Oligonucleosides with a nucleobase-including backbone: Part 4. A convergent synthesis of ethynediyl-linked adenosine tetramers

Article abstract of DOI:10.1002/1522-2675(20001220)83:12<3229::AID-HLCA3229>3.0.CO;2-S

Deprotection of the tetramer 24, obtained by coupling the iodinated dimer 18 with the alkyne 23 gave the 8′,5-ethynediyl-linked adenosine-derived tetramer 27 (Scheme 3). As direct iodination of C(5′)-ethynylated adenosine derivatives failed, we prepared 1

Full text of DOI:10.1002/1522-2675(20001220)83:12<3229::AID-HLCA3229>3.0.CO;2-S

Helvetica Chimica Acta ± Vol. 83 (2000)
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Oligonucleosides with a Nucleobase-Including Backbone
Part 4
A Convergent Synthesis of Ethynediyl-Linked Adenosine Tetramers
by Hiroki Gunji and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich
Deprotection of the tetramer 24, obtained by coupling the iodinated dimer 18 with the alkyne 23 gave the
8',5-ethynediyl-linked adenosine-derived tetramer 27 (Scheme 3). As direct iodination of C(5')-ethynylated
adenosine derivatives failed, we prepared 18 via the 8-amino derivative 17 that was available by coupling the
imine 15 with the iodide 7; 15, in its turn, was obtained from the 8-chloro derivative 12 via the 4-meth-
oxybenzylamine 14 (Scheme 2). This method for the introduction of the 8-iodo substituent was worked out with
the N-benzoyladenosine 1 that was transformed into the azide 2 by lithiation and treatment with tosyl azide
(Scheme 1). Reduction of 2 led to the amine 3 that was transformed into 7. 1,3-Dipolar cycloaddition of 3 and
(trimethylsilyl)acetylene gave 6. The 8-substituted derivatives 4a ± d were prepared similarly to 2, but could not
be transformed into 7. The known chloride 8 was transformed into the iodide 11 via the amines 9 and 10. The
amines 3, 10, and 16 form more or less completely persistent intramolecular C(8)NꢀH ´´´ O(5') H-bonds, while
the dimeric amine 17 forms a ca. 50% persistent H-bond. There is no UVevidence for a base-base interaction in
the protected and deprotected dimers and tetramers.
1. Introduction. ± In the context of the synthesis of 8,5'-ethynediyl-linked analogues
of adenosine-oligonucleosides, we have so far prepared dimers (I, n ˆ 0; Scheme 1) by
cross-coupling C(5')-ethynylated and C(8)-halogenated monomers [1][2]. A conver-
gent route appeared attractive for the preparation of higher oligomers that are required
to test for base-pairing and formation of double-stranded associates. We planned to
synthesise the tetramer I (n ˆ 2, Scheme 1) by cross-coupling dimers III and VI to II,
followed by deprotection. Unfortunately, the method used to directly iodinate
monomers at C(8), which is based on a regioselective lithiation at C(8) [1], failed
for dimers of type IV. Treatment of IV (R1 ˆ Bz, R2 ˆ R3 ˆ Et3Si) with LDA at ꢀ788 in
THF led rapidly to a multitude of products, confirming the previously noted base-
sensitivity of these ethynylated products [1]. The monomeric iodo derivatives had also
been prepared by addition of (trimethylsilyl)ethynylmagnesium bromide to an iodo-
aldehyde [1], but, in view of the base sensitivity of the ethynylated adenosines and the
unsatisfactory diastereoselectivity of the addition, we required a different method to
obtain dimeric iodides III, and considered to introduce a C(8)-substituent that is inert
to the coupling conditions of the monomers (leading to V) and to subsequently displace
it by an I substituent.
We describe the synthesis of two 8-I-substituted monomers (Scheme 2) and of the 8-
iodinated dimer 18 (Scheme 3) by introducing a C(8)-imino group that is inert to the
coupling conditions, and replacing it subsequently by a I substituent. We also describe
the transformation of 18 into the protected 8,5'-ethynediyl-linked adenosine tetramer
24, and its deprotection to 27 (Scheme 4).

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Scheme 1. 8,5'-Acetyleno-Linked Adenosine Oligomers I and Retrosynthetic Pathway for the Tetramer II
Results and Discussion. ± Several at C(8) N-, S-, and Se-substituted adenosines
were considered as precursors of C(8)-iodo compounds. To evaluate these derivatives,
we used the protected adenosine 1, proceeding similarly as for the preparation of 8-Cl-
adenosines [1], i.e., by regioselective lithiation with LDA in THF, followed by
treatment with the appropriate electrophile. Lithiation of 1 with LDA at ꢀ788
followed by treatment with TsN3 at 08 gave the 8-N3 derivative 2 in 84% yield
(Scheme 2), considerably improving the current method that is based on substitution of
8-Br derivatives with NaN3 at 75 ± 908 [3][4]. The monomers 4a ± d were similarly

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prepared in yields of 46 ± 94% by deprotonation of 1 with LDA and treatment with the
appropriate S- or Se-electrophile. Oxidation of the methylseleno compound 4c led to
the 8-OH derivative 5. Considering the potential of azides for the synthesis of
heterocycles, we checked the reactivity of the azide 2 as a 1,3-dipolar reagent. While 2
reacted with (trimethylsilyl)acetylene to afford the triazole 6 in modest yields, it proved
inert towards phenylacetylene, indicating the need for additional activation (appro-
priate substitution at N(6)?).
Scheme 2
a) LDA, TsN3, THF; 84%. b) 10% Pd/C, H2, EtOH; 91%. c) LDA, electrophile ((MeS)2, (PhS)2, (MeSe)2, or
PhSeCl), THF; 4a (89%), 4b (78%), 4c (94%), 4d (46%). d) m-Chloroperbenzoic acid, CH2Cl2; 96%. e)
Me3SiꢀCꢁCH, DMF; 45%. f) C5H11ONO, KI, I2, CH2I2; 7 (71%), 11 (82%). g) 4-Methoxybenzylamine,
EtOH; 93%. h) DDQ, CH2Cl2/H2O 18 :1; 66% from 8.

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Attempts to introduce an 8-I substituent by treating compounds 2, 4a ± d, and 6 with
several sources of I anion failed. However, adoption of the known transformation of 6-
and 2-aminopurines into the corresponding halides [5] proved successful. The amine 3
is available in a yield of 91% by hydrogenation of the azide 2. Its treatment with amyl
nitrite in the presence of KI and I2 [6] in CH2I2 yielded 71% of the 8-I derivative 7 [1].
To test the scope of this iodination, we transformed the C(5')-ethynylated 8-
chloroadenosine derivative 8 [1] into the amine 10. Treatment of 8 with 4-
methoxybenzylamine [7 ± 9] in EtOH afforded 9 that was debenzylated by DDQ in
aqueous CH2Cl2 [10] to provide the amine 10 in an overall yield of 66%. Following the
conditions described above, this amine was smoothly converted to the 8-iodo derivative
11 in 82% yield [1].
These results encouraged us to synthesize the key iodo dimer 18 via the amine 17
(Scheme 3). Desilylation of 12 (TBAF in THF) [1], followed by O-triethylsilylation,
yielded 67% of the protected chloride 13. Its treatment with 4-methoxybenzylamine
gave the secondary amine 14 (95%). Oxidation of 14 with DDQ in aqueous CH2Cl2 led
to a mixture of the imine 15 (18%) and the amine 16 (62%), while analogous oxidation
of the C-trimethylsilylated 9 led only to the amine 101). The analogous oxidation of 14
under anhydrous conditions gave selectively the imine 15 (87%). Following the
observation that the imine 15 is not stable to Et3N, we prepared the amine 16 by
exposing 15 for several hours to neat Et3N. In view of this result and considering that
anhydrous Et3N had proven the best solvent for cross-coupling [2], we exposed 7 and 15
to the established cross-coupling conditions, and obtained the desired amino dimer 17
in 70%. The desired iodo dimer 18 was obtained in 55% yield from the amine 17.
As described in the preceding paper [2], cross coupling of N-benzoylated
acetylenoadenosines requires a temperature of 808, while the analogous amines react
at room temperature. We, therefore, prepared the dimeric amine 23 as the coupling
partner for the iodide 18. For this, we debenzoylated the known iodo derivative 19 [1]
with 4-methoxybenzylamine in EtOH at 8082) to 20 that was isolated in a yield of 81%.
Coupling of 20 and 21 [1] proceeded smoothly at room temperature to give 85% of the
dimer 22, confirming the increased reactivity of the acetylenoadenosines with a free
H2NꢀC(6) group. Cleavage of the CꢀSiMe3 group of 22 was not straightforward.
Treating 22 with AgNO3 in aqueous THF/MeOH for 4.5 h, followed by addition of
aqueous KCN [11][12] removed the Me3Si group, but also led to partial cleavage of the
Et3SiO groups. Silylation of the crude with Et3SiCl and imidazole in DMF was slow, but
led to 23 in a yield of 72% from 22, while silylation with triethylsilyl triflate gave a
complex mixture, containing N-silylated products.
Since the iodo derivative 18 is insoluble in Et3N, the dimers 18 and 23 were coupled
in Et3N/toluene 1:1 to yield 79% of the tetramer 24 (Scheme 4). This coupling
proceeded smoothly at room temperature, but appreciably more slowly than the
analogous coupling of the monomers, illustrating the reduced reactivity of the dimers
18 and 23.
1
)
)
It is not clear whether this difference is due to the Me3Si group or to the configuration at C(5').
The conditions for this deprotection were discovered during an abortive attempt to introduce an NH2
substituent at C(8).
2

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Scheme 3
a) Bu4NF (TBAF), THF; Et3SiCl, imidazole, DMF; 67%. b) 4-Methoxybenzylamine, EtOH; 95%. c) 2,3-
Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), CH2Cl2; 15 ( 87%) or DDQ, CH2Cl2/H2O 18 :1; 15 (18%), 16
(62%). d) CuI, [Pd2(dba)3], P(fur)3, Et3N; 17 (70%), 22 (85%). e) C5H11ONO, KI, I2, CH2I2; 55%. f) 4-
Methoxybenzylamine, toluene; 81%. g) AgNO3, THF/MeOH/H2O; 5% aq. KCN; Et3SiCl, imidazole, DMF;
72%.
The tetramer 24 was desilylated with aqueous AcOH to yield 89% of the tetrol 25.
Debenzoylation of 25 with aqueous NH4OH in toluene/MeOH 1:1 afforded a complex
mixture from which we isolated ca. 25% of the desired, slightly impure tetramine 26,
indicating that 25 and/or 26 are not stable to aqueous base. As HCOOH has proven
effective for the deisopropylidenation of the related monomers [1] and dimers [2], we
used it for the final deprotection of 26. Treatment of 26 with 80% HCOOH at room

