56 ± 3.44, 3.43 ± 3.31 (2m, 2 H C(5')); 3.14 (t, 2 CH2CH2O
(npeoc)); 2.77, 2.53 (2d, OH C(3')); 1.41, 1.28 (2d, MeCH(O)2). Anal. calc. for C58H54FN7O16 (1124.1): C 61.97,
H 4.84, N 8.72; found: C 62.00, H 4.91, N 8.64.
5. Succinylation to 44 ± 55. 5.1. General Procedure. To 5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-acetal-
protected monomer 32 ± 43 (0.1 mmol; ca. 90 ± 130 mg) were added succinic anhydride (0.15 ± 0.3 mmol, 15 ±
30 mg) and N,N-dimethylpyridin-4-amine (DMAP; 0.02 ± 0.04 mmol, 2.5 ± 5.0 mg). The mixture was taken up in
abs. CH2Cl2 (10 ml) and stirred at r.t. for 2 ± 4-h. The reaction was stopped by dilution with AcOEt (100 ml) and
shaken with 1n phosphate buffer (100 ml, pH 7). The extraction was repeated once and the combined org. phase
dried (Na2SO4) and evaporated. The crude oil was purified by FC (silica gel, toluene/AcOEt/MeOH). The
product fractions were evaporated and co-evaporated with MeOH (2 Â 5 ml) and CH2Cl2 (2 Â 5 ml). The
resulting colorless foam was dried in a desiccator under high vacuum. Note: For solid-phase coupling, a
chromatographic purification is not necessary in most cases.

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Helvetica Chimica Acta ± Vol. 84 (2001)
5.2. 2'-O-[1-(1-Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)uridine 3'-(Hydrogen Butanedioate)
(44). According to 5.1, from 32. Yield 93%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.60. UV
(MeOH): 204 (4.85), 234 (4.34), 260 (4.01). 1H-NMR (CDCl3): 9.40 (br. s, H N(3)); 7.87, 7.69 (2d, H C(6));
7.40 ± 7.12 (m, 4 H m to MeO, 5 arom. H); 6.80 (m, 4 H o to MeO); 6.08 (2d, H C(1')); 5.52 ± 5.40 (d, H C(5));
5.13 (m, H C(3')); 4.98 (m, MeCH(O)2); 4.72 ± 4.36 (m, ArCH2 ,
H C(2')); 4.22 (m, H C(4')); 3.78
(s, 2 MeO); 3.46 (m, 2 H C(5')); 2.68 (m, CH2CH2); 1.42, 1.28 (2m, MeCH(O)2). Anal. calc. for C43H44N2O10
(680.8): C 66.19, H 5.58, N 3.59; found: C 66.12, H 5.78, N 3.54.
5.3. 2'-O-[1-(1-Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N2-{[2-(4-nitrophenyl)ethoxy]car-
bonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine 3'-(Hydrogen Butanedioate) (45). According to 5.1, from 33.
Yield 93%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.49, 0.54. UV (MeOH): 203 (4.96), 235
(4.38), 260 (4.30). 1H-NMR ((D6)DMSO): 12.24 (br. s, H N(2)); 11.47 (d, COOH); 8.18 (m, 2 H o to NO2
(npeoc)); 7.69, 7.61 (2d, H C(6)); 7.58 (m, 2 H m to NO2 (npeoc)); 7.40 ± 7.18 (m, 5 arom. H, 2 H m to NO2
(npeoc), H C(2) (Ar), 4 H m to MeO)); 6.86 (m, 4 H o to MeO); 5.91 (2d, H C(1')); 5.38 (dd, H C(5)); 5.23
(m, H C(3')); 4.92, 4.86 (2q, MeCH(O)2); 4.68 (m, H C(2')); 4.57 ± 4.29 (m, 2 CH2CH2O (npeoc), ArCH2);
4.16 (m, H C(4')); 3.75 (s, 2 MeO); 3.43 ± 3.19 (m, 2 H C(5')); 3.16 (t, 2 CH2CH2O (npeoc)); 2.67 ± 2.42
(m, 4 H (succ.)); 1.28, 1.20 (2d, MeCH(O)2). Anal. calc. for C52H51N3O17 ´ H2O (1008.0): C 61.96, H 5.30, N 4.16;
found: C 61.98, H 5.29, N 4.14.
5.4. 2'-O-[1-(1-Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N4-{[2-(4-nitrophenyl)ethoxy]car-
bonyl}cytidine 3'-(Hydrogen Butanedioate) (46). According to 5.1, from 34. Yield 98%. Colorless foam. TLC
(toluene/AcOEt/MeOH 5 :4 :1): Rf 0.50, 0.52. UV (MeOH): 203 (4.94), 236 (4.51), 270 (4.22). 1H-NMR
(CDCl3): 8.42, 8.29 (2d, H C(6)); 8.12 (m, 2 H o to NO2); 7.41 ± 7.13 (m, 2 H m to NO2, H N(4), 4 H m to
MeO, 10 arom. H); 7.44 ± 7.18 (m, 10 arom. H, 4 H m to MeO, 2 H o to NO2); 6.82 (m, 4 H o to MeO, H C(5));
5.99 (2d, H C(1')); 5.30 (m, H C(3')); 5.15 (m, acetal-H); 4.70 ± 4.20 (m, ArCH2, CH2CH2O, H C(2'),
H
C(4')); 3.75 (s, 2 MeO); 3.59 ± 3.42 (2m, 2 H C(5')); 2.97 (m, CH2CH2O); 2.74 ± 2.46 (m, CH2CH2); 1.41,
1.28 (2d, MeCH(O)2). Anal. calc. for C52H53N4O16 (990.0): C 63.09, H 5.40, N 5.66; found: C 63.82, H 5.50,
N 5.64.
