Oligonucleosides with a nucleobase-including backbone: Part 11. Linear and convergent synthesis of ethynylene-linked uridine-derived oligomers

Article abstract of DOI:10.1002/hlca.200490264

A linear and a convergent synthesis of uridine-derived backbone-base- dedifferentiated (backbone including) oligonucleotide analogues were compared. The Sonogashira cross-coupling of the alkyne 1 and the iodide 2 gave the dimer 4 that was C-desilylated and again coupled with 2 to give the trimer 6 (Scheme 1). Repeating this linear sequence led to the pentamer 10. Coupling yields were satisfactory up to formation of the trimer 6, but decreased for the coupling to higher oligomers. Similarly, coupling of the alkynes 5, 7, and 9 with the iodouridine 3 gave, in decreasing yields, the trimer 12, tetramer 13, and pentamer 14, respectively. The dimeric iodouracil 20 was synthesized by coupling the alkyne 17 with the iodide 16 to the dimer 18, followed by iodination at C(6/I) to 19 and O-silylation (Scheme 2). The iodinated dimer 23 was prepared by iodinating and O-silylating the known dimer 21. Coupling of 20 and 23 with the dimer 5, trimer 7, and tetramer 9 gave the tetramers 8 and 13, the pentamers 10 and 14, and the hexamer 15, respectively (Scheme 3). The oligomers up to the pentamer 14 were deprotected to provide the trimer 24, tetramer 25, and pentamer 26 (Scheme 4). There was no evidence for the heteropairing of the pentamer 26 and rA₇, nor for the pairing of rU₅ and rA₇, while a UV melting experiment showed the beginning of a sigmoid curve for the interaction of rU₇ with rA₇. Therefore, the pentamer 26 does not pair more strongly with rA₇ than rU₅.

Full text of DOI:10.1002/hlca.200490264

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Helvetica Chimica Acta Vol. 87 (2004)
Oligonucleosides with a Nucleobase-Including Backbone
Part 11
Linear and Convergent Synthesis of Ethynylene-Linked Uridine-Derived Oligomers
by Simon Eppacher, Nathalie Solladie¬, and Andrea Vasella*
Laboratorium f¸r Organische Chemie, ETH Hˆnggerberg, HCI CH-8093 Z¸rich
A linear and a convergent synthesis of uridine-derived backbone-base-dedifferentiated (backbone
including) oligonucleotide analogues were compared. The Sonogashira cross-coupling of the alkyne 1 and the
iodide 2 gave the dimer 4 that was C-desilylated and again coupled with 2 to give the trimer 6 (Scheme 1).
Repeating this linear sequence led to the pentamer 10. Coupling yields were satisfactory up to formation of the
trimer 6, but decreased for the coupling to higher oligomers. Similarly, coupling of the alkynes 5, 7, and 9 with the
iodouridine 3 gave, in decreasing yields, the trimer 12, tetramer 13, and pentamer 14, respectively. The dimeric
iodouracil 20 was synthesized by coupling the alkyne 17 with the iodide 16 to the dimer 18, followed by
iodination at C(6/I) to 19 and O-silylation (Scheme 2). The iodinated dimer 23 was prepared by iodinating and
O-silylating the known dimer 21. Coupling of 20 and 23 with the dimer 5, trimer 7, and tetramer 9 gave the
tetramers 8 and 13, the pentamers 10 and 14, and the hexamer 15, respectively (Scheme 3). The oligomers up to
the pentamer 14 were deprotected to provide the trimer 24, tetramer 25, and pentamer 26 (Scheme 4). There
was no evidence for the heteropairing of the pentamer 26 and rA7, nor for the pairing of rU5 and rA7, while a UV
melting experiment showed the beginning of a sigmoid curve for the interaction of rU7 with rA7. Therefore, the
pentamer 26 does not pair more strongly with rA7 than rU5.
Introduction. In our quest for autonomously pairing oligonucleotide analogues
that do not, strictly speaking, differentiate nucleobases from the backbone, we have so
far designed three generations of analogues, viz. phosphodiester analogues of DNA
oligomers, neutral, ethynylene-linked (ˆethyne-1,2-diyl-linked) analogues of RNA
oligomers, and ether-linked RNA oligomers. We reported the synthesis of protected
phosphodiester-linked decamers, their partially successful deprotection, and the
incorporation of corresponding deoxyribose- and deoxyerythrose-derived monomers
into a DNA 14-mer [1 3]. The second generation of analogues is still under scrutiny.
We have so far reported the synthesis of monomers and dimers required for the
preparation of ethynylene-linked oligomers [4 6], the synthesis of a corresponding
adenosine-derived tetramer [7], and the conformational analysis of an adenosine-
derived dimer [8]. This analysis showed that the substitution at C(8) of adenosine in
combination with the intramolecular H-bond of the propargylic HOÀC(5') to N(3)
results in a very strong preference for the syn-conformation. As we had assumed, on the
basis of indicative force-field calculations and model studies, that the autonomous
pairing of these analogues required an anti-conformation, we designed a third
generation of analogues that should pair in the syn-conformation. Partially protected,
self-complementary ether-linked dimers indeed pair in CHCl3 solution [9][10].
Independently of pursuing our studies of this type of analogues, we planned to
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

Helvetica Chimica Acta Vol. 87 (2004)
2927
experimentally test the assumption that ethynylene-linked oligomers only pair in the
anti-conformation; we also wished to learn if such oligomers pair with oligomeric RNA.
Uridine-derived oligomers A are required to test the pairing properties with the
C(5')ÀC(8) ethynylene-linked adenosine counterpart B (homopairing) and with RNA
(heteropairing; Fig. 1). We planned to investigate a linear and a convergent approach
to the synthesis of uridine-derived oligomers. The linear approach features a
Sonogashira coupling of the mono- to pentameric alkynes 1, 5, 7, and 9 with the 6-
iodouridine 2, followed by deprotection of the C-silylated coupling products (cf.
Scheme 1). A final coupling with the monomer 3 should introduce a terminal unit that is
devoid of a C(5')-ethynyl group. In a shorter, convergent approach the iodinated
dimers 20 and 23 should be coupled to the monomer 5, trimer 7, and tetramer 9 (cf.
Scheme 3).
Fig. 1. Uridine- and adenosine-derived ethynylene-linked oligonucleosides A and B
Results and Discussion. The first reaction cycle characterising the linear approach
to the uridine-derived oligomers started with the Sonogashira coupling of the acetylene
1 and the iodide 2 in the presence of 5% [Pd2(dba)3], 7% CuI and 7% P(fur)3 to yield
77% of the dimer 4 [4] (Scheme 1). C-Desilylation of 4 led in 63% yield1) to the
dimeric acetylene 5 [4]. In the second cycle, the iodide 2 was coupled to the dimer 5 to
yield 63% of the trimer 6. Yields dropped significantly in the following coupling of 2
with 7 to the tetramer 8. We, therefore, reinvestigated the reaction conditions for this
step (Table 1).
As shown in Table 1, complete conversion of the alkyne 7 required large amounts of
Pd catalyst. Yields remained low, and the coupling product 8 was not readily separated
from 72). Replacing Et3N with 2,2,6,6-tetramethylpiperidine (TMP), or substituting
toluene with DMSO or DMF led to a complex mixture containing small amounts of 8.
Lower yields resulted from replacing P(fur)3 by P(i-Pr)3 or Ph2P(CH2)nPPh2 (n ˆ 2, 3,
or 5). C-Desilylation of 8 yielded 54% of the alkyne 9 that was coupled with 3 equiv. of
the iodide 2 in the presence of 0.5 equiv. of [Pd2(dba)]3 and 1 equiv. each of CuI and
P(fur)3 to yield 15% of the pentamer 10 that was C-desilylated to the alkyne 11 (52%;
Table 2). Analogous conditions were used for the coupling of the iodouracil 3 with the
dimer 5, trimer 7, tetramer 9, and pentamer 11 to yield the products 12 14 in yields of
1
)
)
When the HOÀC(5') groups were protected as Et3Si-ethers instead of (i-Pr)3Si (TIPS)-ethers it was not
possible to C-desilylate under these conditions without partial desilylation of the Et3Si ethers.
Coupling of 7 to the propargylic alcohol corresponding to 2 led in lower yields (ca. 10%) to a more readily
separated mixture of 7 and coupling product [4].
2

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 1
a) [Pd2(dba)3] (dba ˆ dibenzylideneacetone ˆ 1,5-diphenylpenta-1,4-dien-3-one), CuI, P(fur)3, toluene/Et3N
1 :1. b) AgNO3, MeOH/AcOEt, then KCN.
Table 1. Cross-Coupling of the Iodide 2 with the Trimer 7: Reaction Conditions and Yields of 8
Entry
Equiv. of 7
Equiv. of [Pd2(dba)3]/CuI/PX3
Base, solvent
Time [h]
Yield of 8 [%]
1
2
3
4
5
6
7
8
4
2
3
2
2
2
3
3
0.4/0.4/0
Et3N, toluene
Et3N, toluene
Et3N, toluene
TMP, toluene
Et3N, DMF
Et3N, DMSO
Et3N, toluene
Et3N, toluene
100
48
12018
72
72
72
40a)
40a)
0.4/0.8/0.8 (X ˆ fur)
0.6/1.2/1.2 (X ˆ fur)
0.5/1.0/1.0 (X ˆ fur)
0.5/1.0/1.0 (X ˆ fur)
0.5/1.0/1.0 (X ˆ fur)
mixtureb)
0
mixtureb)
tracesb)
tracesb)
0.4/0.8/0.8 (X ˆ i-Pr)
72
72
c
0.4/0.8/1.0
)
a) Less than 50% conversion. b) Compound 8 was detected by MALDI-TOF-MS of the crude after a small-scale
workup. c) PX3 ˆ Ph2P(CH2)nPPh2 (n ˆ 2, 3, or 5).
57, 25, and 11%, respectively. The desired hexamer 15 was only formed in trace
amounts, denoting the practical limits of the linear approach.
To reduce the number of coupling steps and to alleviate the separation problem, we
also investigated a convergent approach, i.e., coupling of the iodinated dimers 20 and 23
(Scheme 2) with the dimer 5, trimer 7, and tetramer 9 (Scheme 3). Coupling of the
alkyne 17 [4] with the iodide 16 [4] yielded 91% of the dimer 18, which was iodinated at
C(6/I) by treatment with a large excess of LDA and then NIS (Scheme 2). This

