Small libraries of fused quinazolinone-sugars. Access to quinazolinedione nucleosides

Article abstract of DOI:10.1016/j.tet.2004.01.032

Unprotected carbohydrates can readily be converted into base-modified nucleosides and deoxynucleosides through a short sequence involving the condensation of anthranilic acid derivatives with a suitably protected sugar-derived 2-alkylthio-1,3-oxazoline.

Full text of DOI:10.1016/j.tet.2004.01.032

Tetrahedron 60 (2004) 2609–2619
Small libraries of fused quinazolinone-sugars.
Access to quinazolinedione nucleosides
a
a
b
Jolanta Girniene,a,b Guillaume Apremont, Arnaud Tatibouet, Algirdas Sackus
,
*
¨
and Patrick Rollina
a
´
´
´
Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite d’Orleans, BP 6759, F-45067 Orleans, France
bDepartment of Organic Chemistry, , Kaunas University of Technology, LT-3028 Kaunas, Lithuania
Received 18 September 2003; revised 3 December 2003; accepted 12 January 2004
Abstract—Unprotected carbohydrates can readily be converted into base-modified nucleosides and deoxynucleosides through a short
sequence involving the condensation of anthranilic acid derivatives with a suitably protected sugar-derived 2-alkylthio-1,3-oxazoline.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
process to assemble entirely the base onto the carbohydrate
template.11 Our study was based on an old reaction between
carbohydrates and thiocyanic acid giving 1,3-oxazolidine-2-
thione (OZT) fused with a carbohydrate furan ring. OZT
was the basic structure to develop a convergent preparation
of fused quinazolinone-sugars and quinazolinedione nucleo-
sides. Earlier approaches performed to obtain quinazoline-
dione nucleosides involve condensation of an activated
ribo- or 2-deoxyribo-donor with quinazoline derivatives.12
We herein develop a new flexible approach to what can be
called iso-quinazolinedione nucleosides (Scheme 1).
Over the past thirty years, natural as well as synthetic
nucleosides and nucleotides have been the cornerstone of
antiviral therapies against hepatitis virus (HBV), herpes
virus (VZV) and human immunodeficiency virus (HIV).1
Many of those compounds exhibit antiproliferative, anti-
biotic and antifungal activities and some have been used as
probes for DNA damages,2 as well as in the anti-sense
approach and DNA-probe technology with fluorescence
properties.3 Investigations were also undertaken on the
physico-chemical parts of DNA base-to-base interactions
(hydrogen bonding and stacking).4,5 It is also well admitted
that introducing diversity either into the carbohydrate or
into the heterocyclic moiety of nucleosides—from natural
modified nucleosides, methylated bases in the bacteria
world or in RNA duplex6 as well as new antibiotic
analogues like oxanosine7 or modified purines or pyrimi-
dines8 but also pyrazoles, imidazoles, phthalimides, pteri-
dines and lumazines9-leads to promising molecules with a
therapeutical potential. In a search for novel structural
features, we have turned our attention to the quinazoline-
dione moiety.
Our convergent approach to synthesize benzopyrimidine-
modified nucleosides involves a sugar derived OZT and
anthranilic acid. Condensation reactions of anthranilic acid
derivatives have already been explored.13 Within the frame
of a research program centered on the preparation and
reactivity of chiral natural OZT, such reactions were
explored.14,15 Application of the process of anthranilic
acid condensation with per-benzylated OZT led to new
homochiral quinazolinone derivatives. Extension of the
cyclocondensation process to sugar-derived OZT consti-
tutes a promising extension of this reaction to new base-
modified nucleosides and nucleotides.16
To construct such bases, two general methods for nucleoside
preparation could be applied from the literature, one using
the glycosylation method,10 which may lead to anomeric
selectivity problems, and the other based on a multistep
Keywords: 1,3-Oxazolidine-2-thione; Nucleoside; Quinazolinone;
Quinazolinedione; Anthranilic acid.
*
Corresponding author. Tel.: þ3323-849-4854; fax: þ3323-841-7281;
e-mail address: arnaud.tatibouet@univ-orleans.fr
Scheme 1. Quinazolinedione nucleoside and its iso derivative.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.01.032

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J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
straightforward.17 Standard conditions were applied to
various series of sugars: D- and L-arabinose, D-xylose,
D-ribose (aldopentose series) as well as D-fructose and
L-sorbose (hexoketose series). On pentoses and partially
protected hexoketoses (1-O-benzyl-D-fructose and 1-O-
benzyl-L-sorbose), the OZT were prepared in one step
using potassium thiocyanate under acidic conditions. This
reaction allowed us to produce diverse OZT in which the
configuration of the sugar ring was unambigously defined. A
furano-conformation and an anomeric configuration con-
trolled by the location of the hydroxyl group on C-2 was
observed. In addition, in D-fructo- and L-sorbo-derivatives,
known to usually give mixtures of furanose or pyranose
OZT, the benzyl protection on the first primary position
determined the formation of only one isomer out of the
seven that could be expected from an unprotected
ketohexoses.
Scheme 2. The cyclocondensation process to quinazolinone via a
benzylthiooxazoline intermediate in the D-arabino series.
2. Results and discussion
2.1. Quinazolinones preparation
Prior to cyclocondensation, the OZT 1 has to be activated
through S-alkylation. This sequence furnishes the per-O-
and -S-benzylated compound 2 in reasonable yields for a
two-step sequence (Table 1). Alkylation of the other OZT
(4–8) afforded the 2-benzylthiooxazolines (9–13) with
yields ranging from 38 to 73%. For most of the compounds
N-alkylation was not observed except with the D-ribo OZT
6, for which 24% of N-benzylation was obtained (Scheme 3).
Our approach is illustrated in Scheme 2 with D-arabinose.
Scheme 2: the cyclocondensation process to quinazolinone
via a benzylthiooxazoline intermediate in the D-arabino
series.
The preparation of the D-arabino derived OZT 1 is
Table 1. Application of the procedure previously described for miscellaneous aldoses and ketoses
˚
Quinazolinone EtOH, m.s. 3 A (tBuOH, CSA, m.s 3 A)
˚
OZT
Alkylthiooxazoline (two step yields)
1
D-arabino
L-arabino
D-xylo
2 38%
3 78% (92%)
4
5
6
7
9 41%
14 79%
10 50%
11 42%
12 64%
15 75%
D-ribo
16 65%
1-O-benzyl-D-fructo
17 14% (50%)
8
1-O-benzyl-L-sorbo
13 38%
18 16% (70%)

J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
Table 2. Application on silylated OZT of cyclocondensation
2611
OZT
Silylated alkylthiooxazoline Quinazolinone tBuOH
D-Arabino 1
L-Arabino 4
D-Xylo 5
21 72%
24 75%
25 79%
26 48%
23 85%
27 83%
28 95%
29 59%
D-Gluco
Scheme 3. N-benzyl derivative isolated from D-ribo OZT.
Condensation of 2-benzylthio-1,3-oxazoline 2 with anthra-
nilic acid in dry ethanol offers an efficient access to the
D-arabino derived quinazolinone 3 in good yield. Appli-
cation of the process to other alkylthiooxazolines (9–11)
generated the quinazolinones (14–16) in similar yields. In
the case of D-fructo 12 and L-sorbo 13 derivatives however,
yields were poor and non-reproducible. Those results might
be explained by a steric hindrance of the benzyloxymethyl
group attached to the anomeric carbon. Moreover, a
competing nucleophilic attack of ethanol providing the
corresponding 2-ethoxy-1,3-oxazoline analogues was
observed.
This sequence of reaction has been successfully applied to
other carbohydrate series—namely L-arabino, D-xylo and
D-gluco (Table 2). The silylation–thioalkylation sequence
led to the formation of alkylthiooxazoline derivatives in
much better yields than through direct per-alkylation. Even
with a more complex structure, such as for the D-gluco
derivative 26, the process is still competitive.
Applying the cyclocondensation conditions with anthranilic
acid on the O-silylated benzylthiooxazolines 21, 24, 25 gave
similar yields as with the perbenzylated derivatives. With
the more complex D-gluco-alkylthiooxazoline 26, a some-
what lower yield was observed, maybe for hindrance reason.
Improvement of the conditions was investigated using
various solvents such as DMF or tert-butanol. In aprotic
media (DMF), no condensation was detected whereas in
tert-butanol only a slow reaction occurred. Activation was
performed through addition of two equivalents of camphor-
sulfonic acid. In such conditions, cyclocondensations
occurred in reasonable yield for D-fructo 17 and L-sorbo
18 derivatives (57 and 70%, respectively). When applied to
the D-arabino derivative 2, the above conditions resulted in
much improved yields (92%).
2.2. The limits of cyclocondensation
A panel of 1,2-aminoaromatic acids was condensed with the
D-arabino per-benzylated alkylthiooxazoline 2 as a model.
Using the first procedure developed, results (Table 3)
showed that the presence of a withdrawing group hampered
to some extent the reaction. Replacing in anthranilic acid of
the benzene ring by pyridine (2-aminonicotinic acid)
expectedly did not allow the transformation into the desired
compound.
Discrimination of hydroxyls versus the OZT moiety allowed
a more flexible approach to cyclocondensations. Selective
protection of hydroxyls was performed either with TBDMS
group or with mixed acetals, thus allowing selective
activation of the OZT as benzylthiooxazoline intermediates
(Scheme 4). Mixed acetal (methoxyisopropylidene, MIP)
did not appear stable enough for an efficient cyclocondensa-
tion. In contrast, silyl derivatives gave the cycloadducts in
70% yield albeit together with some O-deprotection.
Skipping the acidic catalysis resulted in an increased yield
of 85%.
Applying the conditions developed for hindered compounds
led to dramatic improvement of the yields most significantly
with withdrawing groups (chloro-, bromo- and iodoanthra-
nilic acid). However, those conditions remained inefficient
in condensing aminonicotinic acid and dibromoanthranilic
acid.
2.3. Nucleosides synthesis
Having in hand an efficient and short three steps protocol to
generate new base modified 2,20-anhydronucleosides, we
have explored the ability of the newly formed heterocycles
to generate the corresponding nucleosides and deoxynucleo-
sides. To validate our approach to base-modified nucleo-
sides, we have investigated the ring-cleavage of
quinazolinones on the D-arabino model (Scheme 5).
Inspired by the well-documented 2,20-anhydronucleoside
chemistry, we have reacted the D-arabino derivative 3 under
basic and acidic conditions. In both cases hydrolysis of the
anhydro ring was effected with good yields—67 and 73%,
respectively—and complete configuration retention at the
20-hydroxylated position.
All our attempts to induce a direct inversion aimed at
producing the D-ribo-configuration failed. Thus, we
obtained a D-arabino compound 35 which incorporates a
Scheme 4. The alternative approach to quinazolinone.

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J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
Table 3. Extension to diverse amino-aromatic acids
Amino acids
˚
EtOH, ms 4 A
˚
tBuOH, ms 4 A
75% 3
92%
78% 30
89%
38% 31
86%
40% 32
94%
—
78% 33
—
0%
—
65% 34
0%
0%
Finally, the deoxynucleoside analogue was prepared
through a Barton–McCombie process (Scheme 7).
The thionocarbonate 39 was prepared (85%) under basic
conditions, then deoxygenated with tributylstannane to the
deoxynucloside 40 in 62% yield. The fully deprotected
structure 41 was obtained (62% yield) through Pd-catalysed
hydrogenolysis.
3. Conclusion
In summary, a concise (5–8 steps) and practical synthesis
of base-modified nucleosides has been disclosed starting
from native carbohydrates through OZT derivatives. This
procedure constitutes an original application of cyclo-
condensations involving anthranilic acid and analogues.
The reaction has been extended with success to different
sugar series (pentoses and hexoses) and also to diverse
heterocyclic systems (halogenoanthranilic acid and amino-
naphtalenic acid), leading to a small library of base-
modified anhydronucleosides.
