SYNTHESIS OF DEOXY, DIDEOXY AND DIDEHYDRODIDEOXY ANALOGS OF 9-(β-D-HEXOFURANOSYL)ADENINE

Article abstract of DOI:10.1135/cccc19941408

Condensation of 1,2-di-O- acetyl-3,5,6-tri-O-benzoyl-D-glucofuranose with N⁶-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I.Partial deacetylation of I, followed by mesylation, gave 9-(3,5,6-tri-O-benzoyl-2-O-methanesulf

Full text of DOI:10.1135/cccc19941408

1408
Hrebabecky, Dockal, Holy:
SYNTHESIS OF DEOXY, DIDEOXY AND DIDEHYDRODIDEOXY ANALOGS
OF 9-(β-D-HEXOFURANOSYL)ADENINE
Hubert HREBABECKY, Jan DOCKAL and Antonin HOLY
Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic, 166 10 Prague 6, The Czech Republic
Received January 4, 1994
Accepted February 4, 1994
Condensation of 1,2-di-O-acetyl-3,5,6-tri-O-benzoyl-D-glucofuranose with N6-benzoyladenine, cata-
lyzed with tin tetrachloride, afforded nucleoside I. Partial deacetylation of I, followed by mesylation,
gave 9-(3,5,6-tri-O-benzoyl-2-O-methanesulfonyl-β-D-glucofuranosyl)adenine (III). 9-(2,5,6-Tri-O-
acetyl-3-O-methanesulfonyl-β-D-glucofuranosyl)-N6-benzoyladenine (IV) was prepared by condensation
of 1,2,5,6-tetra-O-acetyl-3-O-methanesulfonyl-D-glucofuranose with N6-benzoyladenine. Reaction of
mesyl derivative III with methanolic sodium methoxide and of mesyl derivative IV with methanolic
ammonia led to 2′,3′-anhydronucleosides V and VI which were acetylated to give the respective
9-(5,6-di-O-acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine (VII) and 9-(5,6-di-O-acetyl-2,3-an-
hydro-β-D-allofuranosyl)adenine (VIII). Epoxy derivative VII was cleaved with bromotrimethylsilane,
affording a mixture of 9-(5,6-di-O-acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine (Xa)
and 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine (XIa), epoxy derivative VIII
was cleaved analogously to give 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine
(XIIa). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-β-
D-arabino-hexofuranosyl)adenine (Xc), 9-(3-deoxy-β-D-arabino-hexofuranosyl)adenine (XIc) and
9-(3-deoxy-β-D-ribo-hexofuranosyl)adenine (XIIc). 9-(2,5,6-Tri-O-acetyl-3-bromo-3-deoxy-β-D-glucofu-
ranosyl)adenine (XIId), which was prepared by acetylation of XIIa, on reductive elimination with
Cu/Zn couple and subsequent deacetylation gave 9-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)-
adenine (XIV). 9-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)adenine (XVI) was obtained either by cata-
lytic hydrogenation of bromo derivative XIId followed by deacetylation, or by catalytic
hydrogenation of didehydro derivative XIV. The synthesized nucleosides were tested for antiviral ac-
tivity.
This communication represents a continuation of our previous studies dealing with the
synthesis of hexofuranosyl analogs1,2 of 3′-azido-2′,3′-dideoxy-, 2′,3′-dideoxy- and
2′,3′-didehydro-2′,3′-dideoxynucleosides active against HIV (see refs1,2 and references
therein). The present study concerns the synthesis of the above-mentioned analogs,
containing adenine as the nucleoside base.
As the key compounds for the synthesis of deoxy compounds derived from 9-(β-D-
hexofuranosyl)adenine we have chosen 2′,3′-anhydronucleosides, which are easily ac-
cessible from the mesyl derivatives.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1409
Condensation of 1,2-di-O-acetyl-3,5,6-tri-O-benzoyl-D-glucofuranose3 with N6-ben-
zoyladenine in acetonitrile under catalysis with tin tetrachloride afforded nucleoside I.
Its deacetylation with hydrazine hydrate in a mixture of acetic acid and pyridine4 gave
derivative II with free hydroxy group in position 2′ which was converted into mesyl
derivative III. Starting compound for the preparation of mesyl derivative IV was 5,6-di-
O-acetyl-1,2-O-isopropylidene-3-O-methanesulfonyl-D-glucofuranose5. It was aceto-
lyzed to 1,2,5,6-tetra-O-acetyl-3-O-methanesulfonyl-D-glucofuranose which was condensed
with N6-benzoyladenine to give nucleoside IV. Mesyl derivative III reacted with 0.5 M
methanolic sodium methoxide and the mesyl derivative IV with methanolic ammonia to
give 2′,3′-anhydronucleosides V and VI. Reaction of mesyl derivative IV with methanolic
sodium methoxide afforded 3′,6′-anhydronucleoside IX instead of the expected epox-
ide VI. In this case the 6′-alkoxide anion attacks intramolecularly the position 3′ of the
primarily arising epoxy derivative VI under formation of anhydronucleoside IX. This
assumption is supported by the fact that epoxy derivative VI on treatment with sodium
methoxide also affords the derivative IX.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

1410
Hrebabecky, Dockal, Holy:
Epoxy derivatives V and VI were acetylated with acetic anhydride in acetonitrile
under catalysis with 4-dimethylaminopyridine to give acetyl derivatives VII and VIII.
The anhydride was added gradually in order to prevent acetylation of the base. The
protected epoxides were cleaved with bromotrimethylsilane in the presence of boron
trifluoride etherate. It is known that reaction of hydrogen halides with 9-(2,3-anhydro-
β-D-lyxofuranosyl)adenine6,7 and 9-(2,3-anhydro-β-D-ribofuranosyl)adenine7,8 leads to
3′-halogeno derivatives. Also oxirane VIII is cleaved with the same reagents to give
3′-bromo derivative XIIa. In the case of the manno epoxide VII, this reaction leads to a
mixture of 2′-isomer Xa and 3′-isomer XIa with the latter slightly predominating.
Bromo derivatives Xa, XIa and XIIa were reduced with tributylstannane under cata-
lysis with 2,2′-azobis(2-propionitrile). The obtained deoxy compounds Xb, XIb and
XIIb were deacetylated with methanolic ammonia to the respective free deoxy deriva-
tives Xc, XIc and XIIc.
The 2′- and 3′-deoxy derivatives are easily distinguishable by 1H NMR spectroscopy.