5.5. 2'-O-[1-(1-Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N6-{[2-(4-nitrophenyl)ethoxy]car-
bonyl}adenosine 3'-(Hydrogen Butanedioate) (47). According to 5.1, from 35. Yield 79%. Colorless foam.
TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.60. UV (MeOH): 203 (4.97), 235 (4.43), 267 (4.47), 272 (sh, 4.43).
1H-NMR (CDCl3): 8.62, 8.58 (2d, H C(2)); 8.53 ± 8.36 (br. s, H N(6)); 8.18, 8.02 (2m, 2 H o to NO2, H C(8));
7.49 ± 6.87 (m, 2 H m to NO2, 4 H m to MeO, 8 arom. H); 6.93 (m, 2 H (ArCH2)); 6.84 ± 6.71 (m, 4 H o to MeO);
6.21, 6.12 (2d, H C(1')); 5.56 (m, H C(3')); 5.27 (2m, H C(2')); 4.86, 4.79 (2q, MeCH(O)2); 4.60 ± 4.29
(m, CH2CH2O, H C(4')); 4.03 (m, ArCH2); 3.75 (s, 2 MeO); 3.52 ± 3.37 (m, 2 H C(5')); 3.12 (t, 2 CH2CH2O);
2.70 (m, CH2CH2); 1.32, 1.10 (2d, MeCH(O)2). Anal. calc. for C53H52N6O14 (997.0): C 63.85, H 5.26, N 8.43;
found: C 63.63, H 5.41, N 8.29.
5.6. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}uridine 3'-(Hydrogen Butanedioate) (48). According to 5.1, from 36. Yield 96%. Colorless foam.
TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.30 ± 0.42. UV (MeOH): 203 (4.96), 235 (4.38), 260 (4.30). 1H-NMR
((D6)-DMSO): 12.24 (br. s, H N(3)); 11.47 (s, COOH); 8.18 (m, 2 H o to NO2); 7.65 (d, H C(6)); 7.58 (m, 2 H
m to NO2); 7.40 ± 7.18 (m, 5 arom. H, 2 H o to C6H4OCO, 4 H m to MeO); 7.08 (d, 2 H m to C6H4OCO); 6.86
(m, 4 H o to MeO); 5.91 (2d, H C(1')); 5.38 (m, H C(5)); 5.23 (m, H C(3')); 4.89 (m, MeCH(O)2); 4.68
(m, H C(2')); 4.57 ± 4.29 (m, ArCH2 , CH2CH2O); 4.16 (m, H C(4')); 3.75 (s, 2 MeO); 3.43 ± 3.19
(m, 2 H C(5')); 3.16 (t, CH2CH2O); 2.67 ± 2.42 (m, CH2CH2); 1.28, 1.20 (2d, MeCH(O)2). Anal. calc. for
C52H51N3O17 ´ H2O (1008.0): C 61.96, H 5.30, N 4.16; found: C 61.98, H 5.29, N 4.14.
5.7. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}uridine 3'-(Hydrogen Butanedioate) (49). According to 5.1, from 37. Yield 56%. Colorless
foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.35 ± 0.45. UV (MeOH): 205 (4.89), 235 (4.39), 264 (4.31), 279
(sh, 4.11). 1H-NMR (CDCl3): 9.51, 9.41 (2 br. s, H N(3)); 8.16 (m, 2 H o to NO2 (npeoc)); 7.92, 7.73 (2d,
H
H
C(6)); 7.44 ± 7.02 (m, 5 arom. H, 2 H m to NO2 (npeoc), H C(2) (Ar), 4 H m to MeO, H C(5) (Ar),
C(6) (Ar)); 6.87 ± 6.77 (m, 4 H o to MeO); 6.05, 5.98 (2d, H C(1')); 5.44 (m, H C(5)); 5.21 (d, H C(3'));
4.99 (m, MeCH(O)2); 4.66 ± 4.37 (m, ArCH2 , CH2CH2O (npeoc), H C(2')); 4.27 (m, H C(4')); 3.77
(s, 2 MeO); 3.58 ± 3.39 (m, 2 H C(5')); 3.14 (t, CH2CH2O (npeoc)); 2.94, 2.88 (2s, COOH); 2.73, 2.56 (2m,
CH2CH2); 1.42, 1.30 (2d, MeCH(O)2). Anal. calc. for C52H50FN3O17 ´ H2O (1008.0): C 61.96, H 5.00, N 4.17;
found: C 62.00, H 5.23, N 4.55.
