Synthesis of peracylated derivatives of L-ribofuranose from D-ribose and their use for the preparation of β-L-ribonucleosides

Article abstract of DOI:10.1055/s-2002-19805

A practical synthesis of peracylated derivatives of β-L-ribofuranose 13-15 from D-ribose was accomplished in 6 steps (total yield: 30-45percent). Compound 13 was employed for the preparation of 1-(β-L-ribofuranosyl)thymine (16) and -cytosine (17), which are key intermediates for the preparation of the nucleoside derivatives with β-L-configuration. Simultaneous transformation of 17 into β-L-ddC (19) and β-L-3′dC (20) was studied.

Full text of DOI:10.1055/s-2002-19805

PAPER
253
Synthesis of Peracylated Derivatives of L-Ribofuranose from D-Ribose and
Their Use for the Preparation of -L-Ribonucleosides
S
ynthesis of Perac
r
ylated D
i
e
rivativ
g
es of
L
-Ribo
o
furanose rii G. Sivets, Tatjana V. Klennitskaya, Elena V. Zhernosek, Igor A. Mikhailopulo*
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141 Minsk, Acad. Kuprevicha 5, Belarus
Fax +375(172)648148; E-mail: igormikh@iboch.bas-net.by
Received 6 August 2001; revised 19 November 2001
ABR. Jung and Xu have accomplished the transformation
of the readily available D-ribose into L-ABR in 7 steps in
ca. 40% overall yield.8 The most striking finding consists
in the three step conversion of L-ribose to L-ABR in al-
Abstract: A practical synthesis of peracylated derivatives of -L-ri-
bofuranose 13–15 from D-ribose was accomplished in 6 steps (total
yield: 30–45%). Compound 13 was employed for the preparation of
1-( -L-ribofuranosyl)thymine (16) and -cytosine (17), which are
key intermediates for the preparation of the nucleoside derivatives most quantitative yield (cf Refs 5,6). Chu and co-workers
with -L-configuration. Simultaneous transformation of 17 into
L-ddC (19) and -L-3’dC (20) was studied.
-
have developed another route, which starts from L-arabi-
nose and gives L-ABR in 8 steps in ca. 20% overall yield.9
Moyroud and Strazewski10 have transformed L-xylose
into L-ABR in 6 steps via an oxidation/reduction proce-
dure as the key reaction. The acetolysis of methyl 2,3,5-
tri-O-benzoyl-L-ribofuranoside afforded the crystalline L-
Key words: carbohydrates, steroselective synthesis, acylations, nu-
cleosides
Recently, a number of nucleosides with the unnatural -L- ABR in 39% yield.10
configuration have been found to possess very potent an-
In order to avoid the possible problems during acetolysis,
tiviral activity.1 These data prompted us to synthesize and
to evaluate the biological properties of some -L-nucleo-
sides. In this paper we describe an efficient and scaleable
synthesis of peracylated derivatives of -L-ribofuranose
13–15 from D-ribose (1) and their use for the preparation
of 1-( -L-ribofuranosyl)thymine (16) and -cytosine (17)
as precursors for further chemical transformations.2
we have developed a practical synthesis of peracylated de-
rivatives of -L-ribofuranose 13–15 from D-ribose (1) ex-
cluding acetolysis (Scheme 1). Treatment of D-ribose (1)
with acetone in the presence of p-toluenesulfonic acid and
calcium hydride gave the 2,3-O-isopropylidene derivative
2. Conventional tritylation or p-monomethoxytritylation
of 2 led to the respective 5-O-protected furanosides 3 and
The strategy for the preparation of -L-nucleosides modi- 4 in high yield. Reduction of the carbonyl function of the
fied in the heterocyclic base and/or the sugar moiety con- latter, followed by acylation without isolation of interme-
sists in the convergent synthesis of -L-ribofuranosyl diary 1,4-diols resulted in the acylates 5–7, which were
nucleosides as the key intermediates for further chemical purified by silica gel column chromatography.
transformations. In this context, the practical synthesis of
peracyl derivatives of -L-ribofuranose is crucial. For the
Treatment of the fully blocked D-ribitol 5 with methanoic
acid in diethyl ether at room temperature for 40 minutes,
convergent synthesis of -D-ribofuranosyl nucleosides, 1-
followed by silica gel column chromatography gave the
O-acetyl-2,3,5-tri-O-benzoyl- -D-ribofuranose (D-ABR)
dibenzoate 8 and the monobenzoate 9 in 60% and 5%
yield based on the consumed starting 5, 11% of which was
recovered. Detritylation of 6 by reaction with trifluoroace-
is the best ribosylating agent.3–5 Its most effective synthe-
sis comprises of three steps, (i) transformation of D-ribose
into methyl / -ribofuranosides, (ii) benzoylation, and
tic acid in 1,2-dichloroethane (DCE) at room temperature
(iii) then acetolysis, which furnished the desired com-
for 35 minutes gave, after silica gel column chromatogra-
phy, 6 (10%), 8 (87%; 55% overall yield from 1) and 9
(10%) (the yields of benzoates 8 and 9 are based on the
consumed 6). Treatment of 6 with aqueous 90% acetic
pound in 56% overall yield.5 It should be stressed that the
acetolysis requires very careful control of the reaction
conditions in order to avoid the formation of acyclic de-
rivatives of D-ribose.6
acid in THF at 35 °C for 18 hours, followed by silica gel
1-O-Acetyl-2,3,5-tri-O-benzoyl- -L-ribofuranose
(L- column chromatography gave 8 (76%) and 9 (14%). Fi-
ABR) attracts attention as ribosylating agent for the prep- nally, detritylation of 7 with trifluoroacetic acid in DCE
aration of -L-ribofuranosyl nucleosides. Since the first gave the dibenzoate 10 as the single product in 81% yield
synthesis of L-ABR from L-arabinose and L-xylose,7 dif- (54% overall yield from 1) (Scheme 1).
ferent approaches to this compound have been reported.
Among them, three recently published schemes are of in-
terest from the viewpoint of a large-scale preparation of L-
Oxidation of the primary hydroxyl group of acylates 8 and
10 with pyridinium chlorochromate (PCC) in DCE or
CH2Cl2 resulted in the corresponding compounds 11
(85%) and 12 (82%) containing a free aldehyde function.