Helvetica Chimica Acta Vol. 87 (2004)
2929
Table 2. Conditions and Yields of the Cross-Coupling of the Iodides 2 and 3 with the Acetylenes 1, 5, 7, 9, and 11,
and of the C-Desilylation of 4, 6, 8, and 10
n
[Pd2(dba)3]
[mol-%]
Equiv. of
alkyne
Reaction
time [h]
Yield of
coupling
Equiv. of
KCN/AgNO3
Yield of
desilylation
Dimer
Trimer
1
2
5
20
10
60
38
50
40
100
2 : 1.1
2: 1.4
3: 1.2
2: 3.1
3: 3.3
2: 3.0
3: 2.5
30: 2t.r0a1c0es of
8077% of
80
40
100
100
100
125
4
10/30
10/30
63% of 5
87% of 7
63% of 6
57% of 12
18% of 8
25% of 13
15% of 10
11% of 14
Tetramer
Pentamer
Hexamer
3
4
5
20/50
54% of 9
60/150
52% of 11
15a)
a) A signal of 15 was found in the MALDI-TOF mass spectrum of the crude after a small-scale workup.
Scheme 2
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1:1; 91%. b) Lithium diisopropylamide (LDA), THF, then N-
iodosuccinimide (NIS), then AcOH; 40% of 19; 40 % of 22. c) Triisopropylsilyl trifluoromethanesulfonate
(TIPSOTf), 2,6-di(tert-butyl)pyridine, CH2Cl2; 62% of 20; 50 % of 23.
provided the iodide 19 (40%) besides 20% of starting material. As expected (cf. [4]),
lithiation appears to be promoted by the propargylic OH group; scouting experiments
showed that the TIPSÀO(5') protected derivative of 18 decomposed under the same
reaction conditions. Lithiation of 18 with lithium 2,2,6,6-tetramethylpiperidide

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 3
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1:1.
(LiTMP), followed by iodination, led to similar results as treatment with LDA and
NIS, while lithiation with LiTMP in the presence of HMPT, followed by treatment with
NIS, gave no conversion. Attempted silylation of the iodide 19 with TIPSOTf and
pyridine in CH2Cl2 led to decomposition, while silylation with TIPSOTf and 2,6-di(tert-
butyl)pyridine [11] gave 62% of the silyl ether 20. The iodide 23 was required to
introduce an terminal unit devoid of the C(5')-ethynyl substituent; it was obtained
similarly to 19 in a yield of 20% from the known dimer 21 [4]. The low yields in the
iodination of the dimer 18 did not augur well for the iodination of higher oligomers,
and, since a binomial synthesis requires an iodination step after each reaction cycle, we
restricted our investigation of the convergent synthesis to coupling of the iodides 20 and
23 with the acetylenes 5, 7, and 9.
The results of coupling the iodinated dimers 20 and 23 with the acetylenes 5, 7, and 9
(Scheme 3) are summarised in Table 3. Although this strategy provided hexamer 15,
coupling required excess of the iodides and high concentrations of Pd catalyst to ensure
a complete conversion of the alkyne. Yields decreased considerably from coupling the
iodides 20 and 23 with the alkyne 5 to the tetramers 8 and 13, to coupling with the
alkyne 7 to the pentamers 10 and 14, and further to coupling of 23 with 9 to 15 that was
isolated in a yield of barely 5%. The synthesis of the pentamers 10 and 14 by the
convergent synthesis was difficult to reproduce, and the products were only separated
with difficulty from the starting alkyne. To facilitate the isolation of the products, we
coupled the HOÀC(5') unprotected iodinated dimers 19 and 22 with 5, 7, and 9 so as to
increase the polarity difference between coupling product and starting alkyne.

Helvetica Chimica Acta Vol. 87 (2004)
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Table 3. Conditions and Yields of the Cross-Coupling of the Dimeric Iodides 20 and 23 with the Acetylenes 5, 7,
and 9
n
Alkyne
[Pd2(dba)3] [mol-%]
Equiv. of iodide
Reaction time [h]
Yield
Tetramer
Pentamer
Hexamer
1
5
5
7
7
9
20
20
40
38
90
20: 1.5
23: 1.5
20: 2.0
23: 2.0
23: 4.0170
120
100
100
100
36% of 8
51% of 13
20% of 10
15% of 14
15
2
3
5% of
However, this led to a more-complex reaction mixture and lowered the yield of the
coupling products.
Treatment of the trimer 12, tetramer 13, and pentamer 14 with 0.16n HCl and 0.3n
HF in H2O/MeCN 2 :1 [12] led in one step and in yields of 58 70% to the uridine-
derived oligomers 24 26, respectively (Scheme 4).
Scheme 4
a) H2O/MeCN/37% HCl/40% HF 100 :50 :2 :2; 70% of 24, 67% of 25, 58% of 26.
1
The H-NMR assignment of the dimers 18, 19, 20, 22, and 23 is corroborated by
selective homodecoupling experiments (see Table 5 in the Exper. Part). The downfield
shift of 0.16 ppm for HÀC(2'/I) of 18 relative to the monomer 17 indicates a 1:1 syn/
anti equilibrium [13] for unit I (the alkynylated uridine unit; see [4] for the
nomenclature of the chain numbering) in 18. Similarly, the downfield shift of
HÀC(2'/I) (0.19 and 0.27 ppm) of 4 and 5 relative to the monomer 1 indicates a 1:1
syn/anti equilibrium for unit I in 4 and 5. The downfield shift for HÀC(2'/I) (Dd ˆ
0.51 0.59 ppm) of the iodinated dimers 19, 20, 22, and 23 relative to 1 evidences a syn-
conformation of the nucleobase in unit I. The chemical shifts for HÀC(2'/II) in all
dimers correspond to the chemical shifts for HÀC(2'/I) of the iodinated dimers (Dd ꢀ
0.10 ppm) and indicates a syn-conformation also of the nucleobase in unit II of the
dimers. A ratio J(1',2')/J(3',4') of 0.24 0.74 in both subunits indicates a preference for
the 3T2 conformation of the sugar pucker [13].
The large J(4',5') of 5.6 8.6 Hz for unit II of 4, 5, and 18 20, and for unit I in the
iodinated dimers 19, 20, 22, and 23 indicate a steric interaction between the nucleobase
and the side chain at C(4'); the conformer possessing antiperiplanar HÀC(4') and
HÀC(5') bonds is favoured. J(4',5') value of unit I in the non-iodinated dimers 4, 5, and
18 is significantly smaller (4.6 5.5 Hz). In the 13C-NMR spectra (see Table 6 in the
Exper. Part), introduction of IÀC(6) leads to an upfield shift of C(6/I) of 19, 20, 22, and