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Scheme 4
a) CuI, [Pd2(dba)3], P(fur)3, Et3N; 79%. b) THF/AcOH/H2O 1:2 :1; 89%. c) NH4OH, toluene/MeOH/H2O;
25%. d) HCO2H/H2O 4 :1; 72%.
temperature for 22 h yielded the deprotected acetyleno-adenosine tetramer 27 in an
overall yield of 16% from 24.
1
A comparison of the H-NMR data (Tables 2 and 3 in the Exper. Part) shows that
the 8-substituted monomers 2, 4 ± 6, 13, 15, and 20 possess a flattened ring (J(1',2') ‡
J(3',4') ˆ 4.8 ± 6.3 Hz [13]). The (N) > (S) equilibrium is slightly shifted to the (N)-
conformer (J(1',2') ˆ 1.8 ± 2.5 Hz, J(3',4') ˆ 3.0 ± 3.8 Hz), in agreement with the behav-
iour of the 8-halo analogues 7, 11, 12, and 19 [1]. HꢀC(2') of the sulfides 4a ± b, the
selenides 4c ± d, the triazole 6, and the halides 13 and 20 appears at a similar position as
HꢀC(2') of the halides 7, 11, 12, and 19 (5.76 ± 5.91 ppm), evidencing a complete syn-
orientation of the nucleobase. The relatively weak upfield shift of HꢀC(2') of the imine
15 (5.67 ppm), the azide 2 (5.66 ppm), and the alcohol 5 (5.56 ppm) indicates a
dominant participation of the syn-conformer in the syn > anti equilibrium. However,
HꢀC(2') of the primary amines 3, 10, and 16 is strongly shifted upfield and resonates at
5.06 ± 5.27 ppm at a position similar to the HꢀC(2') of the 8-unsubstituted adenosines 1
and 21. These upfield shifts reveal an anti-conformation (see [1][2] and refs. cit. there) and

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suggest a C(8)NꢀH ´´´ O(5') H-bond, as it is known for related 8-aminopurines [14 ±
16]. The intramolecular H-bond of 3, 10, and 16 is ascertained by a small J(4',5') value
of 1.8 ± 3.5 Hz, evidencing a trans-arrangement of the HꢀC(4') and the OꢀC(5') bonds
and, hence, a small distance between O(5') and H2NꢀC(8). Indeed, MM3* modeling of
3 (Macromodel V. 6.0, gas phase [17]) results in a bifurcated H-bond from HNꢀC(8) to
O(5') (H ´´´ O distance 1.75 Š) and O(4') (H ´´´ O distance 2.24 Š), and in synclinal
HꢀC(4') and HꢀC(5') bonds (calculated J(4',5') values of 0.8 and 3.5 Hz, resp.). Due
to this H-bond, the amines 3, 10, and 16 show an enhanced ring puckering (J(1',2') ‡
J(3',4') ˆ 7.3 ± 8.3 Hz) and a ca. 1:1 (N) > (S) equilibrium. The larger J(3',4') value and
the stronger downfield shift of HꢀC(2') of the d-allo-configured 16 as compared to the
corresponding values of the d-ribo-configured 3 and l-talo-configured 10 (DJ ꢂ 1 Hz,
Dd ꢂ 0.2 ppm) indicate a ca. 80% preference of 16 for the intramolecular H-bond and
the syn-conformation. Monoalkylation at H2NꢀC(8) of 10 and 16 leads to a
destabilisation of the intramolecular H-bond. Again, the d-allo-configured 14 shows
a weaker preference for the intramolecular H-bond than the l-talo-configured 9: 45 vs.
60%, as calculated from J(4',5') ˆ 5.5 and 4.5 Hz, respectively. In agreement with this
assignment, HꢀC(2') of 14 resonates 0.2 ppm downfield to HꢀC(2') of 9.
HꢀC(2'/II)3) of the dimers 17, 18, 22, and 23 resonates at 5.61 ± 5.70 ppm (Table 4,
Exper. Part) indicating a complete preference for the syn-conformation. HꢀC(2'/I) of
these dimers shows only a weak upfield shift (Dd ˆ 0.04 ± 0.07 ppm relative to
d(HꢀC(2'/II)). Neglecting the influence of the ethynyl group on d(HꢀC(2'/II)), this
weak upfield shift suggests a more or less complete preference for the syn-
conformation of unit I of the iodo derivative 18, the 8-unsubstituted 22 and 23, and,
surprisingly, also of the amine 17. However, J(4',5'/I) of the amine 17 (5.5 Hz) is
distinctly smaller than J(4',5'/I) of 18 (8.0 Hz) and reveals a ca. 45% persistent
intramolecular H-bond and thus a ca. 11:9 syn > anti equilibrium. Similarly, the
smaller J(4',5'/I) values of 22 (7.5 Hz) and 23 (7.0 Hz) reflect a weaker steric interaction
of the nucleobase with the propargylic side chain in the anti-conformation (compare
with J(4',5') ˆ 4.8 Hz of 21 [2]; Table 3) and indicate a 7:3 and a 6 :4 syn > anti
equilibrium, respectively. Thus, there is a significant influence of the 8-ethynyl group on
d(HꢀC(2')). The J(4',5'/II ± IV) values of the protected tetramer 24 are large and
evidence a syn-conformation for units II ± IV, whereas J(4',5'/I) ˆ 7.5 Hz indicates a
7:3 syn > anti equilibrium, as already observed for the dimer 22.
2',3'-O-Isopropylidenated 5'-hydroxyadenosines form a completely persistent
intramolecular O(5')ꢀH ´´´ N(3) H-bond in CDCl3 [1]. In (D6)DMSO solution, the
persistence of such a H-bond is ca. 20% [19]. Thus, the tetrols 25 and 26 may form
weakly persistent intramolecular H-bonds. J(5',OH) values of 5 ± 6 Hz suggest more or
less completely solvated OH groups (see [20] and refs. cit. there). However, the J(4',5'/
I ± IV) values of 25 and 26 are smaller than the corresponding values of the protected
24 (Table 4, Exper. Part). They suggest 10 ± 30% persistent intramolecular H-bonds,
which are also evidenced by a downfield shift of the OH signals; the primary HOꢀC(5'/
IV) of 25 and 26 resonate at 4.92 and 5.24 ppm, respectively, and the secondary
HOꢀC(5'/I ± III) at 6.59 ± 6.78 ppm.
3
)
Starting from the downstream end, the units of the oligonucleosides are specified by roman numerals (cf.
[18]).

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To assess interactions between the base units, we compared the UV spectra of the
tetramers 24 (CHCl3) and 27 (DMSO) with those of the related dimers and monomers
(Table 1). We first checked for a possible influence of the ethynyl substituent at C(5')
by comparing the UV spectra of the protected adenosines 28 and 21, the corresponding
benzoates 1 and 29, and the unprotected adenosines 34 and 37. As expected, there is no
evidence for such an interaction; the difference of 6 nm for lmax of 34 and 37 is due to
the solvent. The UV spectra of 8-ethynyladenosine (35 [22]) and 2'-deoxy-8-
ethynyladenosine (36 [23]) show in H2O a band with lmax ˆ 292 nm. Besides this band,
the UV spectrum of 36 shows a shoulder at 303 nm. This shoulder is found in the UV
spectra of a series of 8-(alk-1-ynyl)adenosines [23] [24]; it is characteristic for 8-
ethynyladenosines. On the basis of a solvent correction of 6 nm for the 8-unsubstituted
and for the 8-ethynyl-substituted adenine moiety of 38 in DMSO, one expects bands at
266 and 298 nm and a shoulder at 309 nm, close to the observed bands at 271 and
301 nm, and a shoulder at 312 nm. The maximum at 271 nm does not correctly reflect
the lmax of the 8-unsubstituted adenine moiety as it is also influenced by strong
absorptions of the 8-ethynyladenine moiety. The l values of 301 and 312 nm probably
indicate a larger solvent shift (9 instead of 6 nm) for the 8-ethynyladenine moiety.
Thus, there is no evidence for a base/base interaction in 38. The UV spectrum of the
tetramer 27 resembles that of the dimer 38, again in keeping with the absence of a base/
base interaction. The protected monoamines 28 and 21 show exactly the same lmax as
adenosine (34), suggesting that the bands of the protected diamine 33 should show a
hypsochromic shift of ca. 6 nm (i.e., a solvent shift for the change from H2O to DMSO)