Deblocking of the 3,4-diol function of the aldehyde 11
with aq 85% trifluoroacetic acid at room temperature for
1 hour, followed by standard acetylation gave, after silica
Synthesis 2002, No. 2, 01 02 2002. Article Identifier:
1437-210X,E;2002,0,02,0253,0259,ftx,en;T07501SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

254
G. G. Sivets et al.
PAPER
AcO
OBz
B
RO
O
RO
OH
OR1
O
O
c;d
OR1
a
OH
a;b
D-Ribose
BzO
OAc
OH
O
O
O
O
HO
13
16, B = Thy
17, B = Cyt
1
2, R = H
3, R = Tr
4, R = MTr
5, R = Tr; R1 = Bz
6, R = MTr; R1 = Bz
7, R = MTr; R1 = Tol
b
Thy = thymin-1-yl
Cyt = cytosin-1-yl
Scheme 2 Reagents and conditions: a) 13-persilylated thymine or
N4-benzoylcytosine/SnCl4, (molar ratio
1.0:2.62:1.64 or
1.0:2.25:2.28, respectively), MeCN, r.t., 18 h; b) sat. methanolic am-
HO
HO
OR
OH
=
e
OR
OBz
+
monia (0 °C), r.t., 24 h [a + b, 16 (85%); 17 (88%)]
O
O
O
O
13C NMR: 196.8 and 196.4 (1JC,H = 184.9 and 179.6 Hz
(CH=O)]. The spectral data for -L-nucleosides 16 and 17
were found to be analogous to those for -D-enantiomers
except for the CD curves, which bear a mirror-image rela-
tionship with minor intensity changes.
8, R = Bz
9
10, R = Tol
f
O
AcO
OR
H
O
OR
It is obvious that chemical methods developed for the
modification of natural ribonucleosides are applicable for
similar transformations of L-enantiomers. Earlier, we
have reported the synthesis of 3’-deoxy-2’,3’-didehydro-
-L-thymidine and 3’-deoxy-3’-fluoro- -L-thymidine
from 16 employing previously developed methods for the
corresponding D-enantiomer.2 In this paper, we have stud-
ied the transformation of 17 into 2’,3’-dideoxy- -L-cyti-
dine ( -L-ddC; 19) and 3’-deoxy- -L-cytidine ( -L-3’dC;
20). The chemical literature described many approaches
for the synthesis of such compounds. Among them, an
universal convergent methodology11 allows the prepara-
tion of both compounds starting from L-xylose via the in-
termediate formation of either 1,2-di-O-acetyl-3,5-di-O-
benzoyl-L-xylofuranose or its 3-deoxy derivative. Alter-
natively, Marcuccio et al. described an interesting method
for the simultaneous preparation of -D-ddC and 3’-deox-
ycytidine from N4-acetylcytidine12 (cf. Ref.13). We were
interested in the preparation of both, -L-ddC (19) and -
L-3’dC (20), and, therefore, this method12 attracted our at-
tention.
Nucleoside 17 was transformed to the N4-acetyl derivative
18, and the latter was treated with acetyl bromide in anhy-
drous acetonitrile as described.12,14 HPLC analysis of the
product, obtained as a pale yellow foam after workup of
the reaction mixture, revealed the presence of three main
and three minor compounds (cf. data in Ref.12,13). The UV
spectra of all compounds were very similar to that of the
starting N4-acetyl derivative 18. Hydrogenation of the
mixture of products over 10% palladium on charcoal in
methanol in the presence of potassium hydrogen
carbonate12 gave three main products, which were identi-
fied by TLC as the starting material 17, and two desired
derivatives 19 and 20 (Scheme 3). Thus, deacetylation oc-
curred during the hydrogenation by the action of potassi-
um hydrogen carbonate in methanol. Compounds 17
OR
g;h
R1O
OR2
O
O
13, R = R1 = Bz; R2 = Ac
14, R = R2 = Bz; R1 = Ac
15, R = R1 = Tol; R2 = Ac
11, R = Bz
12, R = Tol
Tr = trityl; MTr = (p-monomethoxy)trityl; Tol = p-toluoyl
Scheme 1 Reagents and conditions: a) acetone, p-TsOH, CaH2,
(80–90%); b) TrCl or MTrCl/pyridine (80–90%); c) NaBH4/EtOH; d)
AcylCl/pyridine (c + d, 80–95%); e) 90% aq HOAc/THF, 35 °C, 18
h (8, 76%; 9, 14%); CF3CO2H/CH2Cl2, r.t., 20–35 min (10, 81%); f)
PCC (PyH+ClCrO3 ), CH2Cl2; 0 °C, 30 min; r.t., 2 h (11, 85%; 12,
–
82%); g) 85% aq CF3CO2H, r.t., 40–60 min; h) Ac2O/pyridine, r.t., 20
h (g + h, 13, 52%; 14, 7%; 15, 61%)
gel column chromatography, the desired peracyl deriva-
tive of -L-ribofuranose 13 as the main product of the re-
action (52%) along with the isomeric acylate 14 (7%).
Successive treatment of 12 with aqueous 85% trifluoro-
acetic acid at room temperature for 40 minutes followed
by standard acetylation afforded peracylate 15 in 61%
yield (Scheme 1). Thus, the removal of the 3,4-O-isopro-
pylidene group of compound 11 is accompanied by the
partial migration of 2-O-benzoyl group of intermediate
derivatives of L-ribofuranose. As a consequence the for-
mation of isomeric 1,2-di-O-acetyl-3,5-di-O-benzoyl- -
L-ribofuranose (14) was observed.
Condensation of 13 with silylated thymine in the presence
of tin tetrachloride in acetonitrile followed by standard
deprotection with ammonia in methanol afforded -L-nu-
cleoside 16 (85%). In a similar way, condensation of 13
with silylated N4-benzoylcytosine and subsequent deacy-
lation gave -L-cytidine (17) in 88% overall yield
(Scheme 2).
The NMR spectral data show unequivocally the presence (recovered, 23%), 19 (18%) and 20 (16%) were isolated
of a free aldehyde group in compounds 11 and 12 [
(CDCl3/TMS): H NMR: 9.80 (s) and 9.78 (s) (CH=O);
by silica gel column chromatography and characterized
1
Synthesis 2002, No. 2, 253–259 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Peracylated Derivatives of L-Ribofuranose
255
mL) was added, the stirring was continued for an additional 20 min,
and the mixture was evaporated to dryness in vacuo. The residue
was purified by silica gel column (3 36 cm) chromatography, elut-
ing with EtOAc–hexane (1:5, 0.4 L; 2:1, 1.1 L) mixture to give 2
(5.3 g, 84%) as a colorless oil; Rf 0.22 (A1).
NHAc
N
N
a
b;c
O
OH
O
17
A solution of compound 2 (5.3 g, 27.9 mmol) and trityl chloride
(9.32 g, 33.43 mmol) in anhyd pyridine (65 mL) was stirred for 48
h, then poured into 5% aq NaHCO3 (300 mL) and extracted with
EtOAc (3 200 mL). The combined organic extracts were dried
and evaporated to dryness. The residue was chromatographed on
silica gel column (3 36 cm), eluting with a linear gradient (0
33%, v/v; 2 1 L) of EtOAc in hexane to afford 3 (9.6 g, 80%) as
an oil; Rf 0.41 (B1).
OH
HO
18
B
B
OH
OH
O
O
+
Analogous to 3, monomethoxytritylation of 2 (9.5 g, 50 mmol) gave
4.
HO
19
20
4
Colorless crystals; yield: 21.3 g (92%); mp 36–37 °C (EtOAc–hex-
ane); Rf 0.31 (B1).