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Helvetica Chimica Acta Vol. 87 (2004)
23, resonating at 114 117 ppm (Dd ˆ 28 ppm) and to a downfield shift of C(5/I),
resonating at 117 ppm (Dd ˆ 15 ppm) and C(1'/I) at 102 104 ppm (Dd ˆ 7 ppm), as it
was already observed for the C(6)-iodinated monomers [4]. The 13C-NMR spectra of
all iodinated dimers showed the expected shifts for C(2') (84 86 ppm), C(3') (81
84 ppm), C(4') (90 92 ppm), and C(5 ') (63 64 ppm). The ss for C(6') and C(7') of the
CꢁCÀSiEt3 groups of 4 and 18 20 appear at 106.3 107.3 and 87.8 88.2 ppm, and the
ss for C(6') and C(7') of the bridging CꢁC units at 100.4 102.2 and 75.8 76.9 ppm,
respectively.
A downfield shift for HÀC(2'/I) of 0.24 0.34 ppm for all protected trimers,
tetramers, and pentamers, and a downfield shift of 0.47 0.52 ppm for HÀC(2'/II V)
relative to the monomer 1 evidence again a 1:1 syn/anti equilibrium for unit I and a
preferred syn-conformation for the units II IV (see Tables 7, 9, and 11 in the Exper.
Part). The ratio of J(1',2') ˆ 0 1.9 to J(3',4') ˆ 2.8 5.6 Hz indicates a preference for
the 3T2 sugar pucker. The large J(4',5') ˆ 5.0 8.0Hz suggests a preponderant
antiperiplanar arrangement of HÀC(4') and HÀC(5'), as observed for the iodinated
dimers. All 13C-NMR signals of the tri- and tetramers resonate at the expected field
(see Tables 8 and 10 in the Exper. Part); C(1') at 94.1 95 ppm and C(2')ÀC(5') as
indicated above for the dimers. The CꢁCH group of 5, 7, and 9 resonates at 73.7 73.1
for C(7')3) and at 83.8 ppm for C(6'). The signals for the CꢁCSiEt3 and the bridging
ethynylene groups appear in the range given for the dimers.
Similarly as for the fully protected analogues, HÀC(2') of the deprotected 24 26
resonate downfield (by 0.2 0.3 ppm for unit I and by 0.54 0.71 ppm for units II V)
as compared to the deprotected monomer of 1 [4], indicating a 1:1 syn/anti equilibrium
for unit I and a preferred syn-conformation of units II V (see Table 12 in the Exper.
Part). The ratio of J(1',2') ˆ 3.6 6.0to J(3',4') ˆ 3.2 5.8 Hz indicates a 1:1 mixture of
3
2
the T2 and T3 conformers for all units. In the 13C-NMR spectra of 24 and 25 (see
Tables 8 and 10 in the Exper. Part), one notes the expected upfield shift for C(2'/I IV)
and C(3'/I IV) (7.6 11.0ppm) and smaller shifts ( Dd < 2 ppm) for the other C-
atoms. The syn-conformation (c ˆ 45 758) is not in agreement with the c angles of
115 1458 or À 45 to À 758 that our model studies suggested to be required for duplex
formation. According to these studies, 24 26 are not preorganized for duplex
formation and are not expected to pair strongly.
The RNA strands rA5, rA7, rU5, and rU7 (Table 4) that we required for first UV
melting experiments of a potential duplex with the pentamer 26 (26 ¥ rA5 and 26 ¥ rA7)
as compared to RNA duplexes (rU5 ¥ rA5 and rU7 ¥ rA7) were prepared by solid-phase
synthesis according to [15].
Neither the 15 :15 mmol mixtures of the pentamer 26 and the RNA strand A5 or A7,
nor the mixtures A5 and U5, nor A7 and U5 showed any sigmoid UV melting curve in a
10-mmol NaH2PO4/Na2HPO4 buffer at pH 7 and at a 0.2m concentration of NaCl
(Fig. 2). A first indication for a sigmoid curve was only visible in the temperature-
dependent UV curve of the RNA duplex rA7 ¥ rU7, indicating that the pentamer 26 does
not bind to RNA more strongly than the RNA strand rU5.
3
)
Surprisingly, both C-atoms of terminal alkynes display in the DEPT spectrum a very weak signal; see [14].

Helvetica Chimica Acta Vol. 87 (2004)
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Table 4. Synthesis and Characterisation of rA5, rA7, rU5, and rU7
Product
Sequence
Yield [%]
Molecular formula
[M À H]Àc
calc.
)
a
b
)
)
obs.
rA5
rA7
rU5
rU7
5'-r(AAAAA)-3'
5'-r(AAAAAAA)-3'
5'-r(UUUUU)-3'
> 99
99
96
6
5
8
4
C50H61N25O28P4
C70H85N35O40P6
C45H56N10O38P4
C63H78N14O54P6
1584.1
2242.6
1469.01467.3
2081.4
1583.5
2242.2
5'-r(UUUUUUU)-3'
94
2080.4
a) Calculated from the yield of the coupling steps, as determined by the detritylation assay. b) Yield after
purification. c) Determined by MALDI-TOF mass spectrometry according to [16].
Fig. 2. Temperature-dependent UV spectra (−melting curves×) of 26 ¥ (rA7), (rU5) ¥ (rA7), and (rU7) ¥ (rA7)
We thank Dr. B. Bernet for checking the experimental part, and the Swiss National Science Foundation and
F. Hoffmann-La Roche AG, Basel, for generous support.
Experimental Part
General. Solvents were distilled: THF from K/benzophenone, CH2Cl2 from CaH2. Reactions were run
under Ar. Qual. TLC: precoated silica-gel plates (Merck silica gel 60 F254); detection by spraying with −mostain×
(400 ml of 10% aq. H2SO4, 20 g of (NH4)6Mo7O24 ¥ H2O, 0.4 g of Ce(SO4)2) and heating. Flash chromatography
(FC): silica gel Merck 60 (0.04 0.063 mm). Optical rotations: 1-dm cell at 258 and 589 nm. FT-IR: 1 2% soln.
in the indicated solvent. 1H- and 13C-NMR: at 200, 300, 400, or 500 MHz and 50, 75, 100, or 125 MHz, resp. MS:
Fast-atom-bombardment (FAB; NOBA: 3-nitrobenzyl alcohol), electron spray ionisation (ESI), or HR-
MALDI (DHB: 2,5-dihydroxybenzoic acid).
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofurano-
syl]uracil-6-yl-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]uracil-6-yl-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofur-
anosyl]uracil (6). A soln. of 5 [4] (1.1 g, 1.2 mmol), 2 [4] (1.2 g, 1.7 mmol), [Pd2(dba)3] (228 mg, 0.24 mmol),
CuI (68 mg, 0.36 mmol), and P(fur)3 (83 mg, 0.36 mmol) in degassed Et3N/toluene 1:1 (40ml) was stirred for
80h at 23 8. After evaporation, FC (AcOEt/hexane 1:3 ! 1 :1) gave 6 (1.13 g, 63%). Brown foam. Rf (AcOEt/
hexane 1:1) 0.23. [a]2D5 ˆ ‡7.6 (c ˆ 0.8, CHCl3). IR (CHCl3): 3373m (br.), 3192m (br.), 2949m, 2869w, 2233w,
2178w, 1699s, 1597w, 1455m, 1382m, 1216m, 1091s. 1H-NMR (500 MHz, CDCl3): see Table 5; additionally, 9.85,

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Helvetica Chimica Acta Vol. 87 (2004)
9.47, 9.35 (3 br. s, 3 NH); 1.57, 1.55, 1.51, 1.36, 1.33, 1.32 (6s, 3 Me2C); 1.23 1.15 (m, 3 (Me2CH)3Si); 1.13 1.08
(m, 3 (Me2CH)3Si); 0.93 (t, J ˆ 7.8, (MeCH2)3Si); 0.55 (q, J ˆ 7.8, (MeCH2)3Si). 13C-NMR (125 MHz, CDCl3):
see Table 6, additionally, 114.8, 113.9, 113.3 (3s, 3 Me2C); 27.22, 27.20, 27.1, 25.4, 25.1, 25.0 (6q, 3 Me2C); 18.10,
18.08, 18.0 (6 C), 17.97, 17.96 (5q, 3 (Me2CH)3Si); 12.5, 12.4, 12.3 (3d, 3 (Me2CH)3Si); 7.3 (q, (MeCH2)3Si); 4.2
‡
‡
(t, (MeCH2)3Si). HR-MALDI-MS (DHB): 1525.748 ([M ‡ Na] , C75H118Si4N6NaO18 ; calc. 1525.748).
1
Table 5. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Trimers 6, 7, and 12 in
CDCl3 (assignment based on selective homodecoupling experiments)
6
7
12
6
7
12
HÀC(5/I)
5.72
6.03, 5.99
7.31
5.72
5.73
6.01, 5.98
J(1',2'/I)
J(1',2'/II III)
1.9
1.2
1.0,
1.00
1.3,
HÀC(5/II III)
HÀC(6/I)
6.03, 6.00
7.307.31
5.71
6.20, 6.18
5.07 4.96
5.22, 5.21
5.07 4.96
5.07 4.96
4.21, 4.08
4.05
0,
1.30
a
a
a
HÀC(1'/I)
5.73
5.72
J(2',3'/I III)
)
)
)
HÀC(1'/II III)
HÀC(2'/I)
6.18, 6.17
5.00 4.98
5.25, 5.21
5.02 4.98
5.05
4.21, 4.08
4.01
5.06
6.21, 6.18
5.02 4.98
5.22, 5.20
5.02 4.98
4.85
4.22, 4.08
4.14
5.06
6.5,
6.4
3.4
4.5
3.8
5.2
6.5
7.5
6.0,
6.2
2.8
4.5
3.8
5.6
6.5
7.6
5.8,
6.0
a
HÀC(2'/II III)
HÀC(3'/I II)
HÀC(3'/III)
HÀC(4'/I II)
HÀC(4'/III)
HÀC(5'/I)
J(3',4'/I)
)
J(3',4'/II)
J(3',4'/III)
J(4',5'/I)
J(4',5'/II)
J(4',5'/III)
4.6
4.6
8.0
8.0
6.2
5.06
4.99
4.64
HÀC(5'/II)
4.99
4.64
5.00
3.86 (2 H)
HÀC(5'/III)
a) Not assigned.
Table 6. Selected 13C-NMR Chemical Shifts [ppm] of the Trimers 6, 7, and 12 in CDCl3, and of 24 in D2O
Solution
6
7
12
24
C(2/IÀIII)
C(4/I III)
C(5/I III)
C(6/I III)
C(1'/I III)
C(2'/I III)
C(3'/I III)
C(4'/I III)
C(5'/I III)
C(6'/I II)
C(6'/III)
163.3, 162.6, 162.5
149.9, 149.6, 149.4
108.7, 108.3, 102.7
142.2, 138.0, 137.3
94.3, 94.23, 94.16
84.0, 83.9, 83.8
82.8, 82.1, 80.6
91.2, 90.1, 88.7
64.3, 63.9, 63.8
101.5, 100.8
163.2, 162.7, 162.5
149.8, 149.6, 149.4
108.6, 108.4, 102.7
142.2, 138.0, 137.3
94.4, 94.3, 94.2
84.2, 83.8, 83.7
82.8, 82.2, 80.7
91.4, 90.1, 88.7
64.3, 63.8, 63.4
101.5, 100.9
163.4, 163.0, 162.7
149.91, 149.88, 149.4
108.5, 108.2, 102.6
142.3, 138.0, 137.4
94.4, 94.1, 93.9
168.7, 167.5, 167.4
154.3, 153.4, 153.0
111.1, 111.0, 105.2
144.6, 140.74, 140.70
96.8, 96.7, 92.0
75.8, 74.1, 73.5
84.5, 83.9, 83.7
82.3, 82.0, 80.7
73.1, 72.7, 71.9
90.0, 89.9, 88.7
88.0, 87.5, 86.6
65.1, 64.8, 64.0a)
102.9, 102.6
64.6, 64.4, 63.8a)
101.5, 100.9
106.5
83.8
C(7'/I III)
87.7, 76.5, 75.9
76.5, 75.9, 73.7
76.5, 76.0,
79.0, 78.6,
a) t of C(5'/III).
1-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-(6 !
7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-
(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil (7).
A soln. of 6 (1.8 g, 1.2 mmol) in MeOH/AcOEt 1:1 (300 ml) was treated dropwise with a soln. of AgNO3 (2.4 g,
49.5 mmol) in H2O/MeOH 1:1 (30ml), stirred at 23 8 under exclusion of light for 4 h, treated with a soln. of
KCN (2.8 g) in H2O (10ml), and stirred for 1 h. After evaporation, a soln. of the residue in AcOEt was washed
with brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:3 ! 2 :1) gave 7 (1.45 g, 87%). Yellow foam.

