Synthesis of a novel uridine analogue and its use in attempts to form new cyclonucleosides using ring-closing metathesis

Article abstract of DOI:10.1007/s11426-010-4063-3

One novel nucleoside analogue having a hex-5-enyl group and an allyl group in the 5′-C and 3-N position was synthesized regio- and diastereoselectively from d-glucose in twelve steps. In order to reach a particular conformation of nucleosides the nucleosi

Full text of DOI:10.1007/s11426-010-4063-3

SCIENCE CHINA
Chemistry
September 2010 Vol.53 No.9: 1932–1936
doi: 10.1007/s11426-010-4063-3
• ARTICLES •
Synthesis of a novel uridine analogue and its use in attempts to
form new cyclonucleosides using ring-closing metathesis
ZHONG Shi1, MONDON Martine1 & LEN Christophe1,2*
1UMR 6514 Université de Poitiers CNRS, Synthèse et Réactivité des Substances Naturelles, 40 avenue du Recteur Pineau,
F-86022 Poitiers cedex, France
2EA4297 Université de Technologie de Compiègne UTC-Ecole Supérieure de Chimie Organique et Minérale ESCOM,
1 allée du Réseau Jean-Marie Buckmaster, 60200 Compiègne, France
Received June 15, 2010; accepted July 20, 2010
One novel nucleoside analogue having a hex-5-enyl group and an allyl group in the 5′-C and 3-N position was synthesized regio-
and diastereoselectively from D-glucose in twelve steps. In order to reach a particular conformation of nucleosides the nucleo-
side formation of restricted cyclonucleoside analogues was studied via Ring-Closing Metathesis.
nucleoside, restrictedconformation, metathesis
only the synthesis of the 3,5′-O-pentanouridine 1 and
3,5′-O-hexanouridine 2. The synthesis of cyclonucleoside
having a butyl linker gave only the formation of cyclic di-
nucleosides 3 and 4 having two butylene between the 5′-O
and N-3 position. In this paper, we described a study con-
cerning the synthesis of cyclonucleoside analogues 5 via
RCM reaction between the N-3 position and the 5′-C posi-
tion. Figure 1 gives the structures of 1–5. We report the in
vitro anti-HIV evaluation of two compounds.
1 Introduction
Natural nucleosides and analogues are of great biological
importance in metabolic pathways and in antitumoral/antiviral
diseases [1–4]. The typical shape of nucleosides has two
molecular moieties: D-ribo- or D-2′-deoxyribopentofuranose
as the sugar moiety and a purine or pyrimidine aglycone.
These two fragments are covalently bonded from N-1 of
pyrimidine or N-9 of purine to C-1′ of the glycone in a
-configuration [5]. In order to investigate the conformational
preference of nucleoside analogues, the limitation of con-
formation of a nucleoside or nucleotide is widely used
[6–10]. Different conformationally constrained nucleosides
have been used and can be classified into three families:
bicyclonucleosides, cyclic phosphoesters, and cyclonucleo-
sides. Metathesis [11–14] is a currently useful method in
organic chemistry for the synthesis of different nucleoside
analogues [15–18]. Len’s group developed a concise
method for the synthesis of cyclonucleosides via ring-closing
metathesis [19, 20]. It was notable that this strategy permits
2 Experimental
2.1 General experimental
1H and 13C NMR spectra were recorded in CDCl3 (internal
Me4Si) at 300.13 MHz and at 75.47 MHz, respectively
(Bruker Advance-300). TLC was performed on Silica F254
(Merck) and detection was by UV light at 254 nm or by
charring with phosphomolybdic-H2SO4 reagent. Column
chromatography was carried out on Silica Gel 60 (Merck,
230 mesh). EtOAc, CH2Cl2 and petroleum ether were dis-
tilled before use. Bases and solvents were used as supplied.