B = cytosin-1-yl
Scheme 3 Reagents and conditions: a) Ac2O/MeOH, 1 h (91%); b)
AcBr/MeCN, 65 °C, 2 h; c) H2, 10% Pd/C, KHCO3, MeOH, r.t., 4 h
[b + c, 19 (23%); 20 (17%); 24% of 17 was recovered]
1H NMR: = 7.44–7.20 (m, 12 H, 2 C6H5 and the ortho protons
of MTr group), 6.84 (d, 2 H, 3Jmeta,ortho = 8.5 Hz, the meta protons of
MTr group), 5.32 (d, 1 H, J1,OH = 9.37 Hz, H-1), 4.80 (d, 1 H,
J3,2 = 5.52 Hz, H-3), 4.67 (d, 1 H, J2,3 = 5.52 Hz, H-2), 4.35 (br t, 1
H, J4,5 = 3.09 Hz, J4,5’ = 3.31 Hz, J4,3 = 0.8 Hz, H-4), 4.16 (d, 1 H,
by 1H NMR spectroscopy as well as by UV and CD spec- J1,OH = 9.37 Hz, 1-OH), 3.78 (s, 3 H, OCH3), 3.42 (dd, 1 H,
troscopy.
J5,4 = 3.09, J5,5’ = 10.5 Hz, H-5), 3.33 (dd, 1 H, J5’,4 = 3.31 Hz, H-
5’), 1.46 and 1.30 [2 s, 2 3 H, =C(CH3)2].
To a solution of 3 (4.52 g, 10.46 mmol) in EtOH (150 mL) was add-
ed NaBH4 (1.58 g, 41.82 mmol) and the mixture was stirred for 18
h and evaporated to dryness. The residue was partitioned between
H2O (150 mL) and EtOAc (250 mL), the organic phase was separat-
ed, and the H2O phase was extracted with EtOAc (2 250 mL). The
combined organic extracts were dried, evaporated, and the residue
(foam, 4.50 g) was treated with benzoyl chloride (2.67 mL, 3.21 g,
23.0 mmol) in anhyd pyridine (40 mL) under stirring at 0 °C for 1 h
and then at r.t. overnight. Standard workup followed by silica gel
column (3 36 cm) chromatography [a linear EtOAc gradient (0
33%, v/v; 2 1.0 L) in hexane] afforded 5.
Column chromatography (CC): on silica gel 60 H (70–230 mesh
ASTM; Merck, Darmstadt, Germany), except where otherwise in-
dicated. TLC: (1) Silufol UV254 (Czech Republic) and (2) aluminum
sheets silica gel 60 F254 (Merck, Germany). Solvent systems for
TLC: hexane–EtOAc (1:1) (A), hexane–EtOAc (3:1) (B), hexane–
EtOAc (2:1) (C), and EtOAc–MeOH–H2O (4:1:0.2) (D) Florisil and
pyridinium chlorochromate (PCC; purum) were purchased from
Fluka (Switzerland). MeOH and MeCN were HPLC grade, KHCO3
was purchased from Merck. Unless otherwise indicated, the reac-
tions were carried out at 20 °C. The solutions of compounds in or-
ganic solvents were dried with anhyd Na2SO4 for 4 h.
UV spectra were measured with a Specord M-400 spectrometer
(Carl Zeiss, Germany). CD spectra and the [ ]D values were ob-
5
20
Oil; yield: 5.41 g (80%); Rf 0.51 (B1).
1H NMR: = 8.04 and 7.94 (2 d, 4H, Jmeta,ortho = 7.0, 7.0 Hz, the
tained on a J-20 (Jasco, Japan) spectropolarimeter. 1H and 13C NMR
Spectra were measured at 200.13 and 50.325 MHz, respectively, at
23 °C on an AC-200 spectrometer, equipped with an Aspect 3000
data system (Bruker, Germany); values are in ppm downfield
from internal SiMe4 (1H, 13C) (s = singlet; d = doublet; t = triplet;
q = quadruplet; m = multiplet; br s = broad signal); coupling con-
stants J are given in Hz; assignments of proton resonances were
confirmed, when possible, by selective homonuclear decoupling ex-
periments. The HPLC analyses were performed on a Merck–Hitachi
chromatograph (Germany): pump L-7100, UV Detector L-7400, and
Integrator D-7500. The solvent employed for recording the NMR
spectra was CDCl3, unless otherwise stated. Mp: Boetius apparatus
(Germany); not corrected. All new crystalline compounds gave sat-
isfactory microanalyses, C 0.38, H 0.40.
3
ortho protons of Bz group), 7.60–7.16 (m, 21 Harom), 5.46 [m, 1 H,
J
4,3 = 7.8, J4,5 = 2.6, J4,5’ = 3.9 Hz, C4HOBz (H-4)], 4.78 (dd, 1 H,
J2,3 = 5.2 Hz, H-3), 4.61 (dd, 1 H, J2,1 = 6.2, J2,1’ = 4.5 Hz, H-2),
4.55 [dd, 1 H, J1,1’ = 11.0 Hz, C1H2OBz (H-1)], 4.34 (dd, 1H, J1,1’
11 Hz Hz, H-1’), 3.54 [dd, 1 H, J5,5’ = 10.4 Hz, C5H2OTr (H-5)],
3.45 (dd, 1 H, J5,5 = 10.4 Hz, H-5’), 1.42 and 1.38 [2 s, 2
H, =C(CH3)2].
=
3
In a similar way, compound 4 (4.73 g, 10.22 mmol) was trans-
formed into compounds 6 and 7.
6
Oil; yield: 6.53 g (95%); Rf 0.43 (B1).
3
1H NMR:
= 8.04 and 7.94 (2 dd, 4 H, Jmeta,ortho = 7.0,
4Jpara,ortho = 1.0 Hz, the ortho protons of Bz group), 7.60–7.12 (m, 18
arom), 6.68 (d, 2 H, Jmeta,ortho = 9.0 Hz, the meta protons of MTr
1,4-Di-O-benzoyl-2,3-O-isopropylidene-5-O-trityl-D-ribitol (5),
1,4-Di-O-benzoyl-2,3-O-isopropylidene-5-O-monomethoxytri-
tyl-D-ribitol (6), and 1,4-Di-O-(p-toluoyl)-2,3-O-isopropylidene-
5-O-monomethoxytrityl-D-ribitol (7)
Compound 3 was prepared from D-ribose in two steps by the follow-
ing modification of a known procedure.15 A suspension of D-ribose
(5.0 g, 33.3 mmol) in anhyd acetone (100 mL), containing p-
TsOH H2O (19.0 g, 0.1 mol), was stirred for 30 min. To the homo-
geneous reaction mixture, powdered CaH2 (2.7 g, 67.1 mol) was
added; the mixture was stirred for 2 h, 1 N aq NaOH solution (100
3
H
group), 5.46 [m, 1 H, J4,3 = 8.0, J4,5 = 2.5, J4,5’ = 4.2 Hz, C4HOBz
(H-4)], 4.78 (dd, 1 H, J2,3 = 5.5 Hz, H-3), 4.60 and 4.55 (m, 2 H,
J2,1 = 6.0, J2,1’ = 4.5 Hz, H-2 and H-1), 4.34 [dd, 1 H, J1,1’ = 11.0,
C1H2OBz (H-1’)], 3.74 (s, 3 H, OCH3), 3.54 [dd, 1 H, J5,5’ = 11.0
Hz, C5H2OMTr (H-5)], 3.45 (dd, 1 H, J5,5’ = 11.0 Hz, H-5’), 1.40
and 1.38 [2 s, 2 3H, =C(CH3)2].
