Oligonucleosides with a nucleobase-including backbone. Part 2. Synthesis and structure determination of adenosine-derived monomers

Article abstract of DOI:10.1002/1522-2675(20000705)83:7<1331::AID-HLCA1331>3.0.CO;2-Z

The synthesis and structure determination of adenosine-derived monomeric building blocks for new oligonucleosides are described. Addition of Me₃Si- acetylide to the aldehyde derived from the known partially protected adenosine 1 led to the epimeric propargylic alcohols 2 and 3, which were oxidised to the same ketone 4, while silylation and deprotection led to 7 and 9 (Scheme 1). Introduction of an I substituent at C(8) of the propargylic silyl ethers 10 and 11 was not satisfactory. The protected adenosine 12 was, therefore, transformed in high yield into the 8-chloro derivative 13 by deprotonation and treatment with PhSO₂CI; the iodide 15 was obtained in a similar way (Scheme 2). The 8-Cl and the 8-I derivatives 13 and 15 were transformed into the propargylic alcohols 17, 18, 25, and 26, respectively (Scheme 3). The propargylic derivatives 2, 10, 17, 19, 23, 25, and 27 were correlated, and their (5'R) configuration was determined on the basis of NOEs of the anhydro nucleoside 19; similarly, correlation of 3, 11, 18, 20, 24, 26, and 28, and NOE's of 20 evidenced their (5'S)-configuration.

Full text of DOI:10.1002/1522-2675(20000705)83:7<1331::AID-HLCA1331>3.0.CO;2-Z

Helvetica Chimica Acta ± Vol. 83 (2000)
1331
Oligonucleosides with a Nucleobase-Including Backbone
Part 2
Synthesis and Structure Determination of Adenosine-Derived Monomers
by Hiroki Gunji and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich
The synthesis and structure determination of adenosine-derived monomeric building blocks for new
oligonucleosides are described. Addition of Me3Si-acetylide to the aldehyde derived from the known partially
protected adenosine 1 led to the epimeric propargylic alcohols 2 and 3, which were oxidised to the same ketone
4, while silylation and deprotection led to 7 and 9 (Scheme 1). Introduction of an I substituent at C(8) of the
propargylic silyl ethers 10 and 11 was not satisfactory. The protected adenosine 12 was, therefore, transformed in
high yield into the 8-chloro derivative 13 by deprotonation and treatment with PhSO2Cl; the iodide 15 was
obtained in a similar way (Scheme 2). The 8-Cl and the 8-I derivatives 13 and 15 were transformed into the
propargylic alcohols 17, 18, 25, and 26, respectively (Scheme 3). The propargylic derivatives 2, 10, 17, 19, 23, 25,
and 27 were correlated, and their (5'R) configuration was determined on the basis of NOEs of the anhydro
nucleoside 19; similarly, correlation of 3, 11, 18, 20, 24, 26, and 28, and NOEꢀs of 20 evidenced their (5'S)-
configuration.
Introduction. ± In the preceding paper [1], we have described the design of a new
class of oligonucleotide analogues, and the synthesis of uridine-derived monomers and
dimers. We now report the synthesis of the analogous adenosine derivatives by addition
of Me3Si-acetylide to the aldehyde derived from N6-benzoyl-2',3'-O-isopropylidene-
adenosine [2], leading to a mixture of diastereoisomeric propargyl alcohols, the
introduction of a halo substituent at C(8) as it is required for the projected cross-
coupling, and the determination of the configuration of these products.
Results and Discussion. ± The known partially protected adenosine 1 [2] was
oxidised by the Pfitzner-Moffatt method [3][4], and the resulting labile aldehyde was
directly treated with Me3Si-ethynylmagnesium bromide in THF at 08 to yield ca. 40 ±
45% of a 1:1 mixture of the epimeric propargylic alcohols (Scheme 1). These were
readily separated by flash chromatography (FC) to afford 2 and 3, each in ca. 20% yield
from 1. Dess-Martin oxidation [5] transformed both alcohols into the same ketone 4,
confirming that 2 and 3 are epimeric at C(5').
Deprotection of 2 and 3 required mild conditions. Treatment of 2 with 1n aqueous
HCl at 258 with 50% aqueous Cl2CHCOOH at 608, or with 50% AcOH at 408, not only
cleaved the 1,3-dioxolane ring, but also caused dehydration, leading to the enyne 5. The
(Z)-configuration of 5 is indicated by the upfield shift of HÀC(5') at 4.71 ppm
(4.80 ppm is a typical value for such (Z)-enynol ethers, whereas the corresponding (E)-
enynol ethers resonate at 5.2 ± 5.4 ppm [6][7]). Milder conditions (5 mol-% of
camphorsulfonic acid in MeOH at 258 or in 75% AcOH at 258) did not affect 2.

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Helvetica Chimica Acta ± Vol. 83 (2000)
Scheme 1
a) N,N'-Dicyclohexylcarbodiimide (DCC), Cl2CHCOOH, DMSO; Me3SiÀCꢀCMgBr, THF; 2 (21%) and 3
(20%). b) Dess-Martin periodinane, CH2Cl2; 94%. c) Cl2CHCOOH/H2O 1:1; 80%. d) 80% aq. HCOOH; 6
(74%), 8 (64%). e) 25% aq. NH4OH, MeOH; 7 (86%), 9 (96%). f) Et3SiCl, imidazole, DMF; 10 (84%), 11
(58%).
Deisopropylidenation of 2 without dehydration was, however, accomplished with 80%
HCOOH at room temperature for 8 h, to yield 74% of the triol 6. The fully deprotected
propargylic alcohol 7 was prepared in 86% by hydrolysis of 6 with aqueous NH4OH. In
the same way, we obtained the epimer 9 via 8 in an overall yield of 61% from 3.
Exploratory experiments to introduce an I substituent at C(8), required for cross-
coupling of the monomer, were performed with the propargylic triethylsilyl ether 10
that was readily available in 84% from 2. Similarly, silylation of 3 afforded 11 (58%).
Unfortunately, yields of the attempted iodination of 10 were not satisfactory (cf.
below), so that we introduced the halogen substituent before the alkynyl group.
8-Chloroadenosine derivatives have been prepared by several methods in yields of
10 ± 63% with HCl and m-chloroperbenzoic acid (MCPBA) [8], N-chlorosuccinimide
(NCS) [9][10], NCS and MCPBA [11], t-butyl hypochlorite [12], or Bu4NICl4 [13].

Helvetica Chimica Acta ± Vol. 83 (2000)
1333
Recently, excellent yields were obtained by lithiation (lithium diisopropylamide
(LDA)) followed by chlorination with C2Cl6 [14]. As a 2-chloroimidazole derivative
had been prepared by deprotonation of N-tritylimidazole with LDA followed by
treatment with TsCl [15], we have independently studied the analogous chlorination of
12, readily available in high yields by silylation of 1 (Scheme 2), but substituting TsCl
with PhSO2Cl, to avoid competitive deprotonation of the reagent. Regioselective
lithiation of 12 with LDA at À788 for 3 h in THF [16], followed by treatment with
PhSO2Cl gave the 8-Cl derivative 13 in 97%1). Formation of the chloride was
confirmed by its mass spectrum, the peaks at m/z 560 and 562 appearing in a 3 :1 ratio.
Treating the anion resulting from 12 with I2 [17] afforded the 8-I derivative 15 in an
excellent yield. Desilylation of 13 and 15 with Bu4NF ´ 3H2O (TBAF) in THF gave
quantitatively the halo alcohols 14 and 16, respectively.
Scheme 2
a) Et3SiCl, imidazole, DMF; 97%. b) LDA, THF, then PhSO2Cl; 97%. c) LDA, THF, then I2; 91%. e) TBAF ´
3H2O, THF; 14 (94%), 16 (100%).
To transform the chloro alcohol 14 into the propargylic alcohols 17 and 18
(Scheme 3), we proceeded similarly as described for the synthesis of 2 and 3. Pfitzner-
Moffatt oxidation of 14, followed by addition of Me3Si-ethynylmagnesium bromide in
THF at 08 and chromatographic separation of the products gave 17 (16%) and 18
(17%). Their treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in toluene at
508 led to the anhydronucleosides 19 and 20, respectively, while NaH, as originally used
for the synthesis of an 8,5'-anhydroadenosine [18] from 8-bromo-2',3'-O-isopropylide-
neadenosine, led to degradation (cf. [19]), presumably by initiating cleavage of the
C(5')-ethynyl bond.
1
)
PhSO2Cl is cheaper and less toxic than C2Cl6, and may well prove the reagent of choice for this chlorination.

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Helvetica Chimica Acta ± Vol. 83 (2000)
Scheme 3
a) DCC, Cl2CHCOOH, DMSO; Me3SiÀCꢀCMgBr, THF; 17 (16%), 17/18 (9%), and 18 (17%). b) DBU,
toluene; 19 (76%); 20 (67%). c) Et3SiCl, imidazole, DMF; 21 (72%); 22 (73%); 27 (10% from 16); 28 (8% from
16). d) N-Phenylthiourea, toluene; 23 (98%); 24 (82%). e) DCC, Cl2CHCOOH, DMSO; Me3SiÀCꢀCMgBr,
THF, then I2; 25 (19%) and 26 (20%). f) Thiourea, toluene; 10 (26%) and 23 (61%); 11 (38%) and 24 (53%).