High resolution ESI mass spectra were obtained on a LCT
*Corresponding author (email: christophe.len@utc.fr)
© Science China Press and Springer-Verlag Berlin Heidelberg 2010
chem.scichina.com
www.springerlink.com

ZHONG Shi, et al. Sci China Chem September (2010) Vol.53 No.9
1933
S, 6.90. Found: C, 59.53; H, 6.14; S, 6.87. HRMS (ESI)
(M+Na+) calcd for C23H28O8SNa: 487.1403, found 487.1401.
5,6-Anhydro-O-benzyl-1,2-O-isopropylidene--D-allofuran-
ose (9)
To a solution of 8 (7.0 g, 15.1 mmol) in CH2Cl2 (10 mL)
and MeOH (100 mL), at 0 °C, was added K2CO3 (3.1 g,
26.2 mmol). The reaction mixture was stirred at this tem-
perature for 1 h, then for 24 h at room temperature. After
dilution with CH2Cl2, the mixture was washed with a 1 N aq
HCl (20 mL) and then with H2O. The organic layer was
dried over Na2SO4 and concentrated under reduced pressure.
The crude product was purified by flash column chroma-
tography on SiO2 (EtOAc/petroleum ether, 10/90 v/v). Yield:
4.0 g of 9 as colorless oil (90%). The physical data were in
accordance with those described by Hanaya [21].
3-O-Benzyl-6-O-deoxy-1,2-O-isopropylidene-6-C-(pent-4-
enyl)--D-allofuranose (10)
To a solution of 9 (2.0 g, 6.85 mmol) in dry THF (30 mL) in
the presence of cuprous iodide (124 mg, 0.69 mmol) was
added dropwise at 70 °C a solution of the Grignard reagent
(9.2 mL, 13.7 mmol) [freshly prepared in the usual way by
controlled addition of 5-bromo-pent-1-ene (2.2 mL, 18.9
mmol) in dry THF (12 mL) to magnesium (1.0 g, 41.6
mmol)]. The solution was stirred for 4 h at 70 °C and then
for 12 h at room temperature. The reaction mixture was
quenched with aq NH4Cl (30 mL) and extracted with
CH2Cl2. The crude product was purified by flash column
chromatography on SiO2 (EtOAc/petroleum ether, 10/90
v/v). Yield: 2.2 g of 10 as colorless oil (89%); Rf 0.3
Figure 1 Structures of 3-N,5′-O-cyclouridines 1 and 2, cyclic dinucleo-
sides 3 and 4 and 3-N,5′-C-cyclouridine 5.
instrument (Micromass-Waters, UK) filled with a lockspray
probe. NaI cluster ions were used as the lock mass for ac-
curate mass measurements (resolution FWMH-5000).
2.2 Synthesis of the 2′-O-acetyl-3-N-allyl-3′,5′-di-O-benzyl-
5′-C-(hex-5-enyl)-uridine
1
3-O-Benzyl-1,2-O-isopropylidene-6-O-p-toluenesulfonic--D-
allofuranose (8)
(hexane-EtOAc, 80:20); H NMR (300 MHz, CDCl3): 
7.35 (m, 5H, H-arom), 5.80 (ddt, J = 6.7, 10.2, 16.7 Hz, 1H,
CH=CH2), 5.73 (d, J = 3.9 Hz, 1H, H-1), 5.02–4.90 (m, 2H,
CH=CH2), 4.75 (d, J = 11.7, 1H, Ph-CH2), 4.57 (m, 1H,
H-2), 4.56 (d, J = 11.7, 1H, Ph-CH2), 4.05 (dd, J = 3.3, 8.7
Hz, 1H, H-4), 3.90 (dd, 1H, J = 4.4, 8.7 Hz, H-4), 3.87 (m,
1H, H-5), 2.04 (m, 2H, CH2), 1,60 (m, 2H, CH2), 1.59 (s,
3H, CH3), 1.39 (m, 4H, 2 CH2), 1.36 (s, 3H, CH3); 13C
NMR (75 MHz, CDCl3):  139.0 (CH=), 137.4 (C-arom),
128.4 (CH-arom), 128.1 (CH-arom), 128.0 (CH-arom), 114.3
(CH2=), 113.0 (C(CH3)2), 104.0 (C-1), 80.7 (C-4), 77.8
(C-2), 77.1 (C-3), 72.1 (Ph-CH2-O), 70.8 (C-5), 33.6 (CH2),
31.8 (CH2), 28.9 (CH2), 26.9 (CH3), 26.6 (CH3), 25.4 (CH2).