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to the bands of the deprotected diamine 38. This is indeed the case (Dl ˆ 4 ± 6 nm);
there is no evidence for a base/base interaction in 33.
Table 1. UVAbsorptions of the Monomers 1, 21, 28, 29, and 34 ± 37, the Dimers 30 ± 33, and 38, and the Tetramers
24 and 27
Compound
Solvent
1 [1]
CHCl3
28 [2]
CHCl3
29 [1]
CHCl3
21 [2]
CHCl3
30 [2]
CHCl3
lmax [nm] (e) 282 (14500)a), 260 (14000)
279 (19000),
247 (11000)a)
260 (13000)
317 (22500), 304 (35000),
292 (39000), 250 (29000)
276 (15000),
249 (9500)
Compound
Solvent
31 [2]
CHCl3
32 [2]
CHCl3
33 [2]
CHCl3
24
CHCl3
34 [21]
H2O (pH 7)
lmax [nm] (e) 317 (23500),
305 (32000),
308 (16500)a), 308 (15500)a), 316 (61000)a), 260 (14400)
284 (32000),
248 (13000)
295 (20000),
266 (21000)
304 (71000),
296 (71000),
251 (55000)
298 (31000),
253 (29000)
Compound
Solvent
35 [22]
H2O
36 [23]
H2O
37 [1]
DMSO
38 [2]
DMSO
27
DMSO
lmax [nm] (e) 292 (17000)
303 (13000)a), 266 (13000)
292 (16800)
312 (13500)a), 311 (29500)a), 301 (48000),
301 (17000),
271 (17000)
278 (28000), 270 (25500)
a) Shoulder.
The situation is more complicated for the protected tetramer 24. Three units can be
distinguished, viz. the 8-unsubstituted adenine (unit I), the 8-ethynylated adenine (unit
II), and the 8-ethynylated N-benzoyladenine (units III and IV). We considered the
monomers 1, 28, 29, and 21, and the dimers 33, 31, and 30 as models to assess the
interactions between the nucleobases of units I/II, II/III, and III/IV of 24. The
comparison of the UV spectra of 28 and 1, and of 21 and 29 shows that N-benzoylation
leads to a new band (for the benzamido moiety) at ca. 250 nm and to a bathochromic
shift of ca. 20 nm of the band for the adenine moiety. The analysis is impaired by the
broad bands of the N6-benzoyladenines. A comparison of the UV spectra of the
dibenzamide 30 and the monobenzamides 1 and 29 shows the expected bathochromic
shift for the 8-ethynyladenine moiety (25 nm) and a band at 317 nm instead of the
expected shoulder. Again, the strong band of the 8-ethynyladenine moiety prevents an
exact assignment of lmax of the 8-unsubstituted adenine moiety. The UV spectrum of
the monobenzamide 31 resembles that of the dibenzamide 30, and that of the
monobenzamide 32 resembles that of the diamine 33 (apart from the band for the
benzamido group at 248 nm), evidencing the dominant contribution of the 8-
ethynyladenine moiety. The UV spectrum of the tetramer 24 is expected to closely
resemble the spectra of 30 and 31; this is indeed the case, again in agreement with the
absence of any base/base interaction.
We thank Dr. B. Bernet for his analytical contributions, and the Swiss National Science Foundation, F.
Hoffmann-La Roche AG, Basel, and Givaudan AG, Dübendorf, for generous support.

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Experimental Part
General. See [1].
8-Azido-N6-benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (2). A soln. of iPr2NH (63 ml,
0.45 mmol) in dry THF (1.4 ml) was cooled to 08, treated dropwise with 1.6m BuLi in hexane (0.28 ml,
0.45 mmol), stirred for 25 min, cooled to ꢀ788, treated dropwise with a soln. of 1 [1] (94.2 mg, 0.18 mmol) in dry
THF (1.4 ml), stirred for 3 h, treated with TsN3 (111 mg, 0.56 mmol), stirred for 15 min, warmed to 08, stirred for
1 h, and treated with sat. aq. NH4Cl soln. (2.0 ml) and H2O (1.0 ml). The layers were separated, and the aq. layer
was extracted with AcOEt (2 Â 1.0 ml). The combined org. layers were washed with brine, dried (Na2SO4), and
evaporated. FC (5.0 g of silica gel; CHCl3/AcOEt 5 :1) gave 2 (85.1 mg, 84%). Light orange plates. Rf (hexane/
AcOEt 1:1) 0.57. M.p. 1148. [a]2D5 ˆ ꢀ25.9 (c ˆ 1.06, CHCl3). UV (CHCl3): 302 (20000), 251 (18000). IR
(CHCl3): 3408w, 2997w, 2957w, 2913w, 2877w, 2156s, 1708m, 1615s, 1589m, 1517w, 1498w, 1478m, 1457s, 1431m,
1376s, 1328w, 1268m, 1159w, 1090s, 1004w, 972w, 946w, 916w, 898w, 868w. 1H-NMR (300 MHz, CDCl3): see Table
2; additionally, 0.52 (q, J ˆ 7.9, (MeCH2)3Si); 0.89 (t, J ˆ 7.9, (MeCH2)3Si); 1.40, 1.61 (2s, Me2C); 7.49 ± 7.58 (m, 2
arom. H); 7.58 ± 7.65 (m, 1 arom. H); 7.96 ± 8.03 (m, 2 arom. H); 8.78 (br. s, NH). 13C-NMR (75 MHz, CDCl3):
164.4 (s, CˆO); 151.8 (s, C(6)); 151.5 (d, C(2)); 148.3 (s, C(4)); 144.1 (s, C(8)); 133.8 (s); 132.8 (d); 129.0 (2d);
127.8 (2d); 121.5 (s, C(5)); 114.3 (s, Me2C); 89.1 (d, C(1')); 87.8 (d, C(4')); 82.7 (d, C(2')); 81.9 (d, C(3')); 62.7 (t,
‡
C(5')); 27.2, 25.5 (2q, Me2C); 6.6 (q, (MeCH2)3Si); 4.2 (t, (MeCH2)3Si). FAB-MS: 567 ([M ‡ 1] ). Anal. calc. for
C26H34N8O5Si (566.69): C 55.11, H 6.05, N 19.77; found: C 54.92, H 5.86, N 19.68.
Table 2. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for the C(8)-Substituted
Adenosines 1 ± 7 in CDCl3 Solution
1 [1]
2
3
4a
8.67
4b
8.75
4c
8.68
4d
8.76
5
6aa)
7 [1]
HꢀC(2)
HꢀC(1')
HꢀC(2')
HꢀC(3')
HꢀC(4')
HaꢀC(5')
HbꢀC(5')
J(1',2')
8.83
6.25
5.26
4.95
4.45
3.75
3.87
2.7
8.69
6.04
5.66
5.10
4.27
3.66
3.77
2.3
8.55
6.41
5.06
4.97
4.24
3.87
4.00
3.8
8.40
6.28
5.56
5.01
4.27
3.76
3.84
2.2
8.81
6.75
5.91
5.20
4.23
3.68
3.78
1.8
8.73
6.14
5.81
5.18
4.32
3.65
3.76
2.3
6.09
5.76
5.13
4.29
3.66
3.76
2.2
6.33
5.77
5.15
4.31
3.70
3.82
2.5
6.09
5.79
5.12
4.33
3.66
3.77
2.2
6.33
5.77
5.13
4.29
3.69
3.80
2.5
J(2',3')
6.0
6.5
6.7
6.5
6.5
6.5
6.5
6.5
6.5
6.3
J(3',4')
2.5
3.5
4.3
3.5
3.8
3.5
3.5
3.5
3.8
3.5
J(4'a,5')
J(4'b,5')
J(5'a,5'b)
4.0
3.7
11.0
6.5
6.5
10.8
1.8
2.2
10.8
6.5
6.5
10.8
6.5
6.5
10.8
6.5
6.5
10.8
6.5
6.5
10.8
6.5
6.5
10.5
7.0
7.0
10.8
6.5
6.5
10.5
a) In CD3OD.
8-Amino-N6-benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (3). At 258, a soln. of 2 (535.5 mg,
0.945 mmol) in EtOH (21 ml) was treated with 10% Pd/C (544.0 mg), stirred for 4 h under H2, treated with Ar
stream, filtered, and evaporated. FC (20 g of silica gel; CHCl3/AcOEt 1:2) gave 3 (464.4 mg, 91%). White solid.
Rf (CHCl3/acetone 3 :1) 0.50. M.p. 1748. [a]2D5 ˆ ꢀ6.5 (c ˆ 1.07, CHCl3). UV (CHCl3): 303 (16000), 246 (14000).
IR (CHCl3): 3467w, 3408w, 3324w, 2998w, 2960m, 2914w, 2878w, 1700m, 1639s, 1612m, 1590w, 1554w, 1500m,
1481m, 1438s, 1417w, 1387m, 1334w, 1255m, 1172w, 1156w, 1129w, 1107m, 1084m, 1048w, 1026w, 973w, 935w,
897w, 859w. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 0.65 (q, J ˆ 7.9, (MeCH2)3Si); 0.99 (t, J ˆ 7.9,
(MeCH2)3Si); 1.37, 1.64 (2s, Me2C); 5.75 (br. s, NH2); 7.44 ± 7.53 (m, 2 arom. H); 7.54 ± 7.62 (m, 1 arom. H); 7.95 ±
8.03 (m, 2 arom. H); 8.59 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 165.0 (s, CˆO); 153.1 (s, C(6)); 153.0 (d,
C(2)); 149.2 (s, C(4)); 144.2 (s, C(8)); 133.8 (s); 132.3 (d); 128.6 (2d); 127.9 (2d); 122.9 (s, C(5)); 115.2 (s, Me2C);
88.2 (d, C(1')); 84.6 (d, C(4')); 82.9 (d, C(2')); 79.3 (d, C(3')); 61.8 (t, C(5')); 27.4, 25.4 (2q, Me2C); 6.6 (q,
‡
(MeCH2)3Si); 4.0 (t, (MeCH2)3Si). FAB-MS: 541 ([M ‡ 1] ). Anal. calc. for C26H36N6O5Si (540.69): C 57.76,
H 6.71, N 15.54; found: C 57.84, H 6.85, N 15.68.
Iodination of 3. At 258, a suspension of 3 (23.1 mg, 42.7 mmol) in CH2I2 (0.35 ml) was treated with
C5H11ONO (0.12 ml, 0.854 mmol), KI (21.3 mg, 0.128 mmol), and I2 (35.1 mg, 0.138 mmol), warmed to 558,