Helvetica Chimica Acta Vol. 87 (2004)
2935
Rf (AcOEt/hexane 1:1) 0.22. [a]2D5 ˆ ‡2.1 (c ˆ 0.7, CH2Cl2). IR (CHCl3): 3372w (br.), 3301w, 2947m, 2868m,
2233w, 1700s, 1597w, 1454m, 1381m, 1091s. 1H-NMR (400 MHz, CDCl3): see Table 5; additionally, 9.90, 9.48
(2 H) (2 br. s, 3 NH); 2.40( d, J ˆ 2.0, HÀC(7'/III)); 1.57, 1.55, 1.51, 1.36, 1.33, 1.32 (6s, 3 Me2C); 1.23 1.08
(m, 3 (Me2CH)3Si). 13C-NMR (125 MHz, CDCl3): see Table 6; additionally, 114.8, 113.9, 113.3 (3s, 3 Me2C);
27.23, 27.21, 27.1, 25.4, 25.1, 25.0(6 q, 3 Me2C); 18.10 (6 C), 18.08, 18.00, 17.97, 17.96 (5q, 3 (Me2CH)3Si); 12.5,
‡
‡
12.4, 12.3 (3d, 3 (Me2CH)3Si). HR-MALDI-MS (DHB): 1141.660([ M ‡ Na] , C69H104N6NaO18Si3 ; calc.
1411.661).
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofurano-
syl]uracil-6-yl-{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]uracil-6-yl}2-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-yno-
furanosyl]uracil (8). a) From 7 and 2. A soln. of 7 (100 mg, 72 mmol), 2 (150mg, 0.22 mmol), [Pd 2(dba)3]
(41.3 mg, 43 mmol), CuI (16 mg, 86 mmol), and P(fur)3 (20mg, 86 mmol) in degassed Et3N/toluene 1 :1 (7 ml)
was stirred for 100 h at 238. After evaporation, FC (AcOEt/hexane 1:2 ! 1:1) gave 8 (25 mg, 18%).
b) From 5 and 20. A soln. of 5 (30mg, 32 mmol), 20 (57 mg, 49 mmol), [Pd2(dba)3] (6.3 mg, 6.4 mmol), CuI
(1.8 mg, 9.4 mmol), and P(fur)3 (2.2 mg, 9.4 mmol) in degassed Et3N/toluene 1:1 (6 ml) was stirred for 120h at
238. After evaporation, FC (AcOEt/hexane 1:2 ! 1 :1) and prep. TLC (AcOEt/hexane 1:1) gave 8 (23 mg,
36%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.23. [a]2D5 ˆ ‡2.6 (c ˆ 0.3, CHCl3). IR (CHCl3): 3375m (br.),
3192w (br.), 2949m, 2868m, 2235w, 1699s, 1596w, 1456m, 1384m, 1215m, 1092s. 1H-NMR (500 MHz, CDCl3): see
Table 7; additionally, 9.90, 9.80, 9.30, 9.00 (4 br. s, 4 NH); 1.56, 1.55, 1.54, 1.51, 1.36, 1.35, 1.33, 1.32 (8s, 4 Me2C);
1.23 1.15 (m, 4 (Me2CH)3Si); 1.13 1.08 (m, 4 (Me2CH)3Si); 0.94 (t, J ˆ 7.5, (MeCH2)3Si); 0.55 (q, J ˆ 7.5,
(MeCH2)3Si). 13C-NMR (125 MHz, CDCl3): see Table 8; additionally, 114.7, 114.0, 113.9, 113.3 (4s, 4 Me2C);
27.2 (3 C), 27.1, 25.35, 25.23, 25.07, 25.04 (6q, 4 Me2C); 18.10, 18.08, 18.02, 17.97 (4q, 4 (Me2CH)3Si); 12.5, 12.34
(6 C), 12.30(3 d, 4 (Me2CH)3Si); 7.3 (q, (MeCH2)3Si); 4.2 (t, (MeCH2)3Si). HR-MALDI-MS (DHB): 1987.967
‡
‡
([M ‡ Na] , C98H152N8NaO24Si5 ; calc. 1987.966).
Table 7. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Tetramers 8, 9, and 13 in
CDCl3
8
9
13
HÀC(5/I)
5.72
6.12, 6.02, 6.00
7.28
5.75
6.13, 6.06, 6.01
7.28
5.75
6.11, 6.05, 5.99
7.28
HÀC(5/II IV)
HÀC(6/I)
HÀC(1'/I)
5.64
5.65
5.66
HÀC(1'/II IV)
HÀC(2'/I)
6.19 (2 H), 6.17
5.07 4.96
5.23 5.19
5.07 4.96
4.19, 4.08, 4.07
4.00
5.06, 5.03, 4.99
4.64
1.9
6.22, 6.19, 6.13
5.06 4.96
5.23 5.19
5.06 4.96
4.20, 4.07, 4.05
4.03
5.06 4.96
4.62
1.8
6.25, 6.19, 6.17
5.01 4.98
5.23 5.19
5.01 4.98, 4.78a)
4.20, 4.14, 4.08
4.08
5.06, 5.03, 5.00
3.85 (2 H)
1.4
HÀC(2'/II IV)
HÀC(3'/I IV)
HÀC(4'/I III)
HÀC(4'/IV)
HÀC(5'/I III)
HÀC(5'/IV)
J(1',2'/I)
J(1',2'/II IV)
J(2',3'/I IV)
J(3',4'/I IV)
J(4',5'/I III)
J(4',5'/IV)
0.0, 1.1, 0.0
1.0, 1.5, 1.0
)
4.0, 5.6, 1.7, 3.9
5.3, 6.9, 4.8
7.3
0.0, 1.2, 1.0
b
b
b
6.4, 6.4, b),
)
)
)
b
3.8, 4.0, 4.6, 3.6
5.3, 6.6, 7.2
8.08.5
b
)
a) HÀC(3/IV). b) Not assigned.
1-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-
{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-
yl}2-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil
(9). A soln. of 8 (39 mg, 20 mmol) in MeOH/AcOEt 1:1 (20ml) was treated dropwise with a soln. of AgNO 3