Anal. calcd for C21H30O5: C, 69.59; H, 8.34. Found: C,
69.61; H, 8.40. HRMS (ESI) (M+Na+) calcd for
C21H30O5Na: 385.1991, found 385.1987.
To a solution of 7 (4.0 g, 12.9 mmol) in CH2Cl2 (50 mL) at
room temperature was added dibutyltin oxide (64 mg, 0.02
equiv), triéthylamine (1.6 mL, 13 mmol) and p-toluenesul-
fonyl chloride (2.4 g, 13.1 mmol). The reaction mixture was
stirred for 24 h and then stopped by adding aq sat NaHCO3
and diluting with CH2Cl2. The organic layer was separated,
washed with H2O, and dried over Na2SO4. The solvent was
removed under reduced pressure. The crude product was
purified by flash column chromatography on SiO2 (EtOAc/
petroleum ether, 10/90 v/v). Yield: 4.5 g of 8 as colorless oil
1
(75%); Rf 0.6 (hexane-EtOAc, 80:20); H NMR (300 MHz,
CDCl3):  7.76 (d, 2H, J = 8.0 Hz, H-Arom), 7.34 (m, 7H,
H-Arom), 5.70 (d, J = 3.6 Hz, 1H, H-1), 4.71 and 4.50 (2d,
J = 11.4 Hz, 2H, Ph-CH2), 4.55 (m, 1H, H-2), 4.17–4.06 (m,
3H, H-6, H-5), 3.99 (dd, J = 3.5, 8.7 Hz, 1H, H-4), 3.88 (dd,
J = 4.2, 8.7 Hz, 1H, H-3), 2.43 (s, 3H, Ph-CH3), 1.56 (s, 3H,
CH3), 1.34 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): 
144.9 (C), 137,0 (C), 132.6 (C), 129.9 (CH), 128.5 (CH),
128.4 (CH), 128.2 (CH), 128.1 (CH), 113.3 (C(CH3)2),
104.3 (C-1), 77.4, 77.3, 77.1 (C-2, C-3, C-4), 72.1
(Ph-CH2-O), 70.7 (C-6), 69.2 (C-5), 26.8 (CH3), 26.5 (CH3),
21.7 (Ph-CH3). Anal. calcd for C23H28O8S: C, 59.47; H, 6.08;
3,5-Di-O-benzyl-6-O-deoxy-1,2-O-isopropylidene-6-C-(pent-
4-enyl)--D-allofuranose (11)
To a solution of 10 (2.9 g, 8.0 mmol) in THF (30 mL) was
added NaH (60% suspension in oil, 800 mg, 20.0 mmol) at
room temperature. After 1 h, tert-butylammonium iodide
(295 mg, 0.8 mmol) and benzyl bromine (2.3 mL, 20 mmol)
were added and the mixture was stirred for 12 h at room

1934
ZHONG Shi, et al. Sci China Chem September (2010) Vol.53 No.9
temperature. The reaction was quenched by controlled addi-
tion of MeOH, poured into sat NH4Cl and the product ex-
tracted with CH2Cl2. The extracts were combined, dried
(Na2SO4), filtered and the solvent was removed in vacuo.