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256
7
G. G. Sivets et al.
PAPER
silica gel column (2.3 25 cm), using a linear EtOAc gradient (0
Oil; yield: 6.3 g (88%); Rf 0.47 (B1).
33%, v/v; 2 0.7 L) in hexane to give, in the order of elution: start-
ing compound 6 (0.22 g, 10%), monobenzoate 9 as a syrup (85 mg,
10%), and dibenzoate 8 (1.0 g, 87% based on 6 consumed).
1H NMR: = 7.82 and 7.94 (2 d, 4 H, 3Jmeta,ortho = 8.0 and 8.0 Hz,
the ortho protons of Tol group), 7.44–7.10 (m, 16 Harom), 6.72 (d, 2
3
H, Jmeta,ortho = 9.0, the meta protons of MTr group), 5.45 [m, 1 H,
Method C: A solution of 6 (1.12 g, 1.66 mmol) in a mixture of THF
(3 mL) and aq 90% HOAc (8.0 mL) was stirred at 35 °C for 18 h
and evaporated to dryness in vacuo. The residue was chromato-
graphed on silica gel column (1.8 20 cm) as described above to af-
ford syrupy 9 (70 mg, 14%) and crystalline 8 (0.51 g, 76%).
J
J
4,3 = 8.0, J4,5 = 2.5, J4,5’ = 4.2 Hz, C4HOTol (H-4)], 4.77 (dd, 1 H,
2,3 = 5.5 Hz, H-3), 4.60 and 4.55 (m, 2 H, J2,1 = 6.5, J2,1’ = 4.5
Hz, H-2 and H-1), 4.32 [dd, 1 H, J1,1’ = 11.0 Hz, C1H2OTol (H-1’)],
3.74 (s, 3 H, OCH3), 3.52 [dd, 1 H, J5,5’ = 11.0 Hz, C5H2OMTr (H-
5)], 3.42 (dd, 1 H, H-5’), 2.42 and 2.38 (2 s, 2 3 H, 2 CH3Carom),
1.40 and 1.38 [2 s, 2 3 H, =C(CH3)2].
Method D: Similar to the one described in Method B. Starting from
7 (0.9 g, 1.28 mmol), compound 10 was prepared.
1,4-Di-O-benzoyl-2,3-O-isopropylidene-D-ribitol (8) and 1,4-Di-
O-(p-toluoyl)-2,3-O-isopropylidene-D-ribitol (10)
10
Yield: 445 mg (81%); mp 86–88 °C (Et2O–hexane); Rf 0.26 (C2);
Method A: To a solution of 5 (5.34 g, 8.31 mmol) in Et2O (25 mL)
was added HCO2H (25 mL), and the mixture was stirred for 40 min.
Then it was diluted with Et2O (400 mL), washed with H2O (2 60
mL), 5% aq NaHCO3 solution (4 50 mL), and again with H2O
(2 80 mL), dried, and evaporated. The oily residue was chromato-
graphed on a silica gel column (2.8 20 cm), using a linear EtOAc
gradient (0 33%, v/v; 2 0.7 L) in hexane to give, in the order of
elution: starting compound 5 (0.6 g, 11%), the monobenzoate 9, and
the dibenzoate 8.
[ ]D20 –62.0 (c = 1.0, CHCl3).
1H NMR: = 7.80 and 7.86 (2 d, 4 H, 3Jmeta,ortho = 8.0 and 8.0 Hz,
the ortho protons of Tol group), 7.12 and 7.16 (2 d, 4 H, the meta
protons of Tol group), 5.25 (dt, 1 H, J4,3 = 8.0, J4,5 = 3.5, J4,5’ = 4.0
Hz, C4HOTol), 4.50–4.68 [m, 3 H, C1H2OTol (H-1 and H-1’) and
H-3], 4.30 (m, 1 H, H-2), 4.07 and 3.96 (2 dd, 2 H, J5,5’ = 12.0 Hz,
C5H2OH), 2.38 (s, 6 H, 2 ArCH3), 1.50 and 1.42 [2 s, 2
H, =C(CH3)2].
3
13C NMR: = 166.2 and 165.8 (2 s, 2 C=O), 144.2 and 143.6 (2
m, 2 CH3-Carom), 129.8 and 129.7 (2 dd, 1JC,H = 162.3, 2JC,H = 6.3
8
Hz, 2
126.9 and 126.5 (2 m, 2
C
ortho), 129.1 and 128.9 (2 dm, 1JC,H = 156.0 Hz; 2 Cmeta),
Yield: 1.78 g (60% based on the consumed 5); mp 79–81 °C (Et2O–
hexane); Rf 0.25 (C2); [ ]D20 –43.0 (c = 1.0, CHCl3).
C
ipso), 109.3 [br s, =C(CH3)2], 75.3 (d,
1JC,H = 151.0 Hz) and 74.9 (d, 1JC,H = 147.8 Hz) (C-2 and C-3), 72.7
3
1H NMR:
= 7.98 and 7.92 (2 dd, 4 H, Jmeta,ortho = 8.0,
(d, JC,H = 145.9 Hz, C4H2OTol) 62.9 and 62.6 (2 t, JC,H = 144.7
and 148.4 Hz, C1H2OTol and C5H2OH), 27.7 and 25.4 [2 q,
1JC,H = 125.8 and 125.8 Hz, =C(CH3)2], 21.6 (2 q, 1JC,H = 125.8 Hz,
1
1
4Jpara,ortho = 1.3 Hz, the ortho protons of Bz groups), 7.46–7.58 (m,
2 H, the para protons of Bz groups), 7.42–7.29 (m, 4 H, the meta
protons of Bz groups), 5.26 (dt, 1 H, J4,3 = 7.8, J4,5 = 3.0 Hz,
C4HOBz), 4.69–4.52 [m, 3 H, C1H2OBz (H-1 and H-1’) and H-3],
4.34 (m, 1 H, H-2), 4.08 and 3.98 (2 dd, 2 H, J5,4 = 3.0, J5’,4 = 3.5,
2
CH3-Carom).
