(3H, s, OCH3), 3.78–4.03 (4H, m, CH2NH, H50, H50 0), 4.19
m/z (MS, FAB) 708.3 [M + H]+ 706.4 [M ꢂ H]ꢂ
,
(1H, m, H40), 4.84 (1H, m, H30), 6.42 (1H, dd, JH1 ,H2 = 5.9 Hz,
(C39H41N5O8 requires 707.3); m/z (HRMS, FAB) 708.3048
([M + H]+ C39H42N5O8 requires 708.3033).
0
0
4
JH1 ,H2 = 7.7 Hz, H10), 6.75 (1H, d, JH5,H2 = 0.7 Hz,
Im-CH-5), 6.76–7.38 (15H, m, MMTr, Im-CH-2), 8.32
(1H, s, H2), 8.40 (1H, s, H8), 8.55 (1H, bs, NHCO), 9.58
(1H, t, JNHa,CHa = 5.5 Hz, CONHCH2).
0
0 0
dH (250 MHz, CDCl3; Me4Si) 2.08 (3H, s, CH3COO od Z),
2.09 (3H, s, CH3COO of Z), 2.03–2.19 (10H, m, 2xCH3COO
of E, H20, H20 0 of Z and E), 2.77 (2H, t, J = 6.7 Hz, ImCH2
of Z), 2.79–2.88 (2H, m, ImCH2 of E), 3.48–3.60 (4H, m,
CH2NH of Z and E), 3.81 (3H, s, OCH3 of Z), 3.82 (3H, s,
OCH3 of E), 3.68–3.98 (4H, m, CH2-6 of Z and E), 3.99–4.39
(6H, m, H40, H50, H50 0 of Z and E), 5.06–5.19 (3H, m, H30 of
5-Modified 20-deoxyuridines
30,50-Di-O-acetyl-5-{2-[N1-(4-methoxytrityl)-imidazol-4-yl]-
ethylaminomethyl}-20-deoxyuridine (11a). 5-Formyl-30,50-di-O-
acetyl-20-deoxyuridine (1) (340 mg, 1 mmol) was dried by
0
0 0
Z and E, CH2NHCH of E), 6.30 (1H, dd, JH1 ,H2 = 5.9 Hz,
JH1 ,H2 = 8.9 Hz, H10 of Z), 6.41 (1H, dd, JH1 ,H2 = 5.9 Hz,
0
0
0
0 0
4
JH1 ,H2 = 8.8 Hz, H10 of E), 6.60 (1H, d, JH5,H2 = 1.0 Hz,
Im-CH-5 of Z), 6.61 (1H, d, 4JH5,H2 = 1.0 Hz, Im-CH-5 of E),
6.70 (1H, d, JH7,NH = 13.1 Hz, H7 of Z), 6.79–7.41 (31H, m,
MMTr, NH-3 of Z and E, Im-CH-2 of E), 7.43 (1H, d,
4JH2,H5 = 1.3 Hz, Im-CH-2 of Z), 7.46 (1H, m, H7 of E), 8.43
(1H, m, CH2NHCH of Z).
0
0
repeated co-evaporation with anhydrous CH2Cl2 (2
ꢄ
10 mL) and finally dissolved in the same solvent (7 mL). To
this stirred solution, NIm-(4-methoxytrityl)histamine (460 mg,
1.2 mmol, 1.2 equiv.) and Et3N (167 mL, 1.2 mmol) was added
followed by immediate addition of NaBH(OAc)3 (254 mg,
1.2 mmol). After 2 h at room temp., when TLC analysis
(CHCl3–MeOH-90 : 10, v/v) revealed some remaining aldehyde
10, the second portion of NaBH(OAc)3 (106 mg, 0.5 mmol)
was added. After stirring for an additional 2 h, the reaction
was quenched with NaHCO3 (10 mL, 5% aq. solution) and
then extracted with CH2Cl2 (3 ꢄ 20 mL). The combined
organic phases were dried (MgSO4), filtered and concentrated
in vacuum. The oily residue was chromatographed on a silica
gel column with increasing amounts (from 0 to 25%) of
CH3OH in CHCl3. The corresponding fractions (checked on
TLC with ninhydrine test) were collected and evaporated to
give 11a (390 mg, 55%) and 12a as a mixture of Z and E
isomers (290 mg, 41%).