Scheme 5. Routes to base-modified nucleosides in the D-arabino series.
quinazolinedione system as the base. Further hydrogenolysis
of benzyl groups (H2 and Pd/C) afforded the D-arabino-
nucleoside analogue 36 with 74% yield.
To obtain the natural carbohydrate analogue, inversion of
configuration was required: among the diverse methods
applied, the most efficient in our hands was the two steps
process involving triflic anhydride activation of the alcohol
followed by inversion with sodium nitrite. An interesting
aspect of our investigations was the clean intramolecular
cyclisation to the anhydro derivative, observed under
standard Garegg conditions (Scheme 6).
4. Experimental
4.1. General methods
¨
Melting points were determined on a Kofler hot-stage
1
apparatus and are uncorrected. H and 13C NMR spectra
were recorded on a Bruker Avance DPX250 at 250 MHz
and 62.89 MHz, respectively. The chemical shifts (d) are
reported in ppm downfield from TMS as the internal
standard. Coupling constants (J) are reported in Hz. Specific
rotations were measured at 20 8C using a Perkin–Elmer
polarimeter 141. HR-ESI-TOF-mass spectra were recorded
on a Micromass LC TOF spectrometer. Evaporation was
conducted in vacuo with a Bu¨chi rotary evaporator.
Analytical TLC was carried out on precoated silica gel
60F-254 plates (E. Merck) and spots were detected by UV
light (254 nm) and by heat treatment with a 10/85/5 mixture
of sulfuric acid, ethanol and water. Flash column chroma-
tography was performed on Kieselgel 60 (230–400 mesh)
silica gel (E. Merck).
Scheme 6. 2,20-Anhydro formation under Garegg conditions.
4.2. Chemical procedure
4.2.1. General protocol for the per-benzylation of sugar-
OZT. The sugar OZT (1 equiv.) was dissolved in DMF and
cooled in an ice-bath. NaH (4 equiv.) was added portionwise
then benzyl bromide (4 equiv.). The reaction was brought to
room temperature and stirred until completion (few hours).
Ice-cold water was poured in and the mixture was extracted
with AcOEt (3£50 mL). Organic phases were collected and
Scheme 7. Deoxynucleoside formation.

J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
2613
washed thoroughly with water, then brine and dried over
MgSO4. Per-benzylated compounds were purified by column
chromatography using petroleum ether–ethyl acetate eluents.
3.76(m, 1H, H-4); 3.80 (dd, 1H, J5b,4¼1.9 Hz, H-5b); 4.01
(dd, 1H, J3,2¼5.1 Hz, J3,4¼8.9 Hz, H-3); 4.27 (d, 1H,
J¼13.2 Hz, SCH2-Ph); 4.34 (d, 1H, SCH2-Ph); 4.51 (d, 1H,
J¼12.0 Hz, CH2-Ph); 4.52 (d, 1H, J¼11.5 Hz, CH2-Ph); 4.82
(dd, 1H, J2,3¼J2,1¼5.3 Hz, H-2); 6.03 (d, 1H, H-1), 7.22–7.42
(m, 15H, CHAr); 13C NMR (CDCl3): d 37.0 (SCH2-Ph); 67.7
(C-5); 72.8 (CH2-Ph); 73.9 (CH2-Ph); 77.0 (C-4); 78.0 (C-3);
80.9 (C-2); 100.1 (C-1); 128.1; 128.1; 128.4; 128.5; 128.8;
128.9; 129.0; 129.5 (CHAr); 136.6; 137.7; 138.4 (Cq); 171.5
(C-S); IR (NaCl): 1605 cm21 (CvN); MS IS m/z¼462.0
[MþHþ]; 484.0 [MþNaþ]; HRMS: calcd for C27H27NO4S
(461.1660), found (461.1662).
4.2.2. 2-Benzylthio-4,5-dihydro-(30,50-di-O-benzyl-10,20-
dideoxy-b-D-arabinofuranoso) [1,2-d]-oxazole 2. Eluent:
petroleum ether–ethyl acetate 80/20, yellow oil (1.83 g,
76%); [a]D¼271 (c 1.2, CHCl3); 1H NMR (CDCl3): d 3.20
(dd, 1H, J5a,4¼7.0 Hz, J5a,5b¼10.2 Hz, H-5a); 3.40 (dd, 1H,
J5b,4¼5.3 Hz, H-5b); 4.00–4.11 (m, 1H, H-3); 4.15–4.28
(m, 3H, H-4, SCH2-Ph); 4.36 (d, 1H, J¼12.1 Hz, CH2-Ph);
4.43 (d, 1H, CH2-Ph); 4.49 (d, 1H, J¼12.1 Hz, CH2-Ph);
4.55 (d, 1H, CH2-Ph); 4.85 (dd, 1H, J2,1¼6.0 Hz, J2,3
¼
1.0 Hz, H-2); 6.01 (d, 1H, H-1), 7.10–7.30 (m, 15H, CHAr);
13C NMR (CDCl3): d 36.1 (S-CH2-Ph); 69.4 (C-5); 76.1
(CH2-Ph); 73.1 (CH2-Ph); 81.9 (C-4); 85.4 (C-3); 88.1
(C-2); 100.7 (C-1); 126.4; 126.7; 127.0; 127.5; 127.7; 127.8;
128.2; 128.3; 128.4; 128.9 (CHAr); 137.5; 137.8; 138.8 (Cq);
169.2 (C-S); IR (NaCl): 1608 cm21 (CvN); MS IS m/z
¼462.0 [MþHþ]; HRMS: calcd for C21H23NO4 (353.1627),
found (353.1632).
4.2.6. 1-N-Benzyl-3,5-di-O-benzyl-1-N,2-O-thiocarbonyl-
b-D-ribofuranosylamine 11a. Eluent: petroleum ether–
ethyl acetate 80/20, oil (1.18 g; 24%); [a]D¼þ128 (c 1.7,
1
CHCl3); H NMR (CDCl3): d 3.56 (dd, 1H, J5a,4¼3.8 Hz,
J5a,5b¼11.3 Hz, H-5a); 3.75 (dd, 1H, J5b,4¼1.9 Hz, H-5b);
3.85 (ddd, 1H, J4,3¼9.1 Hz, H-4); 4.99 (dd, 1H,
J3,2¼5.3 Hz, H-3); 4.42 (d, 1H, J¼14.8 Hz, NCH2-Ph);
4.44 (d, 1H, J¼11.9 Hz, CH2-Ph); 4.51 (d, 1H, J¼11.6 Hz,
CH2-Ph); 4.53 (d, 1H, CH2-Ph); 4.75 (d, 1H, CH2-Ph); 4.85
(dd, 1H, J2,1¼5.3 Hz, H-2); 5.31 (d, 1H, NCH2-Ph); 5.50 (d,
1H, H-1), 7.22–7.41 (m, 15H, CHAr); 13C NMR (CDCl3): d
48.0 (NCH2-Ph); 66.1 (C-5); 71.7 (CH2-Ph); 72.6 (CH2-Ph);
76.1; 76.6; 77.4 (C-4, C-3, C-2); 89.2 (C-1); 126.8; 126.9;
127.0; 127.3; 127.4; 127.5; 127.6; 127.7; 127.9 (CHAr);
133.7; 136.0; 136.7 (Cq); 187.6 (CvS); MS IS m/z¼462,0
[MþHþ]; 484,0 [MþNaþ]; HRMS: calcd C27H27NO4S
(461.1660), found (461.1665).
4.2.3. 2-Benzylthio-4,5-dihydro-(30,50-di-O-benzyl-10,20-
dideoxy-b-L-arabinofuranoso) [1,2-d]-oxazole 9. Eluent:
petroleum ether–ethyl acetate 80/20, yellow oil (0.99 g,
48%); [a]D¼þ72 (c 1.2, CHCl3); 1H NMR (CDCl3): d 3.23
(dd, 1H, J5a,4¼7.1 Hz, J5a,5b¼10.2 Hz, H-5a); 3.41 (dd, 1H,
J5b,4¼5.5 Hz, H-5b); 4.05 (d, 1H, J3,4¼2.2 Hz, H-3); 4.16–
4.28 (m, 3H, H-4, SCH2-Ph); 4.39 (d, 1H, J¼12.3 Hz, CH2-
Ph); 4.45 (d, 1H, CH2-Ph); 4.52 (d, 1H, J¼11.9 Hz, CH2-Ph);
4.57 (d, 1H, CH2-Ph); 4.88 (dd, 1H, J2,1¼6.0 Hz, J2,3¼0.9 Hz,
H-2); 6.03 (d, 1H, H-1), 7.15–7.38 (m, 15H, CHAr); 13C NMR
(CDCl3): d 36.2 (SCH2-Ph); 69.5 (C-5); 71.8; 73.2 (CH2-Ph);
81.7 (C-4); 83.9 (C-3); 88.3 (C-2); 100.8 (C-1); 127.6;
127.7; 127.8; 127.9; 128.0; 128.1; 128.3; 128.4; 128.5;
128,6; 129.0 (CHAr); 136.3; 137.0; 137.9 (Cq); 169.4
(C-S); IR (NaCl): 1608 cm21 (CvN); MS IS m/z¼462.5
[MþHþ]; HRMS: calcd for C27H27NO4S (461.1660), found
(461.1669).
4.2.7. 2-Benzylthio-4,5-dihydro-(10,40,60-tri-O-benzyl-
20,30-dideoxy-b-D-fructofuranoso) [2,3-d]-oxazole 12.
Eluent: petroleum ether–ethyl acetate 80/20, oil (0.75 g;
64%); [a]D¼237 (c 1.1, CHCl3); 1H NMR (CDCl3): d 3.36
(dd, 1H, J6a,6b¼10.3 Hz, J6a,5¼6.1 Hz, H-6a); 3.47 (dd, 1H,
J6b,5¼5.3 Hz, H-6b); 3.70 (d, 1H, J1a,1b¼10.6 Hz, H-1a);
3.78 (d, 1H, H-1b); 4.06 (dd, 1H, J4,3¼1.9 Hz, J4,5¼4.4 Hz,
H-4); 4.20–4.34 (m, 3H, SCH2-Ph, H-5); 4.45–4.65 (m, 6H,
CH2-Ph); 4.96 (d, 1H, H-3); 7.19–7.38 (m, 20H, CHAr); 13
C
4.2.4. 2-Benzylthio-4,5-dihydro-(30,50-di-O-benzyl-10,20-
dideoxy-b-D-xylofuranoso) [1,2-d]-oxazole 10. Eluent:
petroleum ether–ethyl acetate 80/20, yellow oil (1.52 g,
50%); [a]D¼þ37 (c 1.2, CHCl3); 1H NMR (CDCl3): d
3.82–3.88 (m, 2H, H-5); 3.92–3.97 (m, 1H, H-4); 4.06
(d, 1H, J3,4¼3.2 Hz, H-3); 4.31 (d, 1H, J¼13.2 Hz, SCH2-
Ph); 4.37 (d, 1H, J¼13.2 Hz, SCH2-Ph); 4.56 (d, 1H,
J¼11.9 Hz, CH2-Ph); 4.58 (d, 1H, J¼11.9 Hz, CH2-Ph);
4.65 (d, 1H, J¼11.9 Hz, CH2-Ph); 4.72 (d, 1H, J¼11.9 Hz,
CH2-Ph); 4.89 (d, 1H, J2,1¼5.5 Hz, H-2); 6.19 (d, 1H, H-1),
7.28–7.44 (m, 15H, CHAr); 13C NMR (CDCl3): d 36.5
(SCH2-Ph); 67.0 (C-5); 72.2; 73.5 (CH2-Ph); 77.5 (C-4);
81.0 (C-3); 85.5 (C-2); 99.9 (C-1); 127.7; 127.8; 128.0;
128.3; 128.4; 128.5; 128.6; 129.0 (CHAr); 136.2; 137.2;
138.2 (Cq); 165.5 (C-S); IR (NaCl): 1606 cm21 (CvN);
MS IS m/z¼462.5 [MþHþ]; HRMS: calcd for C27H27NO4S
(461.1660), found (461.1665).