Spectrum of 2′-deoxy derivative XIIc exhibits two multiplets of 2′-methylene protons:
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1411
one doublet of doublets at 2.23 ppm and a multiplet centered at 2.76 ppm. 3′-Deoxy
derivatives display one or two multiplets in the region 1.82 – 2.37 ppm (XIc: 2.02 –
2.30 m; XIIc: 1.82 – 1.95 m, 2.22 – 2.37 m). Spectra of the synthesized deoxynucleo-
sides are in accord with those of 2′-deoxyadenosine9, 9-(2-deoxy-β-D-threo-pento-
furanosyl)adenine10, 9-(3-deoxy-β-D-erythro-pentofuranosyl)adenine11, 9-(3-deoxy-
-β-D-threo-pentofuranosyl)adenine12 and also with spectra of pyrimidine analogs1,2.
The UV spectra of deoxy derivatives XIc and XIIc exhibit absorption maximum at
260 nm. Its position proves that the sugar component is bound in position N9 of the
adenine moiety. In the condensation of sugar 1-O-acetyl derivatives with N6-benzoyl-
adenine we did not observe any N3-isomer whose formation was described13 in the
reaction of protected ribofuranosyl bromide with adenine. Under conditions of the tin
tetrachloride-catalyzed reaction the primarily formed N3-isomer rearranges immediately
into the N9-isomer.
The 2′,3′-didehydro-2′,3′-dideoxy derivative XIII was prepared by Zn/Cu couple re-
ductive elimination14 of tri-O-acetylbromo derivative XIId, which in turn was prepared
by acetylation of bromonucleoside XIIa. Because of low stability of purine didehydro-
dideoxynucleosides and also because the reaction with 3′,5′-di-O-acetyl-2′-bromo-2′-
deoxyuridine15 is accompanied by significant cleavage of the nucleoside bond, we
performed the reaction at 0 °C, the solution of the bromo derivative being slowly added
to suspension of the Zn/Cu couple. In this way, we were able to prepare the 2′,3′-un-
saturated nucleoside XIII in 89% yield. The free nucleoside XIV was obtained by meth-
anolysis with methanolic ammonia. Hydrogenation of nucleoside XIV over Pd/C
afforded dideoxynucleoside XVI in an only 48% yield because the hydrogenation was
accompanied with significant cleavage of the nucleoside bond. Therefore, we also tried
an alternative, already described, procedure1 consisting in catalytic hydrogenation of
bromo derivative XIId. In this case, the yield of dideoxynucleoside XV was 72%. The
free nucleoside XVI was obtained from compound XV by methanolysis.
None of the synthesized compounds exhibited activity against HIV. The anhydro
derivative IX was significantly active against vaccinia virus with low cytotoxicity16.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

1412
Hrebabecky, Dockal, Holy:
EXPERIMENTAL
1
Melting points were determined on a Kofler block and are uncorrected. H NMR spectra (δ, ppm; J,
Hz) were measured on a Varian XL-200 (200 MHz) instrument in hexadeuteriodimethyl sulfoxide
with tetramethylsilane as internal standard. UV spectra were measured on a Beckman DU-65 spec-
trometer. Column chromatography was performed on silica gel (particle size 30 – 60 µm; Service
Laboratories of this Institute) and thin-layer chromatography (TLC) on Silufol UV 254 sheets (Kavalier,
Votice, The Czech Republic) in the following systems: S1, ethyl acetate–toluene (4 : 1); S2, ethyl
acetate–acetone–ethanol–water (19 : 3 : 2 : 1); S3, ethyl acetate–acetone–ethanol–water (32 : 6 : 7 : 5);
S4, ethyl acetate. The solvents were evaporated at bath temperature 30 – 60 °C/2 kPa and the com-
pounds were dried over phosphorus pentoxide at 13 Pa.
9-(2-O-Acetyl-3,5,6-tri-O-benzoyl-β-D-glucofuranosyl)-N6- benzoyladenine (I)
Finely ground N6-benzoyladenine (2.39 g, 10 mmol) was added to a solution of 1,2-di-O-acetyl-3,5,6-
tri-O-benzoyl-D-glucofuranose3 (5.76 g, 10 mmol) in acetonitrile (20 ml). The suspension formed was
mixed with tin tetrachloride (2.2 ml, 19 mmol) and the stirring was continued until the mixture be-
came homogeneous. After standing overnight at room temperature, the mixture was added dropwise
into 10% aqueous sodium hydrogen carbonate solution (300 ml). The product was taken up in ethyl
acetate (2 × 100 ml), the ethyl acetate solution was washed with 10% aqueous sodium hydrogen car-
bonate (60 ml), dried over magnesium sulfate and the solvent was evaporated. The residue was chro-
matographed on a column of silica gel (800 g) in ethyl acetate–toluene (3 : 1) to give 6.0 g (79%) of
compound I as a solid foam; RF 0.54 (S1). For C41H33N5O10 (755.7) calculated: 65.16% C, 4.40% H,
1
9.27% N; found: 64.98% C, 4.32% H, 9.11% N. H NMR spectrum: 2.17 s, 3 H (CH3CO); 4.59 dd,
1 H, J(6a′,5′) = 5.8, J(6a′,6b′) = 12.2 (H-6a′); 4.91 dd, 1 H, J(6b′,5′) = 2.2 (H-6b′); 5.06 dd, 1 H,
J(4′,3′) = 4.6, J(4′,5′) = 9.0 (H-4′); 5.87 m, 1 H (H-5′); 5.97 dd, 1 H, J(3′,2′) = 1.8 (H-3′); 6.28 dd,
1 H, J(2′,1′) = 3.1 (H-2′); 6.52 d, 1 H (H-1′); 7.38 – 8.07 m, 20 H (H-arom.); 8.60 s, 1 H (H-2); 8.79 s,
1 H (H-8); 11.26 s, 1 H (NH).
9-(3,5,6-Tri-O-benzoyl-β-D-glucofuranosyl)adenine (II)
Hydrazine hydrate (80%, 1.8 ml) was added to a solution of acetyl derivative I (7.56 g, 10 mmol) in
a mixture of acetic acid and pyridine (1 : 4, 90 ml). After standing at room temperature for 2 days,
acetone (20 ml) was added to the mixture and after 2 h the solvent was evaporated. The residue was
dissolved in ethyl acetate (250 ml) and the solution was washed successively with water (3 × 50 ml),
2% hydrochloric acid to acid reaction of the aqueous layer, water (50 ml) and 10% aqueous sodium
hydrogen carbonate (2 × 50 ml). After drying over magnesium sulfate, the solution was concentrated
and the residue was chromatographed on a column of silica gel (500 g) in ethyl acetate, yielding 5.1 g
(83%) of compound II as a solid foam; RF 0.57 (S4). For C32H27N5O8 (609.6) calculated: 63.05% C,
4.47% H, 11.49% N; found: 62.90% C, 4.70% H, 11.24% N. 1H NMR spectrum: 4.61 dd, 1 H,
J(6a′,5′) = 5.7, J(6a′,6b′) = 12.9 (H-6a′); 4.89 – 5.09 m, 3 H (H-2′, H-4′, H-6b′); 5.63 dd, 1 H,
J(3′,2′) = 1.5, J(3′,4′) = 2.5 (H-3′); 5.86 m, 1 H (H-5′); 6.12 s, 1 H (H-1′); 6.56 d, 1 H, J(OH,2′) =
4.7 (2′-OH); 7.35 – 7.94 m, 17 H (H-arom., NH2); 8.09 s, 1 H (H-2); 8.48 s, 1 H (H-8).
