Oligonucleosides with a nucleobase-including backbone: Part 12 - Synthesis of mixed ethynylene-linked uridine- and adenosine-derived tetramers

Article abstract of DOI:10.1002/hlca.200490269

In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with the 5′-oxoadenosine 3 diastereoselectively to the β-D-allo-hept-6-ynofuranosyladenine 5. Lithiation/iodination of the monomeric propargyl alcohol 5 a

Full text of DOI:10.1002/hlca.200490269

Helvetica Chimica Acta ± Vol. 87 (2004)
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Oligonucleosides with a Nucleobase-Including Backbone
Part 12
Synthesis of Mixed Ethynylene-Linked Uridine- and Adenosine-Derived Tetramers
by Simon Eppacher, Punit Kumar Bhardwaj, Bruno Bernet, Jose Luis Bravo Gala, Thomas Knöpfel,
and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Hönggerberg, HCI, CH-8093 Zürich
In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with
the 5'-oxoadenosine 3 diastereoselectively to the b-d-allo-hept-6-ynofuranosyladenine 5. Lithiation/iodination
of the monomeric propargyl alcohol 5 and of the dimeric propargyl alcohol 22 provided the 8-iodoadenosines 7
and 18, respectively, considerably shortening the synthesis of the dimeric O-silylated 8-iodoadenosine 25. The
mixed uridine- and adenosine-derived tetramers 21 and 32 were synthesised. The tetramer 21 was prepared by a
linear sequence. Sonogashira coupling of 9 and 13 yielded the trimer 16 that was C-desilylated to 17. A second
Sonogashira coupling of 17 and 19 yielded the tetramer 21. Tetramer 32 was prepared in higher yields by a
convergent route, coupling the acetylene 29 and the iodide 30. The uridine-derived iodides proved more reactive
than the adenosine-derived analogues, and the N6-unprotected adenosine-derived alkynes were more reactive
than their N6-benzoylated analogues.
Introduction. ± We have described the synthesis of uridine-derived pentamers [1][2]
and adenosine-derived tetramers [3 ± 5] that are characterised by an ethynylene link
between C(5') of one nucleoside unit and C(6) of an adjacent uracil, or C(8) of a
adjacent adenosine moiety (cf. A and B, resp.). Inspection of Maruzen models and
Macromodel V. 4.5 (Amber* force-field, gas phase) [6] force-field calculations
suggested that these novel oligonucleotide analogues form autonomous pairing
systems and may hybridise with complementary RNA strands [1].
The crucial C(5'),CꢀCÀC(6) and C(5'),CꢀCÀC(8) bonds of these oligonucleo-
tide analogues were established by a Sonogashira coupling [7] between a hept-6-
ynofuranosyl-uracil or -adenosine, and a 6-iodouracil or 8-iodoadenosine. Depending
on the strategy (linear, convergent, or binomial), this synthesis requires monomeric,
dimeric, or oligomeric coupling partners. While the terminal hept-6-ynofuranosyl-
uracil and -adenosine derivatives were synthesised in good yields, the required iodides ±
particularly the adenosine derivatives ± were less well accessible.
ꢀ 2004 Verlag Helvetica Chimica Acta AG, Zürich

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We now describe an improved synthetic route to iodinated monomers and dimers of
adenosine, a diastereoselective addition of bis[(trimethylsilyl)ethynyl]zinc to the
aldehyde 3, the synthesis of two self-complementary tetramers 21 and 32, and, in this
context, the structural effects on the Sonogashira coupling.
Results and Discussion. ± We reported the preparation of the propargylic alcohols 5
and 6 by addition of BrMgCꢀCSiMe3 to the crude aldehyde 3 [3] (Scheme 1).
Reproducibility problems during scale-up and the low diastereoselectivity prompted us
to re-investigate the preparation of 3 and its reaction with BrMgCꢀCSiMe3.
According to Moffat and co-workers [8], 3 is obtained in 60% yield by oxidation of
1 [9] with DCC and Cl2CHCOOH in DMSO, transformation of the crude aldehyde to
the N,N'-diphenylimidazolidine 2, liberation of the hydrate 3 ´ H2O by treatment with
Scheme 1
a) N,N'-Dicyclohexylcarbodiimide (DCC), Cl2HCCO2H, DMSO, then (PhHNCH2)2, MeOH; 76%. b) Dowex
50WÂ 8, THF/H2O 1:1, then benzene, reflux, Dean ± Stark apparatus; 79%. c) BrMgCꢀCSiMe3, THF; 40% of
5 and 20% of 6. d) Zn(CꢀCSiMe3)2, THF; 54% of 5 and 6% of 6. e) Lithium diisopropylamide (LDA), THF,
then N-iodosucciniimide (NIS), then AcOH; 88%. f) Triisopropylsilyl trifluoromethanesulfonate (TIPSOTf),
pyridine, CH2Cl2; 89% of 8; 8 8 % of11. g) MeNH2, PhMe; 85% of 9; 89% of 12. h) Bu4NF (TBAF) ´ 3 H2O,
THF; > 98%.

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Dowex 50WÂ 8, and dehydration to 3 by azeotropic destillation with benzene using a
Dean ± Stark trap1).
Addition of BrMgCꢀCSiMe3 to pure 3 at À 158 yielded 60% of a 2 :1 mixture of 5
and 6, as independently reported by Matsuda et al. [10] (Scheme 1). Substitution of
BrMgCꢀCSiMe3 by LiCꢀCSiMe3, or the addition of CeCl3 had no influence on the
diastereoselectivity. However, addition of 5 equiv. of bis[(trimethylsilyl)ethynyl]zinc
(generated from 10 equiv. of LiCꢀCSiMe3 and 5 equiv. of ZnCl2) to 3 at 238 yielded a
9 :1 mixture of 5 and 6 in 59% yield2). The 8-iodoadenosine 7 was synthesised by
introducing the alkynyl substituent after iodination, as attempts to iodinate the
triethylsilyl-protected propargyl alcohol 5 did not lead to satisfactory results [3].
However, this synthesis of 7 is rather long, and the intermediate aldehyde (the 8-iodo
analogue of 3) also proved sensitive. For these reasons, we re-investigated the direct
iodination of 5 and obtained the desired 8-iodoadenosine 7 in a yield of 88% upon
treating 5 with 7 equiv. of LDA. Silylation of 7 with TIPSOTf yielded 89% of the silyl
ether 8, which was N-debenzoylated by treatment with MeNH2 in toluene to provide 9
(85%). The coupling partner 12 was obtained in a yield of 78% by C-desilylating 5 with
TBAF ´ 3 H2O to 10, followed by silylation of HOÀC(5') with TIPSOTf to 11, and N-
debenzoylation with MeNH2.
The d-allo-hept-6'-ynosyladenines 5 ± 12 show a similar conformational preference
as related adenosines [3]. The intramolecular H-bond O(5')ÀH ´´´ N(3) of 7 in CDCl3
is evidenced by the downfield shift of HOÀC(5') (7.06 ppm), the small J(5',OH) and
J(4',5') values (<2 Hz), and the (S)-conformation (J(1',2') ˆ 5.3, J(3',4') ˆ 0 Hz; see
Table 2 in the Exper. Part). In CD3OD, the intramolecular H-bond of 10 is mostly
replaced by an intermolecular H-bond to the solvent as evidenced by a larger J(4',5')
(3.7 Hz) and the (N)/(S) conformational equilibrium (J(1',2') ˆ 3.1, J(3',4') ˆ 1.9 Hz),
whereas d(HÀC(2')) ˆ 5.32 ppm agrees with both the syn-conformation of the
intramolecular H-bonded species and an anti-conformation. The HOÀC(5') protected
iodides 8 and 9 adopt preferentially the (N)- (J(1',2')/J(3',4') ˆ 0.71 ± 0.76) and
completely the syn-conformation (d(HÀC(2')) ˆ 5.92 ± 5.93 ppm, J(4',5') ˆ 8.1 ±
8.4 Hz), whereas the corresponding C(8)-unsubstituted analogues 8 and 9 adopt
preferentially the (S)- (J(1',2')/J(3',4') ˆ 1.11 ± 1.16) and completely the anti-confor-
mation (d(HÀC(2')) ˆ 5.33 ± 5.35 ppm, J(4',5') ˆ 4.7 ± 5.4 Hz).
The (5'S)-configuration of 4 was evidenced by 1D-NOE experiments in
(D6)DMSO. Irradiation of HOÀC(5') at 6.82 ppm led to a NOE of 1.5% for
HÀC(3') and of 8% for HÀC(5'), whereas irradiation of HÀC(5') at 5.20 ppm led only
to a NOE of 4% for HOÀC(5'). The 1,3-oxazine ring of 4 adopts an (E)-conformation
with O(4') outside of the common plane, and the furanose ring adopts an EO
conformation as evidenced by J(1',2') ˆ J(3',4') ˆ 0 Hz (see Table 2 in the Exper. Part).
J(5,OH) ˆ 5.6 Hz evidences a fully solvated OH group. The d of C(5') of 4 resonates at
the same position as the d of C(5') of the hept-6-ynofuranosyl nucleosides (63 ppm),
1
)
To obtain the useful but sensitive aldehyde 3, we had to recrystallise the N,N'-diphenylimidazolidine 2,
carefully wash 3 ´ H2O with H2O, pre-dry it (100 mbar 458, 14 h), and perform the dehydration of small
amounts of 3 ´ H2O in benzene. Neglecting these precautions led to a new, polar, benzene-insoluble
product that was identified by 1H- and 13C-NMR spectroscopy, and mass spectrometry as the
cyclonucleoside 4. The (5'R)-epimer of 4 was not isolated.
2
)
The selectivity of the addition is in agreement with the Felkin ± Anh model [11][12].

