120
A. Graziani et al. / Tetrahedron: Asymmetry 18 (2007) 115–122
3
diminished pressure for 5 h. The flask was charged with
CH2Cl2 (2 mL), cooled to ꢀ15 ꢁC and a solution of t-
BuOOH (30 lL of 80% solution in di-tert-butyl peroxide)
in CH2Cl2 (2 mL) was gradually added (ꢂ30 min). The
reaction mixture was warmed to rt and stirred for 2 h.
The solvent was concentrated, the residue dissolved in
CH2Cl2 (50 mL) and washed sequentially with saturated
aq NaHCO3, water and brine. The organic phase was dried
over Na2SO4, concentrated and the residue purified by
flash chromatography on silica gel (20:1!10:1 CH2Cl2–
CH3OH) to give 20,30-di-O-acetyl-adenosine 50-(5,6,7,9,10-
penta-O-acetyl-4,8-anhydro-1,3-dideoxy-L-lyxo-L-manno-
decit-2-yl) 2-cyanoethylphosphate 10 as a diastereomeric
mixture on phosphorus as a syrup (73 mg, 87%). 1H
NMR: d 8.36 and 8.35 (s, 1H, H-8Ade), 8.13 and 8.12 (s,
(C-2Rib), 71.05 (C-2, J2,P = 5.7 Hz), 70.95 (C-5), 70.43
(C-3Rib), 68.98 (C-9), 66.33 (C-7), 64.64 (C-5Rib
2J5,P = 5.3 Hz), 63.05 (C-10), 46.67 (CH2, Et3N), 37.89
,
3
3
(C-3, J3,P = 5.5 Hz), 20.64 (C-1, J1,P = 2.9 Hz), 8.21
(CH3, Et3N); 31P NMR (D2O): d 0.77; TOF-ES-MS: m/
z = 582.133 [M+H]+; calcd 582.181 [M+H]+.
4.1.7. Adenosine 50-(4,8-anhydro-1,3-dideoxy-L-lyxo-L-
gluco-decit-2-yl)phosphate
(triethylammonium
salt)
13. First, 20,30-di-O-acetyl-adenosine 50-(5,6,7,9,10-penta-
O-acetyl-4,8-anhydro-1,3-dideoxy-L-lyxo-L-gluco-decit-2-
yl) 2-cyanoethylphosphate 12 was prepared from
5
(50 mg, 0.11 mmol) by treatment with crude 9 (300 mg,
ꢂ60% purity, 0.32 mmol) in the presence of 1H-tetrazole
(28 mg, 0.4 mmol) in the same manner as described for
3
1
1H, H-2Ade), 6.30 and 6.28 (d, 1H, J1,2 = 6.0 Hz, H-
the synthesis of 10. Yield for 12: 70 mg, 83% (syrup). H
1Rib), 5.95 and 5.90 (br s, 2H, NH), 5.85 and 5.81 (t,
NMR: d 8.34 (s, 1H, H-8Ade), 8.17 (s, 1H, H-2Ade), 6.35
3J2,3 = 5.7 Hz, H-2Rib), 5.69 and 5.686 (m, 1H, H-3Rib),
and 6.33 (d, 1H, J1,2 = 6.4 Hz, H-1Rib), 6.13 (br s, 2H,
3
3
3
5.395 (br d, 1H, J5,6 = 3.5 Hz, H-5), 5.27 (t, 1H,