9-(3,5,6-Tri-O-benzoyl-2-O-methanesulfonyl-β-D-glucofuranosyl)adenine (III)
Methanesulfonyl chloride (3 ml, 39 mmol) was added dropwise under ice-cooling to a stirred solution
of nucleoside II (6.10 g, 10 mmol) in pyridine (50 ml). After standing at room temperature for 5 h,
the mixture was cooled to 0 °C, water (2 ml) was added and after standing for 15 min the solvent
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1413
was evaporated. The residue was partitioned between water (50 ml) and ethyl acetate (400 ml), the or-
ganic layer was washed with water (2 × 100 ml), dried over magnesium sulfate and concentrated.
Column chromatography of the residue on silica gel (400 g) in ethyl acetate afforded 5.30 g (77%)
of mesyl derivative III as a solid foam; RF 0.32 (S1). For C33H29N5O10S (687.7) calculated: 57.63% C,
1
4.25% H, 10.18% N, 4.66% S; found: 57.34% C, 4.40% H, 9.92% N, 4.70% S. H NMR spectrum:
3.38 s, 3 H (CH3SO2); 4.57 dd, 1 H, J(6a′,5′) = 5.5, J(6a′,6b′) = 12.5 (H-6a′); 4.90 dd, 1 H,
J(6b′,5′) = 2.4 (H-6b′); 5.07 dd, 1 H, J(4′,3′) = 4.8, J(4′,5′) = 9.1 (H-4′); 5.92 m, 1 H (H-5′); 6.03
dd, 1 H, J(3′,2′) = 2.6 (H-3′); 6.26 dd, 1 H, J(2′,1′) = 3.9 (H-2′); 6.52 d, 1 H (H-1′); 7.36 – 7.92 m,
17 H (NH2, H-arom.); 8.00 s, 1 H (H-2); 8.51 s, 1 H (H-8).
9-(2,5,6-Tri-O-acetyl-3-O-methanesulfonyl-β-D-glucofuranosyl)-N6-benzoyladenine (IV)
Sulfuric acid (1.1 ml) was added dropwise during 30 min to a stirred and ice-cooled mixture of 5,6-
di-O-acetyl-1,2-O-isopropylidene-3-O-methanesulfonyl-D-glucofuranose5 (3.82 g, 10 mmol), acetic
acid (12 ml) and acetic anhydride (3.5 ml). The mixture was stirred at room temperature until it be-
came homogeneous, left to stand overnight, poured on ice (100 g) and neutralized with solid sodium
hydrogen carbonate. After extraction with ethyl acetate (3 × 50 ml), the combined extracts were
washed with 10% solution of sodium hydrogen carbonate until the evolution of carbon dioxide
ceased. The aqueous layer was extracted with ethyl acetate (2 × 50 ml) and all the combined extracts
were dried over magnesium sulfate. The solvent was evaporated, the residue was dried in vacuo
(13 Pa) at 40 °C for 3 h, dissolved in acetonitrile (20 ml) and mixed with N6-benzoyladenine (2.39 g,
10 mmol). Tin tetrachloride (2.3 ml, 20 mmol) was added dropwise under stirring. The mixture was
stirred to dissolution of benzoyladenine, set aside overnight and added dropwise to 10% solution of
sodium hydrogen carbonate solution (150 ml). After extraction with ethyl acetate (3 × 100 ml), the
combined extracts were washed with 10% sodium hydrogen carbonate solution (60 ml), the aqueous
layer was washed with ethyl acetate (50 ml) and all the combined extracts were dried over magne-
sium sulfate. The solvent was evaporated and the residue was chromatographed on a column of silica
gel (400 g). Elution with ethyl acetate recovered the unreacted sugar derivative, elution with ethyl
acetate–2-propanol (4 : 1) afforded 4.96 g (82%) of compound IV as a solid foam; RF 0.47 (S4). For
C25H27N5O11S (605.6) calculated: 49.58% C, 4.49% H, 11.57% N, 5.29% S; found: 49.65% C,
4.67% H, 11.44% N, 5.10% S. 1H NMR spectrum: 2.01 s, 3 H (CH3CO); 2.04 s, 3 H (CH3CO);
2.16 s, 3 H (CH3CO); 3.31 s, 3 H (CH3SO2); 4.10 dd, 1 H, J(6a′,5′) = 3.6, J(6a′,6b′) = 12.3 (H-6a′);
4.55 dd, 1 H, J(6b′,5′) = 2.3 (H-6b′); 4.67 dd, 1 H, J(4′,3′) = 4.0, J(4′,5′) = 9.2 (H-4′); 5.34 m, 1 H
(H-5′); 5.46 dd, 1 H, J(3′,2′) = 1.5 (H-3′); 6.00 dd, 1 H, J(2′,1′) = 2.4 (H-2′); 6.41 d, 1 H (H-1′); 7.50
– 7.69 m and 8.02 – 8.09 m, 3 H and 2 H (H-arom.); 8.56 s, 1 H (H-2); 8.79 s, 1 H (H-8).