Helvetica Chimica Acta ± Vol. 83 (2000)
1335
Molecular modeling2) confirmed the expected rigidity of the azadioxa[4.2.1]nonane
skeleton of 19 and 20. The furanose ring of 19 and 20 adopts a EO conformation as
evidenced by J(1',2') ˆ J(3',4') ˆ 0 Hz (cf. Table 1 in Exper. Part). The configuration at
C(5') was determined by NOE experiments. The propargylic HÀC(5') of 20 resonates
as a doublet at 5.20 ppm (J(4',5') ˆ 2.3 Hz). Its irradiation led to a NOE of 7.8% for
HÀC(3') at 5.08 ppm, and of 15% for HÀC(4') at 4.73 ppm (cf. [19]), evidencing the
(5'S)-configuration of 20 and, hence, of 18. Irradiation of the propargylic HÀC(5') of
19 resonating as a doublet (J(4',5') ˆ 0.8 Hz) at 4.95 ppm led only to a NOE (14%) for
HÀC(4') at 4.76 ppm, evidencing the (5'R)-configuration of 19 and 17.
To correlate the configuration of 17 and 18 with that of 10 and 11 (respectively 2
and 3), we prepared the triethylsilyl ethers 21 and 22 under standard conditions.
However, attempts to dechlorinate these derivatives (Bu3SnH/AIBN) failed. We
therefore planned to prepare the iodo derivatives 27 and 28, and to correlate these with
the chlorides 21 and 22, on the one hand, and with the dehalo compounds 10 and 11, on
the other hand. Towards this goal, we transformed the chlorides 17 and 18 into the
thiones 23 and 24, respectively, by silylation to 21 and 22 followed by treatment with N-
phenylthiourea in toluene at 6083). The d(C(8)) values of 23 (165.8 ppm) and 24
(169.9 ppm) evidence the preponderance of the thiourea tautomer (cf. [23][24]).
The iodo-propargylic alcohols 25 and 26 were prepared from 16 by oxidation to the
corresponding aldehyde, followed by addition of Me3Si-ethynylmagnesium bromide
(Scheme 3). The I-substituent at C(8) was exchanged with MgBr during the Grignard
reaction, and the crude product had to be treated with I2 to obtain the desired iodides
25 and 26; FC yielded each one in ca. 20%4). Addition of H2O to the crude Grignard
product gave the de-iodinated alcohols 2 and 3.
Initially, we attempted to prepare the 8,5'-anhydro nucleosides 19 and 20 from the
iodides 25 and 26. Treating these iodides with DBU under conditions that had proven
effective for the cyclisation of the chloro alcohols 17 and 18 led only to N-
debenzoylation. No cyclisation products were observed, indicating that I is too bulky
for an effective nucleophilic attack of the alkoxide.
We therefore transformed the iodo alcohols 25 and 26 into the corresponding 8-
thiocarbonyl compounds. The alcohol 25 was protected by triethylsilylation, and the
resulting 27 was treated with thiourea [21][22] at 608 in toluene to give a de-iodinated
product and the thiourea 23 in 26 and 61% yield, respectively. The de-iodinated product
was identified with 10 by comparison with the authentic sample derived from the
propargylic alcohol 2 (Scheme 1). The thiourea 23 was identical with an authentic
sample derived from 17 via 21 for which the (R)-configuration at C(5') had been
deduced, thus also establishing the (5'R)-configuration of 10.
2
)
)
Macromodel V. 6.0 (AMBER* force field, gas phase) [20].
3
Thiourea in EtOH has been used for the analogous transformation of 8-bromoadenosine derivatives
[21][22]. We substituted toluene for EtOH to avoid desilylation; N-phenylthiourea proved more reactive
than thiourea.
As mentioned above, we have also attempted to iodinate 10. Deprotonating 10 with LDA at À788 in THF
led rapidly to blackening. Addition of I2 followed by standard workup and chromatography yielded 15%
only of slightly impure iodo derivative 27, reflecting the sensitivity of the acetylene 10 to strongly basic
conditions.
4
)

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Helvetica Chimica Acta ± Vol. 83 (2000)
Similarly, we prepared the epimeric thiourea 24 (53%) from the epimeric alcohol 26
via the iodo-silyl ether 28; again, the transformation was accompanied by partial de-
iodination, leading in 38% yield to the silyl ether 11, establishing the (5'S)-
configuration.
The J(1',2') values of the secondary alcohols 2, 3, 17, and 18 (cf. Table 1 in Exper.
Part), and of the primary alcohols 1, 14, and 16 (cf. Table 2 in Exper. Part) are sensibly
larger (4.5 ± 5.5 Hz) than the J(1',2') values of the corresponding silyl ethers 10 ± 13, 15,
21 ± 24, 27, and 28 (2.0 ± 3.0 Hz, Tables 1 and 2). This difference correlates with
differences between the J(3',4') values of the alcohols that are small (ꢁ1.5 Hz) and the
J(3',4') values of the silyl ethers that are larger (1.5 ± 4.0 Hz), expressing that the
alcohols prefer the (S)-conformation and the silyl ethers a ca. 1:1 (N)/(S) equilibrium.
The J(4',5') values of the alcohols 1 ± 3, 14, and 16 ± 18 are small (1.5 ± 2.5 Hz),
indicating a synclinal arrangement of HÀC(4') and HÀC(5') of the allyl alcohols, and
of HÀC(4') and both HÀC(5') of the adenosines. The strong downfield shift of the OH
signal in CDCl3 (5.57 ± 5.75 ppm for the primary alcohols 1, 14, and 16; 6.06 and
6.21 ppm for the l-talo-propargyl alcohols 3 and 18, 6.91 and 6.86 ppm for the d-allo-
propargyl alcohols 2 and 17) evidences the intramolecular O(5')H ´´´ N(3) H-bond,
which leads to antiperiplanar HÀC(4') and C(5') À O(5') bonds. The d(HOÀC(5'))
values show that propargylic OH groups are more highly acidic than HOÀC(5') of
adenosine and, thus, better H-bond donors, as mentioned before [25]. Such intra-
molecular H-bonds are well-documented (see, e.g., [26 ± 31]). The nine-membered ring
formed by the H-bond is rigid [26][27][32], leading to characteristic J(5',OH) values of
0 ± 1.5 Hz for the d-allo-propargyl alcohols 2 and 17, and of 10.5 ± 11.0 Hz for the l-talo-
propargyl alcohols 3 and 18. In agreement with the rigid conformation, the J(5'pro-S,OH)
values of the adenosines 1, 14, and 16 are small (1.5 ± 2.0 Hz) and the J(5'pro-R,OH)
values are large (11.0 ± 11.5 Hz). In 2 and 17, the OÀH bond is antiperiplanar to the
Me3Si À CꢀC substituent and in 3 and 18 synclinal; an anisotropy effect of the
acetyleno group is responsible for the shielding of HOÀC(5') of 3 and 18 (Dd ꢂ
0.7 ppm). The J(4',5') value increases from 3.7 ± 4.3 Hz for the 8-unsubstituted silyl
ethers 10 ± 12 to 6.0 ± 6.5 Hz for the 8-halogenated silylated ribosides 13 and 15, and to
7.5 ± 8.0 Hz for the 8-halogenated propargylic silyl ethers 21 ± 23, 27, and 15, indicating a
preferred antiperiplanar orientation of HÀC(4') and HÀC(5') in the 8-halogenated
derivatives due to steric interaction with the bulkier nucleobase.
The orientation of the nucleobase has a strong influence on the chemical shift of
HÀC(1') and HÀC(2'). 8-Unsubstituted adenosines prefer the anti-conformation,
whereas 8-substituted derivatives prefer the syn-conformation, as evidenced by a
downfield shift of the HÀC(2') signal [19][32 ± 36]. The syn-conformation is also
preferred by the alcohols 1 ± 3, 14, and 16 ± 18 on account of the intramolecular H-bond
(see also [26][27][29][32]) that directs X À C(8) close to HÀC(1'). Indeed, the
HÀC(1') signal moves downfield with increasing polarity of the C(8)-substituent (H:
5.94 ± 6.02, I: 6.08, Cl: 6.14 ± 6.21 ppm), whereas HÀC(2') is only weakly influenced (H:
5.15 ± 5.25, I/Cl: 5.32 ppm). The 5',8-anhydrides 19 and 20 adopt an anti-conformation
and show the expected upfield shift for HÀC(2'), which resonates at 4.80 ± 4.81 ppm.
The downfield shift of HÀC(1') appearing at 6.45 ± 6.49 ppm is due to the vicinity of
N(3). The 8-unsubstituted silyl ethers 10 ± 12 should prefer an anti-conformation, and
the 8-halogenated silyl ethers 13, 15, 21 ± 24, 27, and 28 a syn-conformation. Indeed,