5.8. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine-3'-(Hydrogen Butane-

Helvetica Chimica Acta ± Vol. 84 (2001)
1081
dioate) (50). According to 5.1, from 38. Yield 85%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf
0.34 ± 0.46. UV (MeOH): 203 (4.97), 210 (sh, 4.92), 237 (4.54), 268 (4.67), 279 (sh, 4.11). 1H-NMR
((D6)DMSO): 12.29 (br. s, COOH); 10.22 (2s, H N(2)); 8.37, 8.32 (2s, H C(8)); 8.18 ± 8.10 (m, 4 H o to NO2
(npeoc), 2 H o to NO2 (npe)); 7.66 ± 7.53 (m, 4 H m to NO2 (npeoc), 2 H m to NO2 (npe)); 7.34 ± 7.26
(m, H C(3) (Ar), H C(5) (Ar)); 7.24 ± 7.12 (m, 5 arom. H, 4 H m to MeO); 6.98, 6.93 (2s, H C(2) (Ar),
H
C(6) (Ar)); 6.79 ± 6.66 (m, 4 H m to MeO); 6.08 (m, H C(1')); 5.57 ± 5.48 (m, H C(3')); 5.39 ± 5.32
(m, H C(2')); 4.86 ± 4.65 (m, MeCH(O)2), CH2CH2O (npeoc)); 4.50 ± 4.42 (m, CH2CH2O (npeoc)); 4.40 ± 3.97
(m, CH2CH2O (npe), ArCH2 , C(4')); 3.68 (s, 2 MeO); 3.76 ± 3.49 (2m, 2 H C(5')); 3.37 ± 3.21
H
(m, CH2CH2O (npeoc)); 3.18 ± 3.02 (m, CH2CH2O (npeoc), CH2CH2O (npe)); 2.68 ± 2.44 (m, 4 H (succ.));
1.15, 1.08 (2d, MeCH(O)2). Anal. calc. for C70H66N8O22 (1371.3): C 61.31, H 4.85, N 8.17; found: C 60.93, H 4.93,
N 7.98.
5.9. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)-ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O2-[2-(4-nitrophenyl)ethyl]guanosine 3'-(Hydrogen
Butanedioate) (51). According to 5.1, from 39. Yield 91%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.43 ± 0.49. UV (MeOH): 203 (4.97), 211 (sh, 4.58), 237 (4.59), 268 (4.74). 1H-NMR (CDCl3): 8.20 ±
8.04 (m, 4 H o to NO2 (npeoc), 2 H o to NO2 (npe)); 8.03, 7.88 (2s, H C(8)); 7.52 ± 7.43 (m, 2 H m to NO2
(npeoc)); 7.43 ± 7.13 (m, 2 H m to NO2 (npeoc), H N(2), 5 arom. H, 4 H m to MeO, 2 H m to NO2 (npe),
H
H
C(2) (Ar)); 6.89 ± 6.84 (m, H C(5) (Ar)); 6.83 ± 6.64 (m, H C(6) (Ar), 4 H o to MeO); 6.20, 6.14 (2d,
C(1')); 5.55 ± 5.48 (m, H C(3')); 5.28, 5.15 (2m, H C(2')); 4.89, 4.78 (2q, MeCH(O)2); 4.68 (t, CH2CH2O
(npeoc)); 4.52 ± 4.43 (m, CH2CH2O (npeoc)); 4.42 ± 3.85 (m, CH2CH2O (npe), ArCH2, H C(4')); 3.72
(s, 2 MeO); 3.52 ± 3.32 (m, 2 H C(5')); 3.27 (t, CH2CH2O (npeoc)); 3.14 (t, CH2CH2O (npeoc)); 3.05
(t, CH2CH2O (npe)); 2.81 ± 2.60 (m, 4 H (succ.)); 1.32, 1.12 (2d, MeCH(O)2). Anal. calc. for C70H65FN8O22
(1389.3): C 60.52, H 4.72, N 8.07; found: C 60.66, H 4.90, N 7.87.
5.10. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine 3'-(Hydrogen Butanedioate) (52). According to 5.1,
from 40. Yield 87%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.34 ± 0.38. UV (MeOH): 204
(4.92), 209 (sh, 4.88), 236 (4.58), 270 (4.45), 284 (sh, 4.38). 1H-NMR ((D6)DMSO): 12.28 (br. s, COOH); 10.85
(br. s, H N(4)); 8.23 ± 8.05 (m, H C(6), 4 H o to NO2(npeoc)); 7.63 ± 7.52 (m, 4 H m to NO2 (npeoc)); 7.40 ±
7.15 (m, 5 arom. H, 4 H m to MeO, 2 H m to NO2 (npe), H C(3) (Ar), H C(5) (Ar)); 7.10 ± 7.02 (m, H C(2)
(Ar), H C(6) (Ar)); 6.94 ± 6.84 (m, 4 H o to MeO); 6.78 (m, H C(5)); 5.97 (d, H C(1')); 5.28 (m, H C(3'));
5.05, 4.88 (2m, MeCH(O)2); 4.64 ± 4.18 (m, 2 CH2CH2O (npeoc), ArCH2, H C(2'), H C(4')); 3.73 (s, 2 MeO);
3.43 ± 3.25 (m, 2 H C(5')); 3.18 ± 3.02 (m, 2 CH2CH2O (npeoc)); 2.64 ± 2.48 (m, 4 H (succ.)); 1.30, 1.19 (2d,
MeCH(O)2). Anal. calc. for C61H57N5O20 ´ H2O (1198.2): C 61.15, H 4.96, N 5.85; found: C 61.21, H 5.09, N 5.85.