NH), 5.80 and 5.78 (t, J2,3 = 5.7 Hz, H-2Rib), 5.69 and
3J7,8 = 3J7,6 = 9.7 Hz, H-7), 5.30–5.23 (m, 1H, H-9), 5.16
and 5.00 (dd, 1H, H-6), 4.69–4.55 (m, 1H, H-2), 4.44–
4.36 (m, 4H, H-10a, H-5aRib, H-5bRib, H-4Rib), 4.32–4.22
(m, 2H, OCH2), 4.17–4.08 (dd, 1H, H-10b), 3.89 (m, 1H,
5.68 (m, 1H, H-3Rib), 5.50 (br d, 1H, H-5), 5.39 and 5.34
3
3
(dt, 1H, J9,8 = 9.0 Hz, H-9), 5.27 (t, 1H, J7,8
=
=
3J7,6 = 9.7 Hz, H-7), 5.22 and 5.19 (dd, 1H, J6,5
3
3.5 Hz, H-6), 4.77–4.66 (m, 1H, H-2), 4.59 and 4.53 (dd,
3
3
2
H-4), 3.76 and 3.64 (dd, 1H, J8,9 = 2.0 Hz, H-8), 2.82–
1H, J10,9 = 3.1, J10a,10b = 12.1 Hz, H-10a), 4.44–4.22
2.75 (m, 2H, CH2CN), 2.17, 2.15, 2.11, 2.10, 2.06, 2.05,
2.03, 2.01, 2.00 and 1.95 (10s, total 15H, 5Ac), 2.00 (m,
1H, H-3a), 1.83–1.71 (m, 1H, H-3b), 1.38 and 1.37 (d,
(m, 6H, OCH2, H-4, H-5aRib, H-5bRib, H-4Rib), 4.25 and
4.19 (dd, 1H, J10b,9 = 8.8 Hz, H-10b), 4.03 and 3.96 (br
3
d, 1H, H-4), 3.92–3.85 (m, 1H, H-8), 2.87–2.71 (m, 2H,
CH2CN), 2.20, 2.19, 2.16, 2.15, 2.05, 2.02, 2.01, 2.00 and
1.95 (9s, total 15H, 5Ac), 1.90–1.80 (m, 1H, H-3a), 1.70–
3
1H, J1,2 = 6.2 Hz, H-1); 13C NMR (CDCl3): d 170.71,
170.44, 170.25, 170.09, 169.58, 169.41, (5C, CO, Ac),
155.46 (C-6Ade), 153.11 (C-2Ade), 149.89 (C-4Ade), 138.90
(C-8Ade), 119.83 and 116.55 (C-5Ade), 85.43 and 85.34 (C-
3
1.57 (m, 1H, H-3b), 1.38 (d, 1H, J1,2 = 6.3 Hz, H-1); 13C
NMR: d 171.02, 170.67, 170.42, 170.23, 170.18, 169.79,
169.72, 169.33 (5C, CO, Ac), 155.58 (C-6Ade), 153.00 (C-
2Ade), 150.06 (C-4Ade), 119.77 and 116.80 (C-5Ade), 85.10
1Rib), 81.19 (C-4Rib,
3J4,P = 7.6 Hz), 77.15 (C-8), 74.08
(C-2Rib), 73.89 and 73.80 (C-4), 73.35 and 73.16 (C-2),
72.51 and 72.42 (C-6), 70.58 (C-3Rib), 69.74 and 69.58 (C-
5), 67.19 and 67.07 (C-9), 66.67 (C-5Rib), 64.75 and 64.67
(C-7), 62.88 and 62.72 (C-10), 62.78 and 62.48 (OCH2,
3JC,P = 5.0 Hz), 37.69 and 37.60 (C-3), 21.43 and 21.30
(C-1), 20.78, 20.62, 20.34, 19.76, 19.56, 19.45 (CO, Ac);
31P NMR (CDCl3): d ꢀ1.69 and ꢀ1.75. TOF-ES-MS: m/
z = 929.294 [M+H]+; calcd 929.281 [M+H]+.
