764
F. Roussel et al. / Bioorg. Med. Chem. 10 (2002) 759–768
2
3
[(2S) 3-Oxypropyl] 3,4-O-[(2S,3S) (2,3-dimethoxy
butane-2,3-dyl)]-ꢀ-D-xylopyranoside (18). Small
3.73 (dd, J(5a,5b)=10 Hz, 1H; H-5b), 3.63 (dd, J(1,2)
3
3.5 Hz, J(2,3)=10 Hz, 1H; H-2), 3.69 (m, 1H; H-300b),
2
3
0
0
0
0
amounts of 18 was obtained from 21 by column chro-
matography . Rf 0.44 (EtOAc/hexane, 1:9); [a]D +261.4
3.46 (dd, J(1 a-1 b)=10 Hz, J(1 a-2 )=7 Hz, 1H; H-1 b),
2.41 (s, 3H; CH3); 13C NMR (62.9 MHz, CDCl3) d
165.5, 165.4 (C¼O), 132.4, 144.8 (Ar ipso), 128.8, 129.4
(Ar ipso), 127.7, 127.8, 128.2, 128.2, 129.5, 129.7, 132.4,
132.9 (Ar), 97.5 (C-1), 69.2, 70.0 (C-10, C-30), 67.8, 69.9,
71.2, 76.7 (C-2, C-3, C-4, C-20), 58.6 (C-5), 21.3 (CH3);
C36H36O11S (676.20): calcd C 63.89, H 5.37, S 4.73;
found C 63.98, H 5.35, S 4.75.
1
(c 0.96 in chloroform); H NMR (250 MHz, CDCl3) d
4.88 (d, J(1,2)=3 Hz, 1H; H-1), 4.68 (s, 2H; CH2Ph),
3
3.52–3.91 (m, 7H; H-2, H-3, H-4, H-5b, H-5a, H-10a, H-
10b), 3.30 (s, 3H; OCH3), 3.26 (s, 3H; OCH3), 3.20 (m,
1H; H-200), 2.84 (dd, J(2 ,3 a)=4.4 Hz, J(3 a,3 b)=5.1 Hz,
3
3
0
0
0
0
1H; H-3 a), 2.66 (dd, J(2 ,3 b)=2.2 Hz, 1H; H-30b), 2.14
(d, 3J(H,OH)=9.5 Hz 1H; OH), 1.35 (s, 3H; CH3), 1.30 (s,
3H; CH3) 13C NMR (62.9 MHz, CDCl3) d 99.6, 99.2
(CH3COCH3), 98.9 (C-1), 70.4, 69.6, 65.7 (C-2, C-3, C-
4), 68.4 (C-10), 59.8 (C-5), 49.8(C-20), 47.7 (OCH3), 44.7
(C-30), 17.5 and 17.1 (CH3). C14H24O8 (320.3): calcd C
52.5, H 7.6, Found C 52.62, H, 7.42.
3
0
0
[(2R)
[2-Hydroxy-3-(6-amino-9H-purin-9-yl)]-propyl]
3,4-di-O-benzoyl-2-O-benzyl-ꢀ-D-xylo-pyranoside (30).
To a solution of adenine (398 mg, 2.94 mmol) in DMF
(6 mL) was added sodium hydride (60% dispersion in
mineral oil, 113 mg, 2.94 mmol). The mixture was stirred
at 80 ꢁC under inert atmosphere for 90 min then a solu-
tion of 29 (710 mg, 0.98 mmol) in DMF (5 mL) was
added dropwise. After 3 h of heating, the reaction was
cooled to room temperature and filtered through Celite.
The filtrate was concentrated under reduced pressure,
and the residue was purified by column chromato-
graphy (CH2Cl2/MeOH 9:1) to give compound 30
[(2S) (3-Oxypropyl)] 2-O-benzyl-3,4-O-[(2S,3S) (2,3-di-
methoxybutane-2,3-dyl)]-ꢀ-D-xylopyranoside (20). To a
solution of 18 (176 mg, 0.55 mmol) in dry THF (3 mL)
was added NaH (22 mg of a 60% dispersion in oil,
0.6 mmol). The mixture was stirred at room temperature
for 15 min, and then benzyl bromide (70 mL) was added.