5.11. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine 3'-(Hydrogen Butanedioate) (53). According
to 5.1, from 41. Yield 87%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.34 ± 0.38. UV (MeOH):
205 (4.93), 236 (4.54), 269 (4.43), 287 (sh, 4.30). 1H-NMR (CDCl3): 8.49, 8.41 (2d, H C(6)); 8.17 ± 8.08 (m, 4 H
o to NO2 (npeoc)); 7.42 ± 7.18 (m, H N(4), 5 arom. H, 4 H m to MeO, H C(2) (Ar), 4 H m to NO2 (npeoc));
7.08 ± 6.95 (m, H C(5) (Ar), H C(6) (Ar)); 6.94 ± 6.77 (m, H C(5), 4 H o to MeO); 6.00, 5.92 (2s, H C(1'));
5.34 ± 5.23, 5.22 ± 5.10 (2m, H C(3'), MeCH(O)2); 4.78 ± 4.17 (m, 2 CH2CH2O (npeoc), ArCH2, H C(2'),
H
C(4')); 3.75 (s, 2 MeO); 3.66 ± 3.55, 3.47 ± 3.35 (m, 2 H C(5')); 3.09 (t, CH2CH2O (npeoc)); 2.93
(t, CH2CH2O (npeoc)); 2.72 ± 2.48 (m, 4 H (succ.)); 1.41, 1.29 (2d, MeCH(O)2). Anal. calc. for
C61H56FN5O20 ´ H2O (1216.2): C 60.25, H 4.81, N 5.76; found: C 60.45, H 4.95, N 5.59.
5.12. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine 3'-(Hydrogen Butanedioate) (54). According to
5.1, from 42. Yield 76%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.38 ± 0.43. UV (MeOH): 203
(5.00), 235 (4.47), 267 (4.57), 272 (sh, 4.54). 1H-NMR (CDCl3): 8.62, 8.58 (2d, H C(2)); 8.51 ± 8.37 (br. s,
H
N(6)); 8.19 ± 8.10, 8.04 (2m, 4 H o to NO2 (npeoc), H C(8)); 7.47 ± 7.33 (m, 4 H m to NO2 (npeoc), H C(3)
(Ar), H C(5) (Ar)); 7.32 ± 7.13 (m, 4 H m to MeO, H C(2) (Ar), H C(6) (Ar), 4 arom. H); 6.82 ± 6.72
(m, 4 H o to MeO); 6.21, 6.12 (2d, H C(1')); 5.54 (m, H C(3')); 5.37, 5.18 (2m, H C(2')); 4.88, 4.81 (2q,
MeCH(O)2); 4.53 ± 4.40 (m, 2 CH2CH2O (npeoc)); 4.38 ± 4.24, 4.10 ± 3.92 (2m, ArCH2, H C(4')); 3.74
(s, 2 MeO); 3.57 ± 3.47, 3.46 ± 3.35 (m, 2 H C(5')); 3.12 (t, 2 CH2CH2O (npeoc)); 2.80 ± 2.51 (m, 4 H (succ.));
1.32, 1.12 (2d, MeCH(O)2). Anal. calc. for C62H59N7O19 (1206.2): C 61.74, H 4.93, N 8.13; found: C 61.56, H 5.00,
N 7.86.
5.13. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-{{4-[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine 3'-(Hydrogen Butanedioate) (55). Accord-

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Helvetica Chimica Acta ± Vol. 84 (2001)
ing to 5.1, from 43. Yield 78%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.33 ± 0.41. UV
(MeOH): 203 (5.98), 235 (4.44), 267 (4.55), 272 (sh, 4.52). 1H-NMR (CDCl3): 8.62, 8.58 (2d, H C(2)); 8.66 ±
8.49 (br. s, H N(6)); 8.18 ± 8.10, 8.04 (2m, 4 H o to NO2 (npeoc), H C(8)); 7.47, 7.33 (2m, 4 H m to NO2
(npeoc), 4 H m to MeO); 7.33 ± 7.18 (m, 4 arom. H, H C(2) (Ar)); 7.00 ± 6.88 (m, H C(5) (Ar)); 6.84 ± 6.58
(m, H C(6) (Ar), 4 H o to MeO); 6.20, 6.13 (2d, H C(1')); 5.53 (m, H C(3')); 5.31 ± 5.21 (2m, H C(2'));
4.89, 4.81 (2q, MeCH(O)2); 4.54 ± 4.41 (m, 2 CH2CH2O (npeoc)); 4.38 ± 3.86 (m, ArCH2, H C(4')); 3.74
(s, 2 MeO); 3.60 ± 3.49, 3.48 ± 3.35 (2m, 2 H C(5')); 3.12 (t, 2 CH2CH2O (npeoc)); 2.78 ± 2.57 (m, 4 H (succ.));
1.33, 1.14 (2d, MeCH(O)2). Anal. calc. for C62H58FN7O19 (1224.1): C 60.83, H 4.78, N 8.01; found: C 60.44,
H 4.65, N 7.58.
6. Phosphitylation to 56 ± 67. 6.1. General Procedure. The 5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-acetal-
protected monomer 32 ± 43 (0.5 mmol, 450 ± 640 mg) was co-evaporated with abs. CH2Cl2 (2 Â 30 ml).
Subsequently, 4 ± 8 ml (0.6 ± 1.2 mmol, 181 ± 362 mg) of a stock soln. of 2-cyanoethyl tetraisopropylphosphor-
odiamidite (0.15m in abs. CH2Cl2) were added in portions of 1 ± 2 ml. The mixture was evaporated, the oil taken
up with MeCN (10 ml), and 1H-tetrazole (0.5 ± 0.7 mmol, 35 ± 50 mg) was added. The soln. was stirred at r.t. for
1 ± 4 h. The reaction was stopped by pouring into sat. NaHCO3 soln. (150 ml) after dilution with AcOEt
(100 ml). The aq. phase was extracted with AcOEt (50 ml), the combined org. phase washed with twice with sat.