NMR (CDCl3): d 36.3 (SCH2); 69.6 (C-6); 71.8; 73.4; 73.6
(CH2-Ph); 72.1 (C-1); 82.1 (C-5); 84.6 (C-4); 89.0 (C-3);
110.0 (C-2); 127.6; 127.7; 127.8; 127.9; 128.4; 128.5;
128.6; 129.1; 136.5 (CHAr); 137.2; 138.0; 138.1 (CqAr);
168.6 (C-S); IR (NaCl): 1596 cm21 (CvN); MS IS
m/z¼582.5 [MþHþ]; HRMS: calcd for C35H35NO5S
(581.2235), found (581.2244).
4.2.8. 2-Benzylthio-4,5-dihydro-(10,40,60-tri-O-benzyl-
20,30-dideoxy-a-L-sorbofuranoso) [2,3-d]-oxazole 13. Elu-
ent: petroleum ether–ethyl acetate 80/20, oil (0.17 g; 42%);
[a]D¼232 (c 1.2, CHCl3); 1H NMR (CDCl3): d 3.73–3.88
(m, 2H, H-6, H-1); 3.92–4.00 (m, 2H, H-5, H-4); 4.23
(d, 1H, J¼13.2 Hz, SCH2-Ph); 4.31 (d, 1H, SCH2-Ph); 4.44
(d, 1H, J¼11.9 Hz; CH2-Ph); 4.46 (d, 1H, CH2-Ph); 4.52–
4.65 (m, 4H, CH2-Ph); 4.83 (s, 1H, H-3); 7.12–7.40
(m, 20H, CHAr); 13C NMR (CDCl3): d 36.5 (SCH2); 67.0
(C-6); 71.5 (C-1); 71.8; 73.5; 73.7 (CH2-Ph); 78.6; 81.2
(C-4, C-5); 85.7 (C-3); 109.4 (C-2); 127.6; 127.7; 127.8;
127.9; 128.3; 128.4; 128.5; 128.6; 129.1 (CHAr); 136.3;
137.4; 138.0; 138.2 (CqAr); 188.8 (CvS); IR (NaCl):
1600 cm21 (CvN); MS IS m/z¼582.5 [MþHþ];; HRMS:
calcd for C35H35NO5S (581.2235), found (581.2231).
4.2.5. 2-Benzylthio-4,5-dihydro-(30,50-di-O-benzyl-1,2-
dideoxy-b-D-ribofuranoso) [1,2-d]-oxazole 11. Eluent:
petroleum ether–ethyl acetate 80/20, white solid (3.5 g;
73%); [a]D¼þ34 (c 1.1, CHCl3); 1H NMR (CDCl3): d 3.62
(dd, 1H, J5a,4¼3.6 Hz, J5a,5b¼10.9 Hz, H-5a); 3.66–

2614
J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
4.2.9. 2-Benzylthio-4,5-dihydro-(30,50-bis-O-(1-methoxy-
1-methylethyl)-10,20-dideoxy-b-D-arabinofuranoso) [1,2-
d]-oxazole 22. The sugar OZT 1 (0.1 g, 0.52 mmol) was
dissolved in DMF under Ar and cooled in an ice-bath.
2-Methoxypropene (5 equiv.) then CSA (0.1 equiv.) were
added. The reaction was run at room temperature for 16 h.
At completion, the solution was basified with Et3N, diluted
with water, then extracted with AcOEt. The organic phases
obtained were collected and washed thoroughly with water
then brine. After evaporation, the residue was dissolved in
DMF and after cooling in an ice bath, NaH (2 equiv.) was
added portionwise then benzyl bromide (2 equiv.). The
reaction was brought to room temperature and stirred until
completion of the reaction (2 h). Ice-cold water was poured
in then the mixture was extracted with AcOEt (3£50 mL).
Organic phases were collected and washed thoroughly with
water, then brine. Purification was effected by column
chromatography with eluents of petroleum ether–ethyl
acetate, yielding 22; eluent: petroleum ether–ethyl acetate
(dd, 1H, J2,1¼6.0 Hz, J2,3¼1.1 Hz, H-2); 6.07 (d, 1H, H-1);
7.23–7.42 (m, 5H, CHAr); 13C NMR (CDCl3): d 25.3; 24.8
(CH3Si); 18.1; 18.4 ((CH3)3C); 25.8; 26.0 ((CH3)3C); 36.4
(SCH2-Ph); 62.3 (C-5); 76.6 (C-3); 86.4 (C-4); 91.0 (C-2);
100.6 (C-1); 127.7; 128.7; 129.1 (CHAr); 136.5 (Cq); 169.6
(C-S); IR (NaCl): 1609 cm21 (CvN); MS IS m/z¼510.0
[MþHþ]; HRMS: calcd for C25H43NO4SSi2 (509.2451),
found (509.2458).
4.2.12. 2-Benzylthio-4,5-dihydro-(30,50-di-O-tertbutyl-
dimethylsilyl-10,20-dideoxy-a-L-arabinofuranoso) [1,2-d]-
oxazole 24. Eluent: petroleum ether–ethyl acetate 90/10,
1
white foam (2.42 g; 80%); [a]D¼þ51 (c 1.1, CH2Cl2); H
NMR (CDCl3): d 20.07; 0.02; 0.03 (3 s, 12H, CH3Si); 0.78;
0.80 (2 s, 18H, (CH3)C); 3.21 (dd, 1H, J5a,5b¼10.5 Hz,
J5b,4¼8.8 Hz, H-5b); 3.49 (dd, 1H, J5a,4¼4.9 Hz, H-5b);
3.86 (m, 1H, H-4); 4.21 (d, 1H, J¼13.2 Hz, SCH2-Ph); 4.24
(d, 1H, SCH2-Ph); 4.30 (s, 1H, H-3); 4.67 (d, 1H,
J2,1¼5.8 Hz, H-2); 5.96 (d, 1H, H-1); 7.16–7.29 (m, 5H,
CHAr); 13C NMR (CDCl3): d 25.1; 24.6 (CH3Si); 18.2;
18.5 ((CH3)3C); 25.9; 26.0; 26.1; 26.2 ((CH3)3C); 36.6
(SCH2-Ph); 62.5 (C-5); 77.1 (C-3); 86.6 (C-4); 91.2 (C-2);
100.7 (C-1); 127.9; 128.9; 129.3 (CHAr); 136.9 (Cq); 169.8
(C-S); IR (NaCl): 1609 cm21 (CvN); MS IS m/z¼510.5
[MþHþ]; HRMS: calcd for C25H43NO4SSi2 (509.2451),
found (509.2455).
1
95/5, oil (0.22 g; 94%); [a]D¼2115 (c 0.1, CHCl3); H
NMR (CDCl3): d 1.29; 1.31; 1.37; 1.41 (4 s, 12H, (CH3)2C);
3.18; 3.22 (2 s, 6H, CH3O); 3.22–3.32 (m, 1H, H-5a); 3;39
(dd, 1H, J5b,4¼8.2 Hz, J5b,5a¼9.7 Hz, H-5b); 4.15 (ddd, 1H,
J4,5a¼6.0 Hz, H-4); 4.28 (s, 2H, SCH2-Ph); 4.42 (d, 1H,
J3,4¼2.2 Hz, H-3); 4.87 (d, 1H, J2,1¼6.0 Hz, H-2); 6.08 (d,
1H, H-1); 7.25–7.45 (m, 5H, CHAr); 13C NMR (CDCl3): d
24.3; 24.4; 24.8; 25.3 ((CH3)2C); 36.4 (SCH2-Ph); 48.7;
49.1 (CH3O); 60.8 (C-5); 75.8 (C-3); 84.2 (C-4); 90.1 (C-2);
100.9 (C-1); 101.1; 101.7 (Cq); 127.7; 128.7; 129.1 (CHAr);
136.7 (Cq); 169.1 (C-S); IR (NaCl): 1603 cm21 (CvN);
MS IS m/z¼426.0 [MþHþ]; 448.0 [MþNaþ]; HRMS: calcd
for C21H31NO6S (425.1872), found (425.1876).
4.2.13. 2-Benzylthio-4,5-dihydro-(30,50-di-O-tertbutyl-
dimethylsilyl-10,20-dideoxy-b-D-xylofuranoso) [1,2-d]-
oxazole 25. Eluent: petroleum ether–ethyl acetate 90/10,
1
oil (0.23 g; 95%); [a]D¼þ41 (c 1.1, MeOH); H NMR
(CDCl3): d 0.07; 0.11; 0.13 (3 s, 12H, CH3Si); 0.91; 0.92
(2s, 18H, (CH3)C); 3.55–3.77 (m, 1H, H-4); 3.80–3.90 (m,
2H, H-5); 4.25 (d, 1H, J3,4¼3.0 Hz, H-3); 4.32 (s, 2H,
SCH2-Ph); 4.70 (d, 1H, J2,1¼5.4 Hz, H-2); 6.09 (d, 1H,
H-1); 7.20–7.35 (m, 5H, CHAr); 13C NMR (CDCl3): d
24.6; 24.5; 24.3; 24.1; 23.8; 23.5 (CH3Si); 18.1; 18.3
((CH3)3C); 25.7; 26.0 ((CH3)3C); 36.5 (SCH2-Ph); 59.9
(C-5); 74.9 (C-3); 79.8 (C-4); 88.8 (C-2); 99.6 (C-1); 127.7;
128.6; 129.0 (CHAr); 136.3 (Cq); 169.4 (C-S); IR (NaCl):
1609 cm21 (CvN); MS IS m/z¼510.5 [MþHþ]; HRMS:
calcd for C25H43NO4SSi2 (509.2451), found (509.2452).
4.2.10. General protocol for the silylation/benzylation of
sugar-OZTs. The sugar-OZT (1 equiv.) was dissolved in
DMF (0.2 M) under Ar and cooled in an ice-bath. Imidazole,
then TBDMSCl (1.2 equiv./OH group) were added. The
reaction was kept at room temperature until completion,
then extracted with AcOEt and water. The organic phases
were collected and washed with water (4–5 times) and
brine, then dried over MgSO4. After evaporation, the
silylated OZT was purified by column chromatography
with petroleum ether-AcOEt solvent mixtures. The purified
OZT was dissolved in DMF, cooled in an ice-bath, NaH
(1.2 equiv.) was added portionwise then benzyl bromide
(1.2 equiv.). The reaction was brought to room temperature
and stirred until completion of the reaction (few hours). Ice-
cold water was poured in then the mixture was extracted
with AcOEt (3£50 mL). Organic phases were collected and
washed thoroughly with water, then brine and dried over
MgSO4. The benzylated compounds were purified by
column chromatography with eluents of petroleum ether–
ethyl acetate.
4.2.14. 2-Benzylthio-4,5-dihydro-(30,50,70-tri-O-tertbutyl-
dimethylsilyl-10,20-dideoxy-b-D-glucofuranoso) [1,2-d]-
oxazole 26. Eluent: petroleum ether–ethyl acetate 90/10,
1
oil (0.23 g; 95%); [a]D¼þ60 (c 1.1, MeOH); H NMR
(CDCl3): d 0.09; 0.10; 0.11; 0.15; 0.17 (5s, 18H, CH3Si);
0.88–0.93 (m, 27H, (CH3)C); 3.55 (dd, 1H, J4,3¼2.6 Hz,
J4,5¼6.6 Hz, H-4); 3.69 (dd, 1H, J6a,6b¼10.9 Hz, H-6b);
3.90 (dd, 1H, H-6a); 4.04–4.13 (m, 1H, H-5); 4.23 (d, 1H,
SCH2-Ph); 4.31–4.28 (m, 1H, H-3); 4.34 (d, 1H, SCH2-Ph);
4.69 (d, 1H, J2,1¼5.4 Hz, H-2); 6.01 (d, 1H, H-1); 7.23–
7.26 (m, 5H, CHAr); 13C NMR (CDCl3): d 25.2; 25.1;
24.4; 24.2; 4.1; 23.4 (CH3Si); 18.1; 18.3; 18.4 ((CH3)3C);
25.9; 26.1 ((CH3)3C); 36.5 (SCH2-Ph); 65.2 (C-6); 71.5 (C-
5); 75.0 (C-3); 80.2 (C-4); 87.2 (C-2); 99.1 (C-1); 127.6;
128.6; 129.0 (CHAr); 136.3 (Cq); 169.3 (C-S); MS IS
m/z¼654.5 [MþHþ]; HRMS: calcd for C33H51NO5SSi2
(629.3026), found (629.3031).