After 1 h, excess NaH was destroyed by addition of
MeOH, and the solvents were removed by evaporation
under reduced pressure. The residue was diluted with
CH2Cl2 (50 mL) and washed with water (2 ꢂ 5 mL). The
organic layer was dried over MgSO4 and evaporated to
dryness. The residue was purified by column chromato-
graphy (hexane/EtOAc 3:2) to give 20 (205 mg, 91%).
Rf 0.39 (hexane/EtOAc, 3:2); [a]D=+166.4 (c 0.93 in
1
(420 mg, 63%): Rf 0.55 (CH2Cl2/MeOH 9:1); H NMR
(250 MHz, CDCl3) d 8.29 (s, 1H; H-200), 7.96 (m, 4H;
Ar), 7.89 (s, 1H; H-800), 7.51 (m, 2H; Ar), 7.38 (m, 5H;
Ar), 7.20 (m, 4H; Ar), 5.93 (dd, 3J(2,3)=10 Hz, 1H; H-3),
5.84 (m, 2H; NH2), 5.23 (ddd, J(3,4)=3J(4,5)=10 Hz,
3
3
1H; H-4), 4.90 (d, J(1,2)=3 Hz, 1H; H-1), 4.60 (s, 2H;
CH2Ph), 4.41 (m, 1H; H-30a), 4.30 (m, 2H; H-20, H-30b),
3.96 (dd, 3J(4,5a)=6 Hz, 2J(5a,5b)=11 Hz, 1H; H-5a), 3.82
(dd, J(1 a,2 )=4 Hz, J(1 a,1 b)=11 Hz, 1H; H-10a), 3.74
1
3
2
0
0
0
0
chloroform); H NMR (250 MHz, CDCl3) d 7.40–7.19
2
3
0
0
(m, 5H, Ar), 4.85 (d, J(H,H)=12.4 Hz; 1H; CH2Ph),
3
(m, 2H; H-2, H-5b), 3.41 (dd, J(1 b,2 )=6.5 Hz, 1H; H-
10b); 13C NMR (62.9 MHz, CDCl3) d 166.2, 165.9
(C¼O), 156.0 (C-600), 153.0 (C-200), 150.1 (C-400), 142.0
(C-800), 137.2 (Ar ipso), 129.2, 128.9 (Ar ipso), 133.6,
133.5, 130.0, 128.6, 128.3, 128.2 (Ar), 119.2 (C-5), 97.8
(C-1), 73.3 (CH2Ph), 70.6 (C-10), 77.3, 71.7, 70.3, 68.8
(C-2, C-3, C-4, C-20), 59.1 (C-500), 47.1 (C-30);
C34H33N5O8 (639.3): calcd C 63.83, H 5.20, N 10.95;
found C 63.95, H 5.18, N 10.92.