9-(2,3-Anhydro-β-D-mannofuranosyl)adenine (V)
A solution of mesyl derivative III (3.44 g, 5 mmol) in 0.5 M methanolic sodium methoxide (30 ml)
was set aside at room temperature overnight. After neutralization with acetic acid and evaporation of
the solvent, the residue was crystallized from water to give 810 mg (58%) of anhydro nucleoside V,
m.p. 221 – 222 °C; RF 0.31 (S3). For C11H13N5O4 (279.3) calculated: 47.31% C, 4.69% H, 25.08% N;
1
found: 47.21% C, 4.75% H, 24.97% N. H NMR spectrum: 3.27 – 3.42 m, 1 H (H-6a′); 3.46 – 3.68 m,
2 H (H-5′, H-6b′); 3.97 d, 1 H, J(4′,5′) = 8.5 (H-4′); 4.14 d, 1 H, J(3′,2′) = 3.1 (H-3′); 4.27 d, 1 H
(H-2′); 4.54 t, 1 H, J(OH,6′) = 5.6 (6′-OH); 5.15 d, 1 H, J(OH,5′) = 5.8 (5′-OH); 6.24 s, 1 H (H-1′);
7.36 s, 2 H (NH2); 8.14 s, 1 H (H-2); 8.17 s, 1 H (H-8); after exchange with D2O: 3.32 dd, 1 H,
J(6a′,5′) = 5.6, J(6a′, 6b′) = 11.4 (H-6a′); 3.50 dd, 1 H, J(6b′,5′) = 2.6 (H-6b′); 3.63 m, 1 H (H-5′).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

1414
Hrebabecky, Dockal, Holy:
9-(2,3-Anhydro-β-D-allofuranosyl)adenine (VI)
A solution of mesyl derivative IV (3.03 g, 5 mmol) in methanolic ammonia (saturated at 0 °C, 50 ml)
was allowed to stand at room temperature for 50 h. The separated crystalline compound VI was col-
lected (1.09 g, 78%) and the mother liquors were concentrated to one third of the original volume to
give further 80 mg (6%) of the same product, m.p. 168 – 170.5 °C; RF 0.41 (S3). For C11H13N5O4
1
(279.3) calculated: 47.31% C, 4.69% H, 25.08% N; found: 47.20% C, 4.72% H, 25.01% N. H NMR
spectrum: 3.15 – 3.40 m, 2 H (H-5′, H-6a′); 3.56 m, 1 H, J(6b′,5′) = 5.4, J(6b′,6a′) = 11.0 (H-6b′);
4.11 d, 1 H, J(4′,5′) = 6.3 (H-4′); 4.31 d, 1 H, J(3′,2′) = 2.7 (H-3′); 4.45 d, 1 H (H-2′); 4.65 t, 1 H,
J(OH, 6a′) = J(OH,6b′) = 4.5 (6′-OH); 5.28 d, 1 H, J(OH,5′) = 5.2 (5′-OH); 6.20 s, 1 H (H-1′); 7.33 s,
2 H (NH2); 8.17 s, 1 H (H-2); 8.33 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine (VII)
4-Dimethylaminopyridine (250 mg) and acetic anhydride (0.5 ml) were added to a stirred suspension
of epoxide V (1.40 g, 5 mmol) in acetonitrile (15 ml). After 3 h, another portion of acetic anhydride
(0.5 ml) was added and the mixture was stirred at room temperature overnight. The separated crys-
talline compound was filtered and washed with ethanol; yield 1.42 g (78%) of acetyl derivative VII.
The combined mother liquors and washings were concentrated, the residue was dissolved in chloro-
form (20 ml), washed with water (2 × 2 ml) and dried over magnesium sulfate. Evaporation
of the solvent and crystallization from 2-propanol afforded further 190 mg (10%) of the product, m.p.
215 – 218 °C; RF 0.65 (S3). For C15H17N5O6 (363.3) calculated: 49.58% C, 4.72% H, 19.28% N;
found: 49.32% C, 4.71% H, 19.37% N. 1H NMR spectrum: 2.01 s, 3 H (CH3CO); 2.09 s, 3 H
(CH3CO); 4.04 dd, 1 H, J(6a′,5′) = 6.1, J(6a′,6b′) = 12.4 (H-6a′); 4.23 d, 1 H, J(3′,2′) = 2.9 (H-3′);
4.29 d, 1 H, J(4′,5′) = 7.5 (H-4′); 4.35 d, 1 H (H-2′); 4.41 dd, 1 H, J(6b′,5′) = 2.8 (H-6b′); 5.25 m,
1 H (H-5′); 6.31 s, 1 H (H-1′); 7.41 s, 2 H (NH2); 8.16 s, 1 H (H-2); 8.18 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-2,3-anhydro-β-D-allofuranosyl)adenine (VIII)
Epoxide VI (1.40 g, 5 mmol) was acetylated as described for the preparation of acetyl derivative VII;
yield 1.66 g (91%) of compound VIII, m.p. 194 – 195 °C; RF 0.71 (S3). For C15H17N5O6 (363.3)
1
calculated: 49.58% C, 4.72% H, 19.28% N; found: 49.49% C, 4.69% H, 19.41% N. H NMR spec-
trum: 1.92 s, 3 H (CH3CO); 2.02 s, 3 H (CH3CO); 3.80 dd, 1 H, J(6a′,5′) = 4.6, J(6a′,6b′) = 12.0
(H-6a′); 4.12 dd, 1 H, J(6b′,5′) = 2.8 (H-6b′); 4.32 d, 1 H, J(4′,5′) = 8.0 (H-4′); 4.38 d, 1 H, J(3′,2′)
= 2.8 (H-3′); 4.58 d, 1 H (H-2′); 5.23 m, 1 H (H-5′); 6.27 s, 1 H (H-1′); 7.35 s, 2 H (NH2); 8.12 s,
1 H (H-2); 8.25 s, 1 H (H-8).
9-(3,6-Anhydro-β-D-glucofuranosyl)adenine (IX)
A. A solution of mesyl derivative IV (606 mg, 1 mmol) in 1 M methanolic sodium methoxide
(5 ml) was allowed to stand at room temperature overnight. After neutralization with acetic acid, the
separated crystalline compound was collected on filter and recrystallized from water to give 200 mg
(72%) of compound IX. The residue after concentration of the mother liquors on crystallization from
water gave 13 mg (5%) of the same product, m.p. 228 – 229 °C; RF 0.36 (S3). For C11H13N5O4
1
(279.3) calculated: 47.31% C, 4.69% H, 25.08% N; found: 47.25% C, 4.71% H, 24.89% N. H NMR
spectrum: 3.56 dd, 1 H, J(6a′,5′) = 7.8, J(6a′,6b′) = 8.2 (H-6a′); 3.84 dd, 1 H, J(6b′,5′) = 6.4 (H-6b′);
4.21 m, 1 H (H-5′); 4 44 dd, 1 H, J(3′,2′) = 2.3, J(3′,4′) = 4.7 (H-3′); 4.60 t, 1 H, J(4′,5′) = 4.7
(H-4′); 4.21 m, 1 H (H-2′); 5.18 d, 1 H, J(OH,5′) = 6.1 (5′-OH); 5.93 d, 1 H, J(1′,2′) = 4.3 (H-1′);
5.96 d, 1 H, J(OH,2′) = 4.9 (2′-OH); 7.32 s, 2 H (NH2); 8.16 s, 1 H (H-2); 8.31 s, 1 H (H-8).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1415
B. A suspension of epoxide VI (100 mg, 0.36 mmol) in 0.1 M methanolic sodium methoxide (8 ml)
was stirred at room temperature overnight. The mixture was neutralized with acetic acid and the sep-
arated product was collected and washed on filter with water and ether. Yield 86 mg (86%) of anhy-
dronucleoside IX, m.p. 228 – 229 °C.