2936
Helvetica Chimica Acta Vol. 87 (2004)
Table 8. Selected 13C-NMR Chemical Shifts [ppm] of the Tetramers 8, 9, and 13 in CDCl3, and of 25 in D2O
Solution
8
9
13
25
C(2/I IV)
C(4/I IV)
C(5/I IV)
C(6/I IV)
163.1, 162.7,
162.4, 162.3
149.7, 149.6,
149.42, 149.41
108.7, 108.6,
108.4, 102.6
142.5, 138.0,
137.7, 137.3
163.4, 163.0,
162.7, 162.6
149.8, 149.7,
149.6, 149.5
108.7, 108.6,
108.4, 102.7
142.5, 137.9,
137.7, 137.3
163.6, 163.5,
163.0, 162.8
150.1, 149.8,
149.51, 149.48
108.6, 108.5,
108.3, 102.7
168.6, 167.42,
167.39, 167.2
154.2, 153.3,
153.1, 153.0
111.1, 110.93,
110.89, 105.2
144.6, 140.8,
142.5, 137.9,
137.7, 137.4
140.7, 140.6
C(1'/I IV) 95.0, 94.3, 94.2, 93.9
94.8, 94.1, 94.0, 93.6
94.7, 94.0, 93.7, 93.2
96.5 (2 C), 92.0 (2 C)
C(2'/I IV) 84.0, 83.8 (2 C), 83.7 84.5, 83.9, 83.8, 83.6
83.9, 83.8 (2 C), 83.6 75.7, 74.1, 73.54, 73.48
C(3'/I IV) 82.7, 82.2, 82.1, 80.9
C(4'/I IV) 91.1, 90.1, 89.7, 87.7
C(5'/I IV) 64.4 (2 C),
63.90, 63.86
82.8, 82.7, 81.9, 80.8
91.3, 89.9, 89.8, 88.9
64.4 (2 C),
82.2, 81.9, 81.6, 80.8
89.9, 89.6, 88.9, 84.6
64.6, 64.44,
73.2, 73.0, 72.6, 71.8
88.0, 87.64, 86.61, 86.5
65.09, 65.06,
63.8, 63.4
64.38, 63.8a)
64.8, 63.9a)
C(6'/I III) 101.6, 101.5, 100.9
101.6, 101.4, 100.9
83.8
101.2, 101.02 (2 C)
103.2, 103.0, 102.6
C(6'/IV)
106.4
C(7'/I IV) 88.8, 76.4, 75.8 (2 C)
76.4, 75.8 (2 C), 73.1 76.0, 75.9, 76.5,
79.0, 78.6 (2 C),
a) t of C(5'/IV).
(67 mg, 0.4 mmol) in H2O/MeOH 1 :1 (2 ml), stirred at 238 under exclusion of light for 5 h, treated with a soln. of
KCN (67 mg, 1 mmol) in H2O (1 ml), and stirred for 3 h. After evaporation, a soln. of the residue in AcOEt was
washed with brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:1 ! 2 :1) gave 9 (20mg, 54%).
Yellow foam. Rf (AcOEt/hexane 1 :1) 0.22. [a]D25 ˆ 2.7 (c ˆ 0.7, CH2Cl2). IR (CHCl3): 3372w (br.), 3301w, 3193w,
3068w, 2947m, 2868m, 2234w, 1699s, 1597w, 1455m, 1382m, 1090s. 1H-NMR (400 MHz, CDCl3): see Table 7;
additionally, 10.05 (br. s, 2 NH); 9.42 (br. s, 2 NH); 2.41 (d, J ˆ 2.0, HÀC(7'/IV)); 1.57, 1.56, 1.54, 1.52, 1.36, 1.34,
1.33, 1.32 (8s, 4 Me2C); 1.21 1.08 (m, 4 (Me2CH)3Si). 13C-NMR (100 MHz, CDCl3): see Table 8; additionally,
114.66, 114.02, 113.9, 113.4 (4s, 4 Me2C); 27.25, 27.21, 27.18, 27.11, 25.4, 25.3, 25.10, 25.08 (8q, 4 Me2C); 18.03
(12 C), 18.00, 17.96 (3q, 4 (Me2CH)3Si); 12.4, 12.32 (6 C), 12.27 (3d, 4 (Me2CH)3Si). HR-MALDI-MS (DHB):
‡
‡
1873.879 ([M ‡ Na] , C92H138N8NaO24Si4 ; calc. 1873.880).
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofurano-
syl]uracil-6-yl-{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]uracil-6-yl}3-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-yno-
furanosyl]uracil (10). a) From 9 and 2. A soln. of 9 (20mg, 11 mmol), 2 (23 mg, 32 mmol), [Pd2(dba)3] (5 mg,
11 mmol), CuI (2.1 mg, 11 mmol), and P(fur)3 (2.5 mg, 11 mmol) in degassed Et3N/toluene 1 :1 (3 ml) was stirred
for 100 h at 238. After evaporation, FC (AcOEt/hexane 1:2 ! 1:1) and prep. TLC (AcOEt/hexane 1:1) gave 10
(4 mg, 15%).
b) From 7 and 20. A soln. of 7 (20mg, 14 mmol), 20 (34 mg, 29 mmol), [Pd2(dba)3] (5.5 mg, 5.8 mmol), CuI
(1.6 mg, 8.6 mmol), and P(fur)3 (2.0mg, 8.6 mmol) in degassed Et3N/toluene 1:1 (6 ml) was stirred for 100 h at
238. After evaporation, FC (AcOEt/hexane 1:2 ! 1 :1) and prep. TLC (AcOEt/hexane 1:1) gave 10 (7 mg,
20%). Yellow foam. Rf (AcOEt/hexane 1 :1) 0.23. [a]2D5 ˆ 5.1 (c ˆ 1.3, CHCl3). IR (CH2Cl2): 3372m (br.), 3193m
(br.), 2946m, 2235w, 1699s, 1595w, 1457m, 1384m, 1214m, 1091s. 1H-NMR (500 MHz, CDCl3): see Table 9;
additionally, 10.12 (br. s, 3 NH); 9.42 (br. s, 2 NH); 1.56, 1.55, 1.54 (2 C), 1.51, 1.36, 1.34, 1.33 (2 C), 1.32
(8s, 5 Me2C); 1.23 1.08 (m, 5 (Me2CH)3Si); 0.94 (t, J ˆ 7.5, (MeCH2)3Si); 0.55 (q, J ˆ 7.5, (MeCH2)3Si). HR-
‡
‡
MALDI-MS (DHB): 2450.184 ([M ‡ Na] , C121H186Si6N10NaO30 ; calc. 2450.185).
1-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-
{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-
yl}3-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil
(11). A soln. of 10 (60mg, 25 mmol) in MeOH/AcOEt 1 :1 (15 ml) was treated dropwise with a soln. of AgNO3
(250mg, 1.5 mmol) in H 2O/MeOH 1 :1 (1 ml), stirred at 238 under exclusion of light for 5 h, treated with a soln.

Helvetica Chimica Acta Vol. 87 (2004)
2937
Table 9. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Pentamers 10, 11, and 14
in CDCl3
10
11
14
HÀC(5/I)
5.75
5.72
5.75
HÀC(5/II V)
HÀC(6/I)
6.18 (2 H), 6.01 (2 H)
7.27
5.62
6.12, 6,00 (2 H), 5.98
7.23
5.605.57
6.17, 6.14, 6.02, 6.01
7.24
HÀC(1'/I)
HÀC(1'/II V)
HÀC(2'/I V)
HÀC(3'/I V)
HÀC(4'/I)
6.22, 6.20, 6.19, 6.16
5.24 4.96
5.06 4.96
4.19
6.21 (3 H), 6.15
5.26 4.95
5.08 4.95
4.21
6.23, 6.22 (2 H), 6.17
5.24 4.95
5.08 4.95, 4.85a)
4.19
HÀC(4'/II V)
HÀC(5'/I IV)
HÀC(5'/V)
J(1',2'/I V)
J(2',3'/I V)
J(3',4'/I IV)
J(3',4'/V)
4.13 4.03, 4.00b)
5.06, 5.03, 5.02, 4.99
4.64
4.13 4.02, 4.07b)
5.08 4.95
4.62
4.14 4.03
5.08 4.95
3.86 (2 H)
ca. 1
ca. 1
ca. 1
c
c
c
)
)
)
)
)
)
)
)
c
c
c
c
3.8
5.0
8.08.3
4.7
c
c
J(4',5'/I IV)
J(4',5'/V)
)
6.2
a) HÀC(3'/V). b) HÀC(4'/V). c) Not assigned.
of KCN (241 mg, 3.6 mmol) in H2O (1 ml), and stirred for 3 h. After evaporation, a soln. of the residue in
AcOEt was washed with brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:1 ! 2 :1) and prep. TLC
(AcOEt/hexane 1 :1) gave 11 (30mg, 52%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.22. [a]2D5 ˆ 2.3 (c ˆ 0.4,
CH2Cl2). IR (CH2Cl2): 3374w (br.), 3302w, 3192w, 2946m, 2868m, 2235w, 1699s, 1596w, 1456m, 1384m, 1090s.
1H-NMR (400 MHz, CDCl3) see Table 9; additionally, 9.90, 9.62, 9.45 (2 H), 9.30 (4 br. s, 5 NH); 2.40( d, J ˆ 2.2,
HÀC(7'/V)); 1.57 1.52, 1.36 1.32 (several s, 5 Me2C); 1.21 1.08 (m, 5 (Me2CH)3Si). HR-MALDI-MS
‡
‡
(DHB): 2336.097 ([M ‡ Na] , C115H172N10NaO30 ; calc. 2336.098).
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-
5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropyl-
idene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil (12). A soln. of 5 (50mg, 54 mmol), 3 [4]
(35 mg, 67 mmol), [Pd2(dba)3] (5 mg, 5.4 mmol), CuI (2 mg, 10 mmol), and P(fur)3 (2.5 mg, 10 mmol) in degassed
Et3N/toluene 1 :1 (5 ml) was stirred for 40h at 23 8. After evaporation, FC (AcOEt/hexane 1:3 ! 1:1) gave 12
(42 mg, 57%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.19. [a]2D5 ˆ ‡2.5 (c ˆ 1.0, CHCl3). UV (MeOH): 286
(19400). IR (CHCl3): 3386m (br.), 3192w (br.), 2945m, 2868m, 2220w, 1697s, 1596m, 1455m, 1384m, 1090m.
1H-NMR (500 MHz, CDCl3): see Table 5; additionally, 10.10, 9.92, 9.65 (3 br. s, 3 NH); 1.57, 1.56, 1.53, 1.37, 1.34
(6 H) (5s, 3 Me2C); 1.21 1.10( m, 3 (Me2CH)3Si; 1.09 1.01 (m, 3 (Me2CH)3Si). 13C-NMR (125 MHz, CDCl3):
see Table 6; additionally, 114.8, 114.0, 113.4 (3s, 3 Me2C); 27.3, 27.21, 27.19, 25.43, 25.36, 25.1 (6q, 3 Me2C); 17.98
(6 C), 17.97, 17.95, 17.92, 17.90(5 q, 3 (Me2CH)3Si); 12.34, 12.31, 12.0(3 d, 3 (Me2CH)3Si). HR-MALDI-MS
‡
‡
(DHB): 1387.661 ([M ‡ Na] , C67H104Si3N6NaO18 ; calc. 1387.660).
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-
5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl}2-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropyl-
idene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil (13). a) From 7 and 3. A soln. of 7 (120mg,
89 mmol), 3 (151 mg, 270 mmol), Pd2(dba)3 (34 mg, 34 mmol), CuI (14 mg, 71 mmol), and P(fur)3 (16 mg,
69 mmol) in degassed Et3N/toluene 1:1 (25 ml) was stirred for 100 h at 238. After evaporation, FC (AcOEt/
hexane 1:3 ! 2 :1) gave 13 (40mg, 25%).
b) From 5 and 23. A soln. of 5 (30mg, 33 mmol), 23 (49 mg, 48 mmol), [Pd2(dba)3] (6.3 mg, 6.6 mmol), CuI
(1.9 mg, 10 mmol), and P(fur)3 (2.3 mg, 10 mmol) in degassed Et3N/toluene 1 :1 (25 ml) was stirred for 100 h at
238. After evaporation, FC (AcOEt/hexane 1:3 ! 2 :1) and prep. TLC (AcOEt/hexane 1:1) gave 13 (30mg,
51%). Yellow foam. Rf (AcOEt/hexane 3 :1) 0.44. [a]2D5 ˆ ‡5.5 (c ˆ 1.6, CHCl3). UV (MeOH): 285 (29800). IR
(CHCl3): 3375m (br.), 3192w (br.), 2945m, 2868m, 2235w, 1699s, 1596m, 1457m, 1384m, 1090m. 1H-NMR