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whereas the s of C(8) of 4 (150 ppm) is shifted downfield by ca. 8ppm as compared to
the corresponding d of 2 and 3 ´ H2O (see Table 3 in the Exper. Part).
Considering the poor H2O solubility of the purely adenosine-derived tetramers [3 ±
5], we aimed at the synthesis of self-complementary oligomers. We first investigated a
linear synthesis of the tetramer 21 (Scheme 2). Sonogashira coupling of the known
dimeric uridine-derived acetylene 13 [2] with the 8-iodoadenosine 8 yielded 49% of the
mixed trimer 14; similarly, coupling of 13 with the debenzoylated 8-iodoadenosine 9
gave the mixed trimer 16 (38%). The trimers were C-desilylated with AgNO3 and KCN
in MeOH/AcOEt to the acetylenes 15 (49%) and 17 (74%), respectively. Coupling the
trimer 15 with the 8-iodoadenosine 18 [3] gave only traces of the tetramer 20, while
coupling the debenzoylated trimer 17 with the debenzoylated iodide 19 [4] yielded 50%
of the mixed tetramer 21. This result confirms the higher reactivity of adenosine-
Scheme 2
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1 :1; 49% of 14; 38 % of16; traces of 20; 50% of 21. b) AgNO3,
MeOH/AcOEt, then KCN; 49% of 15; 74% of 17.

Helvetica Chimica Acta ± Vol. 87 (2004)
2973
derived acetylenes with a free primary NH2 group as compared to their N6-benzoylated
analogues [4].
For the convergent route to the mixed tetramer 21, we wished to shorten the
synthesis of the known iodinated dimer 25 [5] by lithiation and iodination of 22, which
is accessible in 57% yield by Sonogashira coupling of the iodide 18 [3] with the alkyne
10 (Scheme 3). When the iodination was performed by treating 22 with 8equiv. of LDA
and NIS, we obtained the desired iodide 23 in 36% yield besides 30% of starting
material and 10% of a new product (Table 1). It was assigned the structure of the 2-
1
(diisopropylamino)adenosine 24 on the basis of its H- and 13C-NMR, and mass
spectral data. The analogous iodination in the presence of 16 equiv. of HMPA failed;
only starting material was isolated. However, substituting LDA by lithium 2,2,6,6-
tetramethylpiperidide in the presence of 16 equiv. of HMPA led in 77% yield to the
iodinated dimer 23 without formation of any by-products. The dimeric iodoadenosine
23 was silylated with Et3SiCl to yield 86% of the silyl ether 25.
Scheme 3
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1:1; 57%. b) See Table 1. c) Et3SiCl, 1H-imidazole, DMF; 86%.
Table 1. Conditions and Yields in the Iodination of 22 (LiTMP ˆ lithium 2,2,6,6-tetramethylpiperidide)
Base
NIS
Additive
22
23
24
8equiv. of LDA
8equiv. of LDA
8equiv. of LiTMP
8equiv.
8equiv.
8equiv.
±
30%
> 85%
36%
±
77%
10%
±
±
16 equiv. of HMPA
16 equiv. of HMPA
±
An attempt to prepare the mixed tetramer analogue of 20 (Et3Si protecting group
at HOÀC(4/III)) by Sonogashira coupling of the uridine-derived dimer 13 and the N-

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benzoylated iodoadenosine 25 failed. Only traces of product were formed3) even upon
prolonging the duration of the reaction (120 h) in the presence of 0.5 equiv. of
[Pd2dba3]. This differs significantly from the results of Gunji and Vasella [5] who
showed that coupling of the Et3Si-protected analogue of 29 (see below and Scheme 4)
with the dimeric 8-iodoadenosine 25 proceeded in 79% yield to the corresponding
tetramer, indicating that the adenosine-derived acetylenes are more reactive than the
uracil-derived counterparts. The higher reactivity, in the Sonogashira coupling, of the
dimeric 6-iodouridine 30 (Scheme 5) as compared to the dimeric 8-iodoadenosine 25 is
evidenced by the formation, in 51% yield, of the tetramer resulting from the dimeric
uridine-derived acetylene 13 and the dimeric uridine-derived iodide 30 [2].
Scheme 4
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1:1; 76% of 26; 83% of 28. b) AgNO3, MeOH/AcOEt, then KCN;
98% of 27; 86% of 29.
Besides the mixed tetramer 21 (Scheme 2) with the sequence A(8± 7 ')aHepA(8±
7')aHepU(6 ± 7')aHepU (for the nomenclature, see [1]), we wished to synthesise the
tetramer 32 (Scheme 5) with the complementary sequence U(6 ± 7')aHepU(6 ± 7')-
aHepA(8± 7)aHepA. The dimeric N-benzoyladenosine-derived alkyne 27 (Scheme 4)
was required for a convergent synthesis of 32. It was obtained in a yield of 74% by
coupling the acetylene 11 with the 8-iodoadenosine 8, followed by C-desilylation;
similarly, the N-debenzoylated dimer 29 was prepared in a yield of 72% by coupling the
acetylene 12 and the iodide 9, and C-desilylation.
3
)
Workup of an aliquot led to a crude that showed a signal in its MALDI-TOF mass spectrum corresponding
to the coupling product.

Helvetica Chimica Acta ± Vol. 87 (2004)
2975
Scheme 5
a) [Pd2(dba)3], CuI, P(fur)3, toluene/Et3N 1:1; traces of 31; 69% of 32.
The tetramer 32 was obtained in 69% yield by Sonogashira coupling of the
acetylene 29 with the iodide 30 [2], while coupling of the acetylene 27 with 30 yielded
only traces of the tetramer 31, again illustrating the higher reactivity of adenosine
derived acetylenes with a free 6-NH2 group.
The coupling constants of the ribofuranosyl units in the tetramers 21 in CDCl3 and
32 in CDCl3/CD3OD 9 :1 differ slightly, but significantly from each other. This allows an
unambiguous assignment of HÀC(3') to HÀC(5'). The assignment of HÀC(1'),
HÀC(2'), HÀC(2), HÀC(5), and HÀC(8) is based on DQF-COSY spectra of 21 and
32 and on a HMBC spectrum of 32. Surprisingly, HÀC(5/III) of 32 appears as broad s.
A comparison of the 1H-NMR data shows that the adenosyl units of the dimers 22 ±
29 (25 ± 29 in CDCl3 and 22 ± 24 in (D6)DMSO), the mixed trimers 14 ± 17 (CDCl3),
and the tetramers 21 (CDCl3) and 32 (CDCl3/CD3OD 9 :1) possess all a flattened
furanose ring (J(1',2') ‡ J(3',4') ˆ 3.8± 6.9 Hz; see Tables 4, 6, 8, and 10 in the Exper.
Part). J(1',2') ˆ 0 ± 2.9 Hz and J(3',4') ˆ 2.1 ± 5.1 Hz evidence a slight preference for the
(N)-conformation. The HOÀC(5') protected units II of 22 ± 29 and 32, units III of 14 ±
17 and 21, and unit IV of 21 adopt a syn-conformation as evidenced by the downfield
shift of HÀC(2') (5.57 ± 5.70 ppm; the solvent and the N6-protection have a negligible
influence on this chemical shift) and the large J(4',5') value (7.3 ± 8.5 Hz for the hept-6-
ynofuranosyladenines and 6.0 ± 6.9 Hz for the ribofuranosyladenines). Unit I of the
HOÀC(5')-protected iodide 25 also adopts completely the syn-conformation
(d(HÀC(2') ˆ 5.63 ppm, J(4',5') ˆ 8.0 Hz [4]). The downfield shift of HÀC(2'/I)
(5.71 ppm) and the large J(4',5'/I) values (7.1 ± 8.5 Hz) of the C(8/I)-unsubstituted
diamines 28, 29, and 32 indicate the complete preference for the syn-conformation or
an equilibrium between a syn-conformer and further conformers leading to similar
d(HÀC(2') and J(4',5') values. The upfield shift of HÀC(2'/I) (5.46 ± 5.49 ppm) and a

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Helvetica Chimica Acta ± Vol. 87 (2004)
smaller J(4',5'/I) value (6.2 ± 6.5 Hz) of the C(8/I)-unsubstituted dibenzamides 26 and
27 evidences a 25 ± 40% contribution of the anti-conformer in the conformational
equilibrium. The complete preference for the anti-conformation of the HOÀC(5')
protected and 8-unsubstituted monomeric adenosine derivatives and a strongly
decreased preference for this conformation of closely related oligomeric adenosines
has already been observed [4].
In (D6)DMSO, HOÀC(5'/I) of 22 ± 24 is completely solvated as evidenced by
J(5',OH) ˆ 6.0 ± 6.6 Hz (cf. [4][13 ± 15]) and by J(4',5') ˆ 6.2 ± 8.8 Hz. Unit I of the
iodides 23 and 24 adopts completely the syn-conformation (J(4',5') ˆ 8.0 ± 8.8 Hz),
whereas a ca. 35% population of an anti-conformation is deduced from J(4',5'/I) ˆ
6.2 Hz of the C(8/I)-unsubstituted 22. In agreement with this finding, HÀC(2'/I) of 22
resonates upfield to HÀC(2'/I) of 23 (5.51 vs. 5.71 ppm). However, the upfield shift of
HÀC(2'/I) of 24 resonating at 5.47 ppm is surprising; it must be due to the (i-Pr)2N
group, and reveals an electronic interaction between the two nucleobases.
The downfield shift for HÀC(2') of the uridyl units II ± IV of 14 ± 17, 21, and 32
(5.16 ± 5.31 ppm; compare with monomeric 6-substituted (5.19 ± 5.30 ppm [1][16]) and
6-unsubstituted uridines (4.72 ± 4.90 ppm [1])) evidences the complete preference for
the syn-conformation. The steric demand of the uridyl group is smaller than that of the
adenyl group, as indicated by J(4',5'/II) of 21 and J(4',5'/III) of 32 (6.1 ± 6.3 Hz).
However, J(4',5'/II) of 14 ± 17 (8.1 ± 8.3 Hz) has the same size as J(4',5') of the
corresponding adenosyl units. HÀC(2'/I) of 14 and 15 resonates at 4.93 ± 4.94 ppm and
still evidences a preference for the anti-conformation, whereas the downfield shift of
HÀC(2'/I) of 16, 17, and 21 (5.21 ± 5.26 ppm) indicates at best a weak contribution of
the anti-conformer to the conformational equilibrium.
1
The position of the (i-Pr)2N group of 24 was deduced as follows. In the H-NMR
range that is typical for the HÀC(2) and the HÀC(8) signals, we found only one signal
corresponding to HÀC(2). In the 13C-NMR spectra of 24, one C(2) gives rise to a s at
157.6 ppm, shifted downfield by 5.1 ppm as compared to C(2) of 23, resonating at
152.5 ppm. The second C(2) resonates as a d at 149.73 ppm, shifted by 1.6 ppm to higher
fields, as compared to C(2) of 23 (151.3 ppm). The location of the (i-Pr)2N group ± at
C(2/I) or C(2/II) ± was deduced from the FAB-MS. A signal at m/z 365.9 corresponds to
an iodinated, doubly protonated N6-benzoyladenosine that possesses no (i-Pr)2N group
and can be formed only by depurination of unit I. In addition, a signal at m/z 819.3
corresponds to the remaining ribofuranosyladenine residue possessing the (i-Pr)2N
group.
We thank the ETH-Zürich and F. Hoffmann-La Roche AG, Basel, for generous support.
Experimental Part
General. See [2].
N6-Benzoyl-5'-deoxy-2',3'-O-isopropylidene-5',5'-(N,N'-diphenylethylenediamino)adenosine (2). Prepared
according to [8] from 27 g of 1 [9]. Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.51. M.p. 132 ± 1348 ([8]: 132 ±
1358). [a]2D5 ˆ ‡18.7 (c ˆ 1.1, CHCl3) ([8]: [a]2D3 ˆ ‡34.8( c ˆ 0.1, MeOH)). IR (CHCl3): 3405w, 3007m, 2934w,
1708s, 1612s, 1598s, 1502s, 1487w, 1456m, 1082s. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 9.51 (br.
s, NH); 8.05 ± 7.98 (m, 2 arom. H); 7.63 ± 7.47 (m, 3 arom. H); 7.26 ± 7.13 (m, 4 arom. H); 6.81 ± 6.70 (m, 6 arom.
H); 3.75 ± 3.56 (m, CH2CH2); 1.49, 1.32 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 164.9
(s, CˆO); 146.5, 146.4, 133.7 (3s); 132.8( d); 129.4 (2d); 129.1 (2d); 128.8 (2d); 128.0 (2d); 118.4, 118.3 (2d);