9-(5,6-Di-O-acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine (Xa)
and 9-(5,6-Di-O-acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine (XIa)
Bromotrimethylsilane (1 ml) and boron trifluoride etherate (2 ml) were added to a solution of epoxide
VII (1.82 g, 5 mmol) in dioxane (25 ml) and the mixture was stirred at room temperature for 3 h.
After addition of 1 M triethylammonium hydrogen carbonate (20 ml), the mixture was concentrated
to half of the original volume and extracted with chloroform (2 × 50 ml). The chloroform extracts
were combined, dried over magnesium sulfate and the solvent was evaporated. The residue was chro-
matographed on a column of silica gel (300 g) in chloroform–methanol (10 : 1). The first fraction
afforded 916 mg (41%) of bromo derivative Xa as a solid foam; RF 0.59 (S2). For C15H18BrN5O6
(444.2) calculated: 40.55% C, 4.08% H, 17.99% Br, 15.77% N; found: 40.23% C, 4.21% H, 17.50% Br,
1
15.49% N. H NMR spectrum: 2.01 s, 3 H (CH3CO); 2.02 s, 3 H (CH3CO); 4.12 dd, 1 H, J(6a′,5′)
= 5.5, J(6a′,6b′) = 12.4 (H-6a′); 4.45 – 4.58 m, 3 H (H-3′, H-4′, H-6b′); 4.92 dd, 1 H, J(2′,1′) = 3.0,
J(2′,3′) = 1.9 (H-2′); 5.37 m, 1 H, J(5′,6b′) = 2.4 (H-5′); 6.41 d, 1 H (H-1′); 6.61 d, 1 H, J(OH,3′) = 5.3
(3′-OH); 7.41 s, 2 H (NH2); 8.17 s, 1 H (H-2); 8.30 s, 1 H (H-8).
The second fraction gave 1.05 g (47%) of bromo derivative XIa as a solid foam; RF 0.57 (S2). For
C15H18BrN5O6 (444.2) calculated: 40.55% C, 4.08% H, 17.99% Br, 15.77% N; found: 40.27% C,
1
4.19% H, 17.48% Br, 15.46% N. H NMR spectrum: 2.01 s, 3 H (CH3CO); 2.05 s, 3 H (CH3CO);
4.11 dd, 1 H, J(6a′,5′) = 6.7, J(6a′,6b′) = 12.2 (H-6a′); 4.41 t, 1 H, J(4′,3′) = J(4′,5′) = 6.4 (H-4′);
4.43 dd, 1 H, J(6b′,5′) = 3.0 (H-6b′); 4.65 m, 1 H, J(2′,1′) = 5.5, J(2′,3′) = 6.4, J(2′,OH) = 5.7 (H-2′);
4.80 t, 1 H (H-3′); 5.43 m, 1 H (H-5′); 6.37 d, 1 H (H-1′); 6.39 d, 1 H (2′-OH); 7.30 s, 2 H (NH2);
8.14 s, 1 H (H-2); 8.24 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIIa)
Bromotrimethylsilane (1 ml, 7.6 mmol) and boron trifluoride etherate (2 ml, 16.3 ml) were added to
a stirred suspension of epoxide VIII (1.82 g, 5 mmol) in dioxane (30 ml). After stirring at room
temperature for 3 h, the mixture was neutralized with 1 M triethylammonium hydrogen carbonate solu-
tion (25 ml), concentrated to one third of the original volume and extracted with chloroform (150 ml).
The chloroform layer was washed with water (10 ml), dried over magnesium sulfate and concen-
trated. Crystallization of the residue from 2-propanol afforded 2.20 g (99%) of bromo derivative
XIIa, m.p. 122 – 124 °C; RF 0.56 (S2). For C15H18BrN5O6 (444.2) calculated: 40.55% C, 4.08% H,
1
17.99% Br, 15.77% N; found: 40.15% C, 4.15% H, 18.23% Br, 15.54% N. H NMR spectrum: 2.03 s,
3 H (CH3CO); 2.04 s, 3 H (CH3CO); 4.17 dd, 1 H, J(6a′,5′) = 3.7, J(6a′,6b′) = 12.4 (H-6a); 4.50 –
4.60 m, 3 H (H-2′, H-4′, H-6b′); 5.01 m, 1 H (H-3′); 5.27 m, 1 H (H-5′); 5.94 d, 1 H, J(1′,2′) = 2.4
(H-1′); 6.68 d, 1 H, J(OH,2′) = 4.4 (2′-OH); 7.36 s, 2 H (NH2); 8.17 s, 1 H (H-2); 8.33 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-2-deoxy-β-D-arabino-hexofuranosyl)adenine (Xb)
A solution of tributylstannane in toluene (1 M, 4 ml), followed by 2,2′-azobis(2-propionitrile) (50 mg),
was added at 100 °C to a solution of bromo derivative Xa (888 mg, 2 mmol) in dioxane (6 ml). The
mixture was heated for 20 min and filtered while hot. After cooling, the solution deposited crystals
which were collected and washed on filter with toluene. Yield 231 mg (32%) of deoxy derivative Xb.
The filtrate was concentrated and the residue was dissolved in 2-propanol (3 ml). On standing over-
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

1416
Hrebabecky, Dockal, Holy:
night at 4 °C, the solution deposited crystals which were washed with 2-propanol; this afforded fur-
ther 263 mg (36%) of compound Xb, m.p. 185.5 – 187.5 °C; RF 0.28 (S2). For C15H19N5O6 (365.3)
1
calculated: 49.31% C, 5.24% H, 19.17% N; found: 49.52% C, 5.19% H, 19.29% N. H NMR spec-
trum: 1.99 s, 3 H (CH3CO); 2.01 s, 3 H (CH3CO); 2.32 dd, 1 H, J(2a′,1′) = 1.8, J(2a′,2b′) = 14.6
(H-2a′); 2.84 m, 1 H, J(2b′,1′) = 5.8, J(2b′,3′) = 8.8 (H-2b′); 3.98 dd, 1 H, J(6a′,5′) = 5.5, J(6a′,6b′)
= 12.2 (H-6a′); 4.06 dd, 1 H, J(4′,3′) = 3.3, J(4′,5′) = 7.9 (H-4′); 4.35 m, 1 H (H-3′); 4.47 dd, 1 H,
J(6b′,5′) = 2.4 (H-6b′); 5.23 m, 1 H (H-5′); 6.30 m, 2 H (H-1′, 3′-OH); 7.38 s, 2 H (NH2); 8.15 s, 1
H (H- 2); 8.15 s, 1 H (H-8).