2938
Helvetica Chimica Acta Vol. 87 (2004)
(500 MHz, CDCl3): see Table 7; additionally, 10.50, 10.20, 10.0, 9.70 (4 br. s, 4 NH); 1.56, 1.55, 1.54, 1.52, 1.36,
1.35, 1.32, 1.31, (8s, 4 Me2C); 1.21 1.15 (m, 3 (Me2CH)3Si); 1.13 1.10( m, 3 (Me2CH)3Si; 1.09 1.05
(m, (Me2CH)3Si); 1.04 1.01 (m, (Me2CH)3Si). 13C-NMR (125 MHz, CDCl3): see Table 8; additionally, 114.7,
114.0(2 C), 113.3 (3 s, 4 Me2C); 27.4 (2 C), 27.22, 27.19, 25.46, 25.36 (2 C), 25.1 (6q, 4 Me2C); 18.03, 18.00, 17.99
(6 C), 17.96 (6 C), 17.92, 17.89 (6q, 4 (Me2CH)3Si); 12.33, 12.28 (6 C), 12.0(3 d, 4 (Me2CH)3Si). HR-MALDI-
‡
‡
MS (DHB): 1849.880([ M ‡ Na] , C90H138N8NaO24Si4 ; calc. 1849.880).
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-
5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl}3-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropyl-
idene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil (14). a) From 9 and 3. A soln. of 9 (35 mg,
19 mmol), 3 (27 mg, 47 mmol), [Pd2(dba)3] ( 7.2 mg, 7.6 mmol), CuI (2.2 mg, 11 mmol), and P(fur)3 (2.6 mg,
10 mmol) in degassed Et3N/toluene 1:1 (3 ml) was stirred for 125 h at 238. After evaporation, FC (AcOEt/
hexane 1:3 ! 2 :1) and prep. TLC gave 14 (4.6 mg, 11%).
b) From 7 and 23. A soln. of 7 (25 mg, 18 mmol), 23 (37 mg, 36 mmol), [Pd2(dba)3] (6.8 mg, 7.2 mmol), CuI
(2.7 mg, 14 mmol), and P(fur)3 (3.3 mg, 14 mmol) in degassed Et3N/toluene 1:1 (5 ml) was stirred for 100 h at
238. After evaporation, FC (AcOEt/hexane 1:3 ! 2 :1) and prep. TLC (AcOEt/hexane 1:1) gave 14 (6 mg,
15%). Yellow foam. Rf (AcOEt/hexane 2 :1) 0.47. IR (CH2Cl2): 3375m (br.), 2945m, 2254w, 1699s, 1596w,
1456m, 1384m, 1215m, 1158w, 1089m, 1067m. 1H-NMR (300 MHz, CDCl3): see Table 9; additionally, 9.85
(br. s, 3 NH); 9.15, 8.85 (2 br. s, 2 NH); 1.56 1.52, 1.35 1.31 (several s, 5 Me2C); 1.21 1.01 (m, 5 (Me2CH)3Si).
‡
‡
HR-MALDI-MS (DHB): 2312.098 ([M ‡ Na] , C113H172N10NaO30Si5 ; calc. 2312.099).
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-{(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-
5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl}4-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropyl-
idene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil (15). A soln. of 9 (20mg, 11 mmol), 23 (44 mg,
43 mmol), [Pd2(dba)3] (9.5 mg, 10 mmol), CuI (1.9 mg, 10 mmol), and P(fur)3 (2.3 mg, 10 mmol) in degassed
Et3N/toluene 1:1 (5 ml) was stirred for 170h at 23 8. After evaporation, FC (AcOEt/hexane 1:3 ! 2 :1) and
prep. TLC (AcOEt/hexane 1:1) gave 15 (1.5 mg, 5%). Rf (AcOEt/hexane 1:1) 0.22. 1H-NMR (300 MHz,
CDCl3): 7.24 (d, J ˆ 8.0, HÀC(6/I)); 6.23 6.14 (m, HÀC(1'/II VI), HÀC(5/II IV)); 6.02 6.00 (sev-
eral s, HÀC(5/V VI)); 5.75 (d, J ˆ 8.0, HÀC(5/I)); 5.57 (s, HÀC(1'/I)); 5.24 5.19 (m, HÀC(2'/II VI));
5.08 4.95 (m, HÀC(2'/I), HÀC(3'/I V), HÀC(5'/I V)); 4.85 (t, J ꢂ 5 , HÀC(3'/VI)); 4.19 4.03 (m, HÀC(4'/
I
VI); 3.86 (d, J ˆ 6.2,
2
HÀC(5'/VI)); 1.56 1.52, 1.35 1.31 (several s, 6 Me2C); 1.21 1.01 (m, 6
‡
(Me2CH)3Si). MALDI-MS (indole-3-acetic acid): 2776.6 (100, [M ‡ Na] ).
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-(6 ! 7'-
C)-1-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl)uracil (18). A soln. of 16 [4] (6.0g,
10.9 mmol), 17 [4] (3.2 g, 10.4 mmol), [Pd2(dba)3] (494 mg, 0.52 mmol), CuI (198 mg, 1.0 mmol), and P(fur)3
(241 mg, 1.0mmol) in degassed Et 3N/toluene 1:1 (400 ml) was stirred for 15 h at 238. After evaporation, FC
(AcOEt/hexane 4 :1) gave 18 (6.9 g, 91%). Brown foam. Rf (AcOEt/hexane 4 :1) 0.22. [a]2D5 ˆ ‡29.1 (c ˆ 0.85,
CHCl3). UV (MeOH): 280(sh), 265 (16300). IR (KBr): 3421 m (br.), 3200m (br.), 3068w, 2956m, 2235w, 2178w,
1696s, 1597s, 1458m, 1384m, 1271w, 1216m, 1158s, 1088s. 1H-NMR (400 MHz, CD3OD): see Table 10;
additionally, 7.78 (d, J ˆ 8.1, HÀC(6/I)); 1.57, 1.53, 1.38, 1.34 (4s, 2 Me2C); 0.98 (t, J ˆ 7.5, (MeCH2)3Si); 0.58
(q, J ˆ 7.5, (MeCH2)3Si). 13C-NMR (100 MHz, CD3OD): see Table 11; additionally, 115.3, 114.8 (2s, 2 Me2C);
27.6, 27.5, 25.7, 25.4 (4q, 2 Me2C); 7.8 (q, (MeCH2)3Si); 4.2 (t, (MeCH2)3Si). FAB-MS (NOBA): 729 (19, [M ‡
‡
‡
‡
H] ), 713 (34, [M À Me] ), 699 (21, [M À Et] ). Anal. calc. for C34H44N4O12Si (728.83): C 56.03, H 6.08, N 7.69;
found: C 55.98, H 6.27, N 7.49.
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]uracil-6-yl-(6 ! 7'-
C)-1-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl)-6-iodouracil (19). At À 788, a soln. of
(i-Pr)2NH (3.5 ml, 25 mmol, distilled from CaH2) in THF (100 ml) was treated dropwise with 1.65m BuLi in
hexane (15.0ml, 24 mmol), stirred at À 788 for 15 min and at 08 for 15 min, cooled to À 788, treated dropwise
with a soln. of 18 (1.5 g, 2.1 mmol) in THF (150ml), stirred for 3 h, treated dropwise with NIS (5.6 g, 25 mmol)
in THF (100 ml), stirred for 2 h, treated with AcOH (3 ml), and allowed to warm to 238. After evaporation, a
soln. of the residue in AcOEt was washed with sat. aq. NaHCO3 soln. and brine, dried (Na2SO4), and
evaporated. FC (AcOEt/hexane 2 :1) gave 19 (714 mg, 40%) and 18 (325 mg, 22%).
Data of 19: Red foam. Rf (AcOEt/hexane 3 :1) 0.45. [a]2D5 ˆ À52.2 (c ˆ 0.6, CHCl3). UV (MeOH): 276
(16000). IR (CHCl3): 3391m (br.), 3008w, 2957w, 2876w, 2225w, 2175w, 1698s, 1600w, 1385w, 1341m, 1157w,
1086m. 1H-NMR (400 MHz, CD3OD): see Table 10; additionally, 1.57, 1.55, 1.36, 1.35 (4s, 2 Me2C); 0.98 (t, J ˆ
7.5, (MeCH2)3Si); 0.59 (q, J ˆ 7.5, (MeCH2)3Si). 13C-NMR (100 MHz, CD3OD): see Table 11; additionally,
115.0, 114.9 (2s, 2 Me2C); 27.8, 27.5, 25.7, 25.5 (4q, 2 Me2C); 7.8 (q, (MeCH2)3Si); 5.3 (t, (MeCH2)3Si). FAB-MS
‡
(NOBA): 855 (4, [M ‡ H] ).