The crude product was purified by flash column chroma-
tography on SiO2 (EtOAc/petroleum ether, 3/97 v/v). Yield:
3.0 g of 11 as colorless oil (84%); Rf 0.8 (hexane-EtOAc,
90:10); 1H NMR (300 MHz, CDCl3):  7.35 (m, 10H,
H-arom), 5.80 (ddt, J = 6.7, 10.2, 16.7 Hz, 1H, CH=CH2),
5.68 (d, J = 3.9 Hz, 1H, H-1), 5.02–4.90 (m, 2H, CH=CH2),
4.73 (d, J=11.7 Hz, 1H, Ph-CH2), 4.67 (d, J = 11.7 Hz, 1H,
Ph-CH2), 4.52 (d, J = 3.9 Hz, 1H, H-2), 4.56 (d, J=11.7 Hz,
2H, Ph-CH2), 4.18 (dd, J = 3.3, 8.7 Hz, 1H, H-4), 4.02 (dd,
1H, J = 4.5, 8.7 Hz, H-3), 3.70 (m, 1H, H-5), 2.00 (m, 2H,
CH2), 1.62 (m, 2H, CH2), 1.59 (s, 3H, CH3), 1.39 (m, 4H, 2
CH2), 1.36 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): 
139.1 (CH=), 138.9 and 137.7 C-arom), 128.4 (CH-arom),
128.2 (CH-arom), 128.0 (CH-arom), 127.8 (CH-arom), 127.7
(CH-arom), 127.4 (CH-arom), 114.3 (CH2=), 112.8
(C(CH3)2), 103.9 (C-1), 81.5, 78.2, 77.9 and 77.3 (C-2, C-3,
C-4, C-5), 73.5 (Ph-CH2-O), 72.1 (Ph-CH2-O), 33.6 (CH2),
30.8 (CH2), 28.8 (CH2), 27.0 (CH3), 26.7 (CH3), 25.7 (CH2).
Anal. calcd for C28H36O5: C, 74.31; H, 8.02. Found: C,
74.27; H, 8.07. HRMS (ESI) (M+Na+) calcd for
C28H36O5Na: 475.2460, found 475.2457.
2.09 (s, 3H, CH3), 1.95–1.20 (m, 8H, 4 CH2).
3′-O-acetyl-3′,5′-di-O-benzyl-5′-C-(hex-5-enyl)-uridine (13)
To a solution of uracile (448 mg, 4 mmol) in CH3CN (8 mL)
was added N,O-bis(trimethylsilyl)acetamide (BSA) (2 mL,
8 mmol) at room temperature. The reaction was refluxed for
4 h and then cooled at 0 °C. After addition of a solution of
12 (500 mg, 1 mmol) in CH3CN (8 mL) SnCl4 (0.94 mL)
were added. The mixture was stirred at room temperature
for 12 h and extracted with CH2Cl2. The organic layer was
washed with sat NH4Cl, dried on Na2SO4 and the solvent
removed in vacuo. The crude product was purified by flash
column chromatography on SiO2 (CH2Cl2). Yield: 425 mg
of 13 as colorless oil (77%); Rf 0.5 (hexane-EtOAc, 70:30);
1H NMR (300 MHz, CDCl3):  ppm 9,2 (br s, NH), 7.36 (m,
11H, H-arom, H-6), 6.14 (d, J = 5.1 Hz, 1H, H-1′), 5.78 (ddt,
J = 5.9, 10.5, 17.3 Hz, 1H, CH2=CH), 5.18 (t, J=5.1 Hz, 1H,
H-2′), 5.13 (d, J = 8.4 Hz, 1H, H-5), 5.0 (m, 2H, CH2=),
4.77 (d, J = 11.1, 1H, Ph-CH2), 4.59 (d, J = 11.1, 1H,
Ph-CH2), 4.49 (d, J = 11.1, 1H, Ph-CH2), 4.38 (d, J = 11.1,
1H, Ph-CH2), 4.33 (t, J = 5.1 Hz, 1H, H-3′), 4.17 (m, 1H,
H-4′), 3.72 (m, 1H, H-5′), 2.10 (s, 3H, CH3CO), 2.04 (m,