4.2.11. 2-Benzylthio-4,5-dihydro-(30,50-di-O-tertbutyl-
dimethylsilyl-10,20-dideoxy-b-D-arabinofuranoso) [1,2-d]-
oxazole 21. Eluent: petroleum ether–ethyl acetate 90/10, oil
(0.23 g; 95%); [a]D¼251 (c 1.0, CHCl3); 1H NMR
(CDCl3): d 0.05; 0.12; 0.13; 0.15 (4s, 12H, CH3Si); 0.90;
0.93 (2s, 18H, (CH3)C); 3.33 (dd, 1H, J5a,5b¼10.6 Hz,
H-5a); 3.61 (dd, 1H, H-5b); 3.97 (ddd, 1H, J4,3¼2.8 Hz,
J4,5a¼4.7 Hz, J4,5b¼8.5 Hz, H-4); 4.29 (d, 1H, J¼13.2 Hz,
SCH2-Ph); 4.33 (d, 1H, SCH2-Ph); 4.42 (sl, 1H, H-3); 4.77
4.2.15. Generals protocols for cyclocondensation. Method
A: The benzylthiooxazoline (1 equiv.) was dissolved in

J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
2615
0
4.2.18. O2, O2 -Anhydro-3-(30,50-di-O-benzyl-a-D-xylo-
furanosyl)-2,4-quinazolinedione 15. (Method A) Eluent:
petroleum ether–ethyl acetate 50/50, yellow foam (144 mg;
˚
ethanol, then molecular sieves 3 A and the anthranilic acid
derivative (1.3 equiv.) were added. The solution was
refluxed overnight, then poured into an aqueous solution
of NaHCO3 (5%) and extracted with CH2Cl2 (3£50 mL).
The organic phases were collected, washed with water,
brine then dried over MgSO4. The crude mixture obtained
after drying in vacuo was purified by column
chromatography.
1
75%); [a]D¼2169 (c 0.55, CHCl3); H NMR (CDCl3): d
3.77 (dd, 1H, J5 a,4 ¼6.0 Hz, J5 a,5 b¼10.0 Hz, H-50a); 3.84
0
0
0
0
(dd, 1H, J5b,4¼6.0 Hz, H-50b); 4.21 (ddd, 1H, J3 ,4 ¼3.5 Hz,
H-40); 4.32 (d, 1H, H-30); 4.48 (d, 1H, J¼12 Hz, CH2-Ph);
4.55 (d, 1H, J¼12 Hz, CH2-Ph); 4.64 (d, 1H, J¼12 Hz,
CH2-Ph); 4.73 (d, 1H, J¼12 Hz, CH2-Ph); 5.16 (d, 1H,
0
0
0
0
0
0
Method B: The benzylthiooxazoline (1 equiv.) was dis-
˚
solved in tert-butanol then molecular sieves 3 A, camphor-
J2 ,1 ¼5.3 Hz, H-2 ); 6.60 (d, 1H, H-1 ); 7.23–7.38 (m, 11H,
Ph-H, H-6); 7.46 -d, 1H, J8,7¼8.2 Hz, H-8); 7.64 (ddd, 1H,
J7,5¼1.6 Hz, J7,6¼7.2 Hz, H-7); 8.17 (dd, 1H, J5,6¼7.8 Hz,
H-5); 13C NMR (CDCl3): d 66.8 (C-50); 72.9 (CH2-Ph); 73.7
(CH2-Ph); 79.7 (C-40); 80.4 (C-30); 83.7 (C-20); 86.5 (C-10);
119.0 (C-9); 125.1 (C-6); 126.3 (C-8); 127.0 (C-5); 127.2;
127.9; 128.0; 128.3; 128.4; 128.7 (CHAr); 135.2 (C-7);
136.8; 137.7; 148.8 (C-10); 154.5 (C-2); 160.2 (C-4); IR
(NaCl): 1659 cm21 (CvN); 1701 cm21 (CvO); MS IS
m/z¼457 [MþHþ]; HRMS: calcd for C27H24N2O5
(456.1685), found (456.1683).
sulfonic acid (CSA) (1.1 equiv.), the anthranilic acid deriva-
tive (1.3 equiv.) were added. The solution was refluxed
overnight, then poured into an aqueous solution of NaHCO3
(5%) and extracted with CH2Cl2 (3£50 mL). The organic
phases were collected, washed with water, brine then dried
over MgSO4. The crude mixture obtained after drying in
vacuo was purified by column chromatography.
0
4.2.16. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabino-
furanosyl)-2,4-quinazolinedione 3. (Method B) Eluent:
0
petroleum ether–ethyl acetate 70/30, yellow solid (2.62 g;
1
4.2.19. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-b-D-ribo-
89%), mp¼101–103 8C; [a]D¼167 (c 0.59, CHCl3); H
furanosyl)-2,4-quinazolinedione 16. (Method A) Eluent:
petroleum ether–ethyl acetate 70/30, yellow solid (1.66 g;
82%); mp¼83–85 8C; [a]D¼263 (c 0.55; CHCl3); 1H NMR
0
0
0
0
NMR (CDCl3): d 3.33 (dd, 1H, J5 a,4 ¼3.8 Hz, J5 a,5 b¼10.4
Hz, H-50a); 3.76 (dd, 1H, J5 b,4 ¼4.4 Hz, H-5 b); 4.17 (d, 1H,
0
0
0
0
0
0
J¼12.2 Hz, CH2-Ph); 4.24 (d, 1H, CH2-Ph); 4.38
(CDCl3): d 3.64 (dd, 1H, J5 a,4 ¼3.2 Hz, J5 a,5 b¼11.3 Hz,
0
0
00
0
0
0
0
(d, 1H, J3 ,4 ¼2.2 Hz, H-3 ); 4.41–4.47 (m, 1H, H-4 ); 4.59
H-50a); 3.81 (dd, 1H, J5 b,4 ¼1.9 Hz, H-5 b); 3.98–4.06
0
0
(d, 1H, J¼11.6 Hz, CH2-Ph); 4.65 (d, 1H, CH2-Ph); 5.23
(m, 1H, H-40); 4.24 (dd, 1H, J3 ,2 ¼5.1 Hz, J3’,4’¼8.5 Hz,
H-30); 4.48 (d, 1H, J¼11.9 Hz, CH2-Ph); 4.58 (d, 1H, CH2-
Ph); 4.63 (d, 1H, J¼11.5 Hz, CH2-Ph); 4.79 (d, 1H, CH2-
0
0
0
0
(d, 1H, J2 ,1 ¼6.0 Hz, H-2 ); 6.60 (d, 1H, H-1 ), 6.68–7.07
(m, 2H, CHAr); 7.14–7.20 (m, 3H, CHAr); 7.27–7.41
(m, 6H, H-60, 5£CHAr); 7.45 (dd, 1H, J8,6¼0.6 Hz,
0
0
0
0
Ph); 5.11 (dd, 1H, J2 ,1 ¼5.3 Hz, H-2 ); 6.55 (d, 1H, H-1 ),
7.24–7.42 (m, 11H, H-6, CHAr); 7.53 (d, 1H, J8,7¼7.7 Hz,
H-8); 7.69 (ddd, 1H, J7,5¼1.3 Hz, J7,6¼7.2 Hz, H-7); 8.22
(d, 1H, J5,6¼8.0 Hz, H-5); 13C NMR (CDCl3): d 67.1 (C-50);
73.0; 73.7 (CH2-Ph); 76.7 (C-30); 78.6 (C-20); 79.1 (C-40);
86.4 (C-10); 119.0 (C-9); 125.1 (C-6); 126.4 (C-8); 127.2
(C-5); 127.8; 127.9; 128.2; 128.4; 128.5; 128.6 (CHAr);
135.3 (C-70); 136.9; 137.7 (Cq); 149.0 (C-10); 155.1 (C-2)
160.3 (C-4); IR (NaCl): 1656 cm21 (CvN); 1702 cm21
(CvO); MS IS m/z¼457 [MþHþ]; HRMS: calcd for
C27H24N2O5 (456.1685), found (456.1691).
J8,7¼8.2 Hz, H-8); 7.64 (ddd, 1H, J7,5¼1.3 Hz, J7,6
¼
7.2 Hz, H-7); 8.31 (dd, 1H, J6,5¼8.2 Hz, H-5); 13C NMR
(CDCl3): d 69.0 (C-50); 72.4; 73.4 (CH2-Ph); 83.3 (C-30);
85.5 (C-40); 85.9 (C-20); 87.7 (C-10); 118.9 (C-9); 124.9
(C-6); 126.3 (C-8); 127.2 (C-5); 127.8; 127.9; 128.1; 128.3;
128.4; 128.7 (CHAr); 135.1 (C-7); 136.5; 137.1 (Cq); 149.1
(C-10); 156.7 (C-2) 160.2 (C-4); IR (NaCl): 1693 cm21
(CvN); 1646 cm21 (CvO); MS IS m/z¼457.5 [MþHþ];
HRMS: calcd for C27H24N2O5 (456.1685), found
(456.1690).
0
0
4.2.17. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-a-L-arabino-
furanosyl)-2,4-quinazolinedione 14. (Method A) Eluent:
4.2.20. O 2, O 3 -Anhydro-3-(10,40,60-tri-O-benzyl-b-D-
fructofuranosyl)-2,4-quinazolinedione 17. (Method B
with 2 equiv. of CSA) Eluent: petroleum ether–ethyl
acetate 80/20, pale yellow oil (90 mg; 57%); [a]D¼231
(c 0.74; CHCl3); 1H NMR (CDCl3): d 3.30 (dd, 1H,
petroleum ether–ethyl acetate 70/30, yellow solid (79 mg;
1
79%); mp¼101–103 8C; [a]D¼2169 (c 0.55, CHCl3); H
0
0
0
0
NMR (CDCl3): d 3.35 (dd, 1H, J5 a,4 ¼3.8 Hz, J5 a,5 b¼10.7
Hz, H-50a); 3.39 (dd, 1H, J5 b,4 ¼4.4 Hz, H-5 b); 4.19
J6 a,5 ¼3.6 Hz, J6 a,6 b¼10.7 Hz, H-60a); 3.37 (dd, 1H,
0
0
0
0
0
0
00
J6 b,5 ¼4.2 Hz, H-6 b); 3.92 (d, 1H, J1 a,1 b¼10.4 Hz, H-10a);
0
0
0
0
(d, 1H, J¼12.3 Hz, CH2-0Ph); 4.25 (d, 1H, CH2-Ph); 4.39
0
0
0
(d, 1H, J3 ,4 ¼2.2 Hz, H-3 ); 4.43–4.48 (m, 1H, H-4 ); 4.61
4.13 (d, 1H, J¼12.3 Hz, CH2-Ph); 4.19 (d, 1H, CH2-Ph);
0
0
0
(d, 1H, J¼11.9 Hz, CH2-Ph); 4.67 (d, 1H, CH2-Ph); 5.23
4.33 (dd, 1H, J4,3¼0.9 Hz, J4 ,5 ¼2.5 Hz, H-4 ); 4.45–4.71
(m, 6H, 2 CH2-Ph, H-10b, H-50); 5.14 (s, 1H, H-30); 6.95–
7.03 (m, 2H, CHAr); 7.11–7.39 (m, 14H, H-6, CHAr); 7.43–
7.50 (m, 1H, H-8); 7.36 (ddd, 1H, J7,5¼1.6 Hz,
J7,6¼J7,8¼7.2 Hz, H-7); 8.20 (d0d, 1H, J5,6¼8.0 Hz, H-5);
13C NMR (CDCl3): d 68.5 (C-6 ); 69.1 (C-10); 72.2; 73.5;
73.7 (CH2-Ph); 84.1 (C-40); 86.3 (C-50); 87.2 (C-30); 100.7
(C-20); 119.4 (C-9); 124.7 (C-6); 126.2 (C-8); 127.1 (C-5);
127.8; 127.9; 128.0; 128.3; 128.4; 128.5; 128.6; 128.7
(CHAr); 135.0 (C-7); 136.6; 137.1; 137.4 (Cq); 149.1 (C-10);
155.2 (C-2) 160.7 (C-4); IR (NaCl): 1695 (CvN); 1648
(CvO); MS IS m/z¼577.5 [MþHþ]; HRMS: calcd for
C35H32N2O6 (576.2260), found (576.2267).