Helvetica Chimica Acta ± Vol. 87 (2004)
2977
1
Table 2. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Monomeric Adenosine
Derivatives 2 ± 4 and 7 ± 12
2
3 ´ H2O
3
4
7
8
9
10
11
12
Solvent CDCl3 (D6)DMSO (D6)DMSO (D6)DMSO CDCl3 CDCl3 CDCl3 CD3OD CDCl3 CDCl3
HÀC(2) 8.72
HÀC(8
8.73
8.60
8
8.65
.62
6.42
4.76
8.66
.59
6.07
5.22
8.69
8.18
8.68
8.80
±
6.21
5.35
8.31
7.9±8
6.31
5.33
)
7.8
0
8
±
±
6.32
5.32
8
.61
8
.22
HÀC(1') 6.16
HÀC(2') 5.15
HÀC(3') 5.20
HÀC(4') 4.63
HÀC(5') 5.74
6.24
5.34
5.05
4.36
4.83
2.5
6.2
< 1
5
6.55
5.40
5.485.07
4.77
9.31
0
6.2
1.9
0
6.12
5.92
5.27
4.22
4.58
2.0
6.2
2.82.5
8.1
6.07
5.93
5.185
4.184.40
4.53
1.9
5.16
5.30
5.15
4.73
5.20
0
5.85.6
0
4.55
4.72
5.3
6.2
0
4.39
4.33
4.56
3.1
6.2
4.76
2.9
4.74
3.1
J(1',2')
J(2',3')
J(3',4')
J(4',5')
2.2
6.2
4.8
2.5
6.2
6.5
2.5
1.9
2.8
6.2
1.9
8.4
3.7
5.4
4.7
Table 3. Selected 13C-NMR Chemical Shifts [ppm] of the Monomeric Adenosine Derivatives 2 ± 4 and 7 ± 12
2
3 ´ H2O
4
7
8
9
10
11
12
Solvent CDCl3 (D6)DMSO (D6)DMSO CDCl3 CDCl3 CDCl3 CD3OD
CDCl3 CDCl3
C(2)
C(4)
C(5)
C(6)
C(8)
C(1')
C(2')
C(3')
C(4')
C(5')
C(6')
C(7')
152.9
149.7
122.9
151.3
141.7
88.4
83.8
80.1
87.0
73.3
±
152.1
150.5
125.7
151.5
143.2
90.4
83.8
80.8
89.3
88.9
±
151.7
150.3
125.5
151.2
149.8
85.7
83.1
77.9
83.7
63.0
±
151.9
149.0
126.3
150.9
103.7
96.2
81.7
80.7
87.1
63.5
152.7
148.6
125.7
152.1
105.4
94.4
82.8
82.4
90.1
63.6
153.0
150.8
123.0
154.6
104.5
94.3
83.3
82.6
90.3
63.7
153.5
151.6
125.4
153.4
144.8
93.5
85.9
82.8
90.7
63.5
153.2
150.0
123.6
151.6
142.2
91.5
84.1
81.4
89.3
63.4
153.5
149.8
120.4
156.1
139.8
91.3
84.1
81.6
89.4
63.4
101.2
92.2
104.2
91.2
101.3
91.1
82.7
76.4
82.0
75.1
82.3
75.0
±
±
±
115.1 (s, Me2C); 113.6 (2d); 113.5 (2d); 47.8, 46.8 (2t, CH2CH2); 27.4, 25.7 (2q, Me2C). FAB-MS (NOBA): 604
‡
(40, [M ‡ H] ).
N6-Benzoyl-9-(2,3-O-isopropylidene-b-d-ribo-pentodialdo-1,5-furanosyl)adenine Hydrate (3 ´ H2O).
A
‡
soln. of 2 (18.5 g, 30.6 mmol) in THF/H2O 1 :1 (1.8l) was treated with Dowex 50W (H form, 36 g), stirred
at 238 for 1.5 h, and filtered (washing of the resin with 4 Â 100 ml of THF). The combined filtrate and washings
was concentrated to ca. 1ꢁ2 of the volume. The resulting colourless, amorphous solid was filtered off, washed with
H2O, and dried for 24 h at 408 and 100 mbar to afford 3a ´ H2O (13.1 g, 79%). White solid. Rf (AcOEt/hexane
3 :1) 0.31. IR (KBr): 3275s (br.), 2989m, 1702s, 1617s, 1588s, 1523s, 1410s, 1291s, 1263m, 1223m, 1172m, 1157m,
1130m, 1059m. 1H-NMR (200 MHz, (D6)DMSO): see Table 2; additionally, 11.15 (br. s, NH); 8.03 ± 8.01 (m, 2
arom. H); 7.65 ± 7.60 (m, 3 arom. H); 6.28, 6.16 (2d, J ˆ 6.2, 2 HOÀC(5')); 1.53, 1.32 (2s, Me2C). 13C-NMR
(75 MHz, (D6)DMSO): see Table 3; additionally, 165.9 (s, CˆO); 133.5 (s); 132.6 (d); 128.6 (4d); 112.8( s,
‡
‡
Me2C); 26.9, 25.0 (2q, Me2C). HR-MALDI-MS (DHB): 432.093 ( [M À H2O ‡ Na] , C20H19N5NaO5 ; calc.
432.128).
N6-Benzoyl-9-(2,3-O-isopropylidene-b-d-ribo-pentodialdo-1,5-furanosyl)adenine (3). A suspension of 3 ´
H2O (5 g, 12.9 mmol) in benzene (75 ml) was heated under reflux for 30 min using a Dean ± Stark condenser and
evaporated. The residue was dried i.v. to afford 3 (4.8g, > 97%). White foam. IR (CHCl3): 3394w, 3041m,
2984w, 1734s, 1712s, 1610s, 1590s, 1503s, 1480m, 1457s, 1385m, 1329m, 1238m, 1211m, 1102m. 1H-NMR