2H, CH2) 1.80 (m, 2H, CH2), 1.50 (m, 4H, 2CH2); 13C NMR
(75 MHz, CDCl3):  170.4 (CH3CO), 163.4 (C-4), 150.7 (C-2),
140.2 (C-6), 138.9 (–CH=), 138.1 and 137.6 C-arom),
129.1 (CH-arom), 128.9 (CH-arom), 128.7 (CH-arom),
128.4 (CH-arom), 128.5 (CH-arom), 127.9 (CH-arom),
115.1 (CH2=), 103.0 (C-5), 86.8 (C-1′), 84.7 (C-4′), 79.6
(C-5′), 75.8 and 74.8 (C-2′ and C-3′), 73.5 (Ph-CH2-O), 72.9
(Ph-CH2-O), 33.9 (CH2), 30.4 (CH2), 29.3 (CH2), 25.7
(CH2), 21.3 (CH3). Anal. calcd for C31H36N2O7: C, 67.87; H,
6.61; N, 5.11. Found: C, 67.83; H, 6.65; N, 5.07. HRMS
(ESI) (M+Na+) calcd for C31H36N2O7Na: 571.2420, found
571.2416.
1,2-Di-O-acetyl-3,5-di-O-benzyl-6-O-deoxy-6-C-(pent-4-enyl)-
-D-allofuranoside and 1,2-di-O-acetyl-3,5-di-O-benzyl-6-
O-deoxy-6-C-(pent-4-enyl)--D-allofuranoside (12)
A solution of 11 (500 mg, 1.1 mmol) in 30 mL of CH2Cl2/
CF3COOH/H2O (5:3:2 v/v/v) was stirred for 18 h at room
temperature and then quenched by sat NaHCO3 and ex-
tracted with CH2Cl2. The organic layer was dried (Na2SO4),
filtered and the solvent was removed in vacuo. To the resi-
due dissolved in pyridine (3 mL) was added acetic anhy-
dride (0.4 mL, 4.4 mmol). The reaction was stirred at room
temperature for 12 h, poured into an iced aq 1 N HCl and
extracted with Et2O. The extracts were combined, dried
(Na2SO4), filtered and the solvent was removed in vacuo.
The crude product was purified by flash column chroma-
tography on SiO2 (EtOAc/petroleum ether, 5/95 v/v). Yield:
1.2 g of a mixture of 12 in a 4:1 ratio (68%); For 12 (-D)
1H NMR (300 MHz, CDCl3):  7.35 (m, 10H, H-arom),
6.10 (s, 1H, H-1), 5.72 (ddt, J = 6.7, 10.2, 16.7 Hz, 1H,
CH=CH2), 5.32 (d, J = 4.5 Hz, H-2), 5.02–4.90 (m, 2H,
CH=CH2), 4.68 (d, J = 11.7 Hz, 1H, Ph-CH2), 4.59–4.17 (m,
3H, Ph-CH2), 4.44 (dd, J = 4.5, 7.6 Hz, 1H, H-3), 4.18 (dd,
1H, J = 2.8, 7.6 Hz, H-4), 3.65 (m, 1H, H-5), 2.10 (m, 3H,
CH3), 1.99 (m, 2H, CH2), 1.82 (s, 3H, CH3), 1.47–1.29 (m,
3′-O-acetyl-3-N-allyl-3′,5′-di-O-benzyl-5′-C-(hex-5-enyl)-uri-
dine (14)
To a solution of 13 (1.2 g, 2.2 mmol) in a mixture of ace-
tone (5 mL) and DMF (5 mL) at room temperature were
added K2CO3 (395 mg, 2.9 mmol) and allyl bromide (0.2
mL, 2.8 mmol). The mixture was stirred at 60 °C for 12 h,
filtered and concentrated in vacuo. The crude product was
purified by flash column chromatography on SiO2 (CH2Cl2).