NaCl soln. (50 ml), dried (Na2SO4), and evaporated, and the crude oil purified by FC (silica gel (20 g), toluene/
AcOEt/MeOH). Note: It is very important that chromatographic purification takes place rapidly. The product
fractions were evaporated and co-evaporated with MeOH (2 Â 5 ml) and CH2Cl2 (2 Â 5 ml). The resulting
colorless foam was dried in a desiccator under high vacuum.
6.2. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)uridine 3'-(2-Cyanoethyl Diisopropyl-
phosphoramidite) (56). According to 6.1, from 32. Yield 85%. Colorless foam. TLC (toluene/AcOEt/MeOH
5 :4 :1): Rf 0.64, 0.68. UV (MeOH): 204 (4.84), 234 (4.40), 260 (4.06). 1H-NMR (CDCl3): 8.60 (br. s, H N(3));
7.93 ± 7.77 (m, H C(6)); 7.40 ± 7.18 (m, 4 H m to MeO, 10 arom. H); 6.81 (m, 4 H o to MeO); 6.09 (2d,
H
C(1')); 5.27 ± 5.01 (m, H C(5), MeCH(O)2); 4.80 ± 4.42 (m, H C(2'), H C(3'), ArCH2); 4.24
(m, H C(4')); 3.99 ± 3.33 (s, 12 H, 2 MeO), 2 H C(5'), CH2CH2CN, 2 Me2CH); 2.63 ± 2.32 (m, CH2CH2CN);
1.40 (m, MeCH(O)2); 1.24 ± 0.98 (2m, 2 Me2CH). Anal. calc. for C48H57N4O10P (881.0): C 65.44, H 6.52, N 6.36;
found: C 65.52, H 6.53, N 6.01.
6.3. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N2-{[2-(4-nitrophenyl)ethoxy]car-
bonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine 3'-(2-Cyanoethyl Diisopropylphosphoramidite) (57). According
to 6.1, from 33. Yield 80%. Colorless foam. TLC (hexane/AcOEt 1:3): Rf 0.57, 0.63. UV (MeOH): 205 (4.96),
236 (4.47), 269 (4.56). 1H-NMR (CDCl3): 8.18 ± 7.85 (m, 4 H o to NO2 (npe), H C(8)); 7.55 ± 6.95 (m, 2 H m to
NO2 (npeoc), 2 H m to NO2 (npe)), 8 arom. H, 4 H m to MeO, H N(2)); 6.80 ± 6.65 (m, 4 H o to MeO); 6.18 ±
5.92 (m, H C(1')); 5.41 ± 4.72 (m, acetal-H, H C(2'), CH2CH2OCO); 4.60 ± 3.81 (m, 10 H, CH2CH2O, ArCH2,
CH2CH2CN, H C(3'), H C(4')); 3.70 (2s, 2 MeO); 3.77 ± 3.83 (m, 2 H C(5')); 3.35 ± 3.21 (m, CH2CH2OCO);
3.07 ± 2.93 (m, CH2CH2O); 2.72 ± 2.61, 2.30 ± 2.19 (2m, CH2CH2CN); 1.39 ± 0.95 (3m, MeCH(O)2, 2 Me2CH).
Anal. calc. for C66H72N9O15P (1262.3): C 62.80, H 5.75, N 9.99; found: C 62.69, H 5.86, N 9.85.
6.4. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N4-{[2-(4-nitrophenyl)ethoxy]carbon-
yl}cytidine 3'-(2-Cyanoethyl Diisopropylphosphoramidite) (58). According to 6.1, from 34. Yield 85%. Colorless
foam. TLC (toluene/AcOEt 1:3): Rf 0.52, 0.57. UV (MeOH): 204 (4.92), 235 (4.53), 277 (4.23), 288 (sh, 4.17).
1H-NMR (CDCl3): 8.45 (m, H C(6)); 8.17 (m, 2 H o to NO2); 7.72 ± 7.53 (br. s, H N(4)); 7.48 ± 7.13 (m, 2 H m
to NO2, 4 H m to MeO, 10 arom. H); 6.90 ± 6.75 (m, 4 H o to MeO); 6.72 ± 6.61 (m, H C(5)); 6.17 ± 6.01
(m, H C(1')); 5.44 ± 5.18 (m, acetal-H); 4.88 ± 4.23 (m, ArCH2, CH2CH2O, H C(2'), H C(3'), H C(4'));
3.90 ± 3.37 (m, 2 MeO, 2 H C(5'), CH2CH2CN, 2 MeCH); 3.06 (t, CH2CH2O); 2.35 (m, CH2CH2CN); 1.40 (2d,
MeCH(O)2); 1.35 (m, 2 Me2CH). Anal. calc. for C57H65N6O13P (1073.2): C 63.80, H 6.11, N 7.83; found: C 63.29,
H 6.23, N 7.63.
6.5. 2'-O-[1-(Benzyloxy)ethyl]-5'-O-(4,4'-dimethoxytriphenylmethyl)-N6-{[2-(4-nitrophenyl)ethoxy]carbon-
yl}adenosine 3'-(2-Cyanoethyl Diisopropylphosphoramidite) (59). According to 6.1, from 35. Yield 78%.