Helvetica Chimica Acta Vol. 87 (2004)
2939
Table 10. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Dimers 4, 5, 20, 22, and
23 in CDCl3, and of 18 and 19 in CD3OD (assignment based on selective homodecoupling experiments)
4 [4]
5 [4]
18
19
20
22
23
HÀC(5/I)
HÀC(1'/I)
HÀC(2'/I)
HÀC(3'/I)
HÀC(4'/I)
HÀC(5'/I)
J(1',2'/I)
5.72
5.83
4.91
4.99
4.22
5.04
2.4
5.72
5.73
4.97
4.99
4.22
5.03
1.9
5.69
5.95
5.00
5.03
4.28
4.86
2.4
6.406.44
6.22
5.29
5.06
4.13
4.77
1.4
6.51
6.44
6.08
5.24
5.05
4.16
4.99
1.5
6.11
5.23
5.14
4.28
4.87
2.01.5
6.5
6.08
5.23
5.00
4.15
4.99
J(2',3'/I)
6.6
6.6
6.4
6.4
6.5
6.3
J(3',4'/I)
J(4',5'/I)
4.3
4.6
3.6
5.5
3.03.7
5.3
4.2
4.1
4.4
8.5
6.8
5.6
6.5
HÀC(5/II)
HÀC(1'/II)
HÀC(2'/II)
HÀC(3'/II)
HÀC(4'/II)
HÀC(5'/II)
J(1',2'/II)
J(2',3'/II)
J(3',4'/II)
J(4',5'/II)
5.97
6.14
5.24
5.05
4.01
4.64
1.2
6.5
3.6
8.1
5.93
6.21
5.19
5.04
4.04
4.64
1.5
6.6
3.6
8.6
5.98
6.24
5.33
5.00
4.00
4.56
2.02.3
6.5
5.96
6.306.21
5.32
5.01
4.07
4.56
1.5
6.5
3.1
7.5
6.04
6.04
6.03
6.24
6.24
5.24
5.00
4.03
4.65
5.21
4.85
4.21
3.87 (2 H)
5.20
4.84
4.15
3.85 (2 H)
1.4
1.1
6.5
3.8
8.06.4
6.5
4.3
6.4
4.5
3.2
7.6
6.4
Table 11. Selected 13C-NMR Chemical Shifts [ppm] of the Dimers 4, 5, 20, 22, and 23 in CDCl3, and of 18 and 19
in CD3OD Solution
4 [4]a)
5 [4]
18
19
20
22
23
C(2/I)
C(4/I)
C(5/I)
C(6/I)
163.3
150.0
102.7
141.6
93.0
84.084.805.7
80.0
88.5
63.6
100.4
76.7
162.4
149.4
108.5
137.6
94.6
162.9
149.8
102.8
142.2
94.2
166.1
152.0
102.8
144.0116.3
96.0
164.8
151.8
117.4
162.3
149.3
117.0
117.5
102.1
162.8
149.6
117.5
162.9
149.6
117.0
114.1
117.0
C(1'/I)
C(2'/I)
C(3'/I)
C(4'/I)
C(5'/I)
C(6'/I)
C(7'/I)
C(2/II)
C(4/II)
C(5/II)
C(6/II)
C(1'/II)
C(2'/II)
C(3'/II)
C(4'/II)
C(5'/II)
C(6'/II)
C(7'/II)
103.7
84.2
102.1
82.2
101.9
82.3
85.9
83.9
84.1
84.3
80.7
89.091.6
63.7
101.0
76.6
161.9
149.3
108.3
137.5
94.7
83.9
82.7
91.3
63.3
83.8
73.7
83.9
82.6
91.089.5 .0
64.3
91.9
90
63.8
102.2
76.9
164.5
151.7
109.3
138.8
95.096.3
84.8
82.4
89.7
63.5
107.3
88.2
63.9
103.5
76.1
163.8
149.4
108.8
139.1
62.9
100.7
76.2
161.3
148.1
108.4
64.3
101.7
75.8
161.5
147.1
107.9
101.8
75.8
161.1
147.1
108.1
138.0137.7
94.1
83.8
138.0
94.0
94.4
83.8
82.7
91.2
63.8
106.3
87.8
84.7
84.082.4 .9
91.4
63.7
107.3
83.6
83.9
80 82.1
90.2
63.8
106.4
87.8
89.1
64.3
89.7
64.4
88.3
a) Assignment based on a HSQC.GRASP spectrum.