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Helvetica Chimica Acta ± Vol. 87 (2004)
(300 MHz, (D6)DMSO): see Table 2; additionally, 11.2 (br. s, NH); 8.04 ± 8.01 (m, 2 arom. H); 7.63 ± 7.51 (m, 3
‡
arom. H); 1.52, 1.34 (2s, Me2C). FAB-MS (NOBA): 410 (47, [M ‡ H] ).
(5'S)-N6-Benzoyl-8,5'-cyclo-2',3'-O-isopropylideneadenosine (4). Neglecting purification of N,N'-diphenyl-
ethylenediamine and careful reaction conditions1), 4 was obtained as a side product in the preparation of 3.
Heating of 3 in benzene under reflux led to 4. [a]2D5 ˆ ‡14.7 (c ˆ 0.37, CH2Cl2). IR (CH2Cl2): 3386w, 3150w (br.),
2988w, 2937w, 1709s, 1611s, 1582m, 1479s, 1388m, 1328s, 1215m, 1087m. 1H-NMR (300 MHz, (D6)DMSO): see
Table 2; additionally, 11.20 (br. s, NH); 8.03 ± 8.01 (m, 2 arom. H); 7.63 ± 7.59 (m, 1 arom. H); 7.55 ± 7.50 (m, 2
arom. H); 6.82 (d, J ˆ 5.6, irrad. at 5.20 ! NOE of 4%, HOÀC(5')); 5.20 (irrad. at 6.82 ! NOE of 8%,
HÀC(5')); 5.07 (irrad. at 6.82 ! NOE of 1.5%, HÀC(3')); 1.42, 1.21 (2s, Me2C). 13C-NMR (50 MHz,
(D6)DMSO): see Table 3; additionally, 165.6 (s, CˆO); 133.3 (s); 132.5 (d); 128.5 (4d); 112.6 (s, Me2C); 25.9,
‡
24.5 (2q, Me2C); 0.2 (q, Me3Si). FAB-MS (NOBA): 410 (100, [M ‡ H] ).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]ade-
nine (5) [3] and N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-a-l-talo-hept-6-ynofura-
nosyl]adenine (6) [3]. A soln. of (trimethylsilyl)acetylene (3.9 ml, 27.8mmol) in THF (50 ml) was cooled to 0 8,
treated dropwise with 3.0m EtMgBr in Et2O (9.3 ml, 27.9 mmol), stirred at 08 for 15 min and at 238 for 45 min,
cooled to À 158, treated dropwise with a soln. of 3 (2.8g, 6.8mmol) in THF (50 ml), stirred for 1.5 h, treated
with sat. aq. NH4Cl soln. (50 ml), and allowed to warm to 238. After evaporation, a soln. of the residue in AcOEt
was washed with sat. aq. NH4Cl soln. and brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:1) and
crystallisation gave 5 (1.4 g, 40%) and 6 (0.7 g, 20%). Data of 5 and 6: see [3].
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-8-
iodoadenine (7). A soln. of (i-Pr)2NH (5.8ml, 41.4 mmol, distilled from CaH 2) in THF (100 ml) was cooled to
À 788, treated dropwise with 1.60m BuLi in hexane (26.0 ml, 41.4 mmol), stirred at À 788 for 15 min and at 08
for 15 min, cooled to À 788, treated dropwise with a soln. of 5 (3.2 g, 6.3 mmol) in THF (100 ml), stirred for 2 h,
treated dropwise with a soln. of NIS (9.3 g, 41.4 mmol) in THF (100 ml), stirred for 2 h, treated with AcOH
(6 ml), and allowed to warm to 238. After evaporation, a soln. of the residue in AcOEt was washed with sat. aq.
NaHCO3 soln., sat. aq. Na2S2O3 soln., and brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:1) gave
7 (3.5 g, 88%). White solid. Rf (AcOEt/hexane 1:1) 0.35. [a]2D5 ˆ À84.5 (c ˆ 1.0, CH2Cl2). IR (CHCl3): 3403w,
3181m, 3008s, 2181w, 1716m 1606s, 1423s, 1320m, 1088s, 929m, 8 49m. 1H-NMR (300 MHz, CDCl3): see Table 2;
additionally, 9.11 (br. s, NH); 8.05 ± 7.98 (m, 2 arom. H); 7.63 ± 7.47 (m, 3 arom. H); 7.06 (d, J ˆ 1.6, HOÀC(5'));
1.68, 1.39 (2s, Me2C); 0.21 (s, Me3Si). 13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 164.4 (s, CˆO);
133.3 (s); 133.0 (d); 129.0 (2d); 127.9 (2d); 114.3 (s, Me2C); 27.8, 25.5 (2q, Me2C); 0.3 (q, Me3Si). FAB-MS
‡
(NOBA): 634 (100, [M ‡ H] ). Anal. calc. for C20H29N5O5Si (633.52): C 47.40, H 4.45, N 11.05; found: C 47.39, H
4.56, N 11.17.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-
6-ynofuranosyl]-8-iodoadenine (8). A soln. of pyridine (1.2 ml, 15 mmol, distilled from CaH2) and 7 (2.0 g,
3.2 mmol) in CH2Cl2 (30 ml) was treated dropwise with TIPSOTf (1.77 ml, 6.6 mmol), stirred at 238 for 30 min,
washed with brine (3 Â 10 ml), dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:2) gave 8 (2.23 g, 89%).
Yellow foam. Rf (AcOEt/hexane 1:2) 0.39. [a]2D5 ˆ À3.3 (c ˆ 1.0, CHCl3). UV (MeOH): 290 (23200). IR
(CHCl3): 3409w, 2893w, 2866w, 2160w, 1710s, 1609s, 1588m, 1461m, 1423s, 1320m, 1095m, 8 46s. 1H-NMR
(300 MHz, CDCl3): see Table 2; additionally, 9.13 (br. s, NH); 8.01 ± 7.98 (m, 2 arom. H); 7.63 ± 7.48( m, 3 arom.
H); 1.62, 1.40 (2s, Me2C); 1.10 ± 1.05 (m, (Me2CH)3Si); 0.07 (s, Me3Si). 13C-NMR (75 MHz, CDCl3): see Table 3;
additionally, 164.8( s, CˆO); 133.9 (s); 133.1 (d); 129.2 (2d); 128.1 (2d); 114.3 (s, Me2C); 27.2, 25.4 (2q, Me2C);
‡
18.0 (q, (Me2CH)3Si); 12.4 (d, (Me2CH)3Si); À 0.4 (q, Me3Si). FAB-MS (NOBA): 790 (90, [M ‡ H] ).
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]-8-iodoadenine (9). At 258, a soln. of 8 (600 mg, 0.76 mmol) in dry toluene (35 ml) was treated dropwise
with a soln. of 8m MeNH2 in MeOH (1.6 ml, 12.8mmol), stirred for 2 h, diluted with AcOEt (10 ml), washed
with sat. aq. NH4Cl soln. and brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 3 :1 ! 1:1) and
crystallisation from AcOEt/hexane gave 9 (441 mg, 85%). Colourless crystals. Rf (AcOEt/hexane 1 :1) 0.51. M.p.
159.5 ± 1618. [a]2D5 ˆ À14.6 (c ˆ 0.62, CH2Cl2). UV (MeOH): 265 (15000). IR (CH2Cl2): 3513w, 3402m, 2947m,
2867m, 2172w, 1630s, 1584m, 1467m, 1377m, 1094s, 8 49s. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally,
5.83 (br. s, NH2); 1.61, 1.39 (2s, Me2C); 1.10 ± 1.05 (m, (Me2CH)3Si); 0.07 (s, Me3Si). 13C-NMR (75 MHz,
CDCl3): see Table 3; additionally, 114.1 (s, Me2C); 27.2, 25.5 (2q, Me2C); 18.1 (q, (Me2CH)3Si); 12.5 (d,
‡
‡
(Me2CH)3Si); 0.3 (q, Me3Si). HR-MALDI-MS (DHB): 708.182 ([M ‡ Na] , C27H44IN5NaO5Si2 ; calc. 708.187).
Anal. calc. for C27H44IN5O5Si2 (685.75): C 47.29, H 6.47, N 10.21; found: C 47.19, H 6.33, N 10.10.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl]adenine (10). A soln. of 5
(705 mg, 1.39 mmol) in dry THF (10 ml) was treated with a 1.0m soln. of TBAF in THF (1.42 ml, 1.42 mmol),

Helvetica Chimica Acta ± Vol. 87 (2004)
2979
stirred for 45 min, treated dropwise with AcOH (0.09 ml), and evaporated. A soln. of the residue in AcOEt was
washed with sat. aq. NaHCO3 soln. and brine, dried (Na2SO4), and evaporated. FC (AcOEt/hexane 3 :1) gave 10
(620 mg, quant.). White foam. Rf (AcOEt/hexane 3 :1) 0.18. [a]2D5 ˆ À111.7 (c ˆ 0.75, CH2Cl2). UV (MeOH):
279 (20300). IR (CHCl3): 3393w, 3300m, 3198m, 3041m, 2989w, 1713s, 1610s, 1456s, 1329m, 1219s, 1089s, 957m,
851m. 1H-NMR (300 MHz, CD3OD): see Table 2; additionally, 8.07 ± 8.04 (m, 2 arom. H); 7.65 ± 7.50 (m, 3 arom.
H); 2.18( d, J ˆ 2.2, HÀC(7')); 1.62, 1.39 (2s, Me2C). 13C-NMR (75 MHz, CD3OD): see Table 3; additionally,
166.0 (s, CˆO); 135.2 (s); 134.2 (d); 130.1 (2d); 129.8(2 d); 115.5 (s, Me2C); 27.7, 25.6 (2q, Me2C). FAB-MS
‡
(NOBA): 436 (100, [M ‡ H] ).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]ade-
nine (11). A soln. of pyridine (0.6 ml, 6.9 mmol, distilled from CaH2) and 10 (530 mg, 1.22 mmol) in CH2Cl2
(100 ml) was treated dropwise with TIPSOTf (0.68ml, 2.56 mmol), stirred at 23 8 for 1 h, washed with brine (3 Â
10 ml), dried (Na2SO4), and evaporated. FC (AcOEt/hexane 1:2) gave 11 (637 mg, 88%). Colourless foam. Rf
(AcOEt/hexane 1:1) 0.19. [a]2D5 ˆ À32.2 (c ˆ 1.1, CHCl3). UV (ClCH2CH2Cl): 280 (23900). IR (CHCl3): 3409w,
3304m, 2999w, 2946m, 2893m, 2868m, 2110w, 1709s, 1612s, 1585m, 1456s, 1091s, 8 8w3. 1H-NMR (300 MHz,
CDCl3): see Table 2; additionally, 9.20 (br. s, NH); 8.04 ± 7.99 (m, 2 arom. H); 7.59 ± 7.45 (m, 3 arom. H); 2.42 (d,
J ˆ 2.1, HÀC(7')); 1.64, 1.41 (2s, Me2C); 1.10 ± 1.05 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 3;
additionally, 164.9 (s, CˆO); 135.6 (s); 133.0 (d); 129.1 (2d); 128.1 (2d); 115.0 (s, Me2C); 27.3, 25.4 (2q, Me2C);
‡
18.0 (q, (Me2CH)3Si); 12.4 (d, (Me2CH)3Si). FAB-MS (NOBA): 592 (100, [M ‡ H] ). Anal. calc. for
C31H41N5O5Si (591.78): C 62.92, H 6.98, N 11.83; found: C 62.92, H 6.92, N 11.65.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (12).
At 258, a soln. of 11 (0.8g, 1.35 mmol) in dry toluene (30 ml) was treated dropwise with a soln. of 8 m MeNH2
in MeOH (1.62 ml, 13.0 mmol), stirred for 4 h, washed with sat. aq. NH4Cl soln. and brine, dried (Na2SO4), and
evaporated. FC (25 g of silica gel; AcOEt/hexane 3 :2 ! 3 :1) gave 12 (585 mg, 89%). White foam. Rf (AcOEt/
hexane 1:1) 0.15. [a]2D5 ˆ À21.7 (c ˆ 0.38, CH2Cl2). UV (MeOH): 258(12300). IR (CH 2Cl2): 3514m, 3403m,
1
3300w, 2946m, 2868m, 1630s, 1586w, 1470m, 1376m, 1209w, 1097m. H-NMR (300 MHz, CDCl3): see Table 2;
additionally, 6.24 (br. s, NH2); 2.42 (d, J ˆ 2.2, HÀC(7')); 1.61, 1.38(2 s, Me2C); 1.10 ± 1.05 (m, (Me2CH)3Si).
13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 114.8( s, Me2C); 27.3, 25.5 (2q, Me2C); 18.1 (q,
‡
‡
(Me2CH)3Si); 12.5 (d, (Me2CH)3Si). HR-MALDI-MS (DHB): 488.262 ([M ‡ H] , C24H38N5O4Si ; calc.
488.269). Anal. calc. for C24H37N5O4Si (487.67): C 59.11, H 7.65, N 14.36; found: C 58.94, H 7.78, N 14.29.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-
6-ynofuranosyl]adenin-8-yl-(8 ! 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-al-
lo-hept-6-ynofuranosyl)uracil (14). A soln. of 13 [2] (142 mg, 0.15 mmol), 8 (182 mg, 0.23 mmol), [Pd2(dba)3]
(70 mg, 82 mmol), CuI (16 mg, 84 mmol), and P(fur)3 (20 mg, 86 mmol) in degassed Et3N/toluene 1:1 (10 ml) was
stirred for 24 h at 238 and evaporated. FC (AcOEt/hexane 2 :3 ! 1:2) gave 14 (120 mg, 49%). Yellow foam. Rf
(AcOEt/hexane 1:1) 0.20. 1H-NMR (500 MHz, CDCl3): see Table 4; additionally, 9.74 (br. s, 2 NH); 9.64 (br. s,
NH); 8.02 ± 8.00 (m, 2 arom. H); 7.59 ± 7.56 (m, 1 arom. H); 7.50 ± 7.46 (m, 2 arom. H); 1.61, 1.57, 1.55, 1.40, 1.33
(6 H) (5s, 3 Me2C); 1.21 ± 1.04 (m, 3 (Me2CH)3Si); 0.07 (s, Me3Si). HR-MALDI-MS (DHB): 1610.754
‡
‡
([M ‡ Na] , C80H117N9NaO17Si4 ; calc. 1610.754).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]ade-
nin-8-yl-(8 ! 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 (15). A soln. of 14 (49 mg, 31 mmol) in MeOH/AcOEt 1 :1 (8ml) was treated dropwise with a soln. of
AgNO3 (78mg, 0.46 mmol) in H 2O/MeOH 1:1 (1 ml), stirred at 238 under exclusion of light for 4 h, treated with
a soln. of KCN (78mg, 1.2 mmol) in H 2O (0.3 ml), 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 2 :3) gave 15 (22 mg,
47%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.20. 1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 9.74,
9.64, 8.92 (3 br. s, 3 NH); 8.03 ± 8.01 (m, 2 arom. H); 7.61 ± 7.46 (m, 3 arom. H); 2.29 (d, J ˆ 1.9, HÀC(7'/III));
1.61, 1.57, 1.55, 1.40, 1.33 (6 H) (5s, 3 Me2C); 1.21 ± 1.04 (m, 3 (Me2CH)3Si). MALDI-MS (IAA): 1540.5 ([M ‡
‡
Na] ).
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]adenin-8-yl-(8 ! 7'-C)-1-(6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-yno-
furanosyl)uracil-6-yl-(6 ! 7'-C)-1-(6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-
ynofuranosyl)uracil (16). A soln. of 13 (193 mg, 0.21 mmol), 9 (200 mg, 0.29 mmol), [Pd2(dba)3] (80 mg,
80 mmol), CuI (30 mg, 0.16 mmol), and P(fur)3 (37 mg, 0.16 mmol) in degassed Et3N/toluene 1 :1 (30 ml) was
stirred for 24 h at 238. After evaporation, FC (AcOEt/hexane 2 :5 ! 2 :1) gave 16 (116 mg, 38%). Yellow foam.