Colorless foam. TLC (hexane/AcOEt 1:3): Rf 0.59, 0.64. UV (MeOH): 204 (5.00), 235 (4.43), 267 (4.47), 22 (sh,
4.44). 1H-NMR (CDCl3): 8.65, 8.59 (2d, H C(2)); 8.24 (m, H N(6)); 8.20 ± 8.04 (m, H C(8), 2 H o to NO2);
7.48 ± 7.10 (m, 2 H m to NO2, 4 H m to MeO, 8 arom. H); 7.09 ± 6.95 (m, 2 arom. H); 6.82 ± 6.71 (m, 4 H o to
MeO); 6.23 ± 6.12 (m, H C(1')); 5.33 ± 4.82 (3m, MeCH(O)2, H C(2')); 4.70 ± 3.79 (m, H C(3'), H C(4'),
CH2CH2O, ArCH2); 3.72 (m, 2 MeO); 3.68 ± 3.25 (m, 2 H C(5'), CH2CH2CN, Me2CH); 3.10 (t, CH2CH2O);
2.64 ± 2.28 (m, CH2CH2CN); 1.31 ± 0.95 (m, MeCH(O)2, 2 Me2CH). Anal. calc. for C57H65N8O12P (1085.2):
C 63.08, H 6.04, N 10.32; found: C 62.93, H 6.16, N 10.06.

Helvetica Chimica Acta ± Vol. 84 (2001)
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6.6. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}uridine 3'-(2-Cyanoethyl Diisopropylphosphoramidite) (60). According to 6.1, from 36. Yield 89%.
Colorless foam. TLC (toluene/AcOEt 1 :1): Rf 0.38, 0.44. UV (MeOH): 205 (4.92), 235 (4.38), 265 (4.30), 279
1
(sh, 4.13). H-NMR (CDCl3): 8.18 (m, 2 H o to NO2 (npeoc)); 8.08 (br. s, H N(3)); 7.99 ± 7.82 (m, H C(6));
7.44 ± 7.00 (m, 5 arom. H, 4 H m to MeO, 2 H m to NO2 (npeoc)), H C(2) (Ar), H C(5) (Ar), H C(6) (Ar));
6.87 ± 6.75 (m, 4 H o to MeO); 6.05, 5.94 (2m, H C(1')); 5.25 ± 5.06 (m, MeCH(O)2, H C(5)); 4.73 ± 4.40
(m, ArCH2 , CH2CH2O (npeoc), H C(2'), H C(3')); 4.30 ± 4.13 (m, H C(4')); 3.97 ± 3.35 (m, 2 MeO,
2 H C(5'), CH2CH2CN, 2 Me2CH); 3.15 (t, CH2CH2O (npeoc)); 2.63 ± 2.49, 2.44 ± 2.35 (2m, CH2CH2CN);
1.49 ± 1.34 (m, MeCH(O)2); 1.27 ± 0.94 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.21, 150.94, 150.73, 150.49 (4 s).
Anal. calc. for C57H64FN5O15P (1109.1): C 61.73, H 5.82, N 6.31; found: C 61.56, H 5.82, N 5.67.
6.7. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-{{4-[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}uridine 3'-(2-Cyanoethyl Diisopropylphosphoramidite) (61). According to 6.1, from 37. Yield
89%. Colorless foam. TLC (toluene/AcOEt 1:1): Rf 0.38, 0.44. UV (MeOH): 205 (4.92), 235 (4.38), 265 (4.30),
279 (sh, 4.13). 1H-NMR (CDCl3): 8.18 (m, 2 H o to NO2 (npeoc)); 8.08 (br. s, H N(3)); 7.99 ± 7.82
(m, H C(6)); 7.44 ± 7.00 (m, 5 arom. H, 4 H m to MeO, 2 H m to NO2(npeoc), H C(2) (Ar), H C(5) (Ar),
H
C(6) (Ar)); 6.87 ± 6.75 (m, 4 H o to MeO); 6.05, 5.94 (2m, H C(1')); 5.25 ± 5.06 (m, MeCH(O)2, H C(5));
4.73 ± 4.40 (m, ArCH2 , CH2CH2O (npeoc), C(2'), C(3')); 4.30 ± 4.13 (m, H C(4')); 3.97 ± 3.35
H
H
(m, 2 MeO, CH2CH2CN, 2 H C(5'), 2 Me2CH); 3.15 (t, CH2CH2O (npeoc)); 2.63 ± 2.49, 2.44 ± 2.35 (2m,
CH2CH2CN); 1.49 ± 1.34 (m, MeCH(O)2); 1.27 ± 0.94 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.21, 150.94, 150.73,
150.49 (4 s). Anal. calc. for C57H64FN5O15P (1109.1): C 61.73, H 5.82, N 6.31; found: C 61.56, H 5.82, N 5.67.