Yield: 1.1 g of 14 as colorless oil (84%); Rf 0.6
1
(hexane-EtOAc, 90:10); H NMR (300 MHz, CDCl3): 
7.36 (m, 11H, H-arom, H-6), 6.13 (d, J = 5.1 Hz, 1H, H-1′),
5.80 (m, 2H, CH2=CH), 5.22–5.07 (m, 4H, H-2′, H-5,
CH2=), 4.95–4.87 (m, 2H, CH2=), 4.76 (d, J = 11.1, 1H,
Ph-CH2), 4.59 (d, J = 11.1, 1H, Ph-CH2), 4.40 (m, 3H,
Ph-CH2, NCH2), 4.38 (d, J = 11.1, 1H, Ph-CH2), 4.33 (t, J=
5.3 Hz, 1H, H-3′), 4.18 (m, 1H, H-4′), 3.75 (m, 1H, H-5′),
2.10 (s, 3H, CH3CO), 2.04 (m, 2H, CH2), 1.38-1.80 (m, 6H,
3 CH2); 13C NMR (75 MHz, CDCl3):  170.3 CH3CO),
162.5 (C-4), 151.0 (C-2), 138.9 (C-6), 138.1 (CH=) 137.6
C-arom), 131.8 (CH=), 129.1 (CH-arom), 128.9
1
6H, 3 CH2). For 12 (-D) H NMR (300 MHz, CDCl3): 
7.35 (m, 5H, H-arom), 6.40 (d, J = 4.5 Hz, 1H, H-1), 5.80
(ddt, J = 6.7, 10.2, 16.7 Hz, 1H, CH=CH2), 5.09 (dd, J =4.6,
6.1 Hz, 1H, H-2), 4.96 (m, 2H, CH=CH2), 4.67–4.51 (m, 4H,
2Ph-CH2), 4.30 (t, J = 3.0 Hz, 1H, H-4), 4.23 (dd, 1H, J =
3.0, 6.1 Hz, H-3), 3.55 (m, 1H, H-5), 2.13 (s, 3H, CH3),

ZHONG Shi, et al. Sci China Chem September (2010) Vol.53 No.9
1935
(CH-arom), 128.7 (CH-arom), 128.4 (CH-arom), 128.5
(CH-arom), 127.9 (CH-arom), 118.3 (CH2=), 115.1 (CH2=),
102.4 (C-5), 87.8 (C-1′), 84.3 (C-4′), 79.4 (C-5′), 75.3 (C-3′),
74.8 (C-2′), 73.5 (Ph-CH2-O), 72.9 (Ph-CH2-O), 43.5 (CH2),
33.9 (CH2), 30.4 (CH2), 29.3 (CH2), 25.7 (CH2), 21.3 (CH3).
Anal. calcd for C34H40N2O7: C, 69.37; H, 6.85; N, 4.76.
Found: C, 69.36; H, 6.91; N, 4.71. HRMS (ESI) (M+Na+)
calcd for C34H40N2O7Na: 611.2733, found 611.2728.