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Helvetica Chimica Acta ± Vol. 87 (2004)
Table 4. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Mixed Trimers 14 ± 17 in
CDCl3
14a)
15b)
16b)
17b)
14
15
16
17
HÀC(5/I)
5.80
7.47
5.585.59
4.94
4.87
4.34
5.04
5.85
6.14
5.17
5.77
7.44
6.13
7.37
6.08
7.36
HÀC(6/I)
HÀC(1'/I)
HÀC(2'/I)
HÀC(3'/I)
HÀC(4'/I)
HÀC(5'/I)
HÀC(5/II)
HÀC(1'/II)
HÀC(2'/II)
HÀC(3'/II)
HÀC(4'/II)
HÀC(5'/II)
HÀC(2/III)
HÀC(1'/III)
HÀC(2'/III)
HÀC(3'/III)
HÀC(4'/III)
HÀC(5'/III)
HÀC(7'/III)
5.59
5.59
J(1',2'/I)
J(2',3'/I)
J(3',4'/I)
J(4',5'/I)
1.6
6.3
2.5
6.2
1.9
6.5
2.82.7
6.2
0
6.3
1.2
6.6
4.93
4.88
4.31
5.03
5.86
6.16
5.185.23
5.21
5.05
4.32
4.99
5.80
6.24
5.23
5.05
4.31
5.00
5.81
6.24
2.8
7.6
7.0
J(1',2'/II)
J(2',3'/II)
J(3',4'/II)
J(4',5'/II)
< 1
6.2
3.7
8.1
< 1
6.2
3.7
8.1
1.6
6.5
3.2
8.3
1.6
6.4
3.2
8.2
5.19
5.085.085.085.07
4.25
5.01
8.78
6.33
5.61
5.37
4.19
4.69
±
4.23
5.01
8.78
6.33
5.66
5.36
4.21
4.75
2.29
4.22
5.03
8.25
6.35
5.61
5.32
4.12
4.60
±
4.20
5.03
8.25
6.34
5.70
5.32
4.14
4.63
2.26
J(1',2'/III)
J(2',3'/III)
J(3',4'/III)
J(4',5'/III)
J(5',7'/III)
1.6
6.2
3.1
8.4
±
1.9
6.4
3.1
8.1
2.2
1.5
6.4
3.2
8.4
±
1.6
6.4
3.2
8.1
2.1
a) Assignment based on
experiments.
a
DQF-COSY spectrum. b) Assignment based on selective homodecoupling
Table 5. Selected 13C-NMR Chemical Shifts [ppm] of the Trimers 16 and 17 in CDCl3
16
17
16
17
C(2/I ± II)
C(4/I ± II)
C(5/I)
164.8, 162.0
150.6, 149.6
103.5
164.8, 162.0
150.6, 149.6
103.4
C(2/III)
C(4/III)
C(5/III)
153.3
148.6
119.6
153.3
148.6
119.6
C(5/II)
107.6
107.6
C(6/I)
C(6/II)
142.9
137.5
96.4, 95.1
84.5, 83.9, 83.3
83.2, 82.9, 82.3
90.8, 90.7, 90.3
142.9
137.5
96.4, 95.1
84.5, 83.8, 83.18
83.18, 82.6, 82.2
90.7, 90.6, 90.2
C(6/III)
C(8/III)
C(1'/III)
155.8155.8
134.6
90.9
136.6
90.9
C(1'/I ± II)
C(2'/I ± III)
C(3'/I ± III)
C(4'/I ± III)
C(5'/I ± III)
C(6'/I)
C(6'/II)
C(7'/I)
C(7'/II)
64.1, 64.0, 63.864.1, 64.0, 63.1
102.2
95.6
76.4
74.2
102.2
95.6
76.4
74.2
C(6'/III)
C(7'/III)
104.9
90.4
82.8
73.9
Rf (AcOEt/hexane 1:1) 0.33. IR (CH2Cl2): 3371w (br.), 3200w, 2945m, 2867m, 2235w, 2167w, 1698s, 1636s,
1599w, 1447m, 1383m, 1328w, 1213m, 1096s, 1067m. 1H-NMR (400 MHz, CDCl3): see Table 4; additionally,
11.75, 9.45 (2 br. s, 2 NH); 7.07 (br. s, NH2); 1.60, 1.58, 1.55, 1.37, 1.36, 1.35 (6s, 3 Me2C); 1.21 ± 1.06 (m,
3 (Me2CH)3Si); 0.06 (s, Me3Si). 13C-NMR (100 MHz, CDCl3): see Table 5; additionally, 113.83, 113.66, 113.56

