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H. Wippo et al. / Bioorg. Med. Chem. 9 (2001) 2411–2428
CH(isoprop)); 55.5 (q, CH3O(DMT)); 63.9, 64.3 (2dt,
JCP=19.3, CH2O(allyl)); 65.5, 65.6 (2t, C(50)); 69.2,
69.4, 70.7, 71.0, 71.5, 72.4 (6d, C(20), C(30), C(40)); 78.1,
78.2 (2d, C(10)); 87.5, 87.8 (2s, CAr); 111.6, 111.7 (2s,
C(5)); 113.6, 113.7 (2d, C(ar)); 115.6, 116.3 (2t,
CH2¼(allyl)); 127.4, 127.5, 128.3, 128.6, 128.8, 130.4,
130.7, 130.9, 133.5, 134.0, 135.3, 135.6, 135.9, 136.0,
136.1, 136.2 (16d, C(ar), CH(allyl), C(6)); 129.4, 130.0,
136.5, 136.7, 136.9, 145.7, 145.9 (7s, C(ar)); 150.7, 150.8
(2s, C(2)); 159.2, 159.3 (2s, C(ar)); 163.9 (s, C(4)); 165.6,
165.9 (2s, CO)); 31P NMR (242 MHz, CDCl3): 149.7,
151.6. HR-FAB-MS (pos, NBA/CsI): 984.2641 (100,
[M+Cs]+).
(40, [M+1]+), 726 (35), 637 (71), 303 (100), 188 (10),
105 (29).
9-[30 -O-((Allyloxy)(diisopropylamino)phosphino)-20 -O-
benzoyl-40-O-((dimethoxy-triphenyl)methyl)-ꢀ-D-ribopyr-
anosyl-(10)]-N2-isobutyrylguanine (4d). To a stirred solu-
tion of 613 mg (0.77 mmol) of 3d in 10 mL dry CH2Cl2
0.25 mL (1.16 mmol) of (allyloxy)(diisopropylamino)-
chlorophosphine and 0.34 mL (1.93 mmol) of diiso-
propylethylamine were added. The reaction was treated
with extra equivalents of the phosphitylating reagent
and base as described for the preparation of 4c. The
solvent was evaporated, and the residue was purified by
chromatography over silica gel (hexane/ethyl acetate 5:1
to 1:1). The product fractions were combined, evapo-
rated and the residue was twice precipitated from
150 mL of ice cold pentane to yield 492 mg (63%) of 4d
as a 1:2 mixture of diastereoisomers.
N4 -Benzoyl-1-[30 -O-((allyloxy)(diisopropylamino)phos-
phino)-20-O-benzoyl-40-O-((dimethoxy-triphenyl)methyl)-
ꢀ-D-ribopyranosyl-(10)]cytosine (4c). To a stirred solution
of 540 mg (0.72 mmol) of 3c in 10 mL of dry CH2Cl2,
0.31 mL (1.8 mmol) of diisopropyl ethylamine and
0.23 mL (1.08 mmol) of (allyloxy)(diisoproylamino)-
chlorophosphine were added. After 3 h stirring at rt,
an additional 0.06 mL (0.36 mmol) of diisopropyl-
ethylamine and 0.07 mL (0.36 mmol) of (allyloxy)(di-
isoproylamino)phosphine were added. After 5 h, the
reaction was quenched by the addition of 1 mL of
methanol. The solvent was evaporated and the residue
was purified by chromatography on silica gel column
(hexane/ethyl acetate 5:1 to 2:1). The product fractions
were combined, evaporated and the residue was further
purified by precipitation from 150 mL of ice cold pen-
tane. This yielded 426 mg (63%) of 4c as a 1:2 mixture
of diastereoisomers.
1
Data of 4d. TLC (hexane/ethyl acetate 3:2): Rf 0.67. H
NMR (400 MHz, CDCl3): 1.15, 1.20, 1.21, 1.23, 1.28
(5d, J=6.8, 12H, CH3(isoprop)); 2.62 (dd, J=4.7, 10.7,
0.7 H, H-C(50)); 2.86 (dd, Jgem=4.8, 10.5, 0.3 H, H–
C(50)); 3.35–3.50 (m, 1H, H–C(isobut)); 3.62–3.70 (m,
0.3H, H2C–O(allyl)); 3.75–3.98 (m, 10.3H, CH3–
O(DMT), CH2–O(allyl), CH(isoprop), H-C(40), H-
C(50)); 4.05–4.12 (m, 0.7 H, CH2–O(allyl)); 4.16–4.22
0
(m, 0.7H, CH2–O(allyl)); 4.54, 4.74 (d, J3 ,P=10.7, 0.7
0
H, H-C(30)); 4.83 (d, J1 ,2 =10.4, 0.3 H, H-C(2 )); 4.90
0
0
(dd, J=1.6, 17.2, 0.3H, H2C¼(allyl)); 4.96–4.99 (m, 2H,
0
0
0
H2C–O(allyl)); 5.05 (d, J1 ,2 =10.3, 0.7 H, H–C(2 ));