Helvetica Chimica Acta ± Vol. 83 (2000)
3239
stirred for 2 h, diluted with CHCl3 (2.0 ml), washed with sat. aq. Na2S2O3 soln. (0.5 ml) and brine (0.5 ml), dried
(Na2SO4), and evaporated. FC (1.5 g of silica gel; hexane/AcOEt 5 :4) gave 7 [1] (19.7 mg, 71%).
General Procedure for the Preparation of 4a ± d. Similarly to the preparation of 2, 1 was treated with LDA
and 3 equiv. of the electrophile ((MeS)2, (PhS)2, (MeSe)2, or PhSeCl), followed by normal workup.
N6-Benzoyl-2',3'-O-isopropylidene-8-(methylthio)-5'-O-(triethylsilyl)adenosine (4a). 89% Yield. Light
yellow solid. Rf (hexane/AcOEt 1 :1) 0.41. 1H-NMR (200 MHz, CDCl3): see Table 2; additionally, 0.50 (q,
J ˆ 7.9, (MeCH2)3Si); 0.88 (t, J ˆ 7.9, (MeCH2)3Si); 1.40, 1.61 (2s, Me2C); 2.77 (s, MeS); 7.46 ± 7.65 (m, 3 arom.
H); 7.94 ± 8.03 (m, 2 arom. H); 8.92 (br. s, NH). 13C-NMR (50 MHz, CDCl3): 164.1 (s, CˆO); 154.8 (s, C(6));
152.9 (s, C(4)); 150.8 (d, C(2)); 146.4 (s, C(8)); 133.7 (s); 132.2 (d); 128.5 (2d); 127.3 (2d); 122.8 (s, C(5)); 113.8
(s, Me2C); 89.8 (d, C(1')); 87.4 (d, C(4')); 82.4 (d, C(2')); 81.6 (d, C(3')); 62.3 (t, C(5')); 26.8, 25.0 (2q, Me2C); 14.3
(q, MeS); 6.1 (q, (MeCH2)3Si); 3.8 (t, (MeCH2)3Si).
N6-Benzoyl-2',3'-O-isopropylidene-8-(phenylthio)-5'-O-(triethylsilyl)adenosine (4b). 78% Yield. Light
yellow solid. Rf (hexane/AcOEt 5 :4) 0.44. 1H-NMR (200 MHz, CDCl3): see Table 2; additionally, 0.53 (q,
J ˆ 7.9, (MeCH2)3Si); 0.90 (t, J ˆ 7.9, (MeCH2)3Si); 1.41, 1.62 (2s, Me2C); 7.30 ± 7.61 (m, 8 arom. H); 7.83 ± 7.91
(m, 2 arom. H); 9.14 (br. s, NH).
N6-Benzoyl-2',3'-O-isopropylidene-8-(methylseleno)-5'-O-(triethylsilyl)adenosine (4c). 94% Yield. White
solid. Rf (hexane/AcOEt 5 :4) 0.38. 1H-NMR (200 MHz, CDCl3): see Table 2; additionally, 0.51 (q, J ˆ 8.0,
(MeCH2)3Si); 0.88 (t, J ˆ 8.0, (MeCH2)3Si); 1.41, 1.62 (2s, Me2C); 2.67 (s, MeSe); 7.45 ± 7.65 (m, 3 arom. H);
7.96 ± 8.06 (m, 2 arom. H); 8.97 (br. s, NH).
N6-Benzoyl-2',3'-O-isopropylidene-8-(phenylseleno)-5'-O-(triethylsilyl)adenosine (4d). 46% Yield. Yellow
solid. Rf (hexane/AcOEt 2 :1) 0.42. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 0.51 (q, J ˆ 8.0,
(MeCH2)3Si); 0.88 (t, J ˆ 8.0, (MeCH2)3Si); 1.40, 1.61 (2s, Me2C); 7.31 ± 7.40 (m, 3 arom. H); 7.45 ± 7.52 (m, 2
arom. H); 7.55 ± 7.62 (m, 1 arom. H); 7.66 ± 7.71 (m, 2 arom. H); 7.90 ± 7.96 (m, 2 arom. H); 9.13 (br. s, NH).
N6-Benzoyl-8-hydroxy-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (5). At 258, a soln. of 4c
(90.8 mg, 0.15 mmol) in dry CH2Cl2 (2.7 ml) was treated with m-chloroperbenzoic acid (52.2 mg, 0.3 mmol),
stirred for 1 h, washed with sat. aq. NaHCO3 soln. (2.0 ml) and brine (1.0 ml), dried (Na2SO4), and evaporated.
FC (3.0 g of silica gel; hexane/AcOEt 2 :1) gave 5 (76.4 mg, 96%). White solid. Rf (hexane/AcOEt 2 :1) 0.48.
1H-NMR (200 MHz, CDCl3): see Table 2; additionally, 0.60 (q, J ˆ 8.0, (MeCH2)3Si); 0.96 (t, J ˆ 8.0,
(MeCH2)3Si); 1.40, 1.61 (2s, Me2C); 7.49 ± 7.60 (m, 2 arom. H); 7.60 ± 7.72 (m, 1 arom. H); 7.96 ± 8.03 (m, 2 arom.
H); 8.89 (br. s, NH); 9.57 (br. s, OH).
N6-Benzoyl-2',3'-O-isopropylidene-8-(1 H-[1,2,3]triazol-1-yl)-5'-O-(triethylsilyl)adenosine (6). At 258, a
soln. of 2 (20.1 mg, 35.5 mmol) in dry DMF (0.6 ml) was treated with (trimethylsilyl)acetylene (40 ml,
0.28 mmol), stirred for 20 h at 808, poured into ice-water (ca. 4 ml), and extracted with Et2O/AcOEt 1:1 (3 Â
1.0 ml). The combined org. layers were washed with H2O, dried (Na2SO4), and evaporated. FC (1.5 g of silica
gel; CH3Cl/AcOEt 7:2) gave 6 (9.4 mg, 45%). Green solid. Rf (CH3Cl/AcOEt 7 :2) 0.43. 1H-NMR (200 MHz,
CD3OD): see Table 2; additionally, 0.48 (q, J ˆ 8.0, (MeCH2)3Si); 0.86 (t, J ˆ 8.0, (MeCH2)3Si); 1.40, 1.59 (2s,
Me2C); 7.50 ± 7.61 (m, 2 arom. H); 7.61 ± 7.72 (m, 1 arom. H); 8.01, 8.83 (2d, J ˆ 1.3, C2H2N3); 8.02 ± 8.09 (m, 2
arom. H).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-hept-6-
ynofuranosyl]-8-{[(4-methoxyphenyl)methyl]amino}adenine (9). At 258, a soln. of 8 [1] (343.2 mg, 0.52 mmol)
in dry EtOH (10.0 ml) was treated with 4-methoxybenzylamine (0.20 ml, 1.57 mmol), stirred for 25 h, and
evaporated. The residue was dissolved in CHCl3 (18 ml), washed with sat. aq. NaHCO3 soln. (5.0 ml) and brine
(5.0 ml), and dried (Na2SO4). Evaporation and FC (20 g of silica gel; hexane/AcOEt 5 :7) gave 9 (366.4 mg,
93%), which contained traces of impurities. White solid. Rf (hexane/AcOEt 1:1) 0.44. 1H-NMR (200 MHz,
CDCl3): see Table 3; additionally, 0.17 (s, Me3Si); 0.52 (q, J ˆ 8.2), 0.53 (q, J ˆ 8.0) ((MeCH2)3Si); 0.85 (t, J ˆ 8.1,
(MeCH2)3Si); 1.42, 1.64 (2s, Me2C); 3.79 (s, MeO); 4.56 (dd, J ˆ 15.0, 4.0), 4.77 (dd, J ˆ 15.0, 7.0) (ArCH2); 6.04
(dd, J ˆ 7.0, 4.0, HNꢀC(8)); 6.87 (d, J ˆ 8.5, 2 arom. H); 7.30 (d, J ˆ 8.5, 2 arom. H); 7.43 ± 7.60 (m, 3 arom. H);
7.93 ± 8.02 (m, 2 arom. H); 8.81 (br. s, HNꢀC(6)).
8-Amino-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-
hept-6-ynofuranosyl]adenine (10). At 258, a soln. of 9 (366.4 mg, ca. 0.48 mmol) in CH2Cl2/H2O 18 :1 (12.8 ml)
was treated with DDQ (150.9 mg, 0.665 mmol), stirred for 5 h, diluted with CHCl3 (40 ml), washed with sat. aq.
NaHCO3 soln. (15 ml) and brine (15 ml), dried (Na2SO4), and evaporated. FC (26 g of silica gel; CHCl3/acetone
3:1) gave 10 (119.6 mg, 66% from 8). Light pink solid. Rf (CHCl3/AcOEt 1:3) 0.60. M.p. 1138. [a]2D5 ˆ ‡ 8.6 (c ˆ
1.02, CHCl3). UV (CHCl3): 303 (17000), 244 (15000). IR (CHCl3): 3464w, 3330w, 2997w, 2960m, 2914w, 2878w,
2176w, 1700m, 1638s, 1612m, 1584w, 1553w, 1500m, 1481m, 1438s, 1418w, 1387m, 1328w, 1304w, 1156w, 1125m,
1
1088s, 1018w, 969w, 942w, 847s. H-NMR (300 MHz, CDCl3): see Table 3; additionally, 0.15 (s, Me3Si); 0.57 ±