dC (63 MHz, CDCl3) 21.00 (CH3COO of E and Z), 21.06
(CH3COO of E and Z), 28.90 (ImCH2 of E), 30.09 (ImCH2 of
Z), 32.69 (C20of E), 33.30 (C20 of Z), 36.84 (C6 of E), 40.32
(C6 of Z), 48.75 (CH2NH of Z), 49.34 (CH2NH of E), 55.42
(OCH3 of Z and E), 63.94 (C50 of E), 64.16 (C50 of Z), 74.34
(C30 of E), 74.46 (C30 of Z), 75.10 (MMTr-CPh3 of Z), 75.22
(MMTr-CPh3 of E), 80.44 (C40of Z), 80.66 (C40 of E), 84.20
(C10 of Z), 84.59 (C10 of E), 85.00 (C5 of Z), 87.43 (C5 of Z),
113.44 (MMtr-o0 of Z and E), 118.91 (Im-CH-5 of E), 119.60
(Im-CH-5 of Z), 128.17 (MMTr-o of Z and E, MMTr-p of Z),
128.44 (MMTr-p of E), 129.74 (MMTr-m of Z and E), 131.23
131.30 (MMTr-m0of Z and E), 134.31 (Im-CH-4 of E), 134.43
(Im-CH-4 of Z), 137.18 (MMTr-i0 of Z), 137.75 (MMTr-i0 of E),
138.57 (Im-CH-2 of E), 138.83 (Im-CH-2 of Z), 142.61
(MMTr-i of E), 142.70 (MMTr-i of Z), 146.72 (C7 of E),
150.15 (C7 of Z), 153.09 (C2 of E), 153.81 (C2 of Z), 159.25
(MMTr-p0 of Z and E), 164.91 (C4 of E), 166.71 (C4 of Z),
170.63 (CH3COO of Z and E), 171.09 (CH3COO of Z and E).
11a: TLC Rf: 0.32 (CHCl3–MeOH 90 : 10); 0.11
(AcOEt–MeOH 90 : 10).
m/z (MS, FAB) 708.4 [M + H]+ 706.5 [M ꢂ H]ꢂ,
,
(C39H41N5O8 requires 707.3); m/z (HRMS, FAB) 708.3052
([M + H]+ C39H42N5O8 requires 708.3033).
dH (250 MHz, CDCl3; Me4Si) 2.10 (3H, s, CH3COO), 2.11
0
0
(3H, s, CH3COO), 2.30 (1H, ddd, JH2 ,H3 = 6.4 Hz,
JH2 ,H1 = 8.6 Hz, Jgem = 14.5 Hz, H20), 2.43 (1H, ddd,
JH2 = 2.0 Hz, JH2
= 5.7 Hz, Jgem = 14.5 Hz, H20 0),
5-{2-[N1-(4-methoxytrityl)-imidazol-4-yl]ethylaminomethyl}-
20-deoxyuridine (13a). Acetylated nucleoside 11a (354 mg,
0.5 mmol) was treated with Et3N/MeOH (1 : 9 v/v, 4 mL) at
r.t. for 24 h. After this period, TLC analysis revealed no
starting protected nucleoside. The reaction mixture was
concentrated to an oil residue, re-dissolved in CH2Cl2 and
applied onto a silica gel column. Elution was performed with a
gradient of 0–15% MeOH in CHCl3 to give nucleoside 13a as
foam (225 mg, 72%).