5,5’ = 12.0 Hz, C5H2OH), 2.52 (br s, 1 H, C5H2OH), 1.52 and 1.42
2,5-Di-O-benzoyl-3,4-O-isopropylidene-aldehydo-L-ribose (11)
and 2,5-Di-O-(p-toluoyl)-3,4-O-isopropylidene-aldehydo-L-
ribose (12)
J
[2 s, 2 3 H, =C(CH3)2].
13C NMR: = 166.2 and 165.7 (2 C=O), 133.4 and 133.0 (2 dt,
To a suspension of PCC (4.2 g, 19.47 mmol) in anhyd DCE (30 mL)
at 0 °C was added a solution of dibenzoyl-D-ribitol 8 (3.0 g, 7.50
mmol) in anhyd DCE (50 mL) followed by freshly dried and
crushed molecular sieves 4 Å (4.2 g). The reaction mixture was
stirred at 0 °C for 30 min and then at r.t. for 2 h, diluted with anhyd
Et2O (25 mL), and applied onto a column (2.3 19.5 cm) packed
with florisil, containing crushed molecular sieves 4 Å on the top.
Elution with Et2O gave the aldehyde 11.
2
1JC,H = 161.0, JC,H = 7.5 Hz, 2 Cpara), 129.8 and 129.7 (2 dt,
2
2
1JC,H = 161.0, JC,H = 7.6 Hz, 2 Cmeta), 129.3 (t, JC,H = 7.5, one
C
ipso resonance; the second one is overlapped by the intense line at
1
2
129.7), 128.4 and 128.2 (2 dd, JC,H = 161.0, JC,H = 7.5 Hz, 2
C
ortho), 109.4 [br s, =C(CH3)2], 75.2 (d, 1JC,H = 161.0 Hz) and 74.9
1
1
(d, JC,H = 151.0 Hz) (C-2 and C-3), 72.7 (d, JC,H = 148.4 Hz,
C4H2OBz), 62.8 and 62.7 (2 t, JC,H = 148.4 and 145.3, C1H2OBz
1
and C5H2OH), 27.7 and 25.4 [2
q, JC,H = 127.8 and 127.8
1
Hz, =C(CH3)2].
11
Yield: 2.55 g (85%); mp 82–83 °C (Et2O–hexane); Rf 0.33 (C2);
9
[ ]D20 –34.0 (c = 1.0, CHCl3).
Syrup; yield: 0.1 g (5%); Rf 0.41 (C2).
1H NMR: = 9.80 (s, 1 H, CH=O), 7.96 and 8.04 (2 br d, 4 H,
3Jmeta,ortho = 7.5 Hz, the ortho protons of Bz groups), 7.46–7.62 (m,
2 H, the para protons of Bz groups), 7.42–7.30 (m, 4 H, the meta
protons of Bz groups), 5.52 [d, 1 H, J2,3 = 6.5 Hz, C2HOBz (H-2)],
4.40–4.80 (m, 4 H, H-3, H-4 and C5H2OBz], 1.56 and 1.44 [2 s,
1H NMR: = 8.04 (dd, 2 H, 3Jmeta,ortho = 7.0, 4Jpara,ortho = 1.0 Hz, the
ortho protons of Bz group), 7.50 (br t, 1 H, 3Jmeta,para = 7.0, the para
proton of Bz group), 7.42 (br t, 2 H, 3Jmeta,ortho = 3Jpara,meta = 7.0, the
meta protons of Bz group), 4.84–4.00 (m, 7 H, H-1,1’,2,3,4,5,5’),
1.48 and 1.36 [2 s, 2 3 H, =C(CH3)2].
2
3 H, =C(CH3)2].
13C NMR: = 167.1 (s, C=O), 133.2 (dt, JC,H = 161.0, 2JC,H = 7.6
1
13C NMR: = 196.8 (s, 1JC,H = 184.9 Hz, CH=O), 166.7 and 165.7
(2 C=O), 134.4 and 133.8 (2 dt, 1JC,H = 165.3, 2JC,H = 7.55 Hz, 2
Cpara), 130.6 and 130.3 (2 Cmeta), 130.1 (t, 2JC,H = 7.5 Hz, one Cipso
resonanace, the second one is overlapped by the intense line at
130.3 ppm), 129.2 and 129.0 (2 dd, 1JC,H = 162.3, 2JC,H = 8.5 Hz,
2
1
Hz, Cpara), 129.9 (t, JC,H 7.5, Cipso), 129.7 (dt, JC,H = 161.0,
2JC,H = 6.3 Hz, Cmeta), 128.4 (dd, JC,H = 161.0, JC,H = 7.6 Hz,
Cortho), 109.4 [br s, =C(CH3)2], 75.6 and 75.1 (2 d, 1JC,H 146 Hz, C-
2 and C-3), 68.5 (d, 1JC,H = 145.9 Hz, C4HOH), 67.6 (t, 1JC,H = 148.4
1
2
Hz, C1H2OBz), 63.8 (t, JC,H = 149.7 Hz, C5H2OH), 27.8 and 25.4
1
1
3
2
Cortho), 110.8 [=C(CH3)2], 76.5 (dd, JC,H = 151.0, JC,H = 28.3
[2 q, 1JC,H = 131.0 Hz, =C(CH3)2].
Hz, C2HOBz), 75.9 and 75.8 (2 d, 1JC,H 150.0, C-3 and C-4), 63.0
1
1
Method B: A solution of 6 (2.15 g, 3.20 mmol) in anhyd DCE (96
mL) containing CF3CO2H (0.97 mL) was stirred for 35 min and
poured into H2O (100 mL). The organic phase was separated,
washed with 5% aq NaHCO3 solution (50 mL), H2O (2 80 mL),
dried, and evaporated. The oily residue was chromatographed on a
(t, JC,H 149.1, C5H2OBz), 28.2 and 25.9 [2 q, JC,H = 117.0
Hz, =C(CH3)2].
In a similar way, starting from 10 (0.33 g, 0.77 mmol), the aldehyde
12 was prepared.
Synthesis 2002, No. 2, 253–259 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Peracylated Derivatives of L-Ribofuranose
257
12
63.6 (t, 1JC,H = 144.7 Hz), C-5), 20.9 and 20.5 (2 q, 1JC,H = 130.2 Hz,
2 CH3C=O).
Yield: 0.27 g (82%); mp 83–85 °C (Et2O–hexane); Rf 0.36 (C2);
[ ]D20 –28.5 (c = 1.0, CHCl3).
1,3-Di-O-acetyl-2,5-di-O-(p-toluoyl)- -L-ribofuranose (15)
A solution of the aldehyde 12 (0.55 g, 1.28 mmol) in 85% aq
CF3COOH (3.7 mL) was stirred at at r.t. for 40 min. The mixture
was worked up and acetylated as described above, and finally chro-
matographed on a silica gel column (1.8 20 cm) using an EtOAc–
heptane (1:6, v/v) mixture as eluent to afford 15.