9-(2-Deoxy-β-D-arabino-hexofuranosyl)adenine (Xc)
A solution of acetyl derivative Xb (183 mg; 0.5 mmol) in methanolic ammonia was allowed to stand
at room temperature overnight. The solvent was evaporated and the residue on crystallization from
2-propanol afforded 110 mg (78%) of compound Xc, m.p. 175 – 177.5 °C; RF 0.21 (S3). For
C11H15N5O4 (281.3) calculated: 46.97% C, 5.38% H, 24.90% N; found: 46.94% C, 5.33% H, 24.92% N.
1H NMR spectrum: 2.23 dd, 1 H, J(2a′,1′) = 1.8, J(2a′,2b′) = 14.6 (H-2a′); 2.76 m, 1 H, J(2b′,1′) =
8.5, J(2b′,3′) = 5.5 (H-2b′); 3.34 m, 1 H, J(6a′,5′) = 5.5, J(6a′,6b′) = 11.3, J(6a′,OH) = 5.8 (H-6a′);
3.55 m, 1 H, J(6b′,5′) = 2.1, J(6b′,OH) = 5.8 (H-6b′); 3.69 dd, 1 H, J(4′,3′) = 2.7, J(4′,5′) = 8.5
(H-4′); 4.37 m, 1 H (H-3′); 4.45 t, 1 H (6′-OH); 4.72 d, 1 H, J = 5.5 (OH); 5.88 d, 1 H, J = 5.5
(OH); 6.25 dd, 1 H (H-1′); 7.33 s, 2 H (NH2); 8.14 s, 1 H (H-2); 8.35 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-3-deoxy-β-D-arabino-hexofuranosyl)adenine (XIb)
A solution of tributylstannane in toluene (1 M, 4 ml), followed by 2,2′-azobis(2-propionitrile) (50 mg),
was added at 100 °C to a solution of bromo derivative XIa (888 mg, 2 mmol) in dioxane (6 ml). The
mixture was heated for 20 min and filtered while hot. After evaporation of the solvent, the residue
was dissolved in 2-propanol. The solution deposited 490 mg (67%) of deoxy derivative XIb, m.p. 130
– 131 °C; RF 0.37 (S2). For C15H19N5O6 (365.3) calculated: 49.31% C, 5.24% H, 19.17% N; found:
49.21% C, 5.15% H, 19.01% N. 1H NMR spectrum: 2.01 s, 3 H (CH3CO); 2.03 s, 3 H (CH3CO);
2.08 m, 1 H, J(3a′,3b′) = 12.6 (H-3a′); 2.44 m, 1 H (H-3b′); 4.06 dd, 1 H, J(6a′,5′) = 6.4, J(6a′,6b′)
= 12.2 (H-6a′); 4.21 m, 1 H, J(4′,3a′) = J(4′,3b′) = 6.3, J(4′,5′) = 5.6 (H-4′); 4.42 dd, 1 H, J(6b′,5′)
= 2.7 (H-6b′); 4.48 m, 1 H (H-2′); 5.27 m, 1 H (H-5′); 5.56 d, 1 H, J(OH,2′) = 4.6 (2′-OH); 6.17 d,
1 H, J(1′,2′) = 4.9 (H-1′); 7.26 s, 2 H (NH2); 8.14 s, 1 H (H-2); 8.15 s, 1 H (H-8).
9-(3-Deoxy-β-D-arabino-hexofuranosyl)adenine (XIc)
Methanolysis of acetyl derivative XIb (183 mg, 0.5 mmol) with methanolic ammonia gave 121 mg
(86%) of compound XIc, m.p. 160 – 161 °C; RF 0.24 (S3). For C11H15N5O4 (281.3) calculated:
46.97% C, 5.38% H, 24.90% N; found: 47.15% C, 5.41% H, 24.81% N. UV spectrum (water): λmax
260 nm, εmax 15 100. 1H NMR spectrum: 2.02 – 2.30 m, 2 H (2 × H-3′); 3.36 t, 2 H, J(6′,5′) =
J(6′,OH) = 5.8 (2 × H-6′); 3.76 m, 1 H, J(2′,1′) = 5.6, J(2′,3a′) = J(2′,3b′) = 5.2 (H-2′); 4.08 m, 1 H
(H-4′); 4.50 m, 1 H (H-5′); 4.64 t, 1 H (6′-OH); 5.37 d, 1 H, J = 4.8 (OH); 5.38 d, 1 H, J = 5.8
(OH); 6.12 d, 1 H (H-1′); 7.21 s, 2 H (NH2); 8.11 s, 1 H (H-2); 8.30 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-3-deoxy-β-D-ribo-hexofuranosyl)adenine (XIIb)
Reaction of bromo derivative XIIa (444 mg, 1 mmol) with tributylstannane, followed by column
chromatography on silica gel (40 g) in ethyl acetate–acetone–ethanol–water (38 : 6 : 3 : 3) and crys-
tallization from 2-propanol–ether afforded 285 mg (78%) of deoxy derivative XIIb, m.p. 85 – 87 °C;
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1417
RF 0.41 (S2). For C15H19N5O6 (365.3) calculated: 49.31% C, 5.24% H, 19.17% N; found: 49.02% C,
1
5.36% H, 18.94% N. H NMR spectrum: 1.92 s, 3 H (CH3CO); 1.99 s, 3 H (CH3CO); 1.98 – 2.10 m,
1 H (H-3a′); 2.40 – 2.53 m, 1 H (H-3b′); 4.02 dd, 1 H, J(6a′,5′) = 6.4, J(6a′,6b′) = 12.2 (H-6a′); 4.31 dd,
1 H, J(6b′,5′) = 3.1 (H-6b′); 4.46 m, 1 H, J(4′,3a′) = 6.2, J(4′,3b′) = 8.6, J(4′,5′) = 5.2 (H-4′); 4.80 m,
1 H (H-2′); 5.22 m, 1 H (H-5′); 5.75 d, 1 H, J(OH,2′) = 4.3 (2′-OH); 5.87 d, 1 H, J(1′,2′) = 2.1
(H-1′); 7.31 s, 2 H (NH2); 8.15 s, 1 H (H-2); 8.22 s, 1 H (H-8).