3240
Helvetica Chimica Acta ± Vol. 83 (2000)
Table 3. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for the C(8)-Substituted Hept-6-
ynofuranosyladenines 9 ± 16 and 19 ± 21 in CDCl3 Solution
9
10
11 [1]
12 [1]
13
14
15
16
19 [1]
20
21 [2]
HꢀC(2)
HꢀC(1')
HꢀC(2')
HꢀC(3')
HꢀC(4')
HꢀC(5')
HꢀC(7')
J(1',2')
8.60
6.13
5.59
4.95
4.30
4.49
±
8.52
6.36
5.07
4.85
4.25
4.66
±
8.76
6.15
5.77
5.29
4.22
4.41
±
8.77
6.24
5.85
5.24
4.22
4.43
±
8.76
6.25
5.78
5.27
4.26
4.55
2.35
2.0
8.59
6.06
5.81
4.96
4.23
4.41
2.10
3.0
8.75
6.76
5.67
5.34
4.27
4.67
2.29
2.0
8.55
6.32
5.27
5.09
4.26
4.71
2.61
3.8
8.73
6.13
5.90
5.26
4.22
4.41
±
8.21
6.07
5.88
5.24
4.19
4.39
±
8.36
6.18
5.25
5.12
4.39
4.63
2.48
3.0
3.7
4.5
2.0
2.0
2.0
1.8
J(2',3')
J(3',4')
J(4',5')
J(5',7')
6.5
3.0
4.5
±
6.5
3.8
2.5
±
6.5
3.0
8.0
±
6.3
2.8
7.5
±
6.5
3.3
7.8
2.2
6.8
3.0
5.5
2.2
6.3
3.5
8.0
2.2
6.5
3.5
3.5
2.2
6.0
2.8
8.0
±
6.5
3.0
8.8
±
6.5
2.5
4.8
2.2
0.79 (m, (MeCH2)3Si); 0.98 (t, J ˆ 8.1, (MeCH2)3Si); 1.35, 1.64 (2s, Me2C); 5.80 (br. s, NH2); 7.44 (br. t, J ꢂ 7.8, 2
arom. H); 7.54 (br. t, J ꢂ 7.8, 1 arom. H); 7.96 (br. t, J ꢂ 7.8, 2 arom. H); 8.95 (br. s, NH). 13C-NMR (75 MHz,
CDCl3): 164.9 (s, CˆO); 153.3 (d, C(2)); 153.0 (s, C(6)); 149.2 (s, C(4)); 144.2 (s, C(8)); 133.8 (s); 132.3 (d);
128.6 (2d); 127.9 (2d); 122.9 (s, C(5)); 115.4 (s, Me2C); 102.5 (s, C(6')); 91.7 (s, C(7')); 88.2 (d, C(1')); 86.2 (d,
C(4')); 82.0 (d, C(2')); 80.0 (d, C(3')); 63.0 (d, C(5')); 27.4, 25.5 (2q, Me2C); 6.7 (q, (MeCH2)3Si); 4.5 (t,
‡
(MeCH2)3Si); ꢀ0.4 (q, Me3Si). FAB-MS: 637 ([M ‡ 1] ). Anal. calc. for C31H44N6O5Si2 (636.90): C 58.46,
H 6.96, N 13.20; found: C 58.50, H 6.99, N 13.13.
Iodination of 10. At 258, a suspension of 10 (12.3 mg, 19.7 mmol) in CH2I2 (0.18 ml) was treated with
C5H11ONO (8.0 ml, 59.2 mmol), KI (38.7 mg, 0.233 mmol) and I2 (61.8 mg, 0.243 mmol), warmed to 558, stirred
for 2 h, diluted with CHCl3 (4.0 ml), washed with sat. aq. Na2S2O3 soln. (1.0 ml) and brine (0.7 ml), dried
(Na2SO4), and evaporated. FC (0.75 g of silica gel; hexane/AcOEt 5 :4) gave 11 [1] (12.2 mg, 82%).
N6-Benzoyl-8-chloro-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-
adenine (13). At 258, a soln. of 12 [1] (149.1 mg, 0.275 mmol) in dry THF (4.5 ml) was treated with 1.0m soln. of
TBAF in THF (0.42 ml, 0.42 mmol), stirred for 7 h, and evaporated. FC (7 g of silica gel; CHCl3/AcOEt 3 :2)
gave the desilylated propargyl alcohol (119.0 mg, 92%). At 258, a soln. of this alcohol (548.0 mg, 1.17 mmol) and
imidazole (246.0 mg, 3.61 mmol) in dry DMF (16 ml) was treated dropwise with Et3SiCl (0.59 ml, 3.51 mmol),
stirred for 15 h, poured into ice-water (ca. 60 ml), and extracted with hexane/AcOEt 1:1 (3 Â 15 ml). The
combined org. layers were washed with H2O, dried (Na2SO4), and evaporated. FC (25 g of silica gel; hexane/
AcOEt 5 :4) gave 13 (466.4 mg, 73%). White solid. Rf (hexane/AcOEt 5 :4) 0.50. M.p. 738. [a]2D5 ˆ ꢀ19.6 (c ˆ
1.02, CHCl3). UV (CHCl3): 279 (19000), 240 (18500). IR (CHCl3): 3408w (br.), 3306w, 3007w, 2958w, 2914w,
2878w, 2100w, 1711m, 1611s, 1589m, 1508w, 1480w, 1450s, 1416w, 1384w, 1376w, 1357w, 1323m, 1248m, 1159w,
1093s, 1005w, 973w, 892w, 872w. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 0.62 (q, J ˆ 8.2), 0.63 (q,
J ˆ 8.0) ((MeCH2)3Si); 0.95 (t, J ˆ 8.1, (MeCH2)3Si); 1.41, 1.62 (2s, Me2C); 7.48 ± 7.56 (m, 2 arom. H); 7.58 ± 7.65
(m, 1 arom. H); 7.97 ± 8.03 (m, 2 arom. H); 8.98 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.4 (s, CˆO); 152.5
(d, C(2)); 151.7 (s, C(6)); 148.5 (s, C(4)); 141.9 (s, C(8)); 133.4 (s); 133.0 (d); 128.9 (2d); 127.8 (2d); 121.7 (s,
C(5)); 114.4 (s, Me2C); 90.9 (d, C(1')); 89.9 (d, C(4')); 82.6 (d, C(2')); 82.2 (s, C(6')); 82.0 (d, C(3')); 74.1 (s,
C(7')); 62.5 (d, C(5')); 27.2, 25.4 (2q, Me2C); 6.6 (q, (MeCH2)3Si); 4.7 (t, (MeCH2)3Si). FAB-MS: 584 (100, [M
‡
‡ 1] ), 585 (37), 586 (43), 587 (12). Anal. calc. for C28H34ClN5O5Si (584.15): C 57.57, H 5.87, N 11.99; found:
C 57.48, H 5.86, N 11.90.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-8-{[(4-
methoxyphenyl)methyl]amino}adenine (14). At 258, a soln. of 13 (597.5 mg, 1.02 mmol) in dry EtOH (18 ml)
was treated with 4-methoxybenzylamine (0.40 ml, 3.06 mmol), stirred for 25 h, and evaporated. The residue was
dissolved in CHCl3 (60 ml), washed with sat. aq. NaHCO3 soln. (20 ml) and brine (20 ml), dried (Na2SO4), and
evaporated. FC (25 g of silica gel; hexane/AcOEt 1 :2) gave 14 (668 mg, 95%). White solid. Rf (hexane/AcOEt
1:2) 0.42. M.p. 848. [a] ˆ ꢀ42.3 (c ˆ 1.04, CHCl3). UV (CHCl3): 309 (19000), 245 (18000). IR (CHCl3): 3400w
(br.), 3305w, 3000m, 2959m, 2913w, 2878w, 2838w, 2100w, 1701m, 1620s, 1577s, 1514s, 1478m, 1452s, 1424m,
1384m, 1329m, 1303m, 1252s, 1174m, 1090s, 1036w, 1004w, 868w, 818w. 1H-NMR (300 MHz, CDCl3): see Table 3;
additionally, 0.57 (q, J ˆ 8.2), 0.58 (q, J ˆ 8.0) ((MeCH2)3Si); 0.90 (t, J ˆ 8.1, (MeCH2)3Si); 1.40, 1.60 (2s, Me2C);