Helvetica Chimica Acta ± Vol. 87 (2004)
2981
(3s, 3 Me2C); 27.2, 27.1, 26.9, 25.3, 25.1, 24.9 (6q, 3 Me2C); 18.09, 18.03, 17.93 (3q, 3 (Me2CH)3Si); 12.51, 12.46,
‡
12.29 (3d, 3 (Me2CH)3Si); À 0.35 (s, Me3Si). HR-MALDI-MS (DHB): 1506.728([ M ‡ Na] ,
‡
C73H113N9NaO16Si4 ; calc. 1506.728). Anal. calc. for C73H113N9O16Si4 (1485.09): C 59.04, H 7.67, N 8.49; found:
C 59.10, H 7.50, N 8.47.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-
(8 ! 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
(17). A soln. of 16 (116 mg, 78 mmol) in MeOH/AcOEt 1 :1 (50 ml) was treated dropwise with a soln. of AgNO3
(395 mg, 2.34 mmol) in H2O (5 ml), stirred at 238 under exclusion of light for 3.5 h, treated with a soln. of KCN
(380 mg, 5.9 mmol) in H2O (6 ml), 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 1:1 ! 2:1) gave 17 (82 mg, 74%).
Colourless crystals. Rf (AcOEt/hexane 1:1) 0.29. IR (CH2Cl2): 3370w (br.), 3303w, 3201w, 2945m, 2868m,
1
2235w, 1698s, 1636m, 1448m, 1383m, 1213m, 1097m, 1067m, 8 8 m2 . H-NMR (400 MHz, CDCl3): see Table 4;
additionally, 11.6, 9.4 (2 br. s, 2 NH); 7.02 (br. s, NH2); 2.26 (d, J ˆ 2.2, HÀC(7'/III)); 1.60, 1.59, 1.55, 1.37 (6 H),
1.35 (5s, 3 Me2C); 1.21 ± 1.06 (m, 3 (Me2CH)3Si). 13C-NMR (100 MHz, CDCl3): see Table 5; additionally, 113.91,
113.76, 113.69 (3s, 3 Me2C); 27.18, 27.11, 26.93, 25.23, 25.1, 24.9 (6q, 3 Me2C); 18.08, 18.06, 17.99 (6 C), 17.94,
‡
17.92 (5q, 3 (Me2CH)3Si); 12.5, 12.4, 12.3 (3d, 3 (Me2CH)3Si). HR-MALDI-MS (DHB): 1434.686 ([M ‡ Na] ,
‡
C70H105N9NaO16Si3 ; calc. 1434.688). Anal. calc. for C70H105N9O16Si3 (1412.91): C 59.51, H 7.49, N 8.92; found: C
59.44, H 7.45, N 8.71.
2',3'-O-Isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7'-C)-9-[6,7-dideoxy-2,3-O-isopropylidene-5-
O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-(8 ! 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 (21). A soln. of 17 (40 mg, 28 mmol), 19 [3] (46.5 mg,
85 mmol), [Pd2(dba)3] (4 mg, 4.2 mmol), CuI (1.6 mg, 8.2 mmol), and P(fur)3 (1.9 mg, 8.2 mmol) in degassed Et3N/
toluene 1:1 (2 ml) was stirred for 24 h at 238 and evaporated. FC (AcOEt/hexane 2 :5 ! 2 :1) gave 21 (26 mg,
50%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.22. [a]2D5 ˆ ‡101.8( c ˆ 0.61, CH2Cl2). UV (CH2Cl2): 297 (43600).
IR (CH2Cl2): 3471w, 3401w, 3317w, 3182w, 2946m, 2868m, 1697s, 1634m, 1602w, 1458m, 1383m, 1328w, 1218m,
1081s. 1H-NMR (500 MHz, CDCl3): see Table 6; additionally, 11.60, 8.00 (2 br. s, 2 NH); 6.45, 6.35 (2 br. s,
2 NH2); 1.64, 1.58, 1.56, 1.54, 1.45 (6 H), 1.40, 1.38 (7s, 4 Me2C); 1.21 ± 1.06 (m, 3 (Me2CH)3Si); 0.86 (t, J ˆ 7.8,
(MeCH2)3Si); 0.47 (q, J ˆ 7.8, ( MeC H2)3Si). 13C-NMR (125 MHz, CDCl3): see Table 7; additionally, 113.9,
113.8, 113.7, 113.5 (4s, 4 Me2C); 27.3, 27.2 (2 C), 27.1, 25.6 (2 C), 25.2, 25.1 (6q, 4 Me2C); 17.97 (12 C), 17.93 (2q,
3 (Me2CH)3Si); 13.51, 12.97, 12.76 (3d, 3 (Me2CH)3Si); 6.6 (q, (MeCH2)3Si); 4.2 (t, (MeCH2)3Si). HR-MALDI-
‡
‡
MS (DHB): 1853.885 ([M ‡ Na] , C89H134N14NaO20Si4 ; calc. 1853.887).
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7'-C)-N6-benzoyl-9-[6,7-dideoxy-
2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl]adenine (22). A soln. of 18 [3] (1.79 g, 2.75 mmol), 10 (1.0 g,
Table 6. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Mixed Tetramers 21 and
32 (assignment based on a DQF-COSY spectrum of 21 and 32, and a HMBC spectrum of 32)
21 (CDCl3)
32 (CDCl3/CD3OD 9 : 1)
Unit IV
Unit III
Unit II
Unit I
Unit IV
Unit III
Unit II
Unit I
HÀC(5)
HÀC(2)
HÀC(1')
HÀC(2')
HÀC(3')
HÀC(4')
HÀC(5')
J(1',2')
±
±
5.86
±
5.84a)
±
5.49
5.26
6.06
±
6.20
5.19
6.12b)
±
6.10
5.16
±
±
8.26
6.10
5.63d)
5.13
4.19
3.69, 3.58
1.4
8.28
6.16
5.63d)
5.39
4.29
4.88
0
8.19
6.35
5.60
8.25c)
6.23 (br.)
5.75 (br.)
6.34
5.31
5.00
4.12
5.09
1.0
4.984.8 5.00
5.31
5.29
4.32
5.07
1.0
4.11
3.84
0.9
4.06
4.97
0.9
4.31
5.21
1.9
4.46
5.02
1.8
J(2',3')
6.2
6.2
6.5
6.5
6.4
6.3
6.2
6.2
J(3',4')
3.9
5.0
3.4
2.9
4.5
5.1
3.2
2.4
J(4',5')
6.8, 6.8
7.0
6.3
6.3
6.3, 6.3
6.2
7.6
7.1
a) HÀC(6/I) at 7.34 ppm. b) Broad signal. c) HÀC(8/I) at 8.11 ppm. d) Overlapping signals.

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Helvetica Chimica Acta ± Vol. 87 (2004)
Table 7. Selected 13C-NMR Chemical Shifts [ppm] of the Tetramers 21 and 32 (assignment of 32 based on a
HMBC spectrum)
21 (CDCl3)
32 (CDCl3/CD3OD 9 : 1)
C(2/I ± IV)
C(4/I ± IV)
C(5/I ± IV)
C(6/I ± IV)
U-Units
A-Units
U-Units
A-Units
U-Units
A-Units
U-Units
A-Units
A-Units
164.3, 162.8163.6 (2 C)
153.2 (2 C)
150.5, 150.3
148.5 (2 C)
102.8 (I), 108.7 (II)
119.7, 119.6
143.3 (I), 137.1 (II)
155.5, 155.4
134.9, 134.5
90.5, 90.4, 90.1, 90.0
84.0, 83.7, 83.5, 83.3
83.1, 82.6 (2 C), 82.3
89.8, 88.4 (3 C)
64.3, 64.2, 64.0
63.0
153.4, 152.6
150.1 (2 C)
148.8 (I), 148.5 (II)
109.4, 108.7
119.8, 119.4
138.0 (IV), 137.3 (III)
155.8(I), 155.6 (II)
140.7 (I), 133.9 (II)
93.9 (IV), 93.6 (III), 91.4 (I), 90.9 (II)
84.4, 84.0, 83.7, 83.0
82.33 (2 C), 82.26, 81.7 (IV)
90.9, 89.9, 89.6, 89.5
64.3 (III), 63.9 (I, II)
64.4
C(8/I ± IV)
C(1'/I ± IV)
C(2'/I ± IV)
C(3'/I ± IV)
C(4'/I ± IV)
C(5'/I ± III)
C(5'/IV)
C(6'/I ± III)
C(7'/I ± III)
97.7, 95.2, 95.0
74.5, 73.9 (2 C)
101.7 (III), 101.5 (II), 95.2 (I)
75.85 (III), 75.75 (II), 74.5 (I)
2.29 mmol), [Pd2(dba)3] (156.6 mg, 0.171 mmol), CuI (45.3 mg, 0.24 mmol), and P(fur)3 (55.7 mg, 0.24 mmol)
in degassed Et3N/toluene 1:1 (100 ml) was stirred for 22 h at 238 and evaporated. FC (AcOEt/hexane 2 :1 !
3 :1) gave 22 (1.26 g, 57%). Yellow foam. Rf (AcOEt/hexane 3 :1) 0.23. [a]2D5 ˆ À82.9 (c ˆ 0.53, CHCl3). UV
(CH2Cl2): 313 (sh), 302 (sh), 291 (32000). IR (CHCl3): 3397w, 3110w (br.), 2955m, 1713s, 1608s, 1458s, 1331m,
1237m, 1089m. 1H-NMR (500 MHz, (D6)DMSO): see Table 8; additionally, 11.30, 11.20 (2 br. s, 2 NH); 8.05 ±
8.03 (m, 4 arom. H); 7.67 ± 7.63 (m, 2 arom. H); 7.57 ± 7.53 (m, 4 arom. H); 6.71 (d, J ˆ 6.0, HOÀC(5'/I)); 1.60,
1.53, 1.38, 1.31 (4s, 2 Me2C); 0.79 (t, J ˆ 7.8, ( MeCH2)3Si); 0.42 (q, J ˆ 7.8, (MeCH2)3Si). 13C-NMR (125 MHz,
(D6)DMSO): see Table 9; additionally, 165.5 (s, 2 CˆO); 133.3, 133.1 (2s); 132.5, 132.4 (2d); 128.6 (2d); 128.5
(2d); 128.42 (2d); 128.40 (2d); 113.4, 113.3 (2s, 2 Me2C); 26.9, 25.2 (2q, 2 Me2C); 6.4 (q, (MeCH2)3Si); 3.7 (t,
‡
(MeCH2)3Si). FAB-MS (NOBA): 959 (100, [M ‡ H] ).
Table 8. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Dimeric Adenosine
Derivatives 22 ± 24 in (D6)DMSO
22a)
23a)
24b)
22
23
24
HÀC(2/I)
HÀC(8/I)
HÀC(1'/I)
HÀC(2'/I)
HÀC(3'/I)
HÀC(4'/I)
HÀC(5'/I)
HÀC(2/II)
HÀC(1'/II)
HÀC(2'/II)
HÀC(3'/II)
HÀC(4'/II)
HaÀC(5'/II)
HbÀC(5'/II)
8.78
8.66
6.39
5.51
5.26
4.39
4.91
8.76
6.25
5.685.62
5.09
4.16
3.72
3.64
8.65
±
8.49
±
6.17
5.71
5.34
4.30
4.88
8.76
6.21
6.10
5.47
5.15
4.15
4.80
±
J(1',2'/I)
J(2',3'/I)
J(3',4'/I)
J(4',5'/I)
2.6
2.4
1.8
6.2
2.5
6.1
6.3
3.2
8.0
6.3
2.8
8.8
6.01
J(1',2'/II)
J(2',3'/II)
J(3',4'/II)
J(4',5a'/II)
J(4',5b''/II)
J(5a',5b''/II)
2.1
6.3
3.5
6.0
6.9
2.3
6.3
3.5
5.9
6.9
2.9
6.6
4.0
6.0
6.0
5.62
5.04
4.14
3.73
3.65
4.87
4.00
3.50
3.46
11.0
10.9
11.3
a) Assignment based on
experiments.
a
DQF-COSY spectrum. b) Assignment based on selective homodecoupling