Helvetica Chimica Acta ± Vol. 83 (2000)
1337
HÀC(2') of 13, 15, 21 ± 24, 27, and 28 appears at lower field (5.60 ± 5.90 ppm) than
HÀC(2') of 10 ± 12 (5.20 ± 5.26 ppm), evidencing the syn-conformation.
De-isopropylidenation shifts the equilibrium strongly to the (S)-conformer as
indicated by the J(1',2') values (7.2 for 8 in (D6)acetone, 7.9 for 9 in CD3OD, 8.4 for 6 in
(D6)acetone, and 8.6 for 7 in (D6)DMSO), and increases the ring pucker (sum of
J(1',2') and J(3',4') varies between 9.1 for 7 and 9.9 for 9) [37].
We thank Dr. B. Bernet for checking the experimental part and F. Hoffmann-La Roche AG, Basel, for
generous support.
Experimental Part
General. Solvents were distilled before use: THF from Na/benzophenone, CH2Cl2 from CaH2. TLC: Merck
silica gel 60F-254 plates; detection by heating with anisaldehyde soln. (5.0 ml of anisaldehyde, 6.7 ml of conc.
H2SO4, 2.0 ml of AcOH, 180 ml of EtOH). Flash chromatography (FC): silica gel Fluka 60 (0.04 ± 0.063 mm).
M.p.: uncorrected. Optical rotations: 1-dm cell at 258 and 589 nm. UV Spectra: 10-mm cell at 258. IR Spectra:
KBr or 2% CHCl3 soln. 1H (300 MHz, if not indicated otherwise) and 13C-NMR (75 MHz, if not indicated
otherwise): chemical shifts d in ppm and coupling constants J in Hz. FAB-MS: 3-nitrobenzyl alcohol, unless
indicated otherwise.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine
(2) and N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-a-l-talo-hept-6-ynofuranosyl]-
adenine (3). At 158, a soln. of 1 (4.32 g, 10.51 mmol) and DCC (6.50 g, 31.50 mmol) in dry DMSO (24.0 ml)
was treated dropwise with Cl2CHCOOH (0.43 ml, 5.21 mmol), stirred for 10 min, warmed to 258, stirred for
90 min, and filtered. The residue was washed with small amounts of DMSO, and the combined filtrates were
washed with hexane (4 Â 150 ml). The DMSO layer was diluted with CHCl3 (650 ml), washed with H2O (2 Â
200 ml), dried (Na2SO4), and evaporated. This crude aldehyde was processed as described below.
At 08, a soln. of EtMgBr (32.0 mmol) in THF (52 ml) was treated dropwise with trimethylsilylacetylene
(4.5 ml, 31.8 mmol), stirred for 10 min, warmed to 258, stirred for 30 min, cooled to 08, and treated with a soln. of
the crude aldehyde in dry THF (129 ml). After stirring for 3 h, the mixture was treated with sat. aq. NH4Cl soln.
(150 ml) and H2O (30 ml). The layers were separated, and the aq. layer was extracted with AcOEt (2 Â 80 ml).
The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC (420 g of silica gel;
CHCl3/AcOEt 1:1) gave 2 (1.099 g, 21%) and 3 (1.044 g, 20%).
Data of 2: Yellow solid. Rf (CHCl3/AcOEt 1:1) 0.45. M.p. 1198. [a]2D5 ˆ À45.4 (c ˆ 1.00, CHCl3). UV
(CHCl3): 278.0 (17000). IR (CHCl3): 3402w, 3202w, 3008m, 2180w, 1712m, 1611s, 1590s, 1505m, 1480m, 1457s,
1419m, 1385m, 1360m, 1332m, 1296m, 1252s, 1155m, 1111s, 1089s, 1046m, 1029w, 1003w, 971w, 957w, 894w, 849s.
1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.20 (s, Me3Si); 1.41, 1.67 (2s, Me2C); 7.47 ± 7.65 (m, 3
arom. H); 7.96 ± 8.05 (m, 2 arom. H); 9.12 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.4 (s, CˆO); 152.2 (d,
C(2)); 150.4 (s, C(6)); 150.2 (s, C(4)); 142.5 (d, C(8)); 133.4 (s); 133.0 (d); 128.9 (2d); 127.9 (2d); 124.3 (s, C(5));
114.3 (s, Me2C); 101.3 (s, C(6')); 94.7 (d, C(1')); 92.2 (s, C(7')); 87.7 (d, C(4')); 82.5 (d, C(2')); 80.8 (d, C(3')); 63.6
‡
(d, C(5')); 27.7, 25.7 (2q, Me2C); À0.2 (q, Me3Si). FAB-MS: 508 ([M ‡ 1] ). Anal. calc. for C25H29N5O5Si ´ H2O
(525.64): C 57.13, H 5.94, N 13.32; found: C 56.83, H 5.74, N 13.01.
Data of 3: Yellow solid. Rf (CHCl3/AcOEt 1:1) 0.36. M.p. 117 ± 1188 (acetone/hexane). [a]2D5 ˆ ‡20.2 (c ˆ
1.10, CHCl3). UV (CHCl3): 278.0 (16000). IR (CHCl3): 3403w, 3269w, 3008m, 2175w, 1710m, 1612s, 1588s,
1506m, 1480m, 1457s, 1419m, 1385m, 1360m, 1330m, 1257s, 1156m, 1119s, 1087s, 1049m, 1030w, 1017w, 928w,
847s, 643w, 563w, 509w. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.08 (s, Me3Si); 1.37, 1.63 (2s,
Me2C); 7.55 ± 7.64 (m, 3 arom. H); 7.96 ± 8.05 (m, 2 arom. H); 9.17 (br. s, NH). 13C-NMR (75 MHz, CDCl3):
164.6 (s, CˆO); 152.4 (d, C(2)); 150.6 (s, C(6)); 150.1 (s, C(4)); 142.5 (d, C(8)); 133.4 (s); 132.9 (d); 128.9 (2d);
127.9 (2d); 124.1 (s, C(5)); 114.5 (s, Me2C); 102.8 (s, C(6')); 94.0 (d, C(1')); 90.7 (s, C(7')); 87.7 (d, C(4')); 83.1 (d,
‡
C(2')); 81.8 (d, C(3')); 63.5 (d, C(5')); 27.5, 25.3 (2q, Me2C); À0.2 (q, Me3Si). FAB-MS: 508 ([M ‡ 1] ).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-ribo-hept-6-ynos-5-ulofuranosyl]-
adenine (4). At 258, a soln. of 2 (24.4 mg, 48.1 mmol) in dry CH2Cl2 (0.98 ml) was treated with Dess-Martin
periodinane [5] (30.0 mg, 70.7 mmol), stirred for 1.5 h, diluted with CH2Cl2 (ca. 0.5 ml), washed with sat. aq.
NaHCO3 soln./sat. aq. Na2S2O3 soln. 1:7 (1.0 ml), and extracted with CH2Cl2 (0.3 ml). The combined org. layers
were dried (Na2SO4) and evaporated. FC (0.8 g of silica gel; CHCl3/AcOEt 5 :4) gave 4 (22.9 mg, 94%). Yellow

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Helvetica Chimica Acta ± Vol. 83 (2000)
1
Table 1. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for the Propargyl Derivatives
2 ± 4, 10, 11, 17 ± 24, 27, and 28 in CDCl3 Solution
2
3
17
18
8.80
19
20
HÀC(2)
HÀC(8)
HÀC(1')
HÀC(2')
HÀC(3')
HÀC(4')
HÀC(5')
HOÀC(5)
J(1',2')
8.75
8.07
5.94
5.15
5.20
4.57
4.73
6.91
5.0
8.78
8.13
6.02
5.19
5.01
4.54
4.63
6.06
4.5
8.71
±
8.67
±
8.77
±
±
6.14
5.20
5.17
4.54
4.73
6.86
5.0
6.21
5.25
5.02
4.56
4.64
6.21
5.0
6.45
4.80
5.26
4.76
4.95
±
6.49
4.81
5.08
4.73
5.20
±
0
0
J(2',3')
J(3',4')
6.0
< 0.5
5.8
1.4
5.0
< 0.5
6.0
1.5
5.5
0
5.5
0
J(4',5')
J(5',OH)
1.5
1.5
2.2
2.0
0
2.5
0.8
±
2.3
±
10.5
10
8.85
8.23
6.25
5.20
5.05
4.45
4.60
3.0
11.0
21
8.77
4
11
22
23
24
27
28
HÀC(2)
HÀC(8)
HÀC(1')
HÀC(2')
HÀC(3')
HÀC(4')
HÀC(5')
J(1',2')
8.72
8.18
6.33
5.58
5.81
4.79
±
8.87
8.45
6.27
5.20
4.92
4.49
4.57
2.8
8.80
±
8.41
±
8.45
±
8.73
±
8.76
±
±
6.24
5.85
5.24
4.22
4.43
2.0
6.25
5.73
5.26
4.26
4.46
2.5
6.81
5.60
5.21
4.22
4.63
2.5
6.81
5.59
5.19
4.21
4.68
2.5
6.13
5.90
5.26
4.22
4.41
2.0
6.15
5.77
5.29
4.22
4.41
2.0
< 0.5
J(2',3')
J(3',4')
J(4',5')
6.5
1.0
±
6.0
2.0
4.3
6.0
1.5
4.0
6.3
2.8
7.5
6.5
3.5
8.0
6.5
4.0
8.0
6.5
4.0
7.8
6.0
2.8
8.0
6.5
3.0
8.0
solid. Rf (CHCl3/AcOEt 5 :4) 0.44. 1H-NMR (200 MHz, CDCl3): see Table 1; additionally, 0.12 (s, Me3Si); 1.45,
1.67 (2s, Me2C); 7.53 ± 7.69 (m, 3 arom. H); 7.98 ± 8.10 (m, 2 arom. H); 8.98 (br. s, NH).
N6-Benzoyl-9-[(Z)-5,6,7-trideoxy-7-C-(trimethylsilyl)-b-d-erythro-hept-4-en-6-ynofuranosyl]adenine (5).
At 258, a soln. of 2 (36.3 mg, 71.5 mmol) in 50% aq. Cl2CHCOOH (1.8 ml) was stirred at 608 for 2 h, diluted
with CHCl3 (10 ml), washed with H2O (5 ml) and brine (3 ml), dried (Na2SO4), and evaporated. FC (1.5 g of
silica gel; CHCl3/acetone 1:1) gave 5 (25.2 mg, 80%). White solid. Rf (CHCl3/acetone 1:1) 0.42. 1H-NMR
(200 MHz, CDCl3): 0.22 (s, Me3Si); 4.39 (d, J ˆ 2.0, HOÀC(2')); 4.61 (dd, J ˆ 5.5, 2.0, HÀC(2')); 4.71 (d, J ˆ 1.0,
HÀC(5')); 4.97 (br. dd, J ˆ 5.9, 5.5, HÀC(3')); 5.93 (s, HÀC(1')); 6.02 (d, J ˆ 5.9, HOÀC(3')); 7.38 ± 7.87 (m, 3
arom. H); 7.97 ± 8.04 (m, 2 arom. H); 8.39 (s, HÀC(8)); 8.53 (s, HÀC(2)); 8.54 (br. s, NH).
N6-Benzoyl-9-[6,7-dideoxy-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine (6). At 258, a soln. of
2 (32.7 mg, 64.4 mmol) in 80% aq. HCOOH (1.6 ml) was stirred for 8 h. The mixture was evaporated and co-
evaporated several times with PhMe. FC (1.5 g of silica gel; CHCl3/acetone 2 :3) gave 6 (22.3 mg, 74%). White
solid. Rf (CHCl3/acetone 2 :3) 0.50. M.p. 1848. [a]2D5 ˆ À102.4 (c ˆ 1.01, acetone). UV (MeOH): 276.0 (16000),
230.0 (12000). IR (KBr): 3322m, 2957w, 2177w, 1704m, 1612s, 1585s, 1514m, 1486m, 1455s, 1411m, 1332m, 1252s,
1121m, 1073s, 955m, 845s, 798m, 760m. 1H-NMR (300 MHz, (D6)acetone): 0.20 (s, Me3Si); 4.23 (dd, J ˆ 3.1, 1.3,
HÀC(4')); 4.49 (br. d, addn. of D2O ! dd, J ˆ 5.5, 1.3, HÀC(3')); 4.56 (br. s, exchanged with D2O, OH); 4.69 (t,
J ˆ 3.1, HÀC(5')); 4.92 ± 5.03 (m, addn. of D2O ! 4.90, dd, J ˆ 8.4, 5.5, HÀC(2')); 5.32 (br. s, exchanged with
D2O, OH); 6.10 (d, J ˆ 8.4, HÀC(1')); 6.31 (d, J ˆ 3.1, exchanged with D2O, HOÀC(5')); 7.51 ± 7.68 (m, 3 arom.
H); 8.11 ± 8.19 (m, 2 arom. H); 8.49 (s, HÀC(8)); 8.60 (s, HÀC(2)); 10.14 (br. s, exchanged with D2O, NH) .
13C-NMR (75 MHz, (D6)acetone): 166.2 (s, CˆO); 152.4 (d, C(2)); 152.2 (s, C(6)); 151.4 (s, C(4)); 144.3 (d,
C(8)); 134.8 (s); 133.3 (d); 129.5 (2d); 129.4 (2d); 125.9 (s, C(5)); 104.7 (s, C(6')); 90.80 (s, C(7')); 90.74 (d,
‡
C(1')); 90.2 (d, C(4')); 74.9 (d, C(2')); 72.0 (d, C(3')); 64.2 (d, C(5')); 0.0 (q, Me3Si). FAB-MS: 468 ([M ‡ 1] ).
Anal. calc. for C22H25N5O5Si (467.56): C 56.52, H 5.39, N 14.98; found: C 56.46, H 5.63, N 14.91.