6.8. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine 3'-(2-Cyanoethyl Di-
isopropylphosphoramidite) (62). According to 6.1, from 38. Yield 72%. Colorless foam. TLC (toluene/AcOEt/
MeOH 5 :6 :1): Rf 0.80, 0.83. UV (MeOH): 204 (5.05), 236 (4.51), 269 (4.62), 278 (sh, 4.56). 1H-NMR (CDCl3):
8.20 ± 8.07 (m, 4 H o to NO2 (npeoc), 2 H o to NO2 (npe)); 8.06, 7.95 (2m, H C(8)); 7.50 ± 7.14 (m, H N(2),
5 arom. H, 4 H m to NO2 (npeoc), 2 H m to NO2 (npe), 4 H m to MeO); 7.04 ± 6.99 (m, H C(3) (Ar), H C(5)
(Ar)); 6.98 ± 6.88 (m, H C(2) (Ar), H C(6) (Ar)); 6.80 ± 6.68 (m, 4 H o to MeO); 6.09, 5.98 (2d, H C(1'));
5.40 ± 5.12 (m, H C(2')); 5.06 ± 4.92, 4.90 ± 4.82 (2m, MeCH(O)2); 4.81 ± 4.70 (m, CH2CH2O (npeoc)); 4.60 ±
4.39, 4.38 ± 3.79 (2m, CH2CH2O (npeoc), CH2CH2O (npe), ArCH2, H C(3'), H C(4'), CH2CH2CN)); 3.72
(2s, 2 MeO); 3.66 ± 3.39 (m, 2 H C(5'), 2 Me2CH); 3.13 (t, CH2CH2O (npeoc)); 2.99 (m, CH2CH2O (npeoc),
CH2CH2O (npe)); 2.72 ± 2.61, 2.30 ± 2.18 (2m, CH2CH2CN); 1.43 ± 1.31 (m, MeCH(O)2); 1.30 ± 0.94
(m, 2 Me2CH). 31P-NMR (CDCl3): 151.63, 151.23, 150.77, 150.43 (4 s). Anal. calc. for C75H79N10O20P (1471.5):
C 61.22, H 5.41, N 9.52; found: C 60.97, H 5.44, N 9.32.
6.9. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)-ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophenyl)ethyl]guanosine 3'-(2-Cya-
noethyl Diisopropylphosphoramidite) (63). According to 6.1, from 39. Yield 70%. Colorless foam. TLC
(toluene/AcOEt/MeOH 10 :8 :1): Rf 0.76, 0.80. UV (MeOH): 203 (4.96), 237 (4.49), 269 (4.63), 279 (sh, 4.56).
1H-NMR (CDCl3): 8.20 ± 8.06 (m, 4 H o to NO2 (npeoc), 2 H o to NO2 (npe)); 8.04,7.96 (2m, H C(8)); 7.54 ±
7.10 (m, H N(2), 5 arom. H, 4 H m to NO2 (npeoc), 2 H m to NO2 (npe), 4 H m to MeO, H C(2) (Ar)); 7.05 ±
6.83 (m, H C(5) (Ar), H C(6) (Ar)); 6.82 ± 6.66 (m, 4 H o to MeO); 6.09, 5.97 (2m, H C(1')); 5.42 ± 5.13
(m, H C(2')); 5.08 ± 4.82 (m, MeCH(O)2); 4.80 ± 4.68 (m, CH2CH2O (npeoc)); 4.60 ± 3.78 (m, CH2CH2O
(npeoc), CH2CH2O (npe), ArCH2 ,
H C(3'), H C(4'), CH2CH2CN)); 3.72 (s, 2 MeO); 3.68 ± 3.41
(m, 2 H C(5'), 2 Me2CH); 3.35 ± 3.20 (m, CH2CH2O (npeoc); 3.18 ± 3.09 (t, CH2CH2O (npeoc)); 3.05 ± 2.92
(m, CH2CH2O (npe)); 2.72 ± 2.61, 2.30 ± 2.20 (2m, CH2CH2CN); 1.39, 1.37 (2d, MeCH(O)2); 1.30 ± 0.94
(m, 2 Me2CH). 31P-NMR (CDCl3): 151.61, 151.18, 150.78, 150.49 (4 s). Anal. calc. for C75H78FN10O20P (1489.4):
C 60.48, H 5.28, N 9.40; found: C 60.53, H 5.32, N 9.23.
6.10. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine 3'-(2-Cyanoethyl Diisopropylphosphoramidite)
(64). According to 6.1, from 40. Yield 86%. Colorless foam. TLC (CHCl3/MeOH 100 :1): Rf 0.43,0.46. UV
(MeOH): 204 (4.92), 235 (4.54), 272 (4.39), 289 (sh, 4.28). 1H-NMR (CDCl3): 8.56 ± 8.38 (m, H C(6)); 8.20 ±
8.09 (m, 4 H o to NO2(npeoc)); 7.56 ± 7.47 (br. s, H N(4)); 7.46 ± 7.12 (m, 5 arom. H, 4 H m to NO2 (npeoc), 4 H
m to MeO, H C(3) (Ar), H C(5) (Ar)); 7.08 ± 6.99 (m, H C(2) (Ar), H C(6) (Ar)); 6.88 ± 6.78 (m, 4 H o to
MeO); 6.72, 6.61 (2m,
H C(5)); 6.13 ± 5.98 (2m, H C(1')); 5.47 ± 5.15 (m, MeCH(O)2); 4.87 ± 4.64
(m, H C(2')); 4.62 ± 4.20 (m, 2 CH2CH2O (npeoc), ArCH2, H C(3'), H C(4')); 3.77 (s, 2 MeO); 3.74 ± 3.37
(m, Me2CH, CH2CH2CN, 2 H C(5')); 3.18 ± 3.02 (m, 2 CH2CH2O (npeoc)); 2.73, 2.34 (2m, CH2CH2CN); 1.43,

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Helvetica Chimica Acta ± Vol. 84 (2001)
1.38 (2d, MeCH(O)2); 1.30 ± 0.89 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.54, 151.67, 150.35, 149.81 (4 s). Anal.
calc. for C66H70N7O18P (1280.3): C 61.92, H 5.51, N 7.66; found: C 61.75, H 5.87, N 5.78.