9-(3-Deoxy-β-D-ribo-hexofuranosyl)adenine (XIIc)
Methanolysis of acetyl derivative XIIb (183 mg, 0.5 mmol) with methanolic ammonia gave 123 mg
(87%) of compound XIIc, m.p. 243 °C (decomp); RF 0.33 (S3). For C11H15N5O4 (281.3) calculated:
46.97% C, 5.38% H, 24.90% N; found: 46.77% C, 5.32% H, 24.89% N. UV spectrum (water): λmax
1
260 nm, εmax 15 200. H NMR spectrum: 1.82 – 1.95 m, 1 H (H-3a′); 2.22 – 2.37 m, 1 H (H-3b′);
3.35 t, 2 H, J(6′,5′) = 5.8, J(6′,OH) = 5.6 (2 × H-6′); 3.77 m, 1 H, J(5′,4′) = 3.6, J(5′,OH) = 4.6
(H-5′); 4.33 - 4.42 m, 1 H (H-4′); 4.50 – 4.58 m, 1 H (H-2′); 4.64 t, 1 H, J(OH,6′) = 5.6 (6′-OH);
5.40 d, 1 H (5′-OH); 5.64 d, 1 H, J(OH,2′) = 4.0 (2′-OH); 5.85 d, 1 H, J(1′,2′) = 2.4 (H-1′); 7.30 s,
2 H (NH2); 8.14 s, 1 H (H-2); 8.37 s, 1 H (H-8).
9-(2,5,6-Tri-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIId)
Acetic anhydride (0.3 ml) and 4-dimethylaminopyridine (150 mg) were added to a stirred mixture of
bromo derivative XIIa (2.22 g, 5 mmol) and acetonitrile (20 ml). After 2 h another portion of acetic
anhydride (0.3 ml) was added and after further 5 h the mixture was mixed with methanol (1 ml) and
stirred for additional 10 min. The solvent was evaporated, the residue was dissolved in chloroform
(80 ml) and the solution was washed with water (2 × 5 ml) and dried over magnesium sulfate. After
evaporation of the solvent, the residue was crystallized from 2-propanol to give 1.99 g (82%) of ace-
tyl derivative XIId, m.p. 176 – 177 °C; RF 0.52 (S2). For C17H20BrN5O7 (486.3) calculated: 41.99% C,
1
4.15% H, 16.43% Br, 14.40% N; found: 42.07% C, 4.18% H, 16.38% Br, 14.62% N. H NMR spec-
trum: 2.04 s, 6 H (2 × CH3CO), 2.14 s, 3 H (CH3CO); 4.18 dd, 1 H, J(6a′,5′) = 4.4, J(6a′,6b′) = 12.6
(H-6a′); 4.50 – 4.60 m, 2 H (H-4′, H-6b′); 4.88 dd, 1 H, J(3′,2′) = 1.1, J(3′,4′) = 4.0 (H-3′); 5.20 – 5.29
m, 1 H (H-5′); 5.90 dd, 1 H (H-2′); 6.24 d, 1 H, J(1′,2′) = 2.1 (H-1′); 7.37 s, 2 H (NH2); 8.16 s,
1 H (H-2); 8.35 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)adenine (XIII)
A solution of bromo derivative XIId (486 mg, 1 mmol) in dimethylformamide (7 ml) was added
at 0 °C during 30 min to a stirred suspension of Cu/Zn couple (prepared from 0.55 g of cupric ace-
tate and 3.4 g of zinc dust according to ref.14). The mixture was stirred at 0 °C for further 15 min
and then filtered through Celite. The insoluble material was washed with dimethylformamide (7 ml)
and the combined filtrates were diluted with chloroform (250 ml). The solution was washed success-
ively with saturated solution of ethylenediaminetetraacetic acid disodium salt (2 × 15 ml), 10%
aqueous sodium hydrogen carbonate (15 ml), dried over magnesium sulfate and the solvent was evap-
orated. The residue was codistilled with xylene and dissolved in a minimum amount of methanol.
Upon slow addition of ether, the solution deposited 309 mg (89%) of crystalline compound XIII, m.p.
169.5 – 172.5 °C; RF 0.39 (S2). For C15H17N5O5 (347.3) calculated: 51.87% C, 4.93% H, 20.16% N;
found: 51.62% C, 5.01% H, 20.02% N. 1H NMR spectrum: 1.98 s, 3 H (CH3CO); 1.99 s, 3 H
(CH3CO); 4.04 dd, 1 H, J(6a′,5′) = 5.9, J(6a′,6b′) = 12.1 (H-6a′); 4.29 dd, 1 H, J(6b′,5′) = 3.2 (H-
6b′); 5.03 – 5.16 m, 2 H (H-4′, H-5′); 6.32 m, 1 H, J(3′,1′) = 1.5, J(3′,2′) = 5.9, J(3′,4′) = 1.8 (H-3′);
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

1418
Hrebabecky, Dockal, Holy:
6.63 dt, 1 H, J(2′,1′) = J(2′,4′) = 1.5 (H-2′); 6.93 m, 1 H (H-1′); 7.33 s, 2 H (NH2); 7.99 s, 1 H (H-2);
8.17 s, 1 H (H-8).
9-(2,3-Dideoxy-β-D-erythro-hex-2-enofuranosyl)adenine (XIV)
Methanolysis of acetyl derivative XIII (174 mg, 0.5 mmol) with methanolic ammonia, followed by
crystallization from 2-propanol afforded 110 mg (84%) of compound XIV, m.p. 175 – 176 °C; RF
0.30 (S3). For C11H13N5O3 (263.3) calculated: 50.18% C, 4.98% H, 26.60% N; found: 50.10% C,
1
5.04% H, 26.59% N. H NMR spectrum: 3.41 m, 2 H (2 × H-6′); 3.61 m, 1 H, J(5′,6a′) = J(5′,6b′)
= J(5′,4′) = 4.8 (H-5′); 4.70 t, 1 H, J(OH,6′) = 5.6 (6′-OH); 4.90 m, 1 H (H-4′); 5.28 d, 1 H,
J(OH,5′) = 4.8 (5′-OH); 6.12 m, 1 H, J(3′,1′) = 1.5, J(3′,2′) = 6.1, J(3′,4′) = 2.1 (H-3′); 6.55 m, 1 H,
J(2′,1′) = 1.8, J(2′,4′) = 1.5 (H-2′); 6.92 m, 1 H, J(1′,4′) = 3.0 (H-1′); 7.30 s, 2 H (NH2); 8.14 s, 1 H
(H-2); 8.18 s, 1 H (H-8).