1H NMR: = 9.78 (s, 1 H, CH=O), 7.96 and 7.82 (2 d, 4 H,
3Jmeta,ortho = 8.0 and 8.0 Hz, the ortho protons of Tol group), 7.16
and 7.12 (2 d, 4 H, the meta protons of Tol group), 5.52 [d, 1 H,
J
2,3 = 6.75 Hz, C2HOTol)], 4.78–4.68 (m, 2 H, H-3,4), 4.58 (dd, 1
H, J5,4 = 4.0, J5,5’ = 11.5 Hz, C5H2OTol, H-5), 4.44 (dd, 1 H,
J
5’,4 = 4.0 Hz, C5H2OTol, H-5’), 2.40 and 2.37 (2 s, 2 3 H, 2
ArCH3), 1.55 and 1.42 [2 s, 2 3 H, =C(CH3)2].
15
13C NMR: = 196.4 (d, 1JC,H = 179.6 Hz, CH=O), 166.1 and 165.2
(2 C=O), 144.6 and 143.9 (2 m, 2 CH3-Carom), 130.0 and 129.7
(2 dd, 1JC,H = 160.5, 2JC,H = 7.9 Hz, 2 Cortho), 126.7 and 125.7 (2
dm, 1JC,H = 158.7 Hz, 2 Cmeta), 126.7 and 125.7 (2 m, 2JC,H = 7.9,
Oil; yield: 0.37 g (61%); Rf 0.44 (C2).
1H NMR: = 7.98 and 7.96 (2 d, 4 H, Jmeta,ortho = 8.0 and 8.0 Hz,
the ortho protons of Tol group), 7.30 and 7.24 (2 d, 4 H, the meta
protons of Tol group), 6.36 (s, 1 H, H-1), 5.66–5.58 (m, 2 H, H-2,3),
4.76–4.58 (m, 2 H, J4,5 = 3.0, H-4,5), 4.40 (dd, 1 H, J5’,4 = 3.5,
J5’,5 = 11.5, H-5’), 2.46 and 2.44 (2 s, 6 H, 2 CH3-Carom), 2.02 and
2.00 (2 s, 6 H, 2 CH3C=O).
3
2
Cipso), 110.1 [br s, =C(CH3)2], 75.7, 75.3 and 75.2 (C-2, C-3 and
1
C-4), 62.2 (t, JC,H 148, C5H2OTol), 27.5 and 25.2 [2 q,
1JC,H = 132.2 Hz, =C(CH3)2], 21.7 (2 CH3-Carom).
1,3-Di-O-acetyl-2,5-di-O-benzoyl- -L-ribofuranose (13) and
1,2-Di-O-acetyl-3,5-di-O-benzoyl- -L-ribofuranose (14)
A solution of the aldehyde 11 (2.55 g, 6.4 mmol) in 85% aq
CF3CO2H (17 mL) was stirred for 1 h. The mixture was evaporated
in vacuo at 35 °C, the residue was co-evaporated with toluene
(3 30 mL) and then dissolved in anhyd pyridine (33 mL). To the
stirred solution, was added Ac2O (7.92 mL, 83.78 mmol), the mix-
ture was stirred for 20 h, and then poured into ice-water (120 mL).
After the ice had melted, the mixture was extracted with EtOAc
(3 200 mL), the combined extracts were washed with 5% aq
NaHCO3 solution (100 mL), water (100 mL), dried, and evaporated.
The residue was chromatographed on a silica gel column (2.8 43
cm) using an EtOAc–hexane (1:5, v/v) mixture as eluent to afford,
in the order of elution: 13 and 14.
13C NMR: = 169.7 and 169.0 (2 CH3C=O), 166.0 and 165.1
(2 CH3C6H4C=O), 144.6 and 144.1 (CH3-Carom), 129.9 and 129.8
(2 Cortho), 129.3 and 129.2 (2 Cmeta), 126.9 and 126.1 (Cipso), 98.4
(C-1), 79.4, 74.5, and 70.8 (C-2, C-3 and C-4), 63.3 (C-5), 21.7,
20.9 and 20.4 (2 CH3C=O and 2 CH3-Carom).
1-( -L-Ribofuranosyl)thymine (16)
To a stirred solution of 13 (0.44 g, 0.99 mmol) and the bis(trimeth-
ylsilyl) derivative of thymine [obtained from (0.33 g, 2.59 mmol)
thymine] in anhyd MeCN (23 mL) was added SnCl4 (0.19 mL,
0.421 g, 1.62 mmol). The reaction mixture was stirred for 18 h and
poured into 5% aq NaHCO3 (60 mL). The organic phase was sepa-
rated, and the H2O phase was extracted with CHCl3 (3 100 mL).
The combined organic extracts were dried and evaporated. The res-
idue was purified by silica gel column (2.8 23 cm) chromatogra-
phy, eluting with an EtOAc–hexane (1:3, v/v) mixture and then
CHCl3, to give the acylated derivative of 16.
13
20
Yield: 1.47 g (52%); mp 120–122 °C (EtOH); Rf 0.39 (C2); [ ]D
–21.5 (c = 1.0, CHCl3).
Acylated Derivative of 16
Foam; yield: 0.48 g (95%); Rf 0.26 (A2).
3
1H NMR: = 8.10 and 8.06 (2 br d, 4 H, Jmeta,ortho = 7.5 Hz, the
ortho protons of Bz groups), 7.64–7.42 (m, 6 H, two para and four
meta protons of Bz groups), 6.36 (s, 1 H, H-1), 5.64 (m, 2 H, H-
2,3), 4.72 (dd, 1 H, J5,4 = 3.0, J5,5’ = 11.5 Hz, H-5), 4.68 (m, 1 H, H-
4), 4.44 (dd, 1 H, J5’,4 = 4.0 Hz, H-5’), 2.02 and 1.98 (2 s, 2 3 H,
1H NMR: = 9.62 (s, 1 H, NH), 8.12 and 8.06 (2 dm, 2 2 H, the
ortho protons of Bz groups), 7.58 (center of m, 2 H, the para pro-
tons of Bz groups), 7.46 (center of m, 4 H, the meta protons of Bz
groups), 7.14 (d, 1 H, JH6,Me 1.0 Hz, H-6), 6.34 (d, 1 H, J1’,2’ = 5.10
Hz, H-1’), 5.72–5.63 (center of m, 2 H, H-2’,3’), 4.84 (dd, 1 H,
J5’,4’ = 3.5, J5’,5” = 13.0 Hz, H-5’), 4.60–4.52 (m, 2 H, H-4’,5”), 2.09
(s, 3 H, CH3C=O), 1.58 (d, 3 H, 5-CH3).
2
CH3C=O).