Helvetica Chimica Acta ± Vol. 87 (2004)
2983
Table 9. Selected 13C-NMR Chemical Shifts [ppm] of the Dimeric Adenosine Derivatives 22 ± 24 in (D6)DMSO
(assignment of 22 and 23 based on a HSQC-GRASP spectrum)
22
23
24
22
23
24
C(2/II)
C(4/II)
C(5/II)
C(6/II)
C(8/II)
C(1'/II)
C(2'/II)
C(3'/II)
C(4'/II)
C(5'/II)
151.7
150.5
124.8127.7
150.7
135.6
89.5
82.5
8
87.4
62.6
152.5
149.2
157.6
149.75
116.8 C(5/I)
C(2/I)
C(4/I)
125.6
152.6
150.5
127.9
150.8152.0
143.1
151.3
150.6
131.4
152.5
109.3
149.73
149.68
150.8151.0
135.6
93.0
82.3
1.2
C(6/I)
138.7
88.5
82.3
C(8/I)
C(1'/I)
C(2'/I)
'/I)8
C(4'/I)
C(5'/I)
C(6'/I)
C(7'/I)
112.5
88.9
82.4
80.9
86.6
61.9
89.9
83.5
811.5.3
88.0
61.7
96.897.3
73.5
89.4
82.4
C8(13.8
87.2
62.6
8
1.3
88.2
61.7
86.2
61.4
96.6
73.1
73.6
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7'-C)-N6-benzoyl-9-[6,7-dideoxy-
2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl]-8-iodoadenine (23). A soln. of 2,2,6,6-tetramethylpiperi-
dine (TMP; 0.79 ml, 4.48mmol) in THF (25 ml) was cooled to À 788, treated dropwise with 1.40m n-BuLi in
hexane (3.2 ml, 4.5 mmol), stirred at À 788 for 15 min and at 08 for 15 min, treated dropwise with HMPA
(1.59 ml, 8.96 mmol), cooled to À 788, treated dropwise with a soln. of 22 (540 mg, 0.56 mmol) in THF (2 ml),
stirred for 20 min, treated dropwise with a soln. of NIS (980 mg, 4.48 mmol) in THF (2 ml), stirred for 10 min,
treated with sat. aq. NH4Cl soln. (20 ml), and allowed to warm to 238. After evaporation, a soln. of the residue in
AcOEt was washed with sat. aq. NaHCO3 soln., sat. aq. Na2S2O3 soln., and brine, dried (Na2SO4), and
evaporated. FC (AcOEt/hexane 2 :1) gave 23 (470 mg, 77%). Yellow solid. Rf (AcOEt/hexane 3 :1) 0.48. [a]D25
ˆ
À80.3 (c ˆ 0.57, CH2Cl2). UV (CH2Cl2): 313 (sh), 302 (sh), 293 (46000). IR (CH2Cl2): 3392w, 3185w (br.),
1
2954w, 1714m, 1605s, 1468s, 1326w, 1089m. H-NMR (500 MHz, (D6)DMSO): see Table 8; additionally, 11.35
(br. s, 2 NH); 8.05 ± 8.02 (m, 4 arom. H); 7.67 ± 7.63 (m, 2 arom. H); 7.56 ± 7.53 (m, 4 arom. H); 6.62 (d, J ˆ 6.6,
HOÀC(5'/I)); 1.61, 1.52, 1.37, 1.29 (4s, 2 Me2C); 0.79 (t, J ˆ 7.8, ( MeCH2)3Si); 0.42 (q, J ˆ 7.8, (MeCH2)3Si).
13C-NMR (125 MHz, (D6)DMSO): see Table 9; additionally, 165.5 (s, 2 CˆO); 133.2 (2s); 132.5 (2d); 128.5
(4d); 128.4 (4d); 113.7, 113.4 (2s, 2 Me2C); 27.1, 26.9, 25.3, 25.2 (4q, 2 Me2C); 6.4 (q, (MeCH2)3Si); 3.7 (t,
‡
(MeCH2)3Si). FAB-MS (NOBA): 1085 (100, [M ‡ H] ). Anal. calc. for C48H53IN10O10Si (1085.00): C 53.14, H
4.92, N 12.91; found: C 53.28H 5.10, N 12.80.
N6-Benzoyl-2-(diisopropylamino)-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7'-C)-N6-
benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl]-8-iodoadenine (24). The iodination
of 22 with 8equiv. of LDA and NIS gave 23 (36%), 22 (30%), and 24 (10%).
Data of 24: Yellow solid. Rf (AcOEt/hexane 3 :1) 0.71. [a]2D5 ˆ À32.2 (c ˆ 0.62, CH2Cl2). IR (CH2Cl2):
3367m, 2965w, 1745m, 1693m, 1630m, 1580m, 1509s, 1484m, 1376m, 1334m, 1220m, 1079m. 1H-NMR (400 MHz,
(D6)DMSO): see Table 8; additionally, 11.32, 10.77 (2 br. s, 2 NH); 8.03 ± 7.99 (m, 2 arom. H); 7.96 ± 7.94 (m, 2
arom. H); 7.65 ± 7.60 (m, 2 arom. H); 6.60 (d, J ˆ 6.5, HOÀC(5'/I)); 7.58± 7.49 ( m, 4 arom. H); 1.54, 1.50, 1.33,
1.27 (4s, 2 Me2C); 1.27 ± 1.18( m, (Me2CH)2N); 0.89 (t, J ˆ 7.8, ( MeCH2)3Si); 0.48( q, J ˆ 7.8, (MeCH2)3Si).
13C-NMR (100 MHz, (D6)DMSO): see Table 9; additionally, 165.8, 165.5 (2s, 2 CˆO); 133.9, 133.8(2 s); 132.5,
132.2 (2d); 128.47 (2d); 128.43 (2d); 128.37 (2d); 128.33 (2d); 113.6, 113.0 (2s, 2 Me2C); 45.7 (d, (Me2CH)2N);
27.0, 26.8, 25.2, 25.0 (4q, 2 Me2C); 20.2, 20.1 (2d, (Me2CH)2N); 6.7 (q, (MeCH2)3Si); 5.9 (t, (MeCH2)3Si). FAB-
‡
MS (NOBA): 1184 (100, [M ‡ H] ).
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7'-C)-N6-benzoyl-9-[6,7-dideoxy-
2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-8-iodoadenine (25) [5]. A soln. of 23
(330 mg, 0.30 mmol) and 1H-imidazole (82 mg, 1.20 mmol) in dry DMF (5.0 ml) was treated dropwise with
Et3SiCl (0.10 ml, 0.60 mmol), stirred for 45 min at 258, and poured into ice-water (ca. 10 ml). After extraction
with Et2O/AcOEt 1:1 (2 Â 20 ml), the combined org. layers were washed with brine, dried (Na2SO4), and
evaporated. FC (AcOEt/hexane 2 :1) gave 25 (308mg, 86%). White foam. Data of 25: see [5].
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-
6-ynofuranosyl]adenine-8-yl-(8 ! 7'-C)-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsil-

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Helvetica Chimica Acta ± Vol. 87 (2004)
yl)-b-d-allo-hept-6-ynofuranosyl]adenine (26). A soln. of 8 (767 mg, 0.97 mmol), 11 (500 mg, 0.84 mmol),
[Pd2(dba)3] (80 mg, 0.084 mmol), CuI (22.4 mg, 0.118 mmol), and P(fur)3 (27.2 mg, 0.118mmol) in degassed
Et3N/toluene 1:1 (30 ml) was stirred for 24 h at 238 and evaporated. FC (AcOEt/hexane 1:1 ! 2 :1) gave 26
(806 mg, 76%). Yellow foam. Rf (AcOEt/hexane 1:1) 0.21. [a]2D5 ˆ ‡13.5 (c ˆ 0.77, CH2Cl2). UV (CH2Cl2): 315
(sh), 302 (sh), 284 (39000). IR (CH2Cl2): 3399m, 2947m, 2868m, 2235w, 2175w, 1712s, 1608s, 1458s, 1331m,
1096s. 1H-NMR (400 MHz, CDCl3): see Table 10; additionally, 9.30, 9.15 (2 br. s, 2 NH); 7.99 ± 7.94 (m, 4 arom.
H); 7.58± 7.49 ( m, 2 arom. H); 7.47 ± 7.43 (m, 4 arom. H); 1.65, 1.57, 1.42, 1.35 (4s, 2 Me2C); 1.18± 1.03 ( m,
2 (Me2CH)3Si); 0.04 (s, Me3Si). 13C-NMR (100 MHz, CDCl3): see Table 11; additionally, 164.54, 164.46 (2s,
2 CˆO); 133.7 (2s); 132.8(2 d); 128.84 (2d); 128.82 (2d); 127.90 (2d); 127.82 (2d); 114.92, 114.01 (2s, 2 Me2C);
27.2, 27.1, 25.4, 25.2 (4q, 2 Me2C); 18.0 (q, 2 (Me2CH)3Si); 12.41, 12.38(2 d, 2 (Me2CH)3Si); À 0.4 (q, Me3Si).
‡
FAB-MS (NOBA): 1253 (100, [M ‡ H] ). Anal. calc. for C65H88N10O10Si3 (1253.73): C 62.27, H 7.07, N 11.17;
found: C 62.23, H 7.10, N 10.92.
Table 10. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Dimeric Adenosine
Derivatives 26 ± 29 in CDCl3 (assignment based on selective homodecoupling experiments)
26
27
28
29
26
27
28
29
HÀC(2/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)
J(5',7'/II)
8.75
6.25
5.62
8.75
6.26
5.67
8.22
6.19
5.57
5.29
4.15
4.69
8.23
6.20
5.61
HÀC(2/I)
HÀC(8/I)
HÀC(1'/I)
ÀC(2'/I)
HÀC(3'/I)
ÀC(4'/I)
ÀC(5'/I)
J(1',2'/I)
J(2',3'/I)
J(3',4'/I)
J(4',5'/I)
8.80
8.31
6.25
5.46
5.29
4.49
5.10
1.82.5
5.1
8.80
8.30
6.25
5.49
5.31
4.49
5.13
8.30
8.17
6.54
5.71
5.33
4.52
4.984.93
1.8
8.31
8.15
6.44
5.71
5.30
4.51
5.285.285.30
H
4.17
4.67
1.82.3
5.2
3.1
8.1
4.21
4.75
1.7
6.4
3.1
8.0
2.1
4.19
4.78H
H
6.4
3.1
1.9
6.4
3.1
8.5
±
1.7
6.4
3.1
6.5
6.4
2.5
8.3
6.3
2.1
8.5
8.0
2.1
3.1
6.2
±
Table 11. Selected 13C-NMR Chemical Shifts [ppm] of the Dimeric Adenosine Derivatives 26 ± 29 in CDCl3
26
27
28
29
26
27
28
29
C(2/II)
C(4/II)
C(5/II)
C(6/II)
C(8/II)
C(1'/II)
C(2'/II)
C(3'/II)
C(4'/II)
C(5'/II)
C(6'/II)
C(7'/II)
152.9
149.7
122.6
150.3
136.0
90.9
82.8
81.5
89.1
63.6
152.9
149.7
122.6
150.2
136.5
91.1
82.8
82.4
89.2
63.0
153.1
148.7
119.5
155.89
133.7
90.890.9
83.3
82.8
90.1
63.863.1
105.0
90.3
153.0
148.7
119.6
153.9
133.8
C(2/I)
C(4/I)
C(5/I)
C(6/I)
C(8/I)
'/I )
C(2'/I)
C(3'/I)
C(4'/I)
'/I)
153.6
149.8
123.3
151.1
142.5
91.1
83.9
82.5
90.1
64.0
153.6
149.8
123.4
151.0
142.6
91.2
83.9
82.7
89.9
64.0
154.0
149.6
120.3
155.91
140.8
91.5
83.8
82.9
90.5
64.0
153.9
149.1
120.3
155.8
140.7
91.5
83.7
82.64
90.2
C(1
83.2
82.56
90.0
C(5
83.1
74.6
64.0
95.0
77.3
104.5
90.6
81.7
74.4
C(6'/I)
C(7'/I)
96.0
77.3
96.1
74.1
94.9
74.5
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]ade-
nin-8-yl-(8 ! 7'-C)-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-
ynofuranosyl]adenine (27). A soln. of 26 (400 mg, 0.32 mmol) in MeOH/AcOEt 1:1 (50 ml) was treated
dropwise with a soln. of AgNO3 (544 mg, 3.2 mmol) in H2O/MeOH 1:1 (20 ml), stirred at 238 under exclusion of
light for 6 h, treated with a soln. of KCN (520 mg, 8.0 mmol) in H2O (2 ml), and stirred for 1.5 h. After
evaporation, a soln. of the residue in AcOEt was washed with brine, dried (Na2SO4), and evaporated. FC
(AcOEt/hexane 3 :2) gave 27 (370 mg, 98%). Yellow foam. Rf (AcOEt/hexane 2 :1) 0.59. [a]2D5 ˆ À3.0 (c ˆ 0.7,