0
0
0
0
(d, 1H, J2 ,1 ¼5.7 Hz, H-2 ); 6.62 (d, 1H, H-1 ), 6.99–7.07
(m, 2H, CHAr); 7.14–7.22 (m, 3H, CHAr); 7.28–7.42
(m, 6H, H-6, 5£CHAr); 7.47 (dd, 1H, J8,6¼0.9 Hz, H-8);
7.66 (ddd, 1H, J7,5¼J7,6¼7.2 Hz, J7,5¼1.6 Hz, H-7); 8,23
(dd, 1H, J5,6¼8.0 Hz, H-5); 13C NMR (CDCl3): d 69.1 (C-50);
72.5; 73.5 (CH2-Ph); 83.6 (C-30); 85.4 (C-40); 86.0 (C-20);
87.7 (C-10); 119.0 (C-9); 125.0 (C-6); 126.4 (C-8); 127. (C-5);
127.9; 128.0; 128.2; 128.4; 128.5; 128.8 (CHAr); 135.2;
136.5 (Cq); 137.1 (C-7); 149.2 (C-10); 154.7 (C-2) 160.3
(C-4); IR (NaCl): 1693 cm21 (CvN); 1646 cm21 (CvO);
MS IS m/z¼457.0 [MþHþ]; HRMS: calcd for C27H24N2O5
(456.1685), found (456.1694).

2616
J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
0
4.2.21. O23, O 3 -Anhydro-3-(10,40,60-tri-O-benzyl-a-L-
sorbofuranosyl)-2,4-quinazolinedione 18. (Method
B without CSA) Eluent: petroleum ether–ethyl acetate
90/10, white solid (124 mg; 99%); mp: 69–71 8C; [a]D¼
þ133 (c 1.1; CH2Cl2); 1H NMR (CDCl3): d 0.04; 0.06; 0.19;
0.22 (4s, 12H, CH3Si); 0.88; 0.96 (2s, 18H, (CH3)C); 3.82–
B
with 2 equiv. of CSA) Eluent: petroleum ether–ethyl
acetate 80/20, pale yellow oil (110 mg; 70%); [a]D¼228
(c 1.04; CHCl3); 1H NMR (CDCl3): d 3.40 (dd, 1H,
3.92 (m, 1H, H-50); 3.97–3.99 (m, 1H, H-40); 4.55 (dd, 1H,
J6 a,5 ¼5.0 Hz, J6 a,6 b¼10.0 Hz, H-60a); 3.79 (dd, 1H,
J3 ,2 ¼1.3 Hz, J3 ,4 ¼3.2 Hz, H-3 ); 5.04 (d, 1H, J2 ,1
¼
0
00
0
0
0
0
0
0
0
0
0
J6 b,5 ¼5.8 Hz, H-6 b); 3.80 (d, 1H, J1 a,1 b¼10.0 Hz, H-10a);
4.19–4.27 (m, 2H, H-40, H-50); 4.43 (d, 1H, J¼11.9 Hz,
CH2-Ph); 4.46 (d, 1H, J¼12.3 Hz, CH2-Ph); 4.47 (d, 1H,
J¼14.4 Hz, CH2-Ph); 4.58 (d, 0 1H, CH2-Ph); 4.62
(d, 1H, CH2-Ph); 4.78 (d 1H, H-1 b); 5.01 (s, 1H, H-30);
7.15–7.36 (m, 16H, H-6, CHAr); 7.49 (dd, 1H, J8,6¼0.6 Hz,
J8,7¼7.9 Hz, H-8); 7.65 (ddd, 1H, J7,5¼1.6 Hz, H-7); 8.19
(dd, 1H, J5,6¼7.9 Hz, H-5); 13C NMR (CDCl3): d 68.4 (C-60);
67.7 (C-10); 72.5; 73.6; 73.7 (CH2-Ph); 80.4; 80.8 (C-40, C-50);
84.4 (C-30); 99.7 (C-20); 119.6 (C-9); 124.9 (C-6); 126.2 (C-8);
127.2 (C-5); 127.8; 127.9; 128.3; 128.4; 128.5; 128.7 (CHAr);
135.1 (C-7); 136.8; 137.4; 137.7 (Cq); 148.8 (C-10); 155.0
(C-2) 160.7 (C-4); IR (NaCl): 1699 (CvN); 1647 (CvO);
MS IS m/z¼577.5 [MþHþ]; HRMS: calcd for C35H32N2O6
(576.2260), found (576.2263).
5.2 Hz, H-20); 6.60 (d, 1H, H-10), 7.30 (dd, 1H, J6,5
¼
0
0
0
0
J6,7¼8.0 Hz, H-6); 7.47 (d, 1H, J8,7¼8.2 Hz, H-8); 7.62 (dd,
1H, H-7); 8.23 (dd, 1H, H-5); 13C NMR (CDCl3): d 25.5;
25.4; 24.8 (CH3Si); 18.0; 18.2((CH3)3C); 25.7; 25.8
((CH3)3C); 59.3 (C-50); 74.0 (C-30); 81.8 (C-40); 86.2 (C-20);
86.3 (C-10); 118.9 (C-9); 124.9 (C-6); 126.2 (C-8); 127.0
(C-5); 135.0 (C-7); 148.8 (C-10); 154.2 (C-2); 160.1 (C-4);
IR (NaCl): 1696 (CvN); 1651 (CvO); MS IS m/z¼505.5
[MþHþ]; HRMS: calcd for C25H40N2O5Si2 (504.2475),
found (504.2483).
0
4.2.25. O 2, O 2 -Anhydro-3-(30,50,60-tri-O-tertbutyldi-
methylsilyl-b-D-glucofuranosyl)-2,4-quinazolinedione
29. (Method B without CSA) Eluent: petroleum ether–ethyl
acetate 90/10, white solid (85 mg; 59%); mp: 71–74 8C;
1
[a]D¼þ140 (c 1.0; CH2Cl2); H NMR (CDCl3): d 20.11;
0
4.2.22. O 2, O 2 -Anhydro-3-(30,50-di-O-tertbutyldimethyl-
silyl-b-D-arabinofuranosyl)-2,4-quinazolinedione 23.
(Method B without CSA) Eluent: petroleum ether–ethyl
20.04; 0.06; 0.08; 0.18; 0.21 (6s, 18H, CH3Si); 0.62; 0.84;
0.93 (3s, 27H, (CH3)C); 3.82–3.92 (m, 2H, H-60); 3.96 (dd,
0
0
0
0
1H, J5 ,4 ¼4.2 Hz, H-4 ); 4.06–4.09 (m, 1H, H-5 ); 4.55
0 0
0 0 0 0
acetate 90/10, white solid (124 mg; 85%); mp: 111–112 8C;
1
(d, 1H, J3 ,4 ¼2.4 Hz, H-3 ); 5.02 (d, 1H, J2 ,1 ¼4.8 Hz, H-2 );
6.56 (d, 1H, H-10), 7.33 (ddd, 1H, J6,8¼1.0 Hz,
J6,5¼J6,7¼8.1 Hz, H-6); 7.50 (d, 1H, J8,7¼7.7 Hz, H-8);
7.64 (ddd, 1H, J7,5¼1.6 Hz, H-7); 8.20 (dd, 1H, H-5); 13C
NMR (CDCl3): d 25.8; 25.7; 24.3; 24.1; 24.0; 23.3
(CH3Si); 18.1; 18.3 ((CH3)3C); 25.7; 25.8; 26.0 ((CH3)3C);
64.1 (C-600); 70.7 (C-50); 74.3 (C-30); 81.7 (C-40); 85.5 (C-20);
86.0 (C-1 ); 119.2 (C-9); 125.2 (C-6); 126.4 (C-8); 127.2
(C-5); 135.2 (C-7); 148.9 (C-10); 154.8 (C-2) 160.2 (C-4);
IR (NaCl): 1701 (CvN); 1647 (CvO); MS IS m/z¼505.5
[MþHþ]; HRMS: calcd for C32H56N2O6Si3 (648.3446),
found (648.3457).
[a]D¼2193 (c 0.45; CHCl3); H NMR (CDCl3): d 0.06;
0.20; 0.23 (3 s, 12H, CH3Si); 0.80; 0.97 (2s, 18H, (CH3)C);
0
3.52 (dd, 1H, J5 a,4 ¼6.9 Hz, J5 a,5 b¼11 Hz, H-50a); 3.67
0
0
0
0
0
0
0
(dd, 1H, J5 b,4 ¼4.2 Hz, H-5 b); 4.14–4.22 (m, 1H, H-4 );
0
0
0
0
0
4.73 (dd, 1H, J3 ,2 ¼1.3 Hz, J3 ,4 ¼3.1 Hz, H-3 ); 5.14 (dd,
0
0
0
0
1H, J2 ,1 ¼5.6 Hz, H-2 ); 6.62 (d, 1H, H-1 ), 7.36 (ddd, 1H,
J6,8¼1.2 Hz, J6,5¼J6,7¼7.2 Hz, H-6); 7.53 (dd, 1H, J8,7
¼
8.2 Hz, H-8); 7.70 (ddd, 1H, J7,5¼1.5 Hz, H-7); 8.23 (dd,
1H, H-5); 13C NMR (CDCl3): d 25.5; 25.4; 24.8; 24.7
(CH3Si); 18.0; 18.2 ((CH3)3C); 25.7; 25.8 ((CH3)3C); 61.8
(C-50); 75.9 (C-30); 86.7 (C-10); 88.4 (C-20); 88.8 (C-40);
118.9 (C-9); 125.1 (C-6); 126.4 (C-8); 127.2 (C-5); 135.2
(C-7); 149.0 (C-10); 154.2 (C-2) 160.1 (C-4); IR (NaCl):
1698 (CvN); 1647 (CvO); MS IS m/z¼505.5 [MþHþ];
HRMS: calcd for C25H40N2O5Si2 (504.2475), found
(504.2486).
0
4.2.26. O2, O2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabino-
furanosyl)-6-methyl-2,4-quinazolinedione 30. (Method
B) Eluent: petroleum ether–ethyl acetate 70/30, white
solid (89 mg; 92%); mp: 125–128 8C; [a]D¼98 (c 1;
CHCl3); 1H NMR (CDCl3): d 2.41 (s, 3H, CH3); 3.35
0
4.2.23. O 2, O 2 -Anhydro-3-(30,50-di-O-tertbutyldimethyl-
silyl-b-L-arabinofuranosyl)-2,4-quinazolinedione
(Method B without CSA) Eluent: petroleum ether–ethyl
(d, 2H, J5 a,5 b¼4.4 Hz, H-50); 4.18 (d, 1H, J¼12.2 Hz, CH2-
0
0
0
0
0
27.