5.19–5.49 (m, 4 H, H2C¼(allyl), HC¼(allyl)), 5.89 (m,
J=5.4, 10.5, 17.1, 0.7H, HC¼(allyl)); 5.99–6.12 (m, 2H,
HC¼(allyl), H-C(10)); 6.83–7.82 (m, 25H, H–C(ar), H–
C(8)). 13C NMR (100 MHz, CDCl3): 19.11, 19.16, 19.22,
19.42 (4q, CH3(isobut)); 24.39, 24.45, 24.48, 24.54,
25.00, 25.09, 25.12, 25.2 (8q, CH3(isoprop)); 34.4 (d,
CH(isobut)); 42.8, 42.9 (2dd, JCP=12.8, CH(isoprop));
55.2 (q, CH3O(DMT)); 63.7 (dt, JCP=22.1, CH2O(al-
lyl)); 64.1 (dt, JCP=19.8, CH2O(allyl)); 65.1, 65.2 (2t,
C(50)); 67.8 (t, CH2O(allyl)); 68.9, 69.1, 70.5, 70.6, 71.3,
71.8, 71.9 (7d, C(20), C(30), C(40)); 78.7, 78.9 (2d, C(10));
87.3, 87.5 (2s, CAr); 113.23, 113.27, 133.31 (3d, C(ar));
115.3, 115.9 (2t, CH2¼(allyl)); 117.9, 118.0 (2s, C(5));
118.6 (t, CH2¼(allyl)); 126.9, 127.0, 127.86, 127.93,
128.1, 128.3, 129.7, 129.9, 130.0, 130.37, 130.40, 132.0,
132.9, 133.3, 135.3, 135.3, 135.5, 135.6 (18d, C(ar), CH–
(allyl)); 128.9, 129.5, 136.0, 136.15, 136.15, 136.4, 145.2,
145.5, 158.7, 158.8 (10s, C(ar)); 139.8, 139.9 (2d, C(8));
151.99, 152.03, 152.9, 153.0 (4s, C(2), C(4)); 160.51,
160.54 (2s, C(6)); 164.6, 164.9, 177.3 (3s, CO); 31P NMR
(162 MHz, CDCl3): 138.5, 139.9. FAB-MS (pos, NBA):
1974 (15, [2M+1]+), 987 (48, [M+1]+), 683 (30), 303
(100), 105 (85).
1
Data of 4c. TLC (hexane/ethyl acetate 1:1): Rf 0.58. H
NMR (400 MHz, CDCl3): 1.13 (d, J=6.8, 0.9H,
H3C(isoprop)); 1.18, 1.27, 1.43 (3d, J=6.7, 11.1H,
CH3(isoprop)); 2.64 (dd, Jgem=4.9, 10.3, 0.7H, H-
C(50)); 2.83 (dd, J4 ,5 =4.9, Jgem=10.3, 0.3 H, H-C(50));
3.76–3.88 (m, 10 H, CH3O(DMT), H–C(isoprop), H-
C(40), H-C(50)); 4.06–4.17 (m, 2H, H2C–O(allyl)); 4.46
(d(br), J=10.0, 0.3H, H–C(30)); 4.62–4.68 (m, 1 H, H-
C(30), H2C¼(allyl)); 4.82 (m, 1H, H–C(20)); 4.90 (dd,
J=1.7, 17.2, 0.3H, H2C¼(allyl)); 5.03 (d(br), J=10.3,
0.7H, H2C¼(allyl)); 5.18 (dd, J=1.6, 17.1, 0.7H,
H2C¼(allyl)); 5.43 (m, J=5.4, 10.3, 17.1, 0.3H,
HC¼(allyl)); 5.82 (m, J=5.4, 10.6, 17.1, 0.7H,
HC¼(allyl)); 6.40–6.46 (m, 1H, H-(C10)); 6.83 (d,
J=9.0, 4H, H-C(ar)); 7.19–8.42 (m, 21H, H–C(ar), H–
C(5), H–C(6), NH). 13C NMR (100 MHz, CDCl3):
24.47, 24.53, 24.59, 24.95, 25.04, 25.09 (6q, CH3(iso-
prop)); 42.8 (dd, JCP=12.6, CH(isoprop)); 43.02 (dd,
JCP=12.8, CH(isoprop)); 55.22 (q, CH3O); 63.8 (dt,
JCP=19.3, CH2–O(allyl)); 65.3, 65.5 (2t, C(50)); 68.9,
69.2, 70.5, 72.05, 72.13 (5d, C(20), C(30), C(40)); 80.0
(d, C(10)); 87.2 (d, C(5)); 87.5 (s, CAr); 113.21,
113.26, 113.28, 126.9, 127.0, 127.8, 128.1, 128.26,
128.32, 128.36, 129.0, 129.62, 130.1, 130.34, 130.36,
130.43, 130.46 (17d, C(ar)); 115.11, 115.76 (2t,
CH2¼(allyl)); 132.9, 133.1, 133.4, 135.8, 136.1, 136.25,
136.28, 136.5, 145.5 (8s, C(ar)); 135.6 (d, CH¼
(allyl)); 145.3 (d, C(6)); 158.7 (s, C(2)); 165.1, 165.5
(2s, C(4), CO). 31P NMR (162 MHz, CDCl3): 138.1;
140.2; FAB-MS (pos, NBA): 1882 (17, [2M+1]+), 941
0
0
N6-Benzoyl-9-[20-O-benzoyl-40-O-((400,4000-dimethoxytri-
phenyl)methyl)-ꢁ-L-lyxopyranosyl-(10)]adenine (7a). To
a stirred soln of 3.21 g (4.13 mmol) of 6a in 196 mL
THF/H2O (2:1) at 0 ꢀC was added dropwise 6.42 mL of
15% aq NaOH soln. After stirring for 2 h, 40 mL of an
1 M E t NHHCO3 soln was added and THF was
3
removed by distillation at rt. The soln was diluted with
CH2Cl2 and the resulting mixture was washed with satd