0
0
0 0,H30
0 0,H10
2.80 (2H, t, J = 7.0 Hz, ImCH2), 2.99 (2H, t, J = 7.0 Hz,
CH2NH), 3.57 (1H, d, Jgem = 13.7 Hz, one of CH2-7), 3.66
(1H, d, Jgem = 13.8 Hz, one of CH2-7), 3.81 (3H, s, OCH3),
4.21 (1H, m, H40), 4.28 (1H, dd, JH5
= 3.5 Hz, Jgem
=
0 0,H40
12.0 Hz, H50 0), 4.39 (1H, dd, JH5 ,H4 = 4.7 Hz, Jgem
=
0
0
12.0 Hz, H50), 5.22 (1H, dt, JH3 ,H2 = JH3 ,H4 = 2.0 Hz,
0
0 0
0
0
JH3 ,H2 = 6.4 Hz, H30), 6.30 (1H, dd, JH1 ,H2 = 5.7 Hz,
0
0
0
0 0
4
JH1 ,H2 = 8.6 Hz, H10), 6.59 (1H, d, JH5,H2 = 1.2 Hz,
Im-CH-5), 6.77–7.37 (14H, m, MMTr), 7.38 (1H, d,
4JH2,H5 = 1.4 Hz, Im-CH-2), 7.66 (1H, s, H6).
TLC Rf: 0.24 (CHCl3–MeOH 85 : 15); 0.05 (AcOEt–MeOH
80 : 20).
0
0
m/z (MS, FAB) 624.3 [M + H]+ 622.2 [M ꢂ H]ꢂ
,
dC (63 MHz, CDCl3) 21.08 (2xCH3COO), 27.56 (ImCH2),
37.34 (C20), 45.52 (C7), 48.85 (CH2NH), 55.47 (OCH3), 64.03
(C50), 74.58 (C30), 75.05 (MMTr-CPh3), 82.52 (C40), 85.30
(C10), 111.73 (C5), 113.45 (MMTr-o0), 118.74(Im-CH-5),
128.19 (MMTr-o,p), 129.82 (MMTr-m), 131.30 (MMTr-m0),
134.64 (Im-CH-4), 138.13 (MMTr-i0), 138.64 (C6),138.71
(Im-CH-2), 142.88 (MMTr-i), 150.43 (C2), 159.25 (MMTr-p0),
163.47 (C4), 170.51 (CH3COO), 170.65 (CH3COO).
(C35H37N5O6 requires 623.3).
dH (250 MHz, CDCl3; Me4Si) 2.24 (1H, m, H20), 2.43
0 0,H30
0 0,H10
(1H, ddd, JH2
= 1.4 Hz, JH2
= 5.5 Hz, Jgem =
14.0 Hz, H200), 2.75 (2H, t, J = 6.7 Hz, ImCH2), 2.93 (2H, t,
J = 6.8 Hz, CH2NH), 3.52 (1H, d, Jgem = 14.1 Hz, one of
CH2-7), 3.60 (1H, d, Jgem = 14.1 Hz, one of CH2-7), 3.81
(3H, s, OCH3), 4.19–4.32 (2H, m, H40, H50 0), 4.37 (1H, dd,
JH5 ,H4 = 4.4 Hz, Jgem = 12.0 Hz, H50), 5.21 (1H, dt, JH3 ,H2
=
0
0
0
0 0
12a: TLC Rf: 0.48, 0.63 (CHCl3–MeOH 90 : 10); 0.23, 0.41
(AcOEt–MeOH 90 : 10).
JH3 ,H4 = 2.0 Hz, JH3 ,H2 = 6.5 Hz, H30), 6.30 (1H, dd,
0 0 0 0
JH1 ,H2 = 5.6 Hz, JH1 ,H2 = 8.7 Hz, H10), 6.58 (1H, d,
0
0 0
0
0
ꢀc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010
944 | New J. Chem., 2010, 34, 934–948