Helvetica Chimica Acta ± Vol. 83 (2000)
1339
9-(6,7-Dideoxy-b-d-allo-hept-6-ynofuranosyl)adenine (7). At 258, a soln. of 6 (22.3 mg, 48.1 mmol) in
MeOH (0.56 ml) was treated with 25% aq. NH4OH (0.56 ml), stirred at 608 for 2 h, evaporated, suspended in
MeOH (2.0 ml), treated with SiO2 (77.1 mg), evaporated, and loaded on a silica-gel column. FC (1.3 g of silica
gel; CHCl3/MeOH 3 :1) gave 7 (12.0 mg, 86%). White solid. Rf(CHCl3/MeOH 3 :1) 0.48. M.p. 2088 (dec.;
MeOH). [a]2D5 ˆ À108.1 (c ˆ 1.03, DMSO). UV (DMSO): 266.0 (13000). 1H-NMR (300 MHz, (D6)DMSO):
3.40 (d, J ˆ 2.2, HÀC(7')); 3.98 (dd, J ˆ 4.5, 0.5, HÀC(4')); 4.23 (br. s, addn. of D2O ! dd, J ˆ 5.9, 0.5,
HÀC(3')); 4.49 (br. s, addn. of D2O ! dd, J ˆ 4.5, 2.2, HÀC(5')); 4.60 ± 4.72 (m, addn. of D2O ! 4.63, dd, J ˆ
8.6, 5.9, HÀC(2')); 5.35 (br. d, J ˆ 4.5, exchanged with D2O, OH); 5.46 (br. d, J ˆ 6.3, exchanged with D2O, OH) ;
5.91 (d, J ˆ 8.6, HÀC(1')); 6.57 (br. d, J ˆ 3.8, exchanged with D2O, OH); 7.40 (br. s, exchanged with D2O, NH2);
8.14 (s, HÀC(8)); 8.30 (s, HÀC(2)). 13C-NMR (75 MHz, (D6)DMSO): 156.1 (s, C(6)); 152.2 (d, C(2)); 148.9 (s,
C(4)); 139.8 (d, C(8)); 119.3 (s, C(5)); 88.2 (d, C(1')); 87.6 (d, C(4')); 82.7 (d, C(7')); 76.0 (s, C(6')); 73.1 (d,
‡
C(2')); 70.3 (d, C(3')); 61.7 (d, C(5')). FAB-MS: 292 ([M ‡ 1] ). Anal. calc. for C12H13N5O4 (291.27): C 49.48,
H 4.50, N 24.04; found: C 49.68, H 4.77, N 23.84.
N6-Benzoyl-9-[6,7-dideoxy-7-C-(trimethylsilyl)-a-l-talo-hept-6-ynofuranosyl]adenine (8). At 258, a soln. of
3 (88.1 mg, 0.174 mmol) in 80% aq. HCOOH (4.4 ml) was stirred for 10 h, evaporated, and co-evaporated
several times with PhMe. FC (5.0 g of silica gel; CHCl3/MeOH 6 :1) gave 8 (55.2 mg, 64%). White solid. Rf
(CHCl3/MeOH 7:1) 0.48. M.p. 1438. [a]2D5 ‡ 2.2 (c ˆ 1.01, MeOH). UV (MeOH): 277.0 (16000); 231.0 (12000).
IR (KBr): 3331m, 2957w, 2173w, 1703m, 1614s, 1584s, 1515m, 1458s, 1411m, 1331m, 1299m, 1250s, 1090m,
1071m, 966w, 894w, 845s, 797m, 760m. 1H-NMR (300 MHz, (D6)acetone ‡ D2O): 0.11 (s, Me3Si); 4.20 (dd, J ˆ
3.8, 2.5, HÀC(4')); 4.41 (dd, J ˆ 5.8, 2.5, HÀC(3')); 4.67 (d, J ˆ 3.8, HÀC(5')); 4.83 (dd, J ˆ 7.2, 5.8, HÀC(2'));
6.16 (d, J ˆ 7.2, HÀC(1')); 7.49 ± 7.69 (m, 3 arom. H); 8.09 ± 8.19 (m, 2 arom. H); 8.51 (s, HÀC(8)); 8.62 (s,
HÀC(2)). 13C-NMR (75 MHz, (D6)acetone): 152.5 (d, C(2)); 152.2 (s, C(6)); 151.3 (s, C(4)); 144.0 (d, C(8));
134.9 (s); 133.3 (d); 129.4 (2d); 129.3 (2d); 125.8 (s, C(5)); 106.3 (s, C(6')); 90.3 (d, C(1')); 89.4 (s, C(7')); 89.3 (d,
‡
C(4')); 74.8 (d, C(2')); 72.7 (d, C(3')); 63.7 (d, C(5')); 0.0 (q, Me3Si). FAB-MS: 468 ([M ‡ 1] ).
9-(6,7-Dideoxy-a-l-talo-hept-6-ynofuranosyl)adenine (9). At 258, a soln. of 8 (52.2 mg, 0.112 mmol) in
MeOH (1.3 ml) was treated with 25% aq. NH4OH (1.3 ml), stirred at 608 for 2 h, evaporated, suspended in
MeOH (6.0 ml), treated with SiO2 (223.6 mg), evaporated, and charged on a silica gel column. FC (3.0 g of silica
gel; CHCl3/MeOH 3 :1) gave 9 (31.3 mg, 96%). White solid. Rf(CHCl3/EtOH 7 :4) 0.46. M.p. 1668 (dec.; DMSO/
CH2Cl2). [a]2D5 ˆ ‡0.1 (c ˆ 1.00, MeOH). UV (MeOH): 257.0 (9800), 218.0 (7000). 1H-NMR (300 MHz,
CD3OD): 2.83 (d, J ˆ 2.9, HÀC(7')); 4.19 (dd, J ˆ 4.3, 2.0, HÀC(4')); 4.32 (dd, J ˆ 6.1, 2.0, HÀC(3')); 4.61 (dd,
J ˆ 4.3, 2.9, HÀC(5')); 4.79 (dd, J ˆ 7.9, 6.1, HÀC(2')); 6.01 (d, J ˆ 7.9, HÀC(1')); 8.19 (s, HÀC(8)); 8.31 (s,
HÀC(2)). 13C-NMR (75 MHz, CD3OD): 157.6 (s, C(6)); 153.6 (d, C(2)); 150.1 (s, C(4)); 142.0 (d, C(8)); 121.0 (s,
C(5)); 90.9 (d, C(1')); 89.9 (d, C(4')); 83.5 (d, C(7')); 75.2 (d, C(2')); 74.7 (s, C(6')); 72.9 (d, C(3')); 63.6 (d,
‡
C(5')). FAB-MS: 292 ([M ‡ 1] ).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-yno-
furanosyl]adenine (10). At 258, a soln. of 2 (101.9 mg, 0.201 mmol) and imidazole (44.7 mg, 0.657 mmol) in dry
DMF (3.1 ml) was treated dropwise with Et3SiCl (100 ml, 0.596 mmol), stirred for 6 h, and poured into ice-water
(ca. 10 ml). After extraction with hexane/AcOEt 1:1 (3 Â 2.0 ml), the combined org. layers were washed with
brine, dried (Na2SO4), and evaporated. FC (3.5 g of silica gel; hexane/AcOEt 1:1) gave 10 (104.8 mg, 84%).
Yellow solid. Rf (hexane/AcOEt 1:2) 0.42. M.p. 728. [a]2D5 ˆ À82.8 (c ˆ 1.04, CHCl3). UV (CHCl3): 279.0
(20000). IR (CHCl3): 3408w, 3008s, 2961s, 2913m, 2887m, 2173w, 1708s, 1612s, 1584s, 1519s, 1478s, 1455s, 1421s,
1385m, 1353m, 1330m, 1295m, 1248s, 1157m, 1089s, 1048s, 1030m, 967m, 928s, 848s, 818s. 1H-NMR (300 MHz,
CDCl3): see Table 1; additionally, 0.14 (s, Me3Si); 0.56 ± 0.73 (m, (MeCH2)3Si); 0.92 (t, J ˆ 8.6, (MeCH2)3Si);
1.43, 1.65 (2s, Me2C); 7.47 ± 7.63 (m, 3 arom. H); 7.97 ± 8.06 (m, 2 arom. H); 9.10 (br. s, NH). 13C-NMR (75 MHz,
CDCl3): 164.6 (s, CˆO); 153.0 (d, C(2)); 151.3 (s, C(6)); 149.5 (s, C(4)); 141.5 (d, C(8)); 133.8 (s); 132.7 (d);
128.9 (2d); 127.9 (2d); 123.2 (s, C(5)); 114.2 (s, Me2C); 102.6 (s, C(6')); 92.7 (s, C(7')); 92.0 (d, C(1')); 89.2 (d,
C(4')); 84.7 (d, C(2')); 81.4 (d, C(3')); 63.9 (d, C(5')); 27.3, 25.4 (2q, Me2C); 6.7 (q, (MeCH2)3Si); 4.8 (t,
‡
(MeCH2)3Si); À0.5 (q, Me3Si). FAB-MS: 622 ([M ‡ 1] ). Anal. calc. for C31H43N5O5Si2 (621.88): C 59.87,
H 6.97, N 11.26; found: C 59.76, H 7.20, N 11.14.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-hept-6-yno-
furanosyl]adenine (11). At 258, a soln. of 3 (61.8 mg, 0.122 mmol) and imidazole (26.5 mg, 0.389 mmol) in dry
DMF (1.9 ml) was treated dropwise with Et3SiCl (61 ml, 0.363 mmol), stirred for 5 h, poured into ice-water
(ca. 5 ml), and extracted with hexane/AcOEt 1:1 (3 Â 3.0 ml). The combined org. layers were washed with
brine, dried (Na2SO4), and evaporated. FC (3.0 g of silica gel; hexane/AcOEt 4 :5) gave 11 (43.7 mg, 58%).
Yellow solid. Rf(hexane/AcOEt 1:2) 0.52. M.p. 66 ± 678. [a]2D5 ˆ ‡7.6 (c ˆ 1.02, CHCl3). UV (CHCl3): 279.0
(19000). IR (CHCl3): 3408w, 3008m, 2960m, 2913w, 2888w, 2175w, 1708s, 1612s, 1584s, 1517w, 1455s, 1405w,