Helvetica Chimica Acta ± Vol. 87 (2004)
2985
CH2Cl2). UV (CH2Cl2): 312 (sh), 302 (sh), 284 (38000). IR (CH2Cl2): 3399w, 3300w, 2946s, 2868m, 2241w, 1712s,
1
1609s, 1458s, 1331m, 1238m, 1214m, 1097s. H-NMR (500 MHz, CDCl3): see Table 10; additionally, 9.27, 9.07
(2 br. s, 2 NH); 8.00 ± 7.98 (m, 2 arom. H); 7.96 ± 7.94 (m, 2 arom. H); 7.59 ± 7.51 (m, 2 arom. H); 7.50 ± 7.45 (m, 4
arom. H); 2.30 (d, J ˆ 2.1, HÀC(7'/II)); 1.65, 1.61, 1.43, 1.42 (4s, 2 Me2C); 1.18± 1.08 ( m, (Me2CH)3Si); 1.08±
1.04 (m, (Me2CH)3Si). 13C-NMR (125 MHz, CDCl3): see Table 11; additionally, 164.6, 164.5 (2s, 2 CˆO); 133.7,
133.6 (2s); 132.81, 132.80 (2d); 128.9 (2d); 128.8 (2d); 127.9 (2d); 127.8(2 d); 114.9, 114.1 (2s, 2 Me2C); 27.2, 27.1,
25.4, 25.3 (4q, 2 Me2C); 18.01, 18.00, 17.98, 17.97 (4q, 2 (Me2CH)3Si); 12.41, 12.36 (2d, 2 (Me2CH)3Si). HR-
‡
‡
MALDI-MS (DHB): 1203.556 ([M ‡ Na] , C62H80N10NaO10Si2 ; calc. 1203.550).
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofura-
nosyl]adenin-8-yl-(8 ! 7'-C)-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-yno-
furanosyl]adenine (28). a) From 9 and 12. A soln. of 9 (200 mg, 0.29 mmol), 12 (123.7 mg, 0.25 mmol),
[Pd2(dba)3] (12 mg, 12.5 mmol), CuI (4.8mg, 25 mmol), and P(fur)3 (5.8mg, 25 mmol) in degassed Et3N/toluene
1:1 (3 ml) was stirred for 16 h at 238 and evaporated. FC (AcOEt/MeOH 1:0 ! 10 :1) gave 28 (220 mg, 83%).
b) From 26. A soln. of 26 (153 mg, 0.12 mmol) in dry toluene (5 ml) was treated dropwise with a soln. of 8m
MeNH2 in MeOH (0.5 ml, 4.0 mmol), stirred for 5 h at 258, diluted with AcOEt (10 ml), washed with sat. aq.
NH4Cl soln. and brine, dried (Na2SO4), and evaporated. FC (15 g of silica gel; AcOEt/MeOH 1 :0 ! 10 :1) gave
28 (84 mg, 66%). Yellow foam. Rf (AcOEt) 0.27. [a]2D5 ˆ ‡57.0 (c ˆ 0.1, CH2Cl2). UV (CH2Cl2): 296 (16700), 264
(21700). IR (CH2Cl2): 3512w, 3402m, 3326m, 3199w, 2947s, 2867m, 2173w, 1632s, 1596m, 1468m, 1375m, 1328m,
1212m, 1098s, 993m, 8 51m. 1H-NMR (400 MHz, CDCl3): see Table 10; additionally, 6.33 (br. s, 2 NH2); 1.65,
1.56, 1.44, 1.35 (4s, 2 Me2C); 1.30 ± 1.15 (m, 2 (Me2CH)3Si); 0.06 (s, Me3Si). 13C-NMR (100 MHz, CDCl3): see
Table 11; additionally, 114.2, 113.6 (2s, 2 Me2C); 27.1, 27.0, 25.5, 25.2 (4q, 2 Me2C); 18.08, 18.05, 18.04 (6 C) (3q,
2 (Me2CH)3Si); 12.5, 12.4 (2d, 2 (Me2CH)3Si); À 0.4 (q, Me3Si). HR-MALDI-MS (DHB): 1067.536 ([M ‡
‡
‡
Na] , C51H80N10NaO8Si3 ; calc. 1067.537). Anal. calc. for C51H80N10O8Si3 (1045.51): C 58.59, H 7.71, N 13.40;
found: C 58.63, H 7.72, N 13.37.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-
(8 ! 7'-C)-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine
(29). A soln. of 28 (170 mg, 0.16 mmol) in MeOH/AcOEt 1:1 (50 ml) was treated dropwise with a soln. of
AgNO3 (277 mg, 1.63 mmol) in H2O/MeOH 1:1 (6 ml), stirred at 238 under exclusion of light for 3.5 h, treated
with a soln. of KCN (222 mg, 3.42 mmol) in H2O (2 ml), and stirred for 1 h. After evaporation, a soln. of the
residue in AcOEt was washed with brine, dried (Na2SO4), and evaporated. FC (AcOEt/MeOH 1:0 ! 10 :1)
gave 29 (137 mg, 86%). Yellow foam. Rf (AcOEt) 0.27. [a]2D5 ˆ ‡92.1 (c ˆ 1.0, CH2Cl2). UV (CH2Cl2): 296
(17000), 264 (19000). IR (CH2Cl2): 3513w, 3401m, 3303m, 3194w, 2946m, 2868m, 1631s, 1595m, 1468m, 1375m,
1329m, 1212m, 1099m. 1H-NMR (400 MHz, CDCl3): see Table 10; additionally, 6.33 (br. s, 2 NH2); 2.31 (d, J ˆ
2.1, HÀC(7'/II)); 1.65, 1.58, 1.44, 1.36 (4s, 2 Me2C); 1.30 ± 1.15 (m, (Me2CH)3Si); 1.15 ± 1.05 (m, (Me2CH)3Si).
13C-NMR (100 MHz, CDCl3): see Table 11; additionally, 114.2, 113.8(2 s, 2 Me2C); 27.1, 27.0, 25.4, 25.2 (4q,
2 Me2C); 18.0 (q, 2 (Me2CH)3Si); 12.44, 12.41 (2d, 2 (Me2CH)3Si). HR-MALDI-MS (DHB): 995.497 ([M ‡
‡
‡
Na] , C48H72N10NaO8Si2 ; calc. 995.497).
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)-9-[6,7-dideoxy-2,3-O-isopropyli-
dene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-(8 ! 7'-C)-9-[6,7-dideoxy-2,3-O-isopro-
pylidene-5-O-(triisopropylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (32). A soln. of 29 (120 mg, 123 mmol),
30 [2] (190 mg, 185 mmol), [Pd2(dba)3] (11.7 mg, 12.3 mmol), CuI (4.7 mg, 25 mmol), and P(fur)3 (5.7 mg,
25 mmol) in degassed Et3N/toluene 1 :1 (25 ml) was stirred for 38h at 23 8, and evaporated. FC (AcOEt/MeOH
1:0 ! 10 :1) gave 32 (160 mg, 69%). Yellow foam. Rf (AcOEt) 0.24. [a]2D5 ˆ ‡82.2 (c ˆ 1.27, CH2Cl2). IR
(CH2Cl2): 3475w, 3310w, 3177w, 2946m, 2867m, 1720s, 1646m, 1602m, 1463m, 1432m, 1221m, 1079s, 8 8s.6
1H-NMR (500 MHz, (CDCl3/CD3OD 9 :1): see Table 6; additionally, 1.66, 1.63, 1.52, 1.51, 1.44, 1.41, 1.33, 1.32
(8s, 4 Me2C); 1.26 ± 1.02 (m, 4 (Me2CH)3Si). 13C-NMR (125 MHz, CDCl3/CD3OD 9:1): see Table 7; additionally,
114.33, 114.30, 114.01, 113.60 (4s, 4 Me2C); 27.35, 27.26, 27.18, 26.95, 25.33, 25.31, 25.27, 25.20 (8q, 4 Me2C); 18.00,
17.99, 17.93, 17.90 (4q, 4 (Me2CH)3Si); 12.42, 12.39 (6 C), 12.01 (3d, 4 (Me2CH)3Si). MALDI-MS (DHB):
‡
‡
1895.934 ([M ‡ Na] , C92H140N14NaO20Si4 ; calc. 1895.934). Anal. calc. for C92H140N14O20Si4 (1874.54): C 58.95,
H 7.53, N 10.46; found: C 58.81, H 7.37, N 10.54.

2986
Helvetica Chimica Acta ± Vol. 87 (2004)
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Received September 20, 2004