9-(5,6-Di-O-acetyl-2,3-dideoxy-β-D-erythro-hexofuranosyl)adenine (XV)
A mixture of bromo derivative XIId (486 mg, 1 mmol), dimethylformamide (3 ml), magnesium oxide
(80 mg) and 10% Pd/C (50 mg) was hydrogenated at room temperature and atmospheric pressure for
30 h. The solids were removed by filtration through Celite, washed with dimethylformamide, the
combined filtrates were concentrated and the residue was chromatographed on a column of silica gel
(50 g) in ethyl acetate–acetone–ethanol–water (19 : 3 : 2 : 1). Crystallization from 2-propanol gave
253 mg (72%) of dideoxy derivative XV, m.p. 155 – 156 °C; RF 0.35 (S2). For C15H19N5O5 (349.3)
1
calculated: 51.57% C, 5.48% H, 20.05% N; found: 51.47% C, 5.42% H, 19.94% N. H NMR spec-
trum: 1.91 s, 3 H (CH3CO); 1.98 s, 3 H (CH3CO); 2.10 – 2.69 m, 4 H (2 × H-2′, 2 × H-3′); 3.97 dd,
1 H, J(6a′,5′) = 6.4, J(6a′,6b′) = 12.2 (H-6a′); 4.23 m, 1 H (H-4′); 4.29 dd, 1 H, J(6b′,5′) = 3.1
(H-6b′); 5.18 m, 1 H, J(5′,4′) = 5.2 (H-5′); 6.21 dd, 1 H, J(1′,2a′) = 6.7, J(1′,2b′) = 3.7 (H-1′); 7.27 s,
2 H (NH2); 8.14 s, 1 H (H-2); 8.25 s, 1 H (H-8).
9-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)adenine (XVI)
A. Methanolysis of acetyl derivative XV (175 mg, 0.5 mmol) with methanolic ammonia and sub-
sequent crystallization from 2-propanol afforded 104 mg (78%) of dideoxy derivative XVI, m.p. 178
– 179.5 °C; RF 0.26 (S3). For C11H15N5O3 (265.3) calculated: 49.80% C, 5.70% H, 26.40% N; found:
1
49.83% C, 5.71% H, 26.27% N. H NMR spectrum: 1.90 – 2.44 m, 4 H (2 × H-2′, 2 × H-3′); 3.35 t,
2 H, J(6′,5′) = J(6′,OH) = 5.6 (2 × H-6′); 3.70 m, 1 H, J(5′,4′) = 4.3, J(5′,OH) = 4.6 (H-5′); 4.09 m,
1 H, J(4′,3a′) = J(4′,3b′) = 6.7 (H-4′); 4.59 t, 1 H (6′-OH); 5.26 d, 1 H (5′-OH); 6.20 dd, 1 H,
J(1′,2a′) = 4.9, J(1′,2b′) = 5.5 (H-1′); 7.27 s, 2 H (NH2); 8.12 s, 1 H (H-2); 8.36 s, 1 H (H-8).
B. Didehydro derivative XIV (100 mg, 0.38 mmol) in dimethylformamide (2.5 ml) was hydroge-
nated over 10% Pd/C (10 mg) at room temperature for 30 h. The catalyst was removed by filtration
through Celite, washed with dimethylformamide and the combined filtrates were taken down. The
residue, which contained a significant amount of adenine in addition to the product XVI (TLC in S3),
was dissolved in hot 2-propanol, the solution was filtered and set aside overnight. Yield 48 mg (48%)
of dideoxy derivative XVI, identical with the product obtained by procedure A.
The authors are indebted to Professor E. De Clerq and Dr J. Balzarini (Rega Institut, Katholieke
Universiteit Leuven, B-3000 Leuven, Belgium) for antiviral activity tests, to Mrs F. Pospisilova for
1
excellent technical assistance, to Mrs M. Snopkova for measurement of the H NMR spectra and to the
staff of the Analytical Laboratory of this Institute (Dr V. Pechanec, Head) for elemental analyses. This
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

9-(Hexofuranosyl)adenine Analogs
1419
work was supported by Grant No. 45512 of the Grant Agency of the Academy of Sciences of the Czech
Republic.
REFERENCES
1. Hrebabecky H., Holy A.: Carbohydr. Res. 216, 179 (1991).
2. Hrebabecky H., Holy A.: Collect. Czech. Chem. Commun. 59, 412 (1994).
3. Ferrier R. J., Haines S. R.: J. Chem. Soc., Perkin Trans. 1 1984, 1675.
4. Ishido Y., Nakazaki N., Sakaiyi N.: J. Chem. Soc., Perkin Trans. 1 1979, 2088.
5. Helferich B., Dressler H., Griebel R.: J. Prakt. Chem. 153, 289 (1939).
6. Miyai K., Robins R. K., Tolman R. L.: J. Med. Chem. 15, 1092 (1972).
7. Mengel R., Wiedner H.: Chem. Ber. 109, 1395 (1976).
8. Robins M. J., Fouron Y., Mengel R.: J. Org. Chem. 39, 1564 (1974).
9. Fukukawa K., Ueda T., Hirano T.: Chem. Pharm. Bull. 31, 1842 (1983).
10. Rosemeyer H., Kreçmerová M., Seela F.: Helv. Chim. Acta 74, 2054 (1991).
11. Bazin H., Chattopadhyaya J.: Synthesis 1985, 1108.
12. Kawana M., Nishikawa M., Yamasaki N., Kuzuhara H.: J. Chem. Soc., Perkin Trans. 1 1989,
1593.
13. Leonard N. J., Laursen R. A.: Biochemistry 4, 354 (1965).
14. Mansuri M. M., Starrett J. E., Wos J. A., Tortolani D. R., Brodfuehrer P. R., Howell J. G.,
Martin J. C.: J. Org. Chem. 54, 4780 (1989).
15. Starret J. E., jr., Tortolani D. R., Baker D. C., Omar M. T., Hebller A. K., Wos J. A., Martin J.
C., Mansuri M. M.: Nucleosides Nucleotides 9, 885 (1990).
16. De Clercq E., Balzarini J.: Unpublished results.
Translated by M. Tichy.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)