1340
Helvetica Chimica Acta ± Vol. 83 (2000)
1385m, 1351m, 1328m, 1293m, 1252s, 1157m, 1130m, 1093s, 1004m, 978w, 930w, 846s. 1H-NMR (300 MHz,
CDCl3): see Table 1; additionally, 0.17 (s, Me3Si); 0.48 ± 0.64 (m, (MeCH2)3Si); 0.86 (t, J ˆ 9.0, (MeCH2)3Si);
1.42, 1.65 (2s, Me2C); 7.47 ± 7.64 (m, 3 arom. H); 7.97 ± 8.06 (m, 2 arom. H); 9.12 (br. s, NH). 13C-NMR (75 MHz,
CDCl3): 164.6 (s, CˆO); 153.0 (d, C(2)); 151.1 (s, C(6)); 149.2 (s, C(4)); 141.8 (d, C(8)); 133.9 (s); 132.7 (d);
128.9 (2d); 127.8 (2d); 123.1 (s, C(5)); 114.2 (s, Me2C); 103.3 (s, C(6')); 92.9 (d, C(1')); 92.0 (s, C(7')); 89.3 (d,
C(4')); 85.3 (d, C(2')); 82.0 (d, C(3')); 64.0 (d, C(5')); 27.2, 25.4 (2q, Me2C); 6.6 (q, (MeCH2)3Si); 4.5 (t,
‡
(MeCH2)3Si); À0.4 (q, Me3Si). FAB-MS: 622 ([M ‡ 1] ). Anal. calc. for C31H43N5O5Si2 ´ 0.5H2O (630.89):
C 59.12, H 7.03, N 11.10; found: C 58.98, H 6.91, N 11.00.
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (12). At 258,
a soln. of 1 (9.10 g,
22.1 mmol) and imidazole (3.89 g, 57.1 mmol) in dry DMF (270 ml) was treated dropwise with Et3SiCl
(5.6 ml, 33.4 mmol), stirred for 10 h, poured into ice-water (ca. 600 ml), and extracted with Et2O/AcOEt 1:1
(4 Â 400 ml). The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC (400 g of
silica gel; CHCl3/AcOEt 5 :3) gave 12 (11.27 g, 97%). White solid. Rf(CHCl3/AcOEt 2 :1) 0.41. M.p. 56 ± 588.
[a]2D5 ˆ À52.1 (c ˆ 1.07, CHCl3). UV (CHCl3): 276.0 (15000). IR (CHCl3): 3407w, 3008s, 2959s, 2913m, 2878w,
1708s, 1612s, 1585s, 1504m, 1479s, 1456s, 1403m, 1385m, 1353m, 1326m, 1292m, 1248s, 1156m, 1134s, 1090s,
1003m, 969w, 928w, 858w, 818w. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 0.54 (q, J ˆ 8.8,
(MeCH2)3Si); 0.88 (t, J ˆ 8.8, (MeCH2)3Si); 1.40, 1.64 (2s, Me2C); 7.47 ± 7.63 (m, 3 arom. H); 7.98 ± 8.05 (m, 2
arom. H); 9.09 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.9 (s, CˆO); 153.1 (d, C(2)); 151.5 (s, C(6)); 149.8
(s, C(4)); 141.9 (d, C(8)); 134.1 (s); 133.0 (d); 129.1 (2d); 128.1 (2d); 123.5 (s, C(5)); 114.4 (s, Me2C); 92.0 (d,
C(1')); 87.7 (d, C(4')); 85.3 (d, C(2')); 81.7 (d, C(3')); 63.3 (t, C(5')); 27.3, 25.4 (2q, Me2C); 6.7 (q, (MeCH2)3Si);
‡
4.1 (t, (MeCH2)3Si). FAB-MS: 526 ([M ‡ 1] ). Anal. calc. for C26H35N5O5Si (525.68): C 59.41, H 6.71, N 13.32;
found: C 59.41, H 6.73, N 13.14.
N6-Benzoyl-8-chloro-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (13). A soln. of (i-Pr)2NH (1.0 ml,
7.14 mmol) in dry THF (23 ml) was cooled to 08, treated dropwise with 1.6m BuLi in hexane (4.6 ml, 7.14 mmol),
stirred for 30 min, cooled to À788, treated dropwise with a soln. of 12 (1.551 g, 2.95 mmol) in dry THF (23 ml),
stirred for 3 h, treated with PhSO2Cl (1.1 ml, 8.63 mmol), stirred for 1 h, and without cooling, treated with sat.
aq. NH4Cl soln. (20 ml) and H2O (20 ml). The layers were separated, and the aq. layer was extracted with
AcOEt (2 Â 30 ml). The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC
(70 g of silica gel; hexane/AcOEt 5 :4) gave 13 (1.603 g, 97%). Light yellow solid. Rf(hexane/AcOEt 3 :2) 0.30.
M.p. 568. [a]2D5 ˆ À15.7 (c ˆ 1.00, CHCl3). UV (CHCl3): 280.0 (19000). IR (CHCl3): 3406w, 3008s, 2976s, 2913m,
2878m, 1711m, 1611s, 1589s, 1514m, 1478s, 1450s, 1420m, 1385m, 1322m, 1248s, 1161m, 1087s, 1046s, 972w, 928s,
875m, 850m, 818s. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 0.49 (q, J ˆ 8.0, (MeCH2)3Si); 0.87 (t,
J ˆ 8.0, (MeCH2)3Si); 1.41, 1.62 (2s, Me2C); 7.47 ± 7.65 (m, 3 arom. H); 7.95 ± 8.05 (m, 2 arom. H); 8.92 (br. s,
NH). 13C-NMR (75 MHz, CDCl3): 164.4 (s, CˆO); 152.7 (d, C(2)); 151.8 (s, C(6)); 148.5 (s, C(4)); 141.8 (s,
1
Table 2. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for Adenosines 1 and 12 ± 16
1
12
8.83
13
8.77
14
8.77
15
8.73
16
8.71
HÀC(2)
HÀC(8)
HÀC(1')
HÀC(2')
HÀC(3')
HÀC(4')
HaÀC(5')
HbÀC(5')
HOÀC(5')
J(1',2')
8.79
8.07
5.94
5.24
5.12
4.56
3.80
3.99
5.75
4.8
8.27
6.25
5.26
4.95
4.45
3.75
3.87
±
2.7
6.0
2.5
4.0
±
±
±
±
6.25
5.76
5.16
4.31
3.66
3.76
±
2.3
6.5
3.7
6.0
6.0
6.17
5.32
5.11
4.55
3.82
4.00
5.57
5.0
5.8
1.5
2.0
2.0
6.14
5.81
5.18
4.32
3.65
3.76
±
2.3
6.3
3.5
6.5
6.5
6.08
5.32
5.10
4.55
3.81
3.98
5.75
5.5
5.5
0.8
2.0
1.5
J(2',3')
J(3',4')
J(4',5a')
6.0
< 1.0
1.8
J(4',5b')
J(5a',5b')
J(5a',OH)
J(5b',OH)
1.5
3.7
13.0
11.0
1.5
11.0
±
±
10.5
±
±
13.1
11.0
2.0
10.5
±
±
13.0
11.5
1.5