4.72 (d, J(1,2)=3.6 Hz, 1H; H-1), 4.65 (d, 1H; CH2Ph),
3
4.09 (dd, J(3,4)=9.4 Hz, H-3), 3.82–3.63 (m, 3H, H-4,
H-5a, H-10a), 3.62–3.44 (m, 3H, H-2, H-5b, H-10b), 3.30
(s, 3H, OCH3), 3;25 (s, 3H, OCH3), 3.16 (m, 1H, H-20),
2.75 (dd, 3J(2 ,3 a)=4.4 Hz, 3J(3 a,3 b)=4.7 Hz, 1H, H-30a),
0
0
0
0
2.65 (dd, J(2 ,3 b)=2.9 Hz, 1H, H-30b), 1.36 (s, 3H,
CH3), 1.31 (s, 3H, CH3); 13C NMR (62.9 MHz, CDCl3)
3
0
0
d
138.5 (Ar ipso), 128.1,127.4 (Ar), 99.5, 99.3
(CH3COCH3), 98.0 (C-1), 76.4 (C-2), 73.2 (CH2Ph),
69.8 (C-3), 68.0 (C-10), 66.3 (C-4), 59.3 (C-20), 47.8
(OCH3), 44.5 (C-30), 17.7 and 17.4 (CH3). C21H30O8
(410.46): calcd C 61.5, H 7.4, found C 61.38, H, 7.32
[(2R) [3-(6-Amino-9H-purin-9-yl)-2-hydroxy]propyl] 2-O-
benzyl-ꢀ-D-xylopyranoside (31). Compound 30 (370 mg,
0.58 mmol) was dissolved in MeOH (50 mL) and a cat-
alytic amount of sodium was added. After completion
of the reaction, TLC monitoring, the mixture was neu-
tralized using Amberlite IRA 120 H+. The resin was
filtered off and the filtrate was concentrated. The residue
was purified by column chromatography (EtOAc/
MeOH 9:1) to afford the triol derivative 31 (165 mg,
66%). Rf 0.12 (EtOAc/MeOH, 9:1); 1H NMR
(250 MHz, CD3OD) d 8.46 (s, 1H; H-200), 8.10 (s, 1H, H-
[(2R) (2-Hydroxy-3-tosyloxy)propyl] 2-O-benzyl-3,4-di-
O-benzoyl-ꢀ-D-xylopyranoside (29). Compound AU26
(750 mg, 1.43 mmol) was dissolved in dry pyridine
(20 mL) and tosyl chloride (300 mg, 1.57 mmol) was
added. The mixture was stirred for 2 h at room temperature
then concentrated under reduced pressure. The residue
was diluted with CH2Cl2 (200 mL) and washed with
aqueous HCl (3 N) and H2O. The organic layer was
dried over MgSO4 and concentrated. The residue was
purified by column chromatography (hexane/EtOAc 4:1
then 1:1) to give 29 (712 mg, 73%). Rf 0. 57 (H /A 1:1);
1H NMR (250 MHz, CDCl3) d 7.97 (m, 4H; Ar), 7.70
(m, 2H; Ar), 7.50 (m, 4H; Ar), 7.35 (m, 5H; Ar), 7.20
(m, 4H; Ar), 5.84 (dd, 1H; H-3), 5.19 (ddd,
800), 7.37 (m, 5H, Ar), 4.70 (d, J(H,H)=12 Hz, 1H,
2
3
CH2Ph), 4.64 (d, J(1,2)=3.5 Hz, 1H, H-1), 4.57 (d, 1H,
CH2Ph), 4.30 (dd, 3J(20,30a)=3 Hz, J(3 a,3 b)=12 Hz,
3
0
0
1H, H-30a), 4.18, (dd, J(2 ,3 b)=7 Hz, 1H, H-30b), 4.06
3
0
0
(m, 1H, H-20), 3.70 (dd, J(2,3)=3J(3,4)=9 Hz, 1H, H-3),
3
0
3
3
0
0
0
0
3.62 (dd, J(1 a,1 b)=11 Hz, J(1 a,2 )=4 Hz, 1H, H-1 a),
3.42 (m, 2H, H-4, H-5a), 3.24 (dd, 2H, H-2, H-10b), 3.18
3
3
3
3
3J(3,4)=10 Hz, J(4,5a)=5.5 Hz, J(4- 5b)=5.5 Hz, 1H; H-
4), 4.87 (d, 1H; H-1), 4.57 (s, 2H; CH2Ph), 4.10 (m, 1H;
H-10a), 3.93 (dd, 1H; H-5a), 3.85 (m, 2H; H-20, H-30a),
(dd, J(4,5b)=5.5 Hz, J(5a,5b)=10 Hz, 1H, H-5b); 13C
NMR (62.9 MHz, CD3OD) d 157.2 (C-600), 154.6 (C-200),
150.8 (C-400), 143.6 (C-800), 139.6 (Ar ipso), 128.9 128.4,