Ph); 4.25 (d, 1H, CH2-Ph); 4.37 (d, 1H, J3 ,4 ¼2.2 Hz, H-3 );
4.40–4.47 (m, 1H, H-40); 4.59 (d, 1H, J¼11.9 Hz, CH2-Ph);
0
0
0
acetate 90/10, white gum (82 mg; 85%); [a]D¼þ144 (c 1.0;
4.64 (d, 1H, CH2-Ph); 5,21 (d, 1H, J2 ,1 ¼6.0 Hz, H-2 ); 6.59
(d, 1H, H-10), 6.69–7.08 (m, 2H, CHAr); 7.13–7.22 (m, 3H,
CHAr); 7.27–7.41 (m, 6H, H-8, CHAr); 7.46 (dd, 1H,
J7,5¼2.0 Hz, J7,8¼8.7 Hz, H-7); 7.98 (s, 1H, H-5); 13C
NMR (CDCl3): 21.0 (CH3); 69.0 (C-50); 72.4; 73.4 (CH2-
Ph); 83.5 (C-30); 85.2 (C-40); 85.8 (C-20); 87.6 (C-10); 118.6
(C-9); 126.1 (C-8); 126.7 (C-5); 126.8; 126.9; 128.0; 128.3;
128.7 (CHAr); 134.9 (C-7); 136.4; 136.5 (Cq); 137.2 (C-6);
146.9 (C-10); 154.2 (C-2); 160.2 (C-4); IR (KBr): 1686
(CvN); 1643 (CvO); MS IS m/z¼471.5 [MþHþ], 493.5
[MþNaþ]; HRMS: calcd for C28H26N2O5 (470.1841),
found (470.1848).
1
CH2Cl2); H NMR (CDCl3): d 0.06; 0.12; 0.32; 0.36 (4s,
12H, CH3Si); 0.93; 1.10 (2s, 18H, (CH3)C); 3.60–3.82 (m,
2H, H-50); 4.27–4.39 (m, 1H, H-40); 4.86 (d, 1H,
0
0
0
0
0
0
J3 ,4 ¼2.2 Hz, H-3 ); 5.26 (d, 1H, J2 ,1 ¼6.3 Hz, H-2 ); 6.75
(d, 1H, H-10), 7.47 (dd, 1H, J6,5¼J6,7¼7.8 Hz, H-6); 7.64 (d,
1H, J8,7¼8.0 Hz, H-8); 7.82 (dd, 1H, H-7); 8.34 (dd, 1H,
H-5); 13C NMR (CDCl3): d 25.5; 25.2; 24.6; 24.5
(CH3Si); 18.2; 18.4 ((CH3)3C); 25.9 ((CH3)3C); 62.0 (C-50);
76.1 (C-30); 86.6 (C-40); 88.6 (C-20); 88.9 (C-10); 123.7 (C-9);
126.1 (C-6); 127.8 (C-8); 129.4 (C-5); 130.8 (C-7); 137.5
(C-10); 143.5 (C-2) 160.9 (C-4); MS IS m/z¼505.5
[MþHþ]; HRMS: calcd for C25H40N2O5Si2 (504.2475),
found (504.2482).
0
4.2.27. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabi-
nofuranosyl)-7-chloro-2,4-quinazolinedione 31. (Method
B) Eluent: petroleum ether–ethyl acetate 90/10, white solid
(91 mg; 86%); mp: 96–98 8C; [a]D¼2128 (c 1; CHCl3); 1H
0
4.2.24. O 2, O 2 -Anhydro-3-(30,50-di-O-tertbutyldimethyl-
silyl-b-D-xylofuraosyl-2,4-quinazolinedione 28. (Method

J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
2617
0
0
0
0
0
0
0
NMR (CDCl3): d 3.33 (dd, 1H, J5 a,4 ¼3.3 Hz, J5 a,5 b¼10.5
Hz, H-50a); 3.41 (dd, 1H, J5 b,4 ¼4.4 Hz, H-5 b); 4.16 (d, 1H,
Hz, H-50a); 3.40 (dd, 1H, J5 b,4 ¼3.9 Hz, H-5 b); 4.15 (d, 1H,
J¼12.3 Hz, CH2-Ph); 4.25 (d, 1H, CH2-Ph); 4.40 (d, 1H,
0
0
0
0
0
0
0
J¼12.2 Hz, CH2-Ph); 4.22 (d, 1H, CH2-Ph); 4.37
J3 ,4 ¼2.2 Hz, H-3 ); 4.44–4.50 (m, 1H, H-4 ); 4,62 (d, 1H, J¼
11.9 Hz, CH2-Ph); 4.68 (d, 1H, CH2-Ph); 5.25 (d, 1H,
J2,1¼5.6 Hz, H-20); 6.65 (d, 1H, H-10), 6.99–7.06 (m, 2H,
CHAr); 7.09–7.16 (m, 3H, CHAr); 7.29–7.43 (m, 5H, CHAr);
7.48 (ddd, 1H, J8,6¼1.3 Hz, J8,7¼6.6 Hz, J8,9¼8.2 Hz, H-8);
7.57 (ddd, 1H, J7,9¼1.3 Hz, J7,6¼6.6 Hz, H-7); 7.84–7.92
(m, 2H, H-9, H-10); 8.00 (d, 1H, H-6); 8.83 (s, 1H, H-5); 13C
NMR (CDCl3): d 69.1 (C-50); 72.5; 73.5 (CH2-Ph); 83.6
(C-30); 85.4 (C-40); 85.9 (C-20); 87.5 (C-10); 118.2 (C-11);
123.3 (C-10); 125.9 (C-8); 127.6 (C-9); 127.8; 127.9; 128.2;
128.4; 128.5; 128.8 (CHAr); 128.9 (C-7); 129.1 (C-5); 129.5
(C-6); 130.4 (C-13); 136.5 (C-14); 137.1; 137.3 (Cq); 143.5
(C-12); 154.0 (C-2) 160.8 (C-4); IR (KBr): 1690 (CvN);
1650 (CvO); MS IS m/z¼507.5 [MþHþ], 529.5 [MþNaþ];
HRMS: calcd for C31H26N2O5 (506.1841), found
(506.1843).
0
0
0
0
(d, 1H, J3 ,4 ¼1.9 Hz, H-3 ); 4.41–4.49 (m, 1H, H-4 ); 4.59
(d, 1H, J¼11.6 Hz, CH2-Ph); 4.65 (d, 1H, CH2-Ph); 5.24
(d, 1H, J2,1¼6.0 Hz, H-20); 6.59 (d, 1H, H-10), 6.96–7.05
(m, 2H, H-6, H-8); 7.12–7.43 (m, 10H, CHAr); 8.10 (d, 1H,
J5,6¼8.5 Hz, H-5); 13C NMR (CDCl3): d 69.1 (C-5); 72.5;
73.5 (CH2-Ph); 83.7 (C-30); 85.7 (C-40); 86.1 (C-20); 87.8
(C-10); 117.4 (C-9); 125.4 (C-6); 126.0 (C-8); 127.8; 127.9;
128.1; 128.3; 128.4; 128.8 (C-5, CHAr); 136.4; 136.9 (Cq);
141.2 (C-7); 150.2 (C-10); 155.5 (C-2) 159.6 (C-4); IR
(KBr): 1687 (CvN); 1647 (CvO); MS IS m/z¼491
[MþHþ], 513 [MþNaþ]; HRMS: calcd for C27H23ClN2O5
(490.1295), found (490.1302).
0
4.2.28. O2, O2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabino-
furanosyl)-6-bromo-2,4-quinazolinedione 32. (Method B)
Eluent: petroleum ether–ethyl acetate 90/10, white solid
(109 mg; 94%); mp: 75–77 8C; [a]D¼2167 (c 1.0; CHCl3);
4.2.31. 3-(30,50-Di-O-benzyl-b-D-arabinosyl)-2,4-quin-
azolinedione 35. The anhydro-nucleoside
1H NMR (CDCl3): d 3.24 (dd, 1H, J5 a,4 ¼3.4 Hz,
3 (0.5 g;
0
0
J5 a,5 b¼10.4 Hz, H-50a); 3.30 (dd, 1H, J5 b,4 ¼4.2 Hz,
1.1 mmol) dissolved in EtOH (40 mL) and HCl (2 M,
10 mL) was heated at 50 8C for 4 days. Ethanol was
removed in vacuo then extraction with ethyl acetate - 5%
aqueous solution of NaHCO3 was performed. The organic
fractions were collected and washed with H2O then dried
over MgSO4. After evaporation, the residue was purified on
column chromatography with petroleum ether–ethyl acet-
ate (6/4). Compound 35 was isolated as a white solid
0
0
0
0
H-50b); 4.06 (d, 1H, J¼12.6 Hz, CH2-Ph); 4.13 (d, 1H, CH2-
0
0
0
Ph); 4.28 (d, 1H, J3 ,4 ¼1.7 Hz, H-3 ); 4.32–4.40 (m, 1H,
H-40); 4.50 (d, 1H, J¼11.6 Hz, CH2-Ph); 4.56 (d, 1H, CH2-
0
0
0
0
Ph); 5.15 (d, 1H, J2 ,1 ¼6.0 Hz, H-2 ); 6,50 (d, 1H, H-1 ),
6.88–7.33 (m, 11H, H-8, CHAr); 7.60 (dd, 1H, J7,5¼2.3 Hz,
J7,8¼8.7 Hz, H-7); 8.21 (d, 1H, H-5); 13C NMR (CDCl3): d
69.0 (C-50); 72.5; 73,4 (CH2-Ph); 83.6 (C-30); 85.7 (C-40);
86.1 (C-20); 87.8 (C-10); 118.0 (C-9); 120.5 (C-6); 127.8;
127.9; 128.0; 128.1; 128.4; 128.5; 128.7; 128.8 (C-8, CHAr);
129.6 (C-5); 136.4; 136.9 (Cq); 138.1 (C-7); 148.0 (C-10);
155.5 (C-2) 159.0 (C-4); IR (NaCl): 1694 (CvN); 1649
(CvO); MS IS m/z¼537 [MþHþ]; 559 [MþNaþ]; HRMS:
calcd for C27H23BrN2O5 (534.0790), found (534.0796).
(390 mg; 76%), mp: 90–92 8C; [a]D¼277 (c 0.59; CHCl3);
0
1H NMR (CDCl3): d 3.53 (d, 1H, JOH,2 ¼11.0 Hz, OH-2 );
0
3.74 (dd, 1H, J5 a,4 ¼3.1 Hz, J5 a,5 b¼10.4 Hz, H-50a); 3.88
0
0
0
0
0
0
0
0
0
(dd, 1H, J5 b,4 ¼7.5 Hz, H-5 b); 4.06–4.17 (m, 1H, H-4 );
0
0
0
0
4.29 (d, 1H, J3 ,2 ¼5.7 Hz, J3 ,4 ¼7.5 Hz, H-3 ); 4.54 (d, 1H,
J¼11.9 Hz, CH2-Ph); 4.60 (d, 1H, CH2-Ph); 4.62–4.75 (m,
2H, H-20, CH2-Ph); 4.85 (d, 1H, J¼11.9 Hz, CH2-Ph); 6.79
0
0
4.2.29. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabino-
(d, 1H, J1 ,2 ¼7.9 Hz, H-1 ), 6.95 (d, 1H, J8,7¼8.2 Hz, H-8);
7.08–7.39 (m, 11H, H-6, CHAr); 7.50 (ddd, 1H, J7,5¼1.3 Hz,
J7,6¼8.5 Hz, H-7); 7.90 (dd, 1H, J5,6¼8.2 Hz, H-5); 9.75
(s, 1H, NH); 13C NMR (CDCl3): d 70.9 (C-50); 72.3; 73.3
(CH2-Ph); 79.1 (C-20); 79.2 (C-40); 82.1 (C-10); 85.9 (C-30);
114.6 (C-9); 115.2 (C-8); 123.7 (C-6); 127.7; 127.8; 127.9;
128.0; 128.4; 128.6 (C-5, CHAr); 135.6 (C-7); 138.0; 138.1
(Cq); 138.4 (C-10); 152.0 (C-2); 163.2 (C-4); IR (KBr):
1661 (CvO); 1724 (CvO); MS IS m/z¼475.5 [MþHþ],
497.5 [MþNaþ]; HRMS: calcd for C27H26N2O6 (474.1791),
found (474.1789).