Helvetica Chimica Acta ± Vol. 83 (2000)
1341
C(8)); 133.5 (s); 133.0 (d); 128.9 (2d); 127.8 (2d); 121.8 (s, C(5)); 114.4 (s, Me2C); 90.6 (d, C(1')); 88.2 (d, C(4'));
82.9 (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: 560 (100, [M ‡ 1] ), 562 (44). Anal. calc. for C26H34ClN5O5Si (560.12): C 55.75, H 6.12, N 12.50;
found: C 55.72, H 6.07, N 12.31.
N6-Benzoyl-8-chloro-2',3'-O-isopropylideneadenosine (14). A soln. of 13 (4.10 g, 7.30 mmol) in dry THF
(123 ml) was treated with a 1.0m soln. of TBAF in THF (11.0 ml, 11.0 mmol), stirred for 15 h, and evaporated.
FC (200 g of silica gel; CHCl3/acetone 3 :1) gave 14 (3.772 g, 100%). Light yellow solid. Rf(CHCl3/acetone 3 :1)
0.48. M.p. 1738. [a]2D5 ˆ À88.5 (c ˆ 1.06, CHCl3). UV (CHCl3): 275.0 (15000). IR (CHCl3): 3401w, 3007m, 2948w,
2874w, 1713s, 1610s, 1592s, 1481s, 1450s, 1423m, 1385m, 1375m, 1356m, 1322s, 1300m, 1248s, 1168w, 1155w, 1112s,
1085s, 1030w, 1000w, 968w, 952w, 928w, 894w, 851m. 1H-NMR (200 MHz, CDCl3): see Table 2; additionally, 1.40,
1.68 (2s, Me2C); 7.50 ± 7.67 (m, 3 arom. H); 7.96 ± 8.05 (m, 2 arom. H); 9.00 (br s, exchanged with D2O, NH) .
13C-NMR (75 MHz, CDCl3): 164.3 (s, CˆO); 152.4 (d, C(2)); 151.3 (s, C(6)); 149.1 (s, C(8), C(4)); 133.3 (s);
133.1 (d); 129.0 (2d); 127.9 (2d); 122.3 (s, C(5)); 114.3 (s, Me2C); 92.8 (d, C(1')); 85.9 (d, C(4')); 82.5 (d, C(2'));
‡
81.5 (d, C(3')); 63.2 (t, C(5')); 27.7, 25.4 (2q, Me2C). FAB-MS: 274 (100), 276 (39), 446 (24, [M ‡ 1] ), 448 (9).
Anal. calc. for C20H20ClN5O5 (445.86): C 53.88, H 4.52, N 15.71; found: C 53.92, H 4.72, N 15.76.
N6-Benzoyl-8-iodo-2',3'-O-isopropylidene-5'-O-(triethylsilyl)adenosine (15). A soln. of (i-Pr)2NH (1.0 ml,
7.14 mmol) in dry THF (23 ml) was cooled to 08, treated dropwise with 1.6m BuLi in hexane (4.6 ml, 7.14 mmol),
stirred for 30 min, cooled to À788, treated dropwise with a soln. of 12 (1.564 g, 2.98 mmol) in dry THF (23 ml),
stirred for 3 h, treated with I2 (1.19 g, 4.69 mmol), stirred for 1 h, and without cooling, treated with sat. aq. NH4Cl
soln. (30 ml) and sat. aq. Na2S2O3 soln. (15 ml). The layers were separated, and the aq. layer was extracted with
AcOEt (2 Â 20 ml). The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC
(85 g of silica gel; hexane/AcOEt 5 :4) gave 15 (1.76 g, 91%). Yellow solid. Rf(hexane/AcOEt 5 :4) 0.39. M.p.
78 ± 808. [a]2D5 ˆ À16.1 (c ˆ 1.00, CHCl3). UV (CHCl3): 290.0 (22000), 245.0 (15000). IR (CHCl3): 3405w, 3007m,
2957m, 2913w, 2877m, 1710s, 1608s, 1588s, 1504m, 1486m, 1461s, 1422s, 1384m, 1376m, 1355m, 1315m, 1270s,
1
1284m, 1160m, 1088s, 1005m, 972w, 872m. H-NMR (300 MHz, CDCl3): see Table 2; additionally, 0.49 (q, J ˆ
8.3, (MeCH2)3Si); 0.87 (t, J ˆ 8.3, (MeCH2)3Si); 1.41, 1.63 (2s, Me2C); 7.47 ± 7.65 (m, 3 arom. H); 7.95 ± 8.04 (m, 2
arom. H); 8.98 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.4 (s, CˆO); 152.4 (d, C(2)); 151.8 (s, C(6)); 148.3
(s, C(4)); 133.6 (s); 133.0 (d); 128.9 (2d); 127.8 (2d); 125.5 (s, C(5)); 114.2 (s, Me2C); 104.8 (s, C(8)); 93.8 (d,
C(1')); 88.3 (d, C(4')); 82.9 (d, C(2')); 82.1 (d, C(3')); 62.8 (t, C(5')); 27.3, 25.5 (2q, Me2C); 6.6 (q, (MeCH2)3Si);
‡
4.2 (t, (MeCH2)3Si). FAB-MS: 652 ([M ‡ 1] ). Anal. calc. for C26H34IN5O5Si (651.58): C 47.93, H 5.26, N 10.75;
found: C 47.93, H 5.24, N 10.61.
N6-Benzoyl-8-iodo-2',3'-O-isopropylideneadenosine (16). At 258, a soln. of 15 (3.17 g, 4.87 mmol) in dry
THF (95 ml) was treated with 1.0m soln. of TBAF ´ 3H2O in THF (7.3 ml, 7.31 mmol), and stirred. After 10 h, the
mixture was concentrated. FC (150 g of silica gel; CHCl3/acetone 3 :1) gave 16 (2.45 g, 94%). White solid.
Rf(CHCl3/acetone 3 :1) 0.52. M.p. 2108 (dec.). [a]2D5 ˆ À75.9 (c ˆ 0.82, CHCl3). UV (CHCl3): 291.0 (22000);
245.0 (15000). IR (CHCl3): 3401w, 3008m, 2938m, 2872w, 1713s, 1607s, 1504w, 1480m, 1462m, 1449m, 1423s,
1385m, 1375m, 1356m, 1316m, 1269m, 1252m, 1166w, 1112m, 1086s, 1030w, 995w, 968w, 951w, 891w, 851m.
1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 1.40, 1.72 (2s, Me2C); 7.48 ± 7.66 (m, 3 arom. H); 7.95 ±
8.04 (m, 2 arom. H); 9.01 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.3 (s, CˆO); 152.1 (d, C(2)); 151.3 (s,
C(6)); 148.9 (s, C(4)); 133.4 (s); 133.0 (d); 129.0 (2d); 127.9 (2d); 126.2 (s, C(5)); 114.3 (s, Me2C); 103.8 (s, C(8));
95.8 (d, C(1')); 85.7 (d, C(4')); 82.3 (d, C(2')); 81.6 (d, C(3')); 63.3 (t, C(5')); 27.8, 25.5 (2q, Me2C). FAB-MS:
‡
537.8 ( [M ‡ 1] ). Anal. calc. for C20H20IN5O5 (537.31): C 44.71, H 3.75, N 13.03; found: C 44.97, H 4.01, N 12.99.
N6-Benzoyl-8-chloro-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-
adenine (17) and N6-Benzoyl-8-chloro-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-a-l-talo-hept-6-
ynofuranosyl]adenine (18). At 158, a soln. of 14 (3.772 g, 8.45 mmol) and DCC (5.10 g, 24.7 mmol) in dry DMSO
(21 ml) was treated dropwise with Cl2CHCOOH (0.35 ml, 4.24 mmol), stirred for 10 min, warmed to 258, stirred
for 90 min, and filtered. The residue was washed with small amounts of DMSO, and the combined filtrates were
washed with hexane (4Â 100 ml). The DMSO layer was diluted with CHCl3 (550 ml), washed with H2O (2Â
200 ml), dried (Na2SO4), and evaporated affording the crude aldehyde. At 08, a soln. of EtMgBr (25.0 mmol) in
THF (38 ml) was treated dropwise with (trimethylsilyl)acetylene (3.6 ml, 25.4 mmol), stirred for 10 min, warmed
to 258, stirred for 30 min, cooled to 08, and treated with a soln. of the crude aldehyde in dry THF (113 ml). After
3 h, the mixture was treated with sat. aq. NH4Cl soln. (75 ml) and H2O (25 ml). The layers were separated, and the
aq. layer was extracted with AcOEt (2Â 50 ml). The combined org. layers were washed with brine, dried
(Na2SO4), and evaporated. FC (400 g of silica gel; C6H6/Et2O/AcOEt 5 :1:2) gave 18 (794 mg, 17%), 17/18
(428.5 mg, 9%), and 17 (726 mg, 16%).

1342
Helvetica Chimica Acta ± Vol. 83 (2000)
Data of 17: Yellow solid. Rf(CHCl3/AcOEt 7:2) 0.53. M.p. 1088. [a]2D5 ˆ À137.9 (c ˆ 1.01, CHCl3). UV
(CHCl3): 280.0 (18000). IR (CHCl3): 3403w, 3203w, 3008m, 2963w, 2181w, 1714m, 1610s, 1594s, 1481s, 1450s,
1423w, 1385m, 1358m, 1343w, 1324s, 1302m, 1252s, 1168w, 1155w, 1112s, 1089s, 1046w, 1028w, 1001w, 972w, 894w,
849s. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.21 (s, Me3Si); 1.41, 1.68 (2s, Me2C); 7.46 ± 7.65 (m,
3 arom. H); 7.94 ± 8.04 (m, 2 arom. H); 8.99 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.3 (s, CˆO); 152.2 (d,
C(2)); 150.9 (s, C(6)); 149.3 (s, C(4)); 141.1 (s, C(8)); 133.2 (s); 133.1 (d); 129.0 (2d); 127.9 (2d); 122.3 (s, C(5));
114.3 (s, Me2C); 101.1 (s, C(6')); 93.2 (d, C(1')); 92.2 (s, C(7')); 87.3 (d, C(4')); 81.9 (d, C(2')); 80.6 (d, C(3')); 63.5
‡
(d, C(5')); 27.7, 25.4 (2q, Me2C); À0.2 (q, Me3Si). FAB-MS: 274 (100), 276 (33), 542 (22, [M ‡ 1] ), 544 (8).
Data of 18: Yellow solid. Rf(CHCl3/AcOEt 3 :2) 0.55. M.p. 1738 (CHCl3/hexane). [a]2D5 ˆ ‡0.1 (c ˆ 1.05,
CHCl3). UV (CHCl3): 280.0 (17000). IR (CHCl3): 3402w, 3252w, 3008m, 2962w, 2175w, 1713m, 1610s, 1593s,
1481s, 1450s, 1422m, 1385m, 1358m, 1324s, 1251s, 1168w, 1155m, 1118s, 1088s, 1030w, 973w, 928w, 848s. 1H-NMR
(300 MHz, CDCl3): see Table 1; additionally, 0.11 (s, Me3Si); 1.38, 1.66 (2s, Me2C); 7.50 ± 7.67 (m, 3 arom. H);
7.97 ± 8.04 (m, 2 arom. H); 8.88 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.4 (s, CˆO); 152.3 (d, C(2)); 151.3
(s, C(6)); 149.1 (s, C(4)); 141.1 (s, C(8)); 133.2 (s); 133.1 (d); 129.0 (2d); 127.9 (2d); 122.3 (s, C(5)); 114.6 (s,
Me2C); 102.8 (s, C(6')); 92.8 (d, C(1')); 90.4 (s, C(7')); 87.2 (d, C(4')); 82.3 (d, C(2')); 81.7 (d, C(3')); 63.6 (d,
‡
C(5')); 27.6, 25.4 (2q, Me2C); À0.2 (q, Me3Si). FAB-MS: 274 (100), 276 (35), 542 (52, [M ‡ 1] ), 544 (23).
5',8-Anhydro-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofur-
anosyl]-8-hydroxyadenine (19). At 258, a soln. of 17 (41.6 mg, 76.7 mmol) in PhMe (1.2 ml) was treated with
DBU (17 ml, 0.113 mmol), stirred at 508 for 90 min, diluted with AcOEt (3 ml), washed with sat. aq. NaHCO3
soln. (0.5 ml) and brine (0.5 ml), dried (Na2SO4), and evaporated. FC (12 g of silica gel; CHCl3/AcOEt 9 :4)
gave 19 (29.3 mg, 76%). Yellow solid. Rf (CHCl3/AcOEt 5 :2) 0.50. M.p. 142 ± 1438. [a]2D5 ˆ À57.0 (c ˆ 1.01,
CHCl3). UV (CHCl3): 283.0 (17000), 263.0 (12000). IR (CHCl3): 3408w, 3007m, 1708m, 1616s, 1590m, 1546m,
1500m, 1482m, 1462m, 1429m, 1402m, 1386w, 1378w, 1356m, 1318s, 1253s, 1164m, 1120w, 1094w, 1058s, 1027w,
974w, 956w, 923w, 854s, 818w. 1H-NMR (300 MHz, CDCl3): 0.23 (s, Me3Si); 1.39, 1.57 (2s, Me2C); 4.76 (d, J ˆ 0.8,
irrad. at 4.95 ! NOE of 14%, HÀC(4')); 4.80 (d, J ˆ 5.5, HÀC(2')); 4.95 (d, J ˆ 0.8, HÀC(5')); 5.26 (d, J ˆ 5.5,
HÀC(3')); 6.45 (s, HÀC(1')); 7.43 ± 7.61 (m, 3 arom. H); 7.93 ± 8.02 (m, 2 arom. H); 8.67 (s, HÀC(2)); 8.95 (br. s,
NH). 13C-NMR (75 MHz, CDCl3): 164.5 (s, CˆO); 153.8 (s, C(6)); 152.2 (d, C(2)); 150.5 (s, C(4)); 148.1 (s,
C(8)); 133.5 (s); 132.7 (d); 128.8 (2d); 127.9 (2d); 119.3 (s, C(5)); 113.5 (s, Me2C); 97.8 (s, C(6')); 95.2 (s, C(7'));
89.2 (d, C(1')); 87.0 (d, C(4')); 85.5 (d, C(2')); 80.6 (d, C(3')); 76.2 (d, C(5')); 26.1, 24.7 (2q, Me2C); À0.5 (q,
‡
Me3Si). FAB-MS: 506 ([M ‡ 1] ).
5',8-Anhydro-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-a-l-talo-hept-6-ynofur-
anosyl]-8-hydroxyadenine (20). At 258, a soln. of 18 (147.9 mg, 0.273 mmol) in PhMe (4.4 ml) was treated with
DBU (61 ml, 0.410 mmol), stirred at 508 for 90 min, diluted with AcOEt (12 ml), washed with sat. aq. NaHCO3
soln. (5.0 ml) and brine (3.0 ml), dried (Na2SO4), and evaporated. FC (17 g of silica gel; CHCl3/AcOEt 1 :1)
gave 20 (92.6 mg, 67%). Yellow solid. Rf(CHCl3/AcOEt 1:1) 0.52. M.p. 1178. [a]2D5 ˆ ‡210.0 (c ˆ 1.01, CHCl3).
UV (CHCl3): 283.0 (17000), 248.0 (12000). IR (CHCl3): 3407w, 3006m, 1708s, 1618s, 1590s, 1549m, 1500m, 1483s,
1463s, 1431s, 1402s, 1386m, 1377m, 1358m, 1321m, 1296w, 1252s, 1163m, 1119w, 1103w, 1056s, 1027w, 1004w,
1
977w, 957w, 853s, 832w. H-NMR (300 MHz, CDCl3): À0.03 (s, Me3Si); 1.36, 1.56 (2s, Me2C); 4.73 (d, J ˆ 2.3,
irrad. at 5.20 ! NOE of 15%, HÀC(4')); 4.81 (d, J ˆ 5.5, HÀC(2')); 5.08 (d, J ˆ 5.5, irrad. at 5.20 ! NOE of
7.8%, HÀC(3')); 5.20 (d, J ˆ 2.3, HÀC(5')); 6.49 (s, HÀC(1')); 7.45 ± 7.63 (m, 3 arom. H); 7.93 ± 8.02 (m, 2 arom.
H); 8.77 (s, HÀC(2)); 8.86 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 164.3 (s, CˆO); 153.6 (s, C(6)); 152.4 (d,
C(2)); 150.2 (s, C(4)); 147.9 (s, C(8)); 133.7 (s); 132.7 (d); 128.9 (2d); 127.7 (2d); 119.3 (s, C(5)); 113.7 (s, Me2C);
99.2 (s, C(6')); 94.6 (s, C(7')); 87.9 (d, C(1')); 86.8 (d, C(4')); 85.3 (d, C(2')); 81.5 (d, C(3')); 74.3 (d, C(5')); 26.1,
‡
24.7 (2q, Me2C); À0.7 (q, Me3Si). FAB-MS: 506 ([M ‡ 1] ). Anal. calc. for C25H27N5O5Si ´ H2O (523.62):
C 57.35, H 5.58, N 13.37; found: C 57.56, H 5.44, N 13.37.
N6-Benzoyl-8-chloro-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-b-d-allo-
hept-6-ynofuranosyl]adenine (21). At 258, a soln. of 17 (56.2 mg, 0.104 mmol) and imidazole (30.0 mg,
0.441 mmol) in dry DMF (1.7 ml) was treated dropwise with Et3SiCl (52 ml, 0.31 mmol), stirred for 12 h, poured
into ice-water (ca. 10 ml), and extracted with hexane/AcOEt 1:1 (3 Â 3.0 ml). The combined org. layers were
washed with brine, dried (Na2SO4), and evaporated. FC (2.0 g of silica gel; hexane/AcOEt 3 :2) gave 21
(48.9 mg, 72%). Light orange solid. Rf (hexane/AcOEt 3 :2) 0.48. M.p. 748. [a]2D5 ˆ ‡5.4 (c ˆ 1.01, CHCl3). UV
(CHCl3): 280.0 (21000). IR (CHCl3): 3406w, 3007m, 2959m, 2913w, 2877w, 2174w, 1711m, 1612s, 1589s, 1508w,
1480m, 1450s, 1415w, 1384m, 1376m, 1356w, 1323m, 1248s, 1160m, 1089s, 1004m, 892w, 847s, 818w, 595w, 568w,
514w. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.09 (s, Me3Si); 0.52 ± 0.75 (m, (MeCH2)3Si); 0.95
(t, J ˆ 8.5, (MeCH2)3Si); 1.41, 1.61 (2s, Me2C); 7.49 ± 7.66 (m, 3 arom. H); 7.96 ± 8.05 (m, 2 arom. H); 8.90 (br. s,
NH). 13C-NMR (75 MHz, CDCl3): 164.3 (s, CˆO); 152.7 (d, C(2)); 151.7 (s, C(6)); 148.5 (s, C(4)); 142.1 (s,