Helvetica Chimica Acta ± Vol. 83 (2000)
3241
3.79 (s, MeO); 4.61 (dd, J ˆ 15.0, 5.0), 4.67 (dd, J ˆ 15.0, 5.0) (ArCH2); 5.76 ± 5.81 (br. s, HNꢀC(8)); 6.88, 7.31
(2d, J ˆ 8.8, 4 arom. H); 7.46 ± 7.56 (m, 2 arom. H); 7.56 ± 7.62 (m, 1 arom. H); 7.98 ± 8.04 (m, 2 arom. H); 8.91 (br.
s, HNꢀC(6)). 13C-NMR (75 MHz, CDCl3): 164.7 (s, CˆO); 159.2 (s); 153.5 (s, C(6)); 152.3 (s, C(4)); 149.2 (d,
C(2)); 144.7 (s, C(8)); 134.4 (s); 132.3 (d); 129.8 (s); 129.2 (2d); 128.7 (2d); 127.8 (2d); 122.0 (s, C(5)); 114.8 (s,
Me2C); 114.1 (2d); 89.6 (d, C(1')); 88.3 (d, C(4')); 81.4 (d, C(2')); 81.3 (s, C(6')); 81.0 (d, C(3')); 74.9 (s, C(7'));
62.6 (d, C(5')); 55.3 (q, MeO); 46.6 (t, ArCH2); 27.1, 25.4 (2q, Me2C); 6.6 (q, (MeCH2)3Si); 4.6 (t, (MeCH2)3Si).
‡
FAB-MS: 685 ([M ‡ 1] ).
Oxidation of 14 with DDQ. a) At 258, a soln. of 14 (348 mg, 0.51 mmol) in dry CH2Cl2 (10.4 ml) was treated
with DDQ (177.5 mg, 0.78 mmol), stirred for 4 h, diluted with CHCl3 (20 ml), washed with sat. aq. NaHCO3
soln. (15 ml) and brine (10 ml), dried (Na2SO4), and evaporated. FC (18 g of silica gel; hexane/AcOEt 1:2)
gave 15 (301.4 mg, 87%).
b) Similarly, a mixture of 14 (314.9 mg, 0.460 mmol) and DDQ (152.4 mg, 0.671 mmol) in CH2Cl2/H2O
18 :1 (12.0 ml) was stirred for 4 h. Analogous workup gave 15 (56.2 mg, 18%) and 16 (160.0 mg, 62%).
Data of N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-
1
8-{[(4-methoxyphenyl)methylidene]amino}adenine (15): Yellow solid. Rf (hexane/AcOEt 3 :4) 0.52. H-NMR
(300 MHz, CDCl3): see Table 3; additionally, 0.66 (q, J ˆ 8.2), 0.67 (q, J ˆ 8.0) ((MeCH2)3Si); 0.98 (t, J ˆ 8.1,
(MeCH2)3Si); 1.43, 1.66 (2s, Me2C); 3.92 (s, MeO); 7.03, 8.03 (2d, J ˆ 9.0, 4 arom. H); 7.51 ± 7.59 (m, 2 arom. H);
7.59 ± 7.66 (m, 1 arom. H); 7.98 ± 8.04 (m, 2 arom. H); 8.93 (br. s, NH, exchange with D2O); 9.39 (s, CHˆN).
Data of 8-Amino-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-yno-
furanosyl]adenine (16): Light orange solid. Rf (CHCl3/AcOEt 1:2) 0.50. 1H-NMR (200 MHz, CDCl3): see Table
3; additionally, 0.73 (q, J ˆ 8.2), 0.74 (q, J ˆ 8.0) ((MeCH2)3Si); 0.99 (t, J ˆ 8.1, (MeCH2)3Si); 1.42, 1.67 (2s,
Me2C); 5.64 (br. s, NH2); 7.44 ± 7.63 (m, 3 arom. H); 7.96 ± 8.04 (m, 2 arom. H); 8.76 (br. s, NH).
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7')-8-amino-N6-benzoyl-9-[6,7-di-
deoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (17). At 258, a soln. of 5
(287.6 mg, 0.44 mmol) and 15 (301.4 mg, 0.38 mmol) in dry Et3N (18 ml) was treated with CuI (8.2 mg, 43 mmol),
P(fur)3 (5.4 mg, 25.8 mmol) and [Pd2(dba)3] (12.0 mg, 13 mmol), stirred for 3 h, warmed to 808, stirred for 2 h,
and evaporated. The residue was dissolved in CHCl3 (60 ml) and washed with 2% aq. Na2(EDTA) soln. (2 Â
15 ml). Drying (Na2SO4), evaporation, and FC (25 g of silica gel; hexane/acetone 5 :4) gave 17 (336.3 mg,
70%). Yellow solid. Rf (hexane/acetone 5 :4) 0.46. M.p. 1448. [a]2D5 ˆ ‡91.2 (c ˆ 1.02, CHCl3). UV (CHCl3): 304
(47000), 248 (32000). IR (CHCl3): 3450w (br.), 3402w (br.), 3338w (br.), 3001m, 2959m, 2913w, 2878w, 1706m,
1637s, 1609s, 1584s, 1501m, 1478s, 1436m, 1385m, 1331m, 1254s, 1170m, 1158m, 1090s, 1003w, 972w, 866w.
1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 0.50 (q, J ˆ 8.0, (MeCH2)3Si); 0.710 (q, J ˆ 8.0), 0.715 (q,
J ˆ 7.8) ((MeCH2)3Si); 0.87, 0.99 (2t, J ˆ 8.0, 2 (MeCH2)3Si); 1.40, 1.42, 1.62, 1.64 (4s, 2 Me2C); 6.06 ± 6.36 (br. s,
NH2); 7.47, 7.52 (2t, J ˆ 8.0, 4 arom. H); 7.53 ± 7.61 (m, 2 arom. H); 7.98 (d, J ˆ 8.0, 4 arom. H); 9.27 (br. s, 2 NH).
13C-NMR (75 MHz, CDCl3): 165.0 (s, 2 CˆO); 153.6, 152.2 (2s, C(6/I), C(6/II)); 153.3, 149.2 (2d, C(2/I), C(2/
II)); 150.6, 149.8 (2s, C(4/I), C(4/II)); 144.6 (s, C(8/I)); 136.2 (s, C(8/II)); 133.8, 133.4 (2s); 132.8, 132.3 (2d);
128.7 (2d); 128.6 (2d); 128.0 (2d); 127.8 (2d); 123.0, 122.1 (2s, C(5/I), C(5/II)); 115.0, 114.2 (2s, 2 Me2C); 95.3 (s,
C(6'/I)); 90.6, 89.2 (2d, C(1'/I), C(1'/II)); 88.5, 88.1 (2d, C(4'/I), C(4'/II)); 83.3, 82.1 (2d, C(2'/I), C(2'/II)); 82.0,
80.8 (2d, C(3'/I), C(3'/II)); 74.5 (s, C(7'/I)); 63.1 (d, C(5/I)); 63.0 (t, C(5/II)); 27.1, 27.0, 25.4, 25.3 (4q, 2 Me2C);
‡
6.6, 6.5 (2q, 2 (MeCH2)3Si); 4.6, 4.2 (2t, 2 (MeCH2)3Si). FAB-MS: 1088 ([M ‡ 1] ). Anal. calc. for
C54H69N11O10Si2 (1088.38): C 59.36, H 6.31, N 14.11; found: C 59.59, H 6.39, N 14.16.
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7')-N6-benzoyl-9-[6,7-dideoxy-2,3-
O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-8-iodoadenine (18). At 258, a suspension of
17 (123.7 mg, 0.114 mmol) in CH2I2 (1.9 ml) was treated with C5H11ONO (0.31 ml, 2.3 mmol), KI (64.2 mg,
0.39 mmol) and I2 (102.2 mg, 0.4 mmol), warmed to 558, stirred for 20 min, diluted with CHCl3 (15 ml), washed
with sat. aq. Na2S2O3 soln. (3 ml) and brine (3 ml), dried (Na2SO4), and evaporated. FC (18 g of silica gel;
hexane/AcOEt 3 :5) gave 18 (75.1 mg, 55%). Yellow solid. Rf (hexane/AcOEt 3 :5) 0.48. M.p. 1198. [a]D25
ˆ
‡17.6 (c ˆ 0.57, CHCl3). UV (CHCl3): 293 (41000), 263 (22000). IR (KBr): 3450w (br.), 3410w (br.), 3220w
(br.), 3062w, 2954m, 2912w, 2877m, 1706m, 1606s, 1583s, 1509m, 1459m, 1425m, 1382w, 1326m, 1245s, 1214m,
1158m, 1093s, 1004w, 974w, 870w, 798w. 1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 0.50 (q, J ˆ 8.0,
(MeCH2)3Si); 0.710 (q, J ˆ 8.0), 0.715 (q, J ˆ 7.8) ((MeCH2)3Si); 0.87, 1.01 (2t, J ˆ 8.0, 2 (MeCH2)3Si); 1.38, 1.43,
1.61, 1.66 (4s, 2 Me2C); 7.47 ± 7.65 (m, 6 arom. H); 7.94 ± 8.02 (m, 4 arom. H); 8.95, 9.01 (2 br. s, 2 NH). 13C-NMR
(75 MHz, CDCl3): 164.4, 164.3 (2s, 2 CˆO); 153.4, 152.4 (2d, C(2/I), C(2/II)); 151.6, 150.2 (2s, C(6/I), C(6/II));
149.5, 148.4 (2s, C(4/I), C(4/II)); 136.6 (s, C(8/II)); 133.7, 133.5 (2s); 133.0, 132.8 (2d); 128.9 (4d); 127.8 (4d);
125.6 (s, C(5/I)); 122.5 (s, C(5/II)); 114.5, 114.1 (2s, 2 Me2C); 104.8 (s, C(8/I)); 96.9 (s, C(6'/I)); 93.9, 90.7 (2d,
C(1'/I), C(1'/II)); 89.8, 88.1 (2d, C(4'/I), C(4'/II)); 83.2, 83.1 (2d, C(2'/I), C(2'/II)); 82.4, 82.2 (2d, C(3'/I), C(3'/

3242
Helvetica Chimica Acta ± Vol. 83 (2000)
1
Table 4. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for the Dimers 17, 18, 22, and
23, and the Tetramers 24 ± 26 in CDCl3 Solution
17
18
22
23a)
Unit II
Unit I
Unit II
Unit I
Unit II
Unit I
8.26b)
Unit II
Unit I
HꢀC(2)
HꢀC(8)
HꢀC(1')
HꢀC(2')
HꢀC(3')
HꢀC(4')
HaꢀC(5')
HabꢀC(5')d)
J(1',2')
J(2',3')
J(3',4')
J(4',5'a)
J(4',5'b)
8.79
±
8.56
±
8.79
±
8.73
±
8.34b)
8.18
6.21
5.64
5.24
4.17
4.55
±
1.8
6.5
3.0
8.5
8.34b)
8.15
6.23
5.61
5.245
4.21
4.64
2.33
2.0
6.4
3.0
8.2
±
8.28b)
±
±
6.33
5.70
5.15
4.31
3.66
3.79
1.8
6.5
3.5
6.5
7.0
6.26
5.65
5.19
4.36
4.83
±
2.0
6.5
3.5
5.5
±
6.26b)
5.72
5.13
4.28
3.66
3.78
2.0
6.20b)
5.63
5.40
4.44
4.89
±
6.45
5.60
5.26
4.51
4.81
±
6.33
5.55
5.22
4.50
4.84
±
2.0
6.3
2.5
7.0
±
2.0
6.5
3.5
8.0
±
< 1.0
6.5
3.5
6.5
6.5
6.5
2.5
7.5
±
±
J(5'a,5'b)e)
10.8
±
10.8
±
±
±
2.1
±
24
25f)
26f)
Unit IV Unit III Unit II Unit I Unit IV Unit III Unit II Unit I Unit IV Unit III Unit II Unit I
HꢀC(2) 8.76b) 8.79b) 7.99c) 8.01c) 8.65b) 8.69b) 8.09c) 8.10c) 8.16b) 8.15b) 8.15b) 8.14b)
HꢀC(8)
±
±
±
8.24
±
±
±
8.25
±
±
±
8.32
HꢀC(1') 6.22b) 6.13b) 6.17b) 6.45 6.18b) 6.15b) 6.11b) 6.04
6.23b) 6.18b) 6.15b) 6.04
HꢀC(2') 5.64
HꢀC(3') 5.14
HꢀC(4') 4.24
HaꢀC(5') 3.63
HbꢀC(5') 3.75
5.55b) 5.575b) 5.59b) 5.47b) 5.36b) 5.45b) 5.29b) 5.44b) 5.42b) 5.42b) 5.38b)
5.37
4.41
4.89
±
5.13
4.40
4.97
±
5.41 4.92
4.35 4.01
4.98
±
5.17b) 5.21b) 5.11
4.18b) 4.20b) 4.24
4.87b) 4.88b) 4.78
4.95
4.12
3.46
3.55
3.0
6.5
3.0
5.0
5.0
5.21b) 5.23b) 5.18
4.23b) 4.26b) 4.30
4.91
±
3.0
6.5
3.0b)
6.5b)
±
g
)
)
4.91
±
4.85
±
3.0
6.5
g
±
±
±
J(1',2')
J(2',3')
J(3',4')
J(4',5'a)
J(4',5'b)
2.0
6.5
3.5
6.5
6.5
1.5b)
6.5
4.0
8.0
±
2.0b) 1.5
2.5b)
6.5
3.0b)
6.5
3.0
7.5b)
±
3.0b) 3.0
3.0
6.5
6.5
2.5
8.8
±
6.5
3.5
7.5
±
6.5
3.0
6.5
2.5
3.5
5.5
2.5b) 2.5
8.0b) 6.5
6.0b) 6.5
5.5
±
±
±
±
±
±
±
±
h
J(5'a,5'b) 10.8
±
±
±
)
±
12.0
±
b
a) Assignment based on a DQFCOSY.GRASP spectrum.
)
c) Assignment to the units may be interchanged.
d) HꢀC(7') of 23. e) J(5',7') of 23. ) In (D6)DMSO. g) At 3.35 ± 3.5 ppm, partially hidden by the HDO signal.
f
h) Not determined.
II)); 73.7 (s, C(7'/I)); 63.3 (d, C(5'/I)); 63.0 (t, C(5'/II)); 27.2, 25.4 (2q, 2 Me2C); 6.7, 6.6 (2q, 2 (MeCH2)3Si); 4.7,
‡
4.2 (2t, 2 (MeCH2)3Si). FAB-MS: 1199 ([M ‡ 1] ). Anal. calc. for C54H67IN10O10Si2 (1199.26): C 54.08, H 5.63,
N 11.68; found: C 54.09, H 5.70, N 11.62.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-5-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-
8-iodoadenine (20). At 258, a soln. of 19 [1] (156.5 mg, 0.21 mmol) in dry toluene (4.7 ml) was treated with 4-
methoxybenzylamine (0.14 ml, 1.07 mmol), stirred at 808 for 3 h, and evaporated. FC (10 g of silica gel; CHCl3/
AcOEt 4 :5) gave 20 (114.5 mg, 81%). White solid. Rf (CHCl3/AcOEt 1:1) 0.56. M.p. 798. [a]2D5 ˆ ꢀ12.3 (c ˆ
1.04, CHCl3). UV (CHCl3): 266 (15000). IR (CHCl3): 3400w (br.), 2959m, 2913w, 2877m, 2173w, 1631s, 1584m,
1520w, 1476m, 1442m, 1417m, 1384m, 1358m, 1321m, 1287m, 1248s, 1158m, 1091s, 1049m, 1004m, 929m, 846s.
1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 0.09 (s, Me3Si); 0.61 (q, J ˆ 9.1), 0.62 (q, J ˆ 9.1)
((MeCH2)3Si); 0.94 (t, J ˆ 8.1, (MeCH2)3Si); 1.40, 1.61 (2s, Me2C); 5.95 (br. s, NH2). 13C-NMR (75 MHz,
CDCl3): 154.0 (s, C(6)); 152.4 (d, C(2)); 150.4 (s, C(4)); 122.7 (s, C(5)); 113.8 (s, Me2C); 104.1 (s, C(8)); 101.0 (s,
C(6')); 93.9 (d, C(1')); 90.6 (s, C(7')); 90.0 (d, C(4')); 82.9 (d, C(2')); 82.5 (d, C(3')); 63.0 (d, C(5')); 27.1, 25.4 (2q,