13C NMR: = 169.8 and 169.0 (2 CH3C=O), 166.0 and 165.0
(2 C6H5C=O), 133.7 and 133.4 (2 Cpara), 129.8 and 129.7 (2
meta), 129.6 and 128.8 (2 Cipso), 128.6 and 128.5 (2 Cortho), 98.3
(d, JC,H = 183.1 Hz, C-1), 79.3 (d, JC,H = 151.0 Hz), 74.6 (d,
1JC,H = 162.3 Hz) and 70.6 (d, 1JC,H = 151.0 Hz) (C-2, C-3 and C-4),
63.4 (t, 1JC,H = 149.1 Hz, C-5), 20.8 and 20.4 (2 q, 1JC,H = 130.8 Hz,
C
1
1
Deacylation of the product (0.48 g) in MeOH (50 mL), saturated
with dry NH3 gas at 0 °C for 72 h followed by a standard workup
and chromatography [silica gel Woelm containing 20% H2O; col-
umn 1.8 8 cm; eluents: EtOAc and EtOAc–MeOH (10:1, v/v)]
gave 16.
2
CH3C=O).
14
Yield: 0.19 g (7%); mp 108–110 °C (Et2O–hexane); Rf 0.38 (C2);
16
18
[ ]D20 +8.5 (c = 1.0, CHCl3).
Yield: 0.22 g (90%); mp 182–184 °C (EtOH); Rf 0.62 (D2); [ ]D
+4.5 (c = 1.0, H2O) [Lit.,16 -D-enantiomer: mp 183–184.5 °C
(EtOH); [ ]D27 –10.0 (c = 4.00, H2O)].
3
1H NMR: = 8.08 and 8.00 (2 br d, 4 H, Jmeta,ortho = 7.5 Hz, the
ortho protons of Bz groups), 7.64–7.38 (m, 6 H, two para and four
meta protons of Bz groups), 6.26 (d, 1 H, J1,2 1.0 Hz, H-1), 5.76
(dd, 1 H, J3,2 = 5.0, J3,4 = 6.0 Hz, H-3), 5.56 (dd, 1 H, H-2), 4.76–
4.64 (m, 2 H, H-4,5), 4.44 (dd, 1 H, J5’,4 = 3.0, J5’,5 = 11.0 Hz, H-5’),
2.10 and 1.98 (2 s, 2 3 H, 2 CH3C=O).
13C NMR: = 169.3 and 169.1 (2 CH3C=O), 165.9 and 165.3
(2 C6H5C=O), 133.7 and 133.3 (2 Cpara), 129.7 (2 Cmeta and
UV (H2O): max ( ) = 266.8 (8100), 207 nm (8400), min 234.7 nm
(2000).
CD (H2O): , nm (
290 (0).
1H NMR (DMSO-d6): = 10.68 (br s, 1 H, NH), 7.76 (d, 1 H, JH6,Me
1.0 Hz, H-6), 5.68 (d, 1 H, J1’,2’ = 5.5 Hz, H-1’), 5.34 (d,
10–3) = 245.0 (+4.5), 272.0 (–4.5), 257 and
C
ipso), 128.8 (Cipso), 128.6 and 128.4 (2
Cortho), 98.3 (d,
JOH,H3’ = 4.0 Hz, 3’-OH), 5.10 (t, JOH,H5’ = JOH,H5” = 4.5 Hz, 5’-OH),
1
1JC,H = 179.4 Hz, C-1), 79.8 (d, JC,H = 147.6 Hz), 76.4 (d,
5.08 (2’-OH), 4.10–3.90 (m, 2 H, H-2’ and H-3’), 3.82 (m, 1 H,
J3’,4’ = 3.0, J4’,5’ = J4’,5” = 2.5 Hz, H-4’), 3.64 (m, 1 H, H-5’), 3.54
1JC,H = 159.1 Hz) and 74.4 (d, 1JC,H = 159.1 Hz) (C-2, C-3 and C-4),
(m, 1 H, H-5”), 1.78 (d, 3 H, 5-CH3).
Synthesis 2002, No. 2, 253–259 ISSN 0039-7881 © Thieme Stuttgart · New York

258
G. G. Sivets et al.
PAPER
13C NMR (DMSO-d6): = 163.8 (C-4), 155.7 (C-2), 136.3 (C-6),
109.3 (C-5), 87.4 (C-1’), 84.7 (C-4’), 73.3 (C-2’), 69.8 (C-3’), 60.8
(C-5’), 12.1 (5-CH3).
To a stirred suspension of 18 (2.85 g, 0.01 mol) in freshly distilled
anhyd MeCN (100 mL) at 65 °C, was added dropwise a solution of
AcBr (3.7 mL, 0.05 mol) in anhyd MeCN (30 mL) during 1 h. The
mixture was stirred for an additional 1 h, cooled to r.t. and evapo-
rated to dryness in vacuo. The viscous yellow oily residue was dis-
solved in CH2Cl2 (100 mL), washed with H2O (2 50 mL), dried
and evaporated to afford a pale yellow foam (3.88 g, ca. 90%). The
HPLC analysis of this product [(column: Waters XTerra RP18,
1-( -L-Ribofuranosyl)cytosine (17)
A mixture of 13 (0.4 g, 0.9 mmol), the bis(trimethylsilyl) derivative
of N4-benzoylcytosine [obtained from 435 mg (2.02 mmol) of N4-
benzoylcytosine] and SnCl4 (0.24 mL, 0.532 g, 2.05 mmol) in an-
hyd MeCN was stirred for 18 h. After standard workup, the residue
was purified by silica gel (2.8 13 cm) column chromatography
with an EtOAc–hexane (1:3, v/v) mixture and then CHCl3 as elu-
ents, to afford 0.47 g (97%) of the acylated derivative of 17.
4.6 150 mm; linear gradient (10
50%) of buffer B (0.05 M
TEAA in 80% aq MeCN) in buffer A (0.05 M TEAA) at a flow rate
of 1.0 mL/min (time of analysis 30 min)] revealed the following
peaks [retention time (tR, min); (%)]: 16.05 (33.6%), 18.06 (9.7%),
19.23 (23.9%), 19.80 (18.1%), 21.36 (9.2%), and 21.87 (3.7%). The
UV spectra of all peaks were very similar ( max 298–300 and 247–
248 in a ratio of ca. 2:1; min 270–272 and 228–230 nm).
Acylated Derivative of 17
Rf 0.18 (A2).
1H NMR: = 9.18 (br s, 1 H, NH), 8.18–7.94 (m, 7 H, the ortho pro-
tons of Bz groups and H-6), 7.60–7.38 (m, 10 H, the para and meta
protons of Bz groups and H-5), 6.32 (d, 1 H, J1’,2’ = 3.7 Hz, H-1’),
5.92 (dd, 1 H, J2’,3’ = 5.7 Hz, H-2’), 6.66 (br t, 1 H, J3’,4’ = 6.0 Hz,
H-3’), 4.80 (dd, 1 H, J5’,4’ = 4.5, J5’,5” = 13.5 Hz, H-5’), 4.70–4.58
(m, 2 H, H-4’,5”), 2.00 (s, 3 H, CH3C=O).