0
0
furanosyl)-6-iodo-2,4-quinazolinedione 33. (Method B)
Eluent: petroleum ether–ethyl acetate 70/30, white solid
(98 mg; 78%); mp: 90–93 8C; [a]D¼2173 (c 0.85; CHCl3);
1H NMR (CDCl3): d 3.32 (dd, 1H, J5 a,4 ¼3.5 Hz,
0
0
J5 a,5 b¼10.4 Hz, H-50a); 3.38 (dd, 1H, J5 b,4 ¼4.1 Hz,
0
0
0
0
H-50b); 4.14 (d, 1H, J¼12.2 Hz, CH2-Ph); 4,21 (d, 1H,
0
0
0
CH2-Ph); 4.36 (d, 1H, J3 ,4 ¼2.2 Hz, H-3 ); 4.41–4.48
(m, 1H, H-40); 4.58 (d, 1H, J¼11.9 Hz, CH2-Ph); 4.64
0
0
0
(d, 1H, CH2-Ph); 5.24 (d, 1H, J2 ,1 ¼6.0 Hz, H-2 ); 6.28
(d, 1H, H-10), 6.96–7.04 (m, 2H, CHAr); 7.13–7.23 (m, 4H,
H-8, CHAr); 7.26–7.40 (m, 5H, CHAr); 7.86 (dd, 1H,
J7,5¼2.2 Hz, J7,8¼8.5 Hz, H-7); 8.48 (d, 1H, H-5); 13C
NMR (CDCl3): d 69.0 (C-50); 72.5; 73.4 (CH2-Ph); 83.6
(C-30); 85.6 (C-40); 86.1 (C-20); 87.8 (C-10); 88.3 (C-6);
120.8 (C-9); 127.8; 127.9; 128.1; 128.2; 128.3; 128.4; 128.7
(C-8, CHAr); 135.7 (C-5); 136.4; 136.9 (Cq); 143.6 (C-7);
148.5 (C-10); 155.1 (C-2) 158.8 (C-4); IR (KBr): 1691
(CvN); 1650 (CvO); MS IS m/z¼583 [MþHþ], 605
[MþNaþ]; HRMS: calcd for C27H23IN2O5 (656.9623),
found (656.9619).
4.2.32. 3-b-D-Arabinosyl-2,4-quinazolinedione 36. The
benzylated compound 35 (0.21 g; 0.44 mmol) was dissolved
in acetic acid (5 mL) containing Pd/C 10% (0.2 g) and
stirred overnight under hydrogen pressure at room tem-
perature. The solution was filtered over Celitew, evaporated
to give pure 36 (96 mg, 74%), mp: 178–183 8C; [a]D¼27 (0c
1.0; pyridine); 1H NMR (CDCl3): d 3.55–3.68 (m, 3H, H-4 ,
H-50); 4.18–4.28 0 (m, 2H, H-20, H-30); 6.55 (d, 1H,
0
0
J1 ,2 ¼7.5 Hz, H-1 ); 7.08–7.22 (m, 2H, H-6, H-8); 7.59
(ddd, 1H, J7,5¼1.5 Hz, J7,6¼J7,8¼8.0 Hz, H-7); 7.850(d, 1H,
J5,6¼8.0 Hz, H-5);; 13C NMR (CDCl3): d 62.1 (C-5 ); 76.2
(C-20); 76.9 (C-30); 81.4 (C-10); 83.1 (C-40); 114.2 (C-9);
115.4 (C-8); 122.8 (C-6); 127.8 (C-5); 135.5 (C-7); 139.9
(C-10); 150.4 (C-2); 162.5 (C-4); IR (KBr): 1688 (CvO);
1744 (CvO); MS IS m/z¼295 [MþHþ], 317 [MþNaþ];
0
4.2.30. O 2, O 2 -Anhydro-3-(30,50-di-O-benzyl-b-D-arabino-
furanosyl)-5,6-naphtyl-2,4-pyrimidinedione 34. (Method B)
Eluent: CH2Cl2-MeOH 98/2, pale yellow solid (71 mg;
1
65%); mp: 97–100 8C; [a]D¼2147 (c 0.64; CHCl3); H
0
0
0
0
NMR (CDCl3): d 3.36 (dd, 1H, J5 a,4 ¼3.6 Hz, J5 a,5 b¼10.4

2618
J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
HRMS: calcd for C13H14N2O6 (294.0852), found
(294.0854); calcd for C13H14N2O6 (H 4.80, C 53.06, N
9.52), found (H 4.85, C 52.64, N 9.45).
b-D-arabinosyl)-2,4-quinazolinedione 39. Compound 35
(0.3 g; 0.63 mmol) was dissolved in CH2Cl2; DMAP
(0.17 g, 1.38 mmol) then phenyl chlorothionoformiate
(0.194 mL; 1.38 mmol) were added successively. The
mixture was stirred overnight at room temperature, then
NaOH (1 M) was added and extraction was performed with
CH2Cl2. The collected organic phases were washed with
HCl 1 M, water and finally dried over MgSO4. After solvent
removal, column chromatography purification (petroleum
ether/AcOEt 6/4) afforded compound 39 (0.33 g, 85%) as a
colourless gum; [a]D¼217 (c 1.0; CDCl3); 1H NMR
4.2.33. 3-(30,50-Di-O-benzyl-b-D-ribosyl)-2,4-quinazoli-
nedione 37. Compound 35 (136 mg; 0.29 mmol) was
dissolved in CH2Cl2 (2 mL) then pyridine (162 ml;
2.01 mmol) and DMAP (4 mg; 0.03 mmol) were added.
The solution was cooled to -78 8C, then triflic anhydride
(218 ml, 0,86 mmol) was slowly added. The reaction was
slowly brought to room temperature and stirred 1 h more.
After treatment with water, the mixture was extracted twice
with CH2Cl2. The organic phases collected were washed
with aqueous solution of NaHCO3 (5%), then water, and
dried over MgSO4. The solvent was removed. The crude
residue was dissolved in DMF (1 mL), then sodium nitrite
(91 mg, 1.32 mmol) was added. The solution was stirred
overnight at room temperature. After hydrolysis with HCl
1 M (2.5 mL), extraction was performed with CH2Cl2.
Collected organic phases were neutralized (5% NaHCO3
aqueous solution) then washed with water and dried over
MgSO4. The solvent was removed in vacuo and the residue
was purified on silica gel to yield compound 37 (60 mg;
0
0
0
00
(CDCl3): d 3.84 (dd, 1H, J5 b,4 ¼3.1 Hz, J5 b,5 a¼10.4 Hz,
H-50b); 4.01 (dd, 1H, J5 a,4 ¼7.9 Hz, H-5 a); 4.25–4.35
(m, 1H, H-40); 4.53 (d, 1H, Jgem¼11.9 Hz, CH2-Ph); 4.62
(d, 1H, CH2-Ph); 4.66 (d, 1H, Jgem¼11.6 Hz, CH2-Ph); 4.73
0
0
0
0
0
0
(d, 1H, CH2-Ph); 4.96 (dd, 1H, J3 ,2 ¼6.6 Hz, J3 ,4 ¼7.9 Hz,
H-30); 6.10 (dd, 1H, J2 ,1 ¼8.2 Hz, H-2 ); 6.57–6.65 (m, 2H,
CHAr); 6.90–7.40 (m, 16H, H-10, H-6, H-8, CHAr); 7.51
(ddd, 1H, J7,6¼J7,8¼J5,6¼8.2 Hz, H-7); 8.04 (dd, 1H,
J5,7¼1.3 Hz, H-5); 10.43 (s, 1H, NH); 13C NMR (CDCl3):
d 71.0 (C-50); 73.1; 73.4 (CH2-Ph); 79.6 (C-10); 79.8 (C-40);
82.4 (C-30); 86.9 (C-20); 114.6 (C-9); 115.2 (C-8); 121.3
(CHAr); 123.7 (C-6); 126.7; 127.9; 128.0; 128.1; 128.4;
128.6; 128.8; 129.6 (C-50,CHAr); 135.6 (C-7); 137.7; 138.0;
138.5 (Cq); 151.4 (C-10); 153.1 (C-2); 161.6 (C-4); 193.7
(CvS); IR (KBr): 1225 (CvS); 1649 (CvO); 1730
(CvO); MS IS m/z¼611,5 [MþHþ]; 633,5 [MþNaþ];
HRMS: calcd for C34H30N2O7S (610.1774), found
(610.1776).
0
0
0
48%) as a white solid; mp: 61–64 8C; [a]D¼2112 (c 0.5;
1
0
CHCl3); H NMR (CDCl3): d 3.22 (d, 1H, JOH,2 ¼4.1 Hz,
OH-20); 3.75 (d, 2H, J5 a,5 b¼5.0 Hz, H-50); 4.21 (ddd, 1H,
0
0
0
0
0
0
J4 ,3 ¼7.2 Hz, H-4 ); 4.53–4.68 (m, 5H, H-3 0, CH2-Ph); 4.79
0
0
0
0
(ddd, 1H, J2 ,1 ¼2.5 Hz, J2 ,3 ¼6.3 Hz, H-2 ); 6,53 (d, 1H,
H-10), 7.02 (d, 1H, J8,7¼7.9 Hz, H-8); 7.13 (ddd, 1H,
J6,8¼0.9 Hz, J6,5¼J6,7¼7.9 Hz, H-6); 7.22–7.37 (m, 10H,
CHAr); 7.49 (ddd, 1H, J7,5¼1.3 Hz, H-7); 7.97 (dd, 1H,
H-5); 10.37 (sl, 1H, NH); 13C NMR (CDCl3): d 70.4 (C-50);
71.4 (C-20); 73.4; 73.5 (CH2-Ph); 78.8 (C-30); 80.9 (C-40);
89.5 (C-10); 114.8 (C-9); 115.3 (C-8); 123.5 (C-6); 127.7;
127.8; 128.2; 128.4; 128.8 (C-5, CHAr); 135.4 (C-7); 137.2;
138.1; 138.7 (C-10, Cq); 151.7 (C-2); 162.0 (C-4); IR
(KBr): 1667 (CvO); 1723 (CvO); MS IS m/z¼475.5
[MþHþ], 497.5 [MþNaþ]; HRMS: calcd for C27H26N2O6
(474.1791), found (474.1797).
4.2.36. 3-(30,50-Di-O-benzyl-20-deoxy-b-D-ribofuranosyl)-
2,4-quinazolinedione40. Compound 39(0.137 g; 0.29 mmol)
dissolved in toluene (2 mL) was reacted with Bu3SnH
(80 mL; 0.3 mmol) and a catalytic amount of AIBN
(0.1 equiv.) under reflux for 3 h. After toluene removal,
the residue was dissolved in pentane (10 mL) then washed
three times with acetonitrile (3£10 mL). The collected
phases were washed twice with pentane, then evaporated
and the residue was purified by column chromatography
(petroleum ether/AcOEt 6/4) to yield 40 (63 mg; 62%) as a
white gum; [a]D¼229 (c 0.8; CDCl3); 1H NMR (CDCl3): d
4.2.34. 3-b-D-Ribosyl-2,4-quinazolinedione38.Thebenzyl-
ated compound 37 (95 mg; 0.2 mmol) was dissolved in
CH3OH (5 mL) containing Pd/C 10% (0.1 g) and stirred
overnight under hydrogen pressure at room temperature.