Helvetica Chimica Acta ± Vol. 83 (2000)
1343
C(8)); 133.5 (s); 133.0 (d); 129.0 (2d); 127.8 (2d); 121.7 (s, C(5)); 114.2 (s, Me2C); 103.6 (s, C(6')); 91.0 (s, C(7'));
91.0 (d, C(1')); 89.8 (d, C(4')); 82.4 (2d, C(2'), C(3')); 63.0 (d, C(5')); 27.1, 25.4 (2q, Me2C); 6.7 (q, (MeCH2)3Si);
‡
4.8 (t, (MeCH2)3Si); À0.4 (q, Me3Si). FAB-MS: 656 (100, M ), 657 (48), 658 (46), 659 (19). Anal. calc. for
C31H42ClN5O5Si2 (656.33): C 56.73, H 6.45, N 10.67; found: C 56.64, H 6.34, N 10.63.
N6-Benzoyl-8-chloro-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-
hept-6-ynofuranosyl]adenine (22). At 258, a soln. of 18 (213.1 mg, 0.393 mmol) and imidazole (80.7 mg,
1.19 mmol) in dry DMF (6.4 ml) was treated dropwise with Et3SiCl (0.20 ml, 1.19 mmol), stirred for 16 h,
poured into ice-water (ca. 15 ml), and extracted with hexane/AcOEt 1:1 (3 Â 7.0 ml). The combined org. layers
were washed with brine, dried (Na2SO4), and evaporated. FC (10 g of silica gel; hexane/AcOEt 3 :2) gave 22
(187.8 mg, 73%). Yellow solid. Rf(hexane/AcOEt 3 :2) 0.32. M.p. 708. [a]2D5 ˆ À57.9 (c ˆ 1.05, CHCl3). UV
(CHCl3): 283.0 (21000). IR (CHCl3): 3405w, 2958w, 2877w, 2359m, 2341w, 1711s, 1611s, 1589s, 1480m, 1450s,
1413m, 1384m, 1376m, 1321m, 1252m, 1159m, 1090m, 1040w, 1003m, 892m, 846m. 1H-NMR (300 MHz, CDCl3):
see Table 1; additionally, 0.19 (s, Me3Si); 0.28 ± 0.48 (m, (MeCH2)3Si); 0.76 (t, J ˆ 7.9, (MeCH2)3Si); 1.41, 1.62 (2s,
Me2C); 7.48 ± 7.66 (m, 3 arom. H); 7.95 ± 8.04 (m, 2 arom. H); 8.91 (br. s, NH). 13C-NMR (75 MHz, CDCl3):
164.6 (s, CˆO); 153.1 (d, C(2)); 152.1 (s, C(6)); 148.8 (s, C(4)); 142.1 (s, C(8)); 133.7 (s); 133.2 (d); 129.2 (2d);
128.1 (2d); 121.9 (s, C(5)); 114.6 (s, Me2C); 103.2 (s, C(6')); 91.8 (s, C(7')); 90.8 (2d, C(1'), C(4')); 82.8 (d, C(2'));
82.2 (d, C(3')); 64.4 (d, C(5')); 27.2, 25.5 (2q, Me2C); 6.4 (q, (MeCH2)3Si); 4.4 (t, (MeCH2)3Si); À0.3 (q, Me3Si).
‡
FAB-MS: 656 (100, M ), 657 (42), 658 (45), 659 (18). Anal. calc. for C31H42ClN5O5Si2 (656.33): C 56.73, H 6.45,
N 10.67; found: C 56.72, H 6.48, N 10.53.
6-(Benzoylamino)-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-
ynofuranosyl]-7,9-dihydropurine-8-thione (23). At 258, a soln. of 21 (48.9 mg, 74.5 mmol) in PhMe (2.4 ml) was
treated with N-phenylthiourea (31.0 mg, 0.204 mmol), stirred at 608 for 25 min, cooled to 258, diluted with
AcOEt (10 ml), washed with sat. aq. NaHCO3 soln. (3 ml) and brine (3 ml), dried (Na2SO4), and evaporated.
FC (2.0 g of silica gel; hexane/AcOEt 7:4) gave 23 (47.9 mg, 98%). Light yellow solid. Rf(hexane/AcOEt 7:4)
0.46. M.p. 848. [a]2D5 ˆ À22.4 (c ˆ 1.01, CHCl3). UV (CHCl3): 259.0 (24000), 342.0 (22000). IR (CHCl3): 3351w,
2993w, 2958m, 2913w, 2877w, 2173w, 1695m, 1623w, 1590m, 1506s, 1490s, 1461s, 1445s, 1412s, 1360m, 1266s, 1251s,
1157m, 1091s, 1002m, 873m, 846m. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.09 (s, Me3Si); 0.60 ±
0.78 (m, (MeCH2)3Si); 0.99 (t, J ˆ 8.5, (MeCH2)3Si); 1.37, 1.61 (2s, Me2C); 7.49 ± 7.69 (m, 3 arom. H); 7.91 ± 7.99
(m, 2 arom. H); 9.17 (br. s, BzNH); 10.97 (br. s, HÀN(7)). 13C-NMR (75 MHz, CDCl3): 169.9 (s, CˆS); 165.8 (s,
CˆO); 152.6 (s, C(6)); 151.3 (d, C(2)); 138.2 (s, C(4)); 133.8 (d); 131.5 (s); 129.2 (2d); 127.7 (2d); 114.2 (s,
Me2C); 111.2 (s, C(5)); 104.8 (s, C(6')); 90.4 (s, C(7')); 89.6, 89.3 (2d, C(1'), C(4')); 82.4, 82.3 (2d, C(2'), C(3'));
63.4 (d, C(5')); 27.3, 25.6 (2q, Me2C); 6.8 (q, (MeCH2)3Si); 4.9 (t, (MeCH2)3Si); À0.2 (q, Me3Si). FAB-MS: 654
‡
([M ‡ 1] ). Anal. calc. for C31H43N5O5SSi2 (653.95): C 56.94, H 6.63, N 10.71; found: C 57.07, H 6.53, N 10.66.
6-(Benzoylamino)-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-hept-6-
ynofuranosyl]-7,9-dihydropurine-8-thione (24). At 258, a soln. of 22 (40.3 mg, 61.4 mmol) in PhMe (2.0 ml) was
treated with N-phenylthiourea (22.6 mg, 0.148 mmol), stirred at 608 for 35 min, diluted with AcOEt (8 ml),
washed with sat. aq. NaHCO3 soln. (2.5 ml), and brine (2.5 ml), dried (Na2SO4), and evaporated. FC (2.0 g of
silica gel; hexane/AcOEt 4 :3) gave 24 (33.0 mg, 82%). White solid. Rf(hexane/AcOEt 2 :1) 0.48. M.p. 938.
[a]2D5 ˆ À53.5 (c ˆ 1.00, CHCl3). UV (CHCl3): 236.0 (22000), 357.0 (26000), 341.0 (23000). IR (CHCl3): 3352w,
2994w, 2958m, 2913w, 2877w, 2173w, 1696m, 1623w, 1590m, 1506s, 1490s, 1461s, 1444s, 1411s, 1385m, 1267s, 1252s,
1157m, 1083s, 1003m, 873m, 846m. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 0.19 (s, Me3Si); 0.38 ±
0.60 (m, (MeCH2)3Si); 0.83 (t, J ˆ 8.5, (MeCH2)3Si); 1.38, 1.61 (2s, Me2C); 7.51 ± 7.70 (m, 3 arom. H); 7.93 ± 8.00
(m, 2 arom. H); 8.86 (br. s, BzNH); 10.98 (br. s, HÀN(7)). 13C-NMR (75 MHz, CDCl3): 169.9 (s, CˆS); 165.8 (s,
CˆO); 152.7 (s, C(6)); 151.3 (d, C(2)); 138.2 (s, C(4)); 133.8 (d); 131.6 (s); 129.2 (2d); 127.7 (2d); 114.2 (s,
Me2C); 111.2 (s, C(5)); 103.5 (s, C(6')); 91.3 (s, C(7')); 90.1 (d, C(1')); 89.5 (d, C(4')); 82.4, 82.1 (2d, C(2'), C(3'));
64.6 (d, C(5')); 27.3, 25.7 (2q, Me2C); 6.5 (q, (MeCH2)3Si); 4.6 (t, (MeCH2)3Si); À0.2 (q, Me3Si). FAB-MS: 654
‡
([M ‡ 1] ). Anal. calc. for C31H43N5O5SSi2 (653.95): C 56.94, H 6.63, N 10.71; found: C 56.65, H 6.75, N 10.89.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-b-d-allo-hept-6-ynofuranosyl]-8-iodo-
adenine (25) and N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-7-C-(trimethylsilyl)-a-l-talo-hept-6-ynofur-
anosyl]-8-iodoadenine (26). At 158, a soln. of 16 (2.45 g, 4.56 mmol) and DCC (2.78 g, 13.47 mmol) in dry
DMSO (13.5 ml) was treated dropwise with Cl2CHCOOH (0.19 ml, 2.30 mmol), stirred for 10 min, warmed to
258, stirred for 90 min, and filtered. The residue was washed with small amounts of DMSO, and the combined
filtrates were washed with hexane (4 Â 40 ml). The DMSO layer was diluted with CHCl3 (350 ml), washed with
H2O (2 Â 100 ml), dried (Na2SO4), and evaporated, affording the crude aldehyde. At 08, a soln. of EtMgBr
(13.7 mmol) in THF (22.4 ml) was treated dropwise with (trimethylsilyl)acetylene (1.9 ml, 13.7 mmol), stirred
for 10 min, warmed to 258, stirred for 30 min, cooled to 08, and treated with a soln. of the crude aldehyde in dry