The aforementioned product (3.80 g) was dissolved in MeOH (50
mL), KHCO3 (3.80 g) and 10% Pd/C (0.85 g) were added, and the
mixture was hydrogenated for 4 h. TLC analysis (developing sol-
vent system: D2) of the mixture showed the presence of three main
products: 17 (Rf 0.25), 19 (Rf 0.33), and 20 (Rf 0.38). Catalyst and
salts were filtered off, washed with MeOH (2 5 mL), silica gel (10
mL) was added to the combined filtrate and washings and the mix-
ture was evaporated to dryness in vacuo. Silica gel with products
was placed on the top of a column [4 25 cm; packed in a CH2Cl2–
MeOH (7:1) mixture] and the column was eluted with a mixture of
CH2Cl2–MeOH–H2O (70:10:1, vol) to afford, in the order of elu-
tion, 19 (0.38 g, 18%), 20 (0.36 g, 16%), and 17 (0.56 g, 23%).
Standard deacylation of the above product and subsequent chroma-
tography [silica gel Woelm containing 20% H2O (1.8 8 cm); elu-
ents: EtOAc and EtOAc–MeOH (4:1, v/v)] afforded 17.
17
20
Yield: 195 mg (91%); mp 207–208 °C (EtOH); Rf 0.25 (D2); [ ]D
–40.0 (c = 1.0, H2O) [Lit.,10 [ ]54625 –33 1 (c = 0.82, H2O)].
19
Mp 209–211 °C (Lit.17 mp 194–196 °C; Lit.11c mp 220–222 °C).
UV (H2O): max ( ) = 270.6 (8100), 229 nm (sh, 6900), min = 250
nm (5700).
UV (H2O):
( ) = 270.6 (8000), 230 nm (sh, 6800),
=
min
max
CD (H2O): , nm (
300 (0).
10–3) = 225.0 (+10.6), 268.0 (–10.5), 238 and
250.5 nm (5600).
CD (H2O): , nm (
237.3 (0).
10–3): 217.0 (+13.7), 272.0 (–15.3),
1H NMR (DMSO-d6): = 7.90 (d, 1 H, J5,6 = 7.5 Hz, H-6), 7.22
(„d“, 2 H, 4-NH2), 5.76 (d, 1 H, J5,6 = 7.5 Hz, H-5), 5.74 (d, 1 H,
1H NMR (CD3OD): = 8.10 (d, 1 H, J5,6 = 8.0, H-6), 6.02 (br d, 1
H, H-1’), 5.90 (d, 1 H, H-5), 4.16 (m, 1 H, H-4’), 3.90 (dd, 1 H,
J5’,4’ = 4.0, J5’,5” = 11.0 Hz, H-5’), 3.70 (dd, 1 H, J5”,4’ = 5.0 Hz, H-
5”), 2.42 (m, 1 H, H-2’), 1.80–2.10 (m, 3 H, H-2”,3’,3”).
J1’,2’ = 3.7 Hz, H-1’), 5.36 (br s, 2’-OH), 5.11 (br m, 3’-OH and 5’-
OH), 3.96 (br s, 2 H, H-2’,3’), 3.84 (m, 1 H, H-4’), 3.64 (m, 1 H, H-
5’), 3.48 (m, 1 H, H-5“).
13C NMR (DMSO-d6): = 165.5 (3JC4,H6 = 10.1 Hz, C-4), 155.5
3
(3JC2,H6 = 5.03, JC2,H1’ = <2.0 Hz, C-2), 141.4 (1JC6,H6 = 181.2,
20
2JC6,H5 = 3.8, 3JC6,H1’ = 3.8 Hz, C-6), 94.0 (1JC5,H5 = 173.8 Hz, C-5),
89.2 (1JC1’,H1’ = 173.8 Hz, C-1’), 84.0 (1JC4’,H4’ = 144.8 Hz, C-4’),
74.0 (1JC2’,H2’ = 141.9 Hz, C-2’), 69.3 (1JC3’,H3’ = 144.8 Hz, C-3’),
60.5 (1JC5’,H5’ = 137.6 Hz, C-5’).
White foam.
UV (H2O):
( ) = 271.0 (8100), 230 nm (sh, 7000);
=
min
max
250.0 nm (5750).
CD (MeOH): , nm (
235.0 and 312.0 (0).
10–3) = 215.0 (+12.6), 269.0 (–18.1),
2’,3’-Dideoxy- -L-cytidine (19) and 3’-Deoxy- -L-cytidine (20)
N4-Acetyl- -L-cytidine (18) was prepared from 17 (4.86 g, 0.02
mol) in a yield of 91% (5.19 g) using a modification12 of the proce-
dure described by Watanabe and Fox.14
1H NMR (CD3OD): = 8.17 (d, 1 H, J5,6 = 7.0 Hz, H-6), 5.84 (d, 1
H, H-5), 5.72 (br s, 1 H, H-1’), 4.46 (m, 1 H, H-4’), 4.28 (dd, 1 H,
J2’,3” = 4.8, J2’,3’ = 1.8 Hz, H-2’), 3.86 (dd, 1 H, J5’,4’ = 3.0,
J
5’,5” = 12.7 Hz, H-5’), 3.69 (dd, 1 H, J5”,4’ = 3.75 Hz, H-5”), 2.00
18
(ddd, 1 H, J4’,3’ = 9.0, J3’,3” = 13.5 Hz, H-3’), 1.83 (ddd, 1 H,
J3”,4’ = 4.65 Hz, H-3”).
Mp 177–179 °C (MeOH) [Lit.,14 -enantiomer: mp 174–178 °C
(MeOH)]; Rf 0.68 (D2).
UV (MeOH): max ( ) = 247.8 (12340), 289.5 nm (5330).
Acknowledgements
CD (MeOH): , nm (
260, and 330 (0).
10–3) = 228.0 (+24.5), 300.0 (–17.8), 214,
I.A.M. is deeply grateful to the Alexander von Humboldt Foundati-
on (Bonn/Bad-Godesberg, Germany) for partial financial support of
this work. The authors are thankful to the Foundation of Advanced
Studies (grant No. X99-263; Republic of Belarus) for partial finan-
cial support of this study and to Dr. Natalja B. Khripach (Institute
of Bioorganic Chemistry) for the measurement of the NMR spectra.
I.A.M. thank Prof. A. Azhayev (University of Kuopio, Finland) for
his support and useful discussions.
1H NMR (DMSO-d6): = 10.88 (s, 1 H, NH), 8.42 (d, 1 H, J5,6 = 8.0
Hz, H-6), 7.20 (d, 1 H, J = Hz, H-5), 5.78 (d, 1 H, J1’,2’ = 2.0 Hz, H-
1’), 5.55 (d, 1 H, JOH,H2’ = 4.0 Hz, 2’-OH), 5.28 (t, 1 H,
JOH,H5’ = JOH,H5“ = 4.0 Hz, 5’-OH), 5.15 (d, 1 H, JOH,H3’ = 2.5 Hz, 3’-
OH), 3.96 (center of m, 3 H, H-2’,3’,4’), 3.60 (center of m, 2 H, H-
5’,5”), 2.10 (s, 3 H, CH3C=O).
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PAPER
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