2940
Helvetica Chimica Acta Vol. 87 (2004)
1-[6,7-Dideoxy-2,3-O-isopropylidene-7-C-(triethylsilyl)-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofurano-
syl]uracil-6-yl-(6 ! 7'-C)-1-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]-6-iodouracil (20). A soln. of 2,6-di(tert-butyl)pyridine (1.6 ml, 8.4 mmol) and 19 (500 mg, 0.7 mmol) in
CH2Cl2 (30ml) was treated dropwise with TIPSOTf (0.76 ml, 3.1 mmol), stirred at 23 8 for 20min, washed with
brine (2 Â 10ml), dried (Na 2SO4), and evaporated. FC (AcOEt/hexane 2 :5) gave 20 (423 mg, 62%). Colourless
powder. Rf (AcOEt/hexane 1:1) 0.58. [a]2D5 ˆ ‡7.9 (c ˆ 1.7, CHCl3). UV (MeOH): 276 (15000). IR (CHCl3):
3385w, 2946m, 2868m, 2225w, 2175w, 1695s, 1595w, 1577w, 1384m, 1339w, 1265w, 1092m, 1068m. 1H-NMR
(400 MHz, CDCl3): see Table 10, additionally, 9.55, 8.85 (2 br. s, 2 NH); 1.57, 1.55, 1.35, 1.33 (4s, 2 Me2C); 1.23
1.15 (m, 2 (Me2CH)3Si); 1.13 1.08 (m, 2 (Me2CH)3Si; 0.94 (t, J ˆ 7.5, ( MeCH2)3Si); 0.55 (q, J ˆ 7.5,
(MeCH2)3Si). 13C-NMR (100 MHz, CDCl3): see Table 11; additionally, 113.5, 113.4 (2s, 2 Me2C); 27.2, 27.1,
25.2, 25.1 (4q, 2 Me2C); 18.09, 18.06, 18.00 (6 C) (3q, 2 (Me2CH)3Si); 12.5, 12.3 (2d, 2 (Me2CH)3Si); 7.3
‡
(q, (MeCH2)3Si); 4.2 (t, (MeCH2)3Si). MALDI-MS (indole-3-acetic acid): 1191 (100, [M ‡ Na] ), 1207 (25,
‡
[M ‡ K] ). Anal. calc. for C52H83IN4O12Si3 (1167.41): C 53.50, H 7.17, N 4.80; found: C 53.37, H 7.00, N 4.80.
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-(6 ! 7'-C)-1-(6,7-dideoxy-2,3-O-isopropylidene-
b-d-allo-hept-6-ynofuranosyl)-6-iodouracil (22). At À 788, a soln. of (i-Pr)2NH (3.4 ml, 24 mmol, distilled from
CaH2) in THF (50ml) was treated dropwise with 1.65 m BuLi in hexane (14.5 ml, 24 mmol), stirred at À 788 for
15 min and at 08 for 15 min, cooled to À 788, treated dropwise with a soln. of 21 [4] (1.5 g, 2 mmol) in THF
(80ml), stirred for 2.5 h, treated dropwise with NIS (5.4 g, 24 mmol) in THF (100ml), stirred for 1.5 h, treated
with AcOH (1 ml), and allowed to warm to 238. After evaporation, a soln. of the residue in AcOEt was washed
with sat. aq. NaHCO3 soln. and brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 2 :1) gave 22
(707 mg, 40%) and 21 (300 mg, 20%).
Data of 22. Red foam. Rf (AcOEt/hexane 3 :1) 0.59. [a]2D5 ˆ ‡16.7 (c ˆ 0.7, CHCl3). UV (MeOH): 276
(16800). IR (CHCl3): 3390w (br.), 3008w, 2944w, 2867w, 2220w, 1721s, 1697s, 1596w, 1433w, 1385m, 1341w,
1158m, 1087m, 1069m, 882m. 1H-NMR (400 MHz, CDCl3): see Table 10; additionally, 10.40, 9.70 (2 br. s, 2 NH);
1.60, 1.56, 1.37, 1.34 (4s, 2 Me2C); 1.08 1.03 (m, (Me2CH)3Si). 13C-NMR (100 MHz, CDCl3): see Table 11;
additionally, 113.8, 113.3 (2s, 2 Me2C); 27.3, 27.1, 25.5, 25.3 (4q, 2 Me2C); 17.93, 17.90(2 q, (Me2CH)3Si); 11.9
‡
‡
‡
(d, (Me2CH)3Si). FAB-MS (NOBA): 874 (80, [M ‡ H] ), 858 (44, [M À Me] ), 829 (100, [M À Me2C] ).
2',3'-O-Isopropylidene-5'-O-(triisopropylsilyl)uridin-6-yl-(6 ! 7'-C)-1-(6,7-dideoxy-2,3-O-isopropylidene-
5'-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl)-6-iodouracil (23). A soln. of 2,6-di(tert-butyl)pyridine
(0.45 ml, 2 mmol) and 22 (150mg, 0.17 mmol) in CH 2Cl2 (10ml) was treated dropwise with TIPSOTf (0.18 ml,
0.69 mmol), stirred at 238 for 30min, washed with brine (2 Â 10ml), dried (Na 2SO4), and evaporated. FC
(AcOEt/hexane 1:2) gave 23 (88 mg, 50%). Colourless powder. Rf (AcOEt/hexane 1:1) 0.36. [a]2D5 ˆ À3.4 (c ˆ
1.2, CHCl3). UV (MeOH): 272 (15500). IR (CHCl3): 3384w, 2945w, 2867w, 2220w, 1695s, 1595w, 1455m, 1384m,
1148w, 1089m, 1068m, 882w. 1H-NMR (400 MHz, CDCl3): see Table 10; additionally, 10.00, 9.50 (2 br. s, 2 NH);
1.57, 1.55, 1.35, 1.34 (4s, 2 Me2C); 1.13 1.10( m, (Me2CH)3Si); 1.07 1.02 ( m, (Me2CH)3Si). 13C-NMR
(100 MHz, CDCl3): see Table 11; additionally, 113.6, 113.5 (2s, 2 Me2C); 27.3, 27.2, 25.4, 25.3 (4q, 2 Me2C);
17.95, 17.92 (2q, 2 (Me2CH)3Si); 12.3, 11.9 (2d, 2 (Me2CH)3Si). MALDI-MS (indole-3-acetic acid): 1051 (100,
‡
‡
[M ‡ Na] ), 1067 (20, [M ‡ K] ). Anal. calc. for C44H69IN4O12Si2 (1029.12): C 51.35, H 6.76, N 5.44; found: C
51.33, H 6.72, N 5.32.
Uridin-6-yl-(6 ! 7'-C)-1-(6,7-dideoxy-b-d-allo-hept-6-ynofuranosyl)uracil-6-yl-(6 ! 7'-C)-1-(6,7-dideoxy-
b-d-allo-hept-6-ynofuranosyl)uracil (24). A soln. of 12 (20mg, 14.6 mmol) in MeCN/H2O/40% HF/37% HCl
100 :50 :2 :2 (3 ml) was stirred at 408 for 100 h. Evaporation and HPLC (H2O/MeOH 10:0 ! 1 :9) gave 24
(8 mg, 70%). White powder. [a]2D5 ˆ ‡2.1 (c ˆ 0.53, H2O). UV (MeOH): 276 (18300). IR (KBr): 3396s (br.),
1
2237w, 1686s, 1598m, 1460m, 1390s, 1267w, 1226w, 1109m, 1054m, 830w, 765w. H-NMR (400 MHz, D2O): see
‡
Table 12. 13C-NMR (100 MHz, D2O): see Table 6. ESI-MS (pos. ions): 799 (100, [M ‡ Na] ), 777 (10, [M ‡
‡
H] ). ESI-MS (neg. ions): 811.3 (35, [M ‡ Cl]À), (100, [M À H]À).
Uridin-6-yl-[(6 ! 7'-C)-1-(6,7-dideoxy-b-d-allo-hept-6-ynofuranosyl)uracil-6-yl]2-(6 ! 7'-C)-1-(6,7-di-
deoxy-b-d-allo-hept-6-ynofuranosyl)uracil (25). A soln. of 13 (20mg, 11 mmol) in MeCN/H2O/40% HF/37%
HCl 100 :50 :2 :2 (3 ml) was stirred at 408 for 125 h. Evaporation and HPLC (H2O/MeOH 10:0 ! 1 :9) gave 25
(7.6 mg, 67%). White powder. [a]2D5 ˆ ‡9.7 (c ˆ 0.35, H2O). UV (MeOH): 283 (27400). IR (KBr): 3410s (br.),
2238w, 1686s, 1597m, 1458w, 1388m, 1113m, 1053m. 1H-NMR (500 MHz, D2O) see Table 12. 13C-NMR
‡
‡
(125 MHz, D2O): see Table 8. MALDI-MS (CCA): 1065.2 (100, [M ‡ Na] ), 1081.4 (13, [M ‡ K] ). ESI-MS
(pos. ions): 1065.4 (60, [M ‡ Na] ), 1043.4 (10, [M ‡ H] ). ESI-MS (neg. ions): 1077.4 (30, [M ‡ Cl]À); 1041.4
‡
‡
(100, [M À H]À).
Uridin-6-yl-[(6 ! 7'-C)-1-(6,7-dideoxy-b-d-allo-hept-6-ynofuranosyl)uracil-6-yl]3-(6 ! 7'-C)-1-(6,7-di-
deoxy-b-d-allo-hept-6-ynofuranosyl)uracil (26). A soln. of 14 (3 mg, 1.3 mmol) in MeCN/H2O/40% HF/37%

Helvetica Chimica Acta Vol. 87 (2004)
2941
Table 12. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Deprotected Trimer 24,
Tetramer 25, and Pentamer 26 in D2O
24
25
26
HÀC(5/I)
5.86
5.79
6.10(2 H), 6.08
5.86
HÀC(5/II V) 6.17, 6.15
6.17 (2 H), 6.16 (2 H)
HÀC(6/I)
HÀC(1'/I)
7.807.74
5.93
7.79
5.86
6.07, 6.06, 6.00
4.46
5.92
HÀC(1'/II V) 6.13, 6.08
6.15, 6.14 (2 H), 6.07
4.54 4.50
HÀC(2'/I)
4.41
HÀC(2'/II V) 4.93, 4.76
4.88 4.82 (2 H), 4.69a)
4.29 (2 H), 4.35 (2 H)
4.18, 3.96, 3.92, 3.81
4.94 4.89 (3 H), 4.73b)
4.54 4.50(2 H), 4.42 4.41 (2 H), 4.36
4.25, 4.02, 3.97, 3.96, 3.89
HÀC(3'/I V) 4.37, 4.42, 4.54
HÀC(4'/I V) 4.25, 4.02, 3.89
HÀC(5'/I V) 4.97, 4.95, 3.82/3.72 4.91, 4.88 4.82 (2 H), 3.76 3.64 4.98, 4.93, 4.90, 4.89, 3.82/3.71
J(1',2'/I)
4.8
4.5
4.7
J(1',2'/II V) 4.1, 3.6
c), 3.6, 4.5
5.7, c), c), 6.6
3.6, 5.8, 5.8, 3.0
4.2, 5.8
6.0, 4.2, 4.2, 3.7
c), c), c), c), 6.5
4.0, 5.9, 5.6, 5,9, 3.0
6.2, 5.6
5.9
6.8
J(2',3'/I V)
J(3',4'/I V)
J(4',5'/I II)
J(4',5'/III)
J(4',5'/IV)
J(4',5'/V)
5.5, 6.1, 6.4
4.0, 5.7, 3.2
4.2, 5.6
3.3, 6.1
5.8
3.0, 5.9
3.2, 5.9
a) HÀC(2'/IV). b) HÀC(2'/V). c) Not assigned.
HCl 100 :50 :2 :2 (1 ml) was stirred at 408 for 150h. Evaporation and HPLC (H 2O/MeOH 10:0 ! 1:9) gave 26
(1.0mg, 58%). White powder. UV (MeOH): 282 (37800). 1H-NMR (500 MHz, D2O): see Table 12. MALDI-
‡
‡
MS (CCA): 1331.8 (100, [M ‡ Na] ), 1348.2 (20, [M ‡ K] ).
Synthesis of the rA5, rA7, rU5, and rU7 Oligomers. The solid-phase syntheses were carried out on a
Pharmacia gene-assembler on a 1.3-mmol scale according to the protocol developed by Pitsch et al. [15]. The
commercial phosphoamidites and the CPG solid supports were obtained from Xeragon. The removal of the
base- and phosphate-protecting groups and the cleavage from the solid support was accomplished with a 1:1
mixture of MeNH2 (40% in H2O) and MeNH2 (30% in EtOH), while the (i-Pr)3SiOCH2 groups at O(2') were
cleaved with 1m Bu4NF in THF. The crude products were desalted on a Sephadex column, and purified or
completely desalted by RP-HPLC. The composition of the oligonucleotides was evidenced by MALDI-TOF-
MS (cf. Table 4).
Measurement of Hyperchromicities. A Cary 3E UV/VIS spectrophotometer (Varian) equipped with Cary
temp. controller, sample transport accessory, multi cell block, and Hellma cuvettes (size: ca. 1 ml, inner
diameter: 4 mm, path of rays: 10mm) was used. The temp. was measured with a reference cuvette (temp.
gradient: 0.58/min). The spectrometer was flushed with N2, and the solns. (15 mmol solns. of the nucleosides in a
10-mmol NaH2PO4/Na2HPO4 buffer at pH 7 and at a 0.2m concentration of NaCl) in the cuvettes were overlaid
with dimethylpolysiloxane.
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Helvetica Chimica Acta Vol. 87 (2004)
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Received August 27, 2004