6.11. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}cytidine 3'-(2-Cyanoethyl Diisopropylphosphorami-
dite) (65). According to 6.1, from 41. Yield 94%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf
0.76, 0.80. UV (MeOH): 205 (4.98), 235 (4.59), 272 (4.43), 288 (sh, 4.32). 1H-NMR (CDCl3): 8.57 ± 8.39
(m, H C(6)); 8.21 ± 8.12 (m, 4 H o to NO2 (npeoc)); 7.63 ± 7.35 (br. s, H N(4)); 7.45 ± 7.02 (m, 5 arom. H, 4 H m
to NO2 (npeoc), 4 H m to MeO, H C(3) (Ar), H C(5) (Ar), H C(6) (Ar)); 6.87 ± 6.78 (m, 4 H o to MeO);
6.74, 6.62 (2m, H C(5)); 6.08, 5.99 (2d, H C(1')); 5.47 ± 5.16 (m, MeCH(O)2); 4.88 ± 4.21 (m, 2 CH2CH2O
(npeoc), ArCH2, H C(2'), H C(3'), H C(4')); 3.79 (d, 2 MeO); 3.73 ± 3.38 (m, 2 Me2CH, CH2CH2CN,
2 H C(5')); 3.18 ± 3.00 (m, 2 CH2CH2O (npeoc)); 2.78 ± 2.31 (m, CH2CH2CN); 1.45 ± 1.36 (m, MeCH(O)2);
1.31 ± 0.91 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.69, 150.87, 150.21, 149.73 (4 s). Anal. calc. for C66H69FN7O18P
(1298.3): C 61.06, H 5.36, N 7.55; found: C 61.76, H 5.63, N 7.95.
6.13. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}-
oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}adenosine 3'-(2-Cyanoethyl Diisopropylphosphoramidite)
(66). According to 6.1, from 42. Yield 82%. Colorless foam. TLC (CHCl3/MeOH 100 :1): Rf 0.65, 0.69. UV
1
(MeOH): 204 (5.01), 235 (4.46), 267 (4.58), 273 (sh, 4.55). H-NMR (CDCl3): 8.60 (dd, H C(2)); 8.23 ± 8.08
(m, 4 H o to NO2 (npeoc), H C(8)); 8.02 (br. s, H N(6)); 7.48 ± 7.36 (m, 4 H m to NO2 (npeoc), H C(3) (Ar),
H
C(5) (Ar)); 7.35 ± 7.12 (m, 5 arom. H, H C(2) (Ar), H C(6) (Ar)); 7.08 ± 6.88 (m, 4 H m to MeO); 6.82 ±
6.72 (m, 4 H o to MeO); 6.23 ± 6.08 (2d, H C(1')); 5.35 ± 4.82 (m, H C(2'), MeCH(O)2); 4.68 ± 3.05
(m, ArCH2, 2 CH2CH2O (npeoc), 2 Me2CH, 2 MeO, H C(3'), H C(4'), CH2CH2CN, 2 H C(5')); 2.67 ±
2.53, 2.38 ± 2.26 (2m, CH2CH2CN); 1.40, 1.35 (2d, MeCH(O)2); 1.31 ± 0.97 (m, 2 Me2CH). 31P-NMR (CDCl3):
151.69, 151.14, 150.81, 150.48 (4 s). Anal. calc. for C67H72N9O17P (1306.3): C 61.60, H 5.56, N 9.65; found:
C 61.18, H 5.71, N 9.48.
6.14. 5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-{1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}-
benzyl}oxy}ethyl}-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}-adenosine 3'-(2-Cyanoethyl Diisopropylphosphoram-
idite) (67). According to 6.1, from 43. Yield 88%. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf
0.78, 0.82. UV (MeOH): 203 (4.97), 236 (4.44), 269 (4.56), 274 (sh, 4.56). 1H-NMR (CDCl3): 8.62, 8.58 (2d,
H
C(2)); 8.20 ± 8.11, 8.07 (2m, 4 H o to NO2 (npeoc), H C(8)); 8.06 ± 7.95 (br. s, H N(6)); 7.47, 7.15 (m, 4 H m
to NO2 (npeoc), H C(2) (Ar), 4 H m to MeO, 5 arom. H); 7.02 ± 6.67 (m, H C(5) (Ar), H C(6) (Ar), 4 H o
to MeO); 6.22 ± 6.11 (m, H C(1')); 5.33 ± 4.85 (m, H C(2'), MeCH(O)2); 4.66 ± 3.79 (m, H C(3'), ArCH2,
2 CH2CH2O (npeoc), 2 MeO, H C(3'), H C(4'), CH2CH2CN)); 3.74 (s, 2 MeO); 3.72 ± 3.24 (m, 2 H C(5'),
Me2CH); 3.19 ± 3.07 (m, 2 CH2CH2O (npeoc)); 2.67 ± 2.55, 2.37 ± 2.28 (2m, CH2CH2CN); 1.42, 1.38 (2d,
MeCH(O)2); 1.32 ± 0.98 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.65, 151.07, 150.83, 150.64 (4 s). Anal. calc. for
C67H71FN9O17P (1324.3): C 60.77, H 5.40, N 9.52; found: C 60.76, H 5.59, N 9.56.
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Received February 15, 2001