1344
Helvetica Chimica Acta ± Vol. 83 (2000)
THF (73 ml). The mixture was stirred for 3 h, treated with I2 (5.22 g, 20.6 mmol), warmed to 258, stirred for 1 h,
and treated with sat. aq. NH4Cl soln. (70 ml) and sat. aq. Na2S2O3 soln. (60 ml). The org. layer was separated,
and the aq. layer was extracted with AcOEt (2 Â 70 ml). The combined org. layers were washed with brine, dried
(Na2SO4), and evaporated. FC (250 g of silica gel; CHCl3/AcOEt 5 :2) gave crude 25 (542.7 mg, 19%), and
crude 26 (566.9 mg, 20%).
Data of 25: Yellow solid. Rf(CHCl3/AcOEt 5 :2) 0.59.
Data of 26: Yellow solid. Rf(CHCl3/AcOEt 5 :2) 0.44.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-b-d-allo-hept-6-yno-
furanosyl]-8-iodoadenine (27). At 258, a soln. of crude 25 (542.7 mg) and imidazole (192.5 mg, 2.83 mmol) in dry
DMF (17 ml) was treated dropwise with Et3SiCl (0.43 ml, 2.56 mmol), stirred for 12 h, poured into ice-water (ca.
20 ml), and extracted with Et2O/AcOEt 1:1 (4 Â 10 ml). The combined org. layers were washed with brine,
dried (Na2SO4), and evaporated. FC (23 g of silica gel; hexane/AcOEt 5 :4) gave 27 (335.5 mg, 10% from 16).
Yellow solid. Rf(hexane/AcOEt 7:4) 0.49. M.p. 888. [a]2D5 ˆ À7.2 (c ˆ 1.04, CHCl3). UV (CHCl3): 290.0 (24000),
246.0 (17000). IR (CHCl3): 3406w, 3008m, 2959m, 2877w, 2173w, 1711m, 1608s, 1588m, 1504m, 1486m, 1460m,
1423s, 1384m, 1356w, 1320m, 1269m, 1248s, 1160m, 1089s, 1004m, 846m. 1H-NMR (300 MHz, CDCl3): see
Table 1; additionally, 0.09 (s, Me3Si); 0.54 ± 0.72 (m, (MeCH2)3Si); 0.95 (t, J ˆ 8.6, (MeCH2)3Si); 1.41, 1.62 (2s,
Me2C); 7.48 ± 7.65 (m, 3 arom. H); 7.96 ± 8.04 (m, 2 arom. H); 9.05 (br. s, NH). 13C-NMR (75 MHz, CDCl3):
164.4 (s, CˆO); 152.4 (d, C(2)); 151.7 (s, C(6)); 148.3 (s, C(4)); 133.6 (s); 132.9 (d); 128.9 (2d); 127.8 (2d); 125.4
(s, C(5)); 114.0 (s, Me2C); 105.2 (s, C(8)); 103.8 (s, C(6')); 94.1 (d, C(1')); 90.8 (s, C(7')); 89.9 (d, C(4')); 82.7 (d,
C(2')); 82.4 (d, C(3')); 63.0 (d, C(5')); 27.2, 25.4 (2q, Me2C); 6.7 (q, (MeCH2)3Si); 4.8 (t, (MeCH2)3Si); À0.3 (q,
‡
Me3Si). FAB-MS: 748 ([M ‡ 1] ). Anal. calc. for C31H42IN5O5Si2 (747.78): C 49.79, H 5.66, N 9.37; found:
C 50.02, H 5.83, N 9.20.
Reaction of 27 with Thiourea. At 258, a soln. of 27 (25.0 mg, 33.4 mmol) in PhMe (1.3 ml) was treated with
thiourea (8.1 mg, 0.106 mmol), stirred at 608 for 35 min, and treated with sat. aq. NaHCO3 soln. (0.90 ml) and
sat. aq. Na2S2O3 soln. (0.30 ml). The org. layer was separated, and the aq. layer was extracted with AcOEt (2 Â
0.5 ml). The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC (1.5 g of silica
gel; hexane/AcOEt 2 :1) gave 10 (5.4 mg, 26%) and 23 (13.4 mg, 61%).
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-(triethylsilyl)-7-C-(trimethylsilyl)-a-l-talo-hept-6-yno-
furanosyl]-8-iodoadenine (28). At 258, a soln. of crude 26 (566.9 mg) and imidazole (196.7 mg, 2.89 mmol) in dry
DMF (17 ml) was treated dropwise with Et3SiCl (0.45 ml, 2.68 mmol), stirred for 11 h, poured into ice-water (ca.
30 ml), and extracted with Et2O/AcOEt 1:1 (3 Â 10 ml). The combined org. layers were washed with brine,
dried (Na2SO4), and evaporated. FC (25 g of silica gel; hexane/AcOEt 5 :4) gave 28 (260.3 mg, 8% from 16).
Light yellow solid. Rf(hexane/AcOEt 5 :4) 0.50. M.p. 878. [a]2D5 ˆ À61.9 (c ˆ 1.00, CHCl3). UV (CHCl3): 291.0
(24000), 245.0 (17000). IR (CHCl3): 3406w, 3007m, 2959m, 2913w, 2877w, 2174w, 1711s, 1608s, 1588s, 1504w,
1486m, 1460s, 1422s, 1384m, 1315m, 1269s, 1248s, 1160m, 1089s, 1043w, 1004m, 892w, 846s. 1H-NMR (300 MHz,
CDCl3): see Table 1; additionally, 0.19 (s, Me3Si); 0.24 ± 0.42 (m, (MeCH2)3Si); 0.75 (t, J ˆ 8.6, (MeCH2)3Si);
1.41, 1.63 (2s, Me2C); 7.48 ± 7.65 (m, 3 arom. H); 7.96 ± 8.05 (m, 2 arom. H); 8.98 (br. s, NH). 13C-NMR (75 MHz,
CDCl3): 164.3 (s, CˆO); 152.5 (d, C(2)); 151.8 (s, C(6)); 148.3 (s, C(4)); 133.6 (s); 132.9 (d); 128.9 (2d); 127.8
(2d); 125.5 (s, C(5)); 114.2 (s, Me2C); 104.9 (s, C(8)); 103.0 (s, C(6')); 93.9 (d, C(1')); 91.6 (s, C(7')); 91.1 (d,
C(4')); 82.7 (d, C(2')); 82.3 (d, C(3')); 64.4 (d, C(5')); 27.2, 25.5 (2q, Me2C); 6.4 (q, (MeCH2)3Si); 4.4 (t,
‡
(MeCH2)3Si); À0.3 (q, Me3Si). FAB-MS: 748 ([M ‡ 1] ). Anal. calc. for C31H42IN5O5Si2 (747.78): C 49.79,
H 5.66, N 9.37; found: C 49.88, H 5.76, N 9.27.
Reaction of 28 with Thiourea. At 258, a soln. of 28 (31.5 mg, 42.1 mmol) in PhMe (1.6 ml) was treated with
thiourea (8.1 mg, 0.106 mmol), stirred at 608 for 35 min, and treated with sat. aq. NaHCO3 soln. (0.70 ml) and
sat. aq. Na2S2O3 soln. (0.70 ml). The org. layer was separated, and the aq. layer was extracted with AcOEt (2 Â
0.5 ml). The combined org. layers were washed with brine, dried (Na2SO4), and evaporated. FC (1.6 g of silica
gel; hexane/AcOEt 2 :1 ! 1:2) gave 11 (10.0 mg, 38%) and 24 (14.7 mg, 53%).
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Received March 30, 2000