The solution was filtered over Celitew, and purified by silica
gel chromatography to give pure 38 (53 mg, 90%); mp:
220–222 8C; [a]D¼2124 (c 1; DMSO); 1H NMR (CDCl3):
0
0
0
0
0
0
2.36 (ddd, 1H, J2 b,3 ¼5.3 Hz, J2 b,1 ¼9.0 Hz, J2 a,2 b¼13.4
Hz, H-20b); 2.95 (ddd, 1H, J2 a,1 ¼4.3 Hz, J2 a,3 ¼7.9 Hz, H-
0
0
0
0
20a); 3.79 (dd, 1H, J5 b,4 ¼4.9 Hz, J5 b,5 a¼10.2 Hz, H-50b);
0
0
0
0
0
0
0
0
3.85 (dd, 1H, J5 a,4 ¼7.0 Hz, H-5 a); 4.23–4.33 (m, 1H, H-4 );
4.47–4.69 (m, 5H, H-30, CH2-Ph); 6.94 (dd, 1H, H-10); 7.01
(d, 1H, H-8); 7.10–7.44 (m, 11H, H-6, CHAr); 7.49 (ddd,
1H, J7,5¼1.3 Hz, J7,6¼J7,8¼8.5 Hz, H-7); 7.97–8.05
(m, 1H, H-5); 10.42 (s, 1H, NH); 13C NMR (CDCl3): d
35.9 (C-20); 71.2 (C-50); 72.2; 73.3 (CH2-Ph); 80.4 (C-30);
82.4 (C-10); 84.0 (C-40); 115.0 (C-8, C-9); 123.5 (C-6);
127.6; 127.8; 127.9; 128.0; 128.4; 128.5; 128.6 (C-5, CHAr);
135.3 (C-7); 138.2; 138.3 (Cq); 138.6 (C-10); 151.6 (C-2);
162.0 (C-4); IR (KBr): 1655 (CvO); 1728 (CvO); MS IS
m/z¼459 [MþHþ]; 481 [MþNaþ]; HRMS: calcd for
C27H26N2O5 (458.1841), found (458.1839).
d 3.39–3.52 (m, 1H, H-50a); 3.58–3.77 (m, 2H, H-40,
0
H-50b); 4.17 (dd, 1H, J3 ,2 ¼6.0 Hz, J3 ,4 ¼6.3 Hz, H-3 );
0
0
0
0
4.48–4.68 (m, 2H, H-20, OH-50); 4.89 (d, 1H, JOH,3 ¼6.6
0
Hz, OH-30); 5.07 (d, 1H, JOH,2 ¼4.7 Hz, OH-2 ); 6.20 (d, 1H,
0
0
0
0
0
J1 ,2 ¼3.6 Hz, H-1 ); 7.10–7.30 (m, 2H, H-6, H-8); 7.66
(ddd, 1H, J7,5¼1.3 Hz, J7,6¼8.5 Hz, J7,8¼8.2 Hz, H-7); 7.93
(d, 1H, J5,6¼7.5 Hz, H-5), 11.45 (sl, 1H, NH); 13C NMR
(CDCl3): d 62.4 (C-50); 70.2 (C-30); 71.1 (C-20); 84.4 (C-40);
88.1 (C-10); 113.8 (C-9); 115.1 (C-8); 122,8 (C-6); 127.7
(C-5); 135.5 (C-7); 139.5 (C-10); 149.8 (C-2); 162.0 (C-4);
IR (KBr): 1664 (CvO); 1724 (CvO); MS IS m/z¼317
[MþNaþ]; HRMS: calcd for C13H14N2O6 (294.0852),
found (294.0853); calcd for C13H14N2O6 (H 4.80, C
53.06, N 9.52), found (H 4.96, C 53.03, N 9.34).
4.2.37. 3-(20-Deoxy-b-D-ribofuranosyl)-2,4-quinazoline-
dione 41. The solution was filtered over Celitew, and
purified by silica gel chromatography to give pure 38 (53
Compound 40 (0.1 g; 0.22 mmol) was dissolved in MeOH
(2 mL) containing Pd/C 10% (0.1 g) and stirred over-
night under hydrogen pressure at room temperature. After
4.2.35. 3-(30,50-Di-O-benzyl-20-O-phenoxythiocarbonyl-

J. Girniene et al. / Tetrahedron 60 (2004) 2609–2619
2619
filtration over Celitew and evaporation, the residue was
purified on silica gel (AcOEt/MeOH 95/5) to give 41
6. Martinez Gimenez, J. A.; Saez, G. T.; Tabraes Seisdedos, R.
J. Theor. Biol. 1998, 194, 485–490.
7. Saito, Y.; Nakamura, M.; Ohno, T.; Chaicharoenpong, C.;
Ichikawa, E.; Yamamura, S.; Kato, K.; Umezawa, K. J. Chem.
Soc. Perkin Trans. 1 2001, 298–304.
(38 mg; 62%) as a white solid; mp: 175–178 8C; [a]D¼0 (c
1
0
0
1.0; DMSO); H NMR (DMSO): d 1.99 (ddd, 1H, J2 b,3
0
¼
4.7 Hz, J2 b,1 ¼8.2 Hz, J2 b,2 a¼13.0 Hz, H-20b); 2.79 (ddd,
0
0
0
0
0
0
0
0
8. Kandimalla, E. R.; Yu, D.; Zhao, Q.; Agrawal, S. Bioorg. Med.
Chem. 2001, 9, 807–813.
1H, J2 a,1 ¼6.0 Hz, J2 a,3 ¼7.2 Hz, H-2 a); 3.43–3.56 (m, 1H,
H-5b); 3.58–3.75 (m, 2H, H-40, 0H-50a); 4.30–4.45 (m, 1H,
H-30); 4.52–4.67 (m, 1H, OH-5 ); 5.10 (d, 1H, JOH,3 ¼4.7
0
9. (a) Sauer, D. R.; Schneller, S. W. Synthesis 1991, 747–750.
(b) Al Mourabit, A.; Beckmann, M.; Poupat, C.; Ahond, A.;
Potier, P. Tetrahedron: Asymmetry 1996, 7, 3455–3464. (c)
Lengeler, D.; Weisz, K. Tetrahedron Lett. 2001, 42,
1479–1481. (d) Jungmann, O.; Pfleiderer, W. Tetrahedron
Hz, OH-30); 6.66 (dd, 1H, H-10); 7.10–7.30 (m, 2H, H-6,
H-8); 7.64 (ddd, 1H, J7,5¼1.3 Hz, J7,6¼J7,8¼8.3 Hz, H-7);
7.91 (dd, 1H, J5,6¼7.9 Hz, H-5); 11.38 (s, 1H, NH); 13C
NMR (DMSO): d 36.8 (C-20); 62.3 (C-50); 71.2 (C-30); 81.4
(C-10); 87.5 (C-40); 1140.0 (C-9); 115.0 (C-8); 122.7 (C-6);
127.6 (C-5); 135.3 (C-7 ); 139.4 (C-10); 149.7 (C-2); 162.0
(C-4); IR (KBr): 1658 (CvO); 1722 (CvO); MS IS m/
z¼279 [MþHþ]; 301 [MþNaþ]; HRMS: calcd for
C13H14N2O5 (278.0802), found (278.0806); calcd for
C13H14N2O5 (H 5.07, C 56.10, N 10.07), found (H 5.12, C
55.64, N 9.97).
¨
Lett. 1996, 37, 8355–8358. (e) Rosler, A.; Pfleiderer, W. Helv.
Chim. Acta 1997, 80, 1869–1881. (f) Wang, Z.; Rizzo, C.
J. Org. Lett. 2000, 2, 227–230. (g) El Ashry, E. S. H.; Awad,
L. F.; Winkler, M. J. Chem. Soc., Perkin Trans. 1 2000,
829–834. (h) Loakes, D.; Guo, M.-J.; Yang, J.-C.; Brown,
D. M. Helv. Chim. Acta 2000, 83, 1693–1700. (i) Bertolini,
R.; Hunziker, J. Helv. Chim. Acta 2000, 83, 1962–1976. (j)
Wu, W.; Bergstrom, D. E. J. Org. Chem. 2003, 68,
3860–3865.
10. (a) Jungmann, O.; Pfleiderer, W. Tetrahedron Lett. 1996, 37,
8355–8358. (b) Guckian, K. M.; Morales, J. C.; Kool, E. T.
J. Org. Chem. 1998, 63, 9652–9656. (c) Sugimura, H.; Osumi,
K.; Kodaka, Y.; Sujino, K. J. Org. Chem. 1994, 59,
7653–7660.
Acknowledgements
The authors wish to thank Dr. L. Agrofoglio for helpful
discussion, and the CNRS for financial support.
11. (a) Gosselin, G.; Bergogne, M-C.; De Rudder, J.; De Clercq,
E.; Imbach, J-L. J. Med. Chem. 1986, 29, 203–213. (b)
Mourier, N. S.; Eleuteri, A.; Hurwitz, S. J.; Tharnish, P. M.;
Shinazi, R. F. Bioorg. Med. Chem. 1999, 7, 2759–2766.
12. (a) Stout, M. G.; Robins, R. K. J. Org. Chem. 1968, 33,
1219–1225. (b) Dunkel, M.; Pfleiderer, W. Nucleosides
Nucleotides 1992, 11, 787–919. (c) El-Barbary, A. A.; El-
Brollosy, R.; Pedersen, E. B. Bull. Soc. Chim. Fr. 1996, 133,
51–57.
References and notes
1. (a) Agrofoglio, L.; Challand, S. R. Acyclic, carbocyclic and
L-nucleosides; Kluwer: London, 1998. (b) Rando, R. F.;
Nguyen-Ba, N. Drug Discov. Today 2000, 5, 465–476. (c)
McGuigan, C.; Yarnold, C. J.; Jones, G.; Velazquez, S.;
Barucki, H.; Brancale, A.; Andrei, G.; Snoeck, R.; De Clercq,
E.; Balzarini, J. J. Med. Chem. 1999, 42, 4479–4484. (d)
Brancale, A.; McGuigan, C.; Andrei, G.; Snoeck, R.;
DeClercq, E.; Balzarini, J. Bioorg. Med. Chem. Lett. 2000,
10, 1215–1217.
¨
13. (a) Sauter, F.; Frohlich, J.; Blasl, K.; Gewald, K. Heterocycles
1995, 40, 851. (b) Preshad, M.; Chen, L.; Repic, O.;
Blacklock, T. J. Synth. Commun. 1998, 28, 2125. (c)
Alexandre, F. R.; Berecibar, A.; Wrigglesworth, R.; Besson,
T. Tetrahedron 2003, 59, 1413–1419.
2. (a) Harwood, E. A.; Hopkins, P. B.; Sigurdsson, S. J. Org.
Chem. 2000, 65, 2959–2964. (b) Kotera, M.; Roupioz, Y.;
Defrancq, E.; Bourdat, A.-G.; Garcia, J.; Coulombeau, C. J.
Chem. Eur. J. 2000, 6, 4163–4169. (c) Suzuki, T.; Ohshimo,
H. FEBS Lett. 2002, 516, 67–70.
14. Leoni, O.; Bernardi, R.; Gueyrard, D.; Rollin, P.; Palmieri, S.
Tetrahedron: Asymmetry 1999, 10, 4775.
15. (a) Gueyrard, D.; Grumel, V.; Leoni, O.; Palmieri, S.; Rollin,
P. Heterocycles 2000, 52, 827. (b) Gueyrard, D.; Leoni, O.;
Palmieri, S.; Rollin, P. Tetrahedron: Asymmetry 2001, 12,
337–340.
´
3. Trevisiol, E.; Defrancq, E.; Lhomme, J.; Laayoun, A.; Cros, P.
Eur. J. Org. Chem. 2000, 1, 211–217.
¨
16. Girniene, J.; Gueyrard, D.; Tatibouet, A.; Sackus, A.; Rollin,
P. Tetrahedron Lett. 2001, 42, 2977–2980.
17. Bromund, W.; Herbst, R. M. J. Org. Chem. 1945, 267–269.
4. Kool, E. T.; Morales, J. C.; Guckian, K. M. Angew. Chem. Int.
Ed. 2000, 39, 990–1009.
5. Kool, E. T. Curr. Opin. Chem. Biol. 2000, 4, 602–608.