Helvetica Chimica Acta ± Vol. 83 (2000)
3243
‡
Me2C); 6.7 (q, (MeCH2)3Si); 4.8 (t, (MeCH2)3Si); ꢀ0.3 (q, Me3Si). FAB-MS: 644 ([M ‡ 1] ). Anal. calc. for
C24H38IN5O4Si2 (643.67): C 44.78, H 5.95, N 10.88; found: C 44.95, H 6.11, N 10.79.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-
adenin-8-yl-(8 ! 7')-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]ade-
nine (22). At 258, a soln. of 20 (268.2 mg, 0.4 mmol) and 21 [2] (178.2 mg, 0.4 mmol) in dry Et3N (13.4 ml) was
treated with CuI (8.3 mg, 43.6 mmol), P(fur)3 (6.5 mg, 28 mmol) and [Pd2(dba)3] (12.3 mg, 13.4 mmol), stirred for
3 h, and evaporated. The residue was dissolved in CHCl3 (60 ml) and washed with 2% aq. Na2(EDTA) soln.
(2 Â 15 ml). Drying (Na2SO4), evaporation, and FC (20 g of silica gel; CHCl3/acetone 1:2) gave 22 (326.9 mg,
85%). Light yellow solid. Rf (CHCl3/acetone 1:2) 0.56. M.p. 1288. [a]2D5 ˆ ‡19.8 (c ˆ 1.00, CHCl3). UV (CHCl3):
296 (21000), 266 (21000). IR (CHCl3): 3412w, 3380w, 3208w, 2992w, 2958m, 2913w, 2878w, 2173w, 1701w, 1633s,
1588m, 1472w, 1414w, 1375m, 1328m, 1296m, 1248w, 1157w, 1095s, 1004m, 856w, 846m. 1H-NMR (300 MHz,
CDCl3): see Table 4; additionally, 0.07 (s, Me3Si); 0.60 ± 0.77 (m, 2 (MeCH2)3Si); 0.97, 0.99 (2t, J ˆ 8.0, 2
(MeCH2)3Si); 1.36, 1.44, 1.57, 1.65 (4s, 2 Me2C); 6.43 (br. s, NH2); 6.9 ± 7.3 (br. s, NH2). 13C-NMR (75 MHz,
CDCl3): 155.8 (s, C(6/I), C(6/II)); 153.8, 152.9 (2d, C(2/I), C(2/II)); 149.0, 148.6 (2s, C(4/I), C(4/II)); 140.7 (d,
C(8/I)); 133.8 (s, C(8/II)); 120.1, 119.4 (2s, C(5/I), C(5/II)); 114.2, 113.7 (2s, 2 Me2C); 104.8 (s, C(6'/II)); 94.9 (s,
C(6'/I)); 91.5, 90.8 (2d, C(1'/I), C(1'/II)); 90.3 (s, C(7'/II)); 90.2, 89.9 (2d, C(4'/I), C(4'/II)); 84.0, 83.3 (2d, C(2'/
I), C(2'/II)); 82.9, 82.6 (2d, C(3'/I), C(3'/II)); 74.5 (s, C(7'/I)); 63.5, 63.3 (2d, C(5'/I), C(5'/II)); 27.1, 27.0, 25.5,
25.4 (4q, 2 Me2C); 6.8, 6.7 (2q, 2 (MeCH2)3Si); 4.8, 4.7 (2t, 2 (MeCH2)3Si); ꢀ0.3 (q, Me3Si). FAB-MS: 961
‡
([M ‡ 1] ).
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-yno-furanosyl]adenin-8-yl-(8 ! 7')-
9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (23). At 258, a
soln. of 22 (55.8 mg, 58 mmol) in THF (0.84 ml) was treated with a soln. of AgNO3 (25.4 mg, 0.15 mmol) in 75%
aq. MeOH (0.84 ml), stirred for 4.5 h, diluted with CHCl3 (12 ml), washed with 5% aq. KCN soln. (5 ml) and
brine (3 ml), dried (Na2SO4), and evaporated. At 258, a soln. of the residue and imidazole (25.4 mg, 0.37 mmol)
in dry DMF (1.7 ml) was treated dropwise with Et3SiCl (49 ml, 0.29 mmol), stirred for 48 h, and poured into ice-
water (ca. 3.5 ml). After extraction with Et2O/AcOEt 1:1 (3 Â 1.2 ml), the combined org. layers were washed
with H2O, dried (Na2SO4), and evaporated. FC (3.0 g of silica gel; CHCl3/acetone 2 :3) gave 23 (37.0 mg, 72%).
Light yellow solid. Rf (CHCl3/acetone 2 :3) 0.46. M.p. 1268. [a]2D5 ˆ ‡33.8 (c ˆ 1.02, CHCl3). UV (CHCl3): 296
(20000), 266 (21000). IR (CHCl3): 3411w, 3307w, 3207w, 3008s, 2975m, 2914m, 2878m, 1633s, 1588m, 1520w,
1474m, 1421m, 1384m, 1375m, 1329m, 1296m, 1248s, 1157m, 1097s, 1048s, 1006m, 971w, 928m, 873m, 850m,
818m. 1H-NMR (500 MHz, CDCl3, assignment based on a DQFCOSY.GRASP spectrum): see Table 4;
additionally, 0.61 ± 0.78 (m, 2 (MeCH2)3Si); 0.98 (t, J ˆ 7.8, 2 (MeCH2)3Si); 1.38, 1.44, 1.59, 1.65 (4s, 2 Me2C);
6.23, 6.70 (2 br. s, 2 NH2). 13C-NMR (75 MHz, CDCl3): 155.9 (s, C(6/I), C(6/II)); 153.8, 152.9 (2d, C(2/I), C(2/
II)); 148.9, 148.6 (2s, C(4/I), C(4/II)); 140.6 (d, C(8/I)); 133.7 (s, C(8/II)); 120.1, 119.5 (2s, C(5/I), C(5/II));
114.2, 113.8 (2s, 2 Me2C); 95.1 (s, C(6'/I)); 91.5, 90.9 (2d, C(1'/I), C(1'/II)); 90.2, 90.0 (2d, C(4'/I), C(4'/II)); 84.0,
83.4 (2d, C(2'/I), C(2'/II)); 83.0, 82.7 (2d, C(3'/I), C(3'/II)); 74.3 (s, C(7'/I)); 73.6, 73.5 (2s, C(6'/II), C(7'/II));
63.5, 62.6 (2d, C(5'/I), C(5'/II)); 27.1, 27.0, 25.4, 25.3 (4q, 2 Me2C); 6.7 (q, 2 (MeCH2)3Si); 4.7 (t, 2 (MeCH2)3Si).
‡
FAB-MS: 889 ([M ‡ 1] ). Anal. calc. for C42H60N10O8Si2 (889.17): C 56.56, H 6.79, N 15.66; found: C 56.73,
H 6.80, N 15.75.
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosin-8-yl-(8 ! 7')-N6-benzoyl-9-[6,7-dideoxy-
2,3-O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-(8 ! 7')-9-[6,7-dideoxy-2,3-
O-isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenin-8-yl-(8 ! 7')-9-[6,7-dideoxy-2,3-O-
isopropylidene-5-O-(triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (24). At 258, a soln. of 18 (81.5 mg,
68 mmol) and 23 (60.5 mg, 68 mmol) in dry Et3N/toluene 1:1 (4.2 ml) was treated with CuI (1.7 mg, 8.9 mmol),
P(fur)3 (1.2 mg, 5.2 mmol) and [Pd2(dba)3] (2.2 mg, 2.4 mmol), stirred for 11 h, and evaporated. The residue was
dissolved in CHCl3 (16 ml) and washed with 2% aq. Na2EDTA soln. (2 Â 4 ml). Drying (Na2SO4), evaporation,
and FC (7.0 g of silica gel; CHCl3/acetone 1:1) gave 24 (105.2 mg, 79%). Light yellow solid. Rf (CHCl3/acetone
1:1) 0.50. M.p. 1528. [a]2D5 ˆ ꢀ6.9 (c ˆ 1.06, CHCl3). UV (CHCl3): 316 (sh. 61000), 304 (71000), 296 (71000), 251
(55000). IR (CHCl3): 3411w (br.), 3370w, 2976s, 2894m, 1709w, 1633m, 1608m, 1585m, 1519s, 1475s, 1423s,
1386m, 1330m, 1080s, 1047s, 929s, 876s, 850s. 1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 0.48 (q, J ˆ
8.0, (MeCH2)3Si); 0.55 ± 0.77 (m, 3 (MeCH2)3Si); 0.85, 0.89, 0.95, 0.98 (4t, J ˆ 8.0, 4 (MeCH2)3Si); 1.37, 1.39 (2
Me); 1.40, 1.56, 1.58, 1.61, 1.68 (7s, 4 Me2C); 6.27 (br. s, NH2); 6.65 (br. s, NH2); 7.36 (t, J ˆ 7.8, 2 arom. H); 7.41 ±
7.58 (m, 4 arom. H); 7.90, 7.94 (2d, J ˆ 7.8, 4 arom. H); 9.24, 9.83 (2 br. s, 2 NH). 13C-NMR (75 MHz, CDCl3):
164.9, 164.6 (2s, 2 CˆO); 156.2, 155.7 (2s, C(6/I), C(6/II)); 153.7, 153.5, 153.3, 152.9 (4d, C(2/I ± IV)); 150.2, 150.1
(2s, C(6/III), C(6/IV)); 149.7, 148.6 (2s, C(4/I ± IV)); 140.7 (d, C(8/I)); 136.8, 136.6, 133.9 (3s, C(8/II ± IV)); 133.6
(2s); 132.7 (2d); 128.8 (2d); 128.7 (2d); 128.0 (2d); 127.9 (2d); 122.6, 122.5 (2s, C(5/III ± IV)); 120.3, 119.6 (2s,

