892
G. Cavigiolio et al.
naphth H3), 7.85 (1H, dd, J 7.3, 8.5, naphth H6), 5.41 (1H, d, J 12.5,
OCH2), 5.29 (0.5H, s, CH2Cl2), 5.26 (1H, t, J 9.5, H3), 5.17 (1H, t,
J 9.5, H4), 5.12 (1H, dd, J 9.5, 8.0, H2), 5.11 (1H, d, J 12.5, OCH2),
4.91 (1H, d, J 8.0, H1), 4.29 (1H, dd, J 4.7, 12.4, H6), 4.18 (1H, dd,
J 2.4, 12.4, H6ꢀ), 3.79 (1H, dq, J 2.4, 10.0, H5), 3.56 (3H, s, NCH3),
2.07, 2.04, 2.01, 1.96 (4 × 3H, 4 s, 4 OAc). δC (CDCl3) 198.5 (Co–CO),
170.6, 170.3, 169.4, 169.1 (4 acetate CO), 164.4, 164.1 (naphth–CO),
142.6 (naphth C4), 131.6 (naphth C7), 131.1, 130.8 (naphth C5 and
2), 130.6 (naphth C3), 129.8, 128.7 (naphth C9 and 10), 126.8 (naphth
C6), 123.3 (naphth C1), 122.0 (naphth C8), 99.9 (C1), 93.9 (CH2C≡C–
naphth), 84.0 (CH2C≡C–naphth), 73.1 (C3), 72.2 (C5), 71.3 (C2), 69.5
(CH2O), 