neighboring group stabilization through the acetyloxonium
ion intermediate to favor the formation of the desired
-nucleoside analogue 13. To prepare selectively the corre-
sponding 3-N-allyl derivative 14 reactions of uridine ana-
logue 13 with allyl bromide using a battery of base catalysts
were studied. In our hand the best result was obtained using
K2CO3. Selective N-allylation was performed with K2CO3
and allyl bromide in DMF and acetone at 55°C to produce
the diene 14 in 84% yield (Scheme 1). The diene 14 was
subject to the Ring-Closing Metathesis in various solvents
and temperatures under first and second generations of
Grubbs catalysts, respectively. Also, the Hoveyda- Grubbs
catalyst was used under the same conditions but with no
ring-closed product formed. A mixture of starting material
14 and dimers was observed as reported by our group for
the preparation of 3-N,5′-O-cyclonucleosides. In our hand,
3 Results and discussion
Toward the synthesis of 3-N,5′-C-cyclonucleosides
To obtain the desired 3-N,5′-C-cyclonucleoside 5, one route
has been investigated starting from D-glucose (6). The choice
to use 6 as starting material conducted us to invert the con-
figuration of the carbon atom in position 3 (hydroxyl group
in  position to  position) to have the D-ribose configura-
tion as natural nucleoside. The well-established protection
of 6 followed by successive oxidation, selective reduction to
obtain the D-allose derivative [22], benzylation of the hy-
droxyl group in position 3 [23, 24] and deprotection of the
diol in position 5,6 [24, 25] gave the D-allose derivative 7 in
51% overall yield (five steps). At this step it was notable
that the oxidative cleavage followed by addition of the
hex-5-ene magnesium bromide could be studied. In our
hand, the reaction was not diastereoselective and a mixture
of two diastereoisomers was obtained. Due to this poor se-
lectivity a strategy generating no stereogenic centre via ep-
oxide intermediate was studied. Selective tosylation of the
primary hydroxyl group using tosyl chloride in presence of
Bu2SnO and triethylamine furnished compound 8 in 75%
yield [26, 27]. Treatment of 8 with K2CO3 in methanol gave
the epoxide 9 in 90% yield [26, 28] and then the oxirane 9
was reacted in presence of CuI in THF with pent-4-ene
magnesium bromide to give selectively the (R) alcohol 10 in
89% yield. This condensation has occurred without any loss
in the chiral integrity of the (R)-configuration at the C5 cen-
tre. Treatment of compound 10 with NaH in THF during
one hour at room temperature followed by addition of
tetrabutylammonium iodide and benzyl bromide gave after
one night at room temperature the dibenzylated D-allose
derivative 11 in 84% yield. Successive hydrolysis of the
acetonide group of compound 11 with acidic treatment us-
ing a mixture of dichloromethane-trifluoroacetic acid-water
(5:3:2) and then acetylation afforded the diacetate 12 as a
mixture of two diastereoisomers -D and -D-allose deriva-
tives in a ratio 4:1 in 68% yield. This later mixture 12 was
successfully subjected to the corresponding -nucleoside 13
in 77% yield as the sole product using Vorbruggen conden-
sation reaction [29]. The uracil was silylated using BSA in
refluxing CH3CN and then the mixture of 12 was added
followed by the addition of SnCl4 at room temperature [30].
It is clear that the acetate group on C-2′ participated in
Scheme 1 Synthesis of 3′-O-acetyl-3-N-allyl-3′,5′-di-O-benzyl-5′-C-(hex-5-
enyl)-uridine (14). Reaction conditions: (i) refs. [21–24]; (ii) 0.02 equiv
Bu2SnO, 1.0 equiv Et3N, 1.0 equiv TsCl, CH2Cl2, 24 h, room temperature;
(iii) 1.7 equiv K2CO3, CH2Cl2, MeOH, 0 °C for 1 h and then room
temperature for 24 h; (iv) 0.1 equiv CuI, 2.7 equiv CH2=CHC3H6MgBr,
THF, 70°C for 4 h and then room temperature for 12 h; (v) 2.5 equiv NaH,
THF, room temperature for 1 h and then 0.1 equiv Bu4NI, 2.5 equiv BnBr,
room temperature for 12 h; (vi) CH2Cl2, CF3COOH, H2O, room
temperature for 18 h and then Ac2O, pyridine, room temperature for 12 h;
(vii) 4 equiv uracile, 8 equiv BSA, CH3CN, reflux for 4 h and then SnCl4,
room temperature, 12 h; (viii) 1.3 equiv K2CO3, 1.3 equiv CH2=CHCH2Br,
acetone, DMF, 60 °C, 12 h.

1936
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