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Helvetica Chimica Acta ± Vol. 83 (2000)
C(5/I ± II)); 114.3 (2 C), 114.1, 114.0 (3s, 4 Me2C); 97.7, 97.2, 95.3 (3s, C(6'/I ± III)); 92.1, 90.7, 90.6, 90.1 (4d, C(1'/
I ± IV)); 89.9, 89.6, 89.3, 88.2 (4d, C(4'/I ± IV)); 83.7, 83.5 (2 C), 83.3 (3d, C(2'/I ± IV)); 82.9, 82.2 (2 C), 81.9 (3d,
C(3'/I ± IV)); 74.2, 73.5, 73.2 (3s, C(7'/I ± III)); 63.3, 63.2, 63.1 (3d, C(5'/I ± III)); 62.9 (t, C(5'/IV)); 27.2 (3 C),
26.9, 25.5, 25.4 (2 C), 25.3 (5q, 4 Me2C); 6.8 (q, 3 (MeCH2)3Si); 6.6 (q, (MeCH2)3Si); 4.80, 4.75, 4.70, 4.2, (4t, 4
‡
(MeCH2)3Si). FAB-MS: 1961 ([M ‡ 1] ). Anal. calc. for C96H126N20O18Si4 (1960.52): C 58.81, H 6.48, N 14.29;
found: C 58.20, H 6.79, N 13.80.
N6-Benzoyl-2',3'-O-isopropylideneadenosin-8-yl-(8 ! 7')-N6-benzoyl-9-(6,7-dideoxy-2,3-O-isopropylidene-
b-d-allo-hept-6-ynofuranosyl)adenin-8-yl-(8 ! 7')-9-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofur-
anosyl)adenin-8-yl-(8 ! 7')-9-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl)adenine (25). At
258, a soln. of 24 (90 mg, 45.9 mmol) in 50% aq. THF (1.8 ml) was treated with AcOH (1.8 ml), stirred for 21 h,
evaporated, and co-evaporated several times with toluene. A soln. of the residue in toluene/MeOH 1:1 (1.0 ml)
was treated with SiO2 (242 mg), evaporated, and the residue was charged on a silica-gel column. FC (4.0 g of
silica gel; CHCl3/MeOH 8 :1) gave crude 25 (61.3 mg, 89%). Yellow solid. Rf (CHCl3/MeOH 8 :1) 0.48.
1H-NMR (300 MHz, (D6)DMSO): see Table 4; additionally, 1.17, 1.24 (2 Me), 1.27, 1.37, 1.44, 1.45, 1.46 (7s, 4
Me2C); 3.35 ± 3.50 (m, partially hidden by HDO signal, addn. of D2O ! change, 2 HꢀC(5'/IV), 2 NH2); 4.78 (br.
t, J ꢂ 6.0, addn. of D2O ! d, J ˆ 6.5, HꢀC(5'/I)); 4.85 (br. t, J ! 6.5, addn. of D2O ! 4.87, d, J ˆ 7.5, ! 4.88, d,
J ˆ 8.0, HꢀC(5'/II ± III)); 4.88 ± 4.96 (signal hidden by a HꢀC(3) signal, exchange with D2O, HOꢀC(5'/IV));
6.59 (br. d, J ꢂ 6.0, exchange with D2O), 6.66 (br. d, J ꢂ 5.5, exchange with D2O), 6.78 (br. d, J ꢂ 5.0, exchange
with D2O) (HOꢀC(5'/I ± III)); 7.32 (br. s, exchange with D2O, 2 NH); 7.44 ± 7.53 (m, 4 arom. H); 7.56 ± 7.63 (m, 2
arom. H); 7.91 ± 7.99 (m, 4 arom. H).
2',3'-O-Isopropylideneadenosin-8-yl-[(8 ! 7')-9-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofur-
anosyl)adenin-8-yl]2-(8 ! 7')-9-(6,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofuranosyl)adenine (26).
At 258, a soln. of 25 (72.7 mg, 48.4 mmol) in MeOH (0.73 ml) was treated with toluene (0.73 ml) and 25%
aq. NH4OH (1.5 ml), stirred for 3.5 h, evaporated, and co-evaporated several times with toluene. A soln. of the
residue in toluene/MeOH 1:1 (2.0 ml) was treated with SiO2 (316 mg), evaporated, and the residue was charged
on a silica-gel column. FC (6.0 g of silica gel; CHCl3/MeOH 5 :1) gave crude 26 (15.4 mg, 25%). Light yellow
solid. Rf (CHCl3/MeOH 5 :1) 0.53. 1H-NMR (300 MHz, (D6)DMSO): see Table 4; additionally, 1.26, 1.29, 1.31,
1.33, 1.45, 1.49, 1.52, 1.54 (8s, 4 Me2C); 3.46 (dt, J ꢂ 12.0, 5.5, addn. of D2O ! dd, J ˆ 12.0, 5.0, HaꢀC(5'/IV));
3.55 (dt, J ˆ 12.0, 5.5, addn. of D2O ! dd, J ˆ 12.0, 5.0, HbꢀC(5'/IV)); 4.85 (br. t, J ꢂ 6.0, addn. of D2O ! 4.83, d,
J ˆ 6.5, HꢀC(5'/I)); 4.91 (br. t, J ꢂ 6.5, addn. of D2O ! 4.87, d, J ˆ 6.0, ! 4.895, d, J ˆ 6.5, HꢀC(5'/II ± III));
5.24 (br. t, J ꢂ 6.0, exchange with D2O, HOꢀC(5'/IV)); 6.71 (br. d, J ꢂ 5.5, exchange with D2O), 6.74 (br. d, J ꢂ
6.0, exchange with D2O), 6.76 (br. d, J ꢂ 5.0, exchange with D2O) (HOꢀC(5'/I ± III)); 7.37 (br. s, exchange with
D2O, NH2 ); 7.50 ± 7.80 (br. s, 3 NH2).
Adenosin-8-yl-[(8 ! 7')-9-(6,7-dideoxy-b-d-allo-hept-6-ynofuranosyl)adenin-8-yl]2-(8 ! 7')-9-(6,7-di-
deoxy-b-d-allo-hept-6-ynofuranosyl)adenine (27). At 258, a soln. of crude 26 (30.6 mg) in 80% aq. HCO2H
(1.0 ml) was stirred for 22 h, evaporated, and co-evaporated several times with toluene. Recrystallisation from
DMSO/MeOH gave 27 (13.9 mg, 72%). White plates. M.p. 1878 (dec.). Rf (BuOH/EtOH/H2O 1 :1:1) 0.06.
[a]2D5 ˆ ꢀ94.2 (c ˆ 0.45, DMSO). UV (DMSO): 311 (sh, 29500), 301 (48000), 278 (28000). IR (KBr): 3600 ±
2500s (br.), 1716w, 1651s, 1602s, 1575m, 1485w, 1423w, 1374m, 1331s, 1303m, 1255m, 1126m, 1075m, 1040m,
1
970,w 909w. H-NMR (300 MHz, (D6)DMSO/D2O): 3.6 ± 3.8 (m, partially hidden by HDO signal, 2 HꢀC(5'/
IV)); 3.94 ± 4.01 (m, HꢀC(4'/IV)); 4.10 ± 4.20 (m, 4 H); 4.30 ± 4.42 (m, 4 H); 4.72 (dd, J ˆ 7.5, 5.0, HꢀC(2'/I));
4.89 (d, J ˆ 4,7), 4.97 (d, J ˆ 5.0) (2 HꢀC(5')); 4.96 ± 5.05 (m, 3 H); 5.91 (d, J ˆ 7.5), 5.95 (d, J ˆ 7.5), 5.97 (d, J ˆ
7.5), 6.00 (d, J ˆ 7.5 ) ( H ꢀ C(1'/I ± IV)); 8.12, 8.14 (2 H), 8.15 (3s, HꢀC(2/I ± IV)); 8.33 (s, HꢀC(8/I)). 13C-NMR
(75 MHz, (D6)DMSO): 156.5 (s, C(6/I ± IV)); 153.5, 152.6 (2d, C(2/I ± IV)); 149.2, 148.1 (2s, C(4/I ± IV)); 140.2
(d, C(8/I)); 133.3 (s, C(8/II ± IV)); 119.5 (s, C(5/I ± IV)); 95.1, 95.0, 94.9 (3s, C(6'/I ± III)); 89.6 (br.), 88.5 (2d,
C(1'/I ± IV)); 87.8, 86.8 (2d, C(4'/I ± IV)); 73.5, 73.1 (2 br. d, C(2'/I ± IV)); 71.6, 70.6 (2d, C(3'/I ± IV)); 71.2, 71.0
(2s, C(7'/I ± III)); 62.6, 62.5 (2d, C(5'/I ± III)); 62.2 (t, C(5'/IV)).
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Received August 23, 2000