(C-1Rib), 81.60 (C-4Rib,
3J4,P = 7.3 Hz), 76.86 and 76.77
(C-8), 73.88 and 73.80 (C-4), 73.51 and 73.27 (C-2, C-
2Rib), 72.76 and 72.53 (C-6), 71.03 and 70.79 (C-3Rib),
70.54 and 70.44 (C-5), 67.80 and 67.60 (C-9), 67.30 and
67.02 (C-5Rib,
3JC,P = 6.6 Hz), 65.03 and 64.89 (C-7),
64.36 and 63.82 (C-10), 62.78 and 62.48 (OCH2,
3JC,P = 4.9 Hz), 38.39 (C-3), 22.28 and 22.08 (C-1), 20.88,
20.84, 20.76, 20.70, 20.64, 20.57, 20.35, and 20.30 (5C,
5Ac), 19.90, 19.80, 19.73 and 19.64 (CH2CN); 31P NMR
A solution of 10 (35 mg, 0.040 mmol) in 7:3:1 MeOH–
water–Et3N (3 mL, pH 12) was stirred at rt for 4 h. The
mixture was concentrated and the residue purified on silica
gel (15:10:1:1, CHCl3/MeOH/H2O/Et3N). Appropriate
fractions were collected, concentrated, the residue redis-
(CDCl3):
d
ꢀ1.37 and ꢀ1.72. TOF-ES-MS: m/z =
929.291; calcd 929.281 [M+H]+. A solution of 12 (50 mg,
0.054 mmol) in 7:3:1 MeOH–water–Et3N (3 mL, pH 12)
was stirred at rt for 20 h. The mixture was concentrated
and the residue purified on silica gel (15:10:1:1, CHCl3/
MeOH/H2O/Et3N). The appropriate fractions were col-
lected and concentrated. The residue was redissolved in
water (10 mL) and lyophilized to give 13 (32 mg, 87%) as
solved in water (10 mL) and lyophilized to give 11
20
(25 mg, 97%) as a white fluffy solid. ½aꢁD ¼ ꢀ34 (c 0.8,
1
H2O); H NMR (D2O): d 8.39 (s, 1H, H-8Ade), 8.14 (s,
3
1H, H-2Ade), 6.03 (d, 1H, J1,2 = 5.7 Hz, H-1Rib), 4.68
20
3
1
(unresolved signal, H-2Rib), 4.43 (t, 1H, J3,4 = 4.0,
a white fluffy solid. ½aꢁD ¼ ꢀ45 (c 0.7, H2O); H NMR
3J2,3 = 4.8 Hz, H-3Rib), 4.29–4.22 (m, 2H, H-2, H-4Rib),
(D2O): d 8.36 (s, 1H, H-8Ade), 8.13 (s, 1H, H-2Ade),
3
3
4.02–3.99 (m, 2H, H-5aRib, H-5bRib), 3.79 (br t, 1H, H-
6.02 (d, 1H, J1,2 = 5.5 Hz, H-1Rib), 4.65 (m, 1H, J2,3 =
5.1 Hz, H-2Rib), 4.42 (dd, 1H, J3,4 = 4.1 Hz, H-3Rib),
3
3
9), 3.74 (br d, 1H, J5,6 = 3.7 Hz, H-5), 3.65 (t, 1H,
3J7,8 = 3J7,6 = 9.6 Hz, H-7), 3.55–3.43 (m, 4H, H-4, H-6,
H-10a, H-10b), 3.10 (q, ꢂ6H, CH2, Et3N), 3.02 (dd, 1H,
3J8,9 = ꢂ2.0 Hz, H-8), 1.90–1.80 (m, 1H, H-3a), 1.66–1.57
(m, 1H, H-3b), 1.83 (t, ꢂ9H, CH3, Et3N), 1.10 (d,
4.35–4.23 (m, 2H, H-4Rib, H-2), 4.07–3.95 (m, 2H, H-5aRib,
3
H-5bRib), 3.81 (ddd, 1H, J9,8 = 1.5, 3J9,10a = 6.1,
3
3J9,10b = 7.6 Hz, H-9), 3.64 (t, 1H, J7,6 = 3J7,8 = 9.8 Hz,
2
H-7), 3.60 (dd, 1H, J10a,10b = 11.5 Hz, H-10a), 3.58
3
3
3
3H, J1,2 = 6.2 Hz, H-1). 13C NMR (D2O): d 155.24
(dd, 1H, J5,6 = 3.4, J4,5 < 1.0 Hz, H-5), 3.53 (dd, 1H, H-
10b), 3.54 (dd, 1H, H-10a), 3.43 (dd, 1H, H-6), 3.43–3.39
(m, 1H, H-4), 3.11 (q, 6H, CH2, Et3N), 3.09 (dd, 1H, H-
8), 1.75–1.65 (m, 1H, H-3a), 1.52 (ddd, 1H,
(C-6Ade), 152.48 (C-2Ade), 149.02 (C-4Ade), 139.60 (C-
8Ade), 118.52 (C-5Ade), 86.98 (C-1Rib), 83.90 (C-4Rib
,
3J4,P = 8.7 Hz), 78.35 (C-8), 74.75, 74.46 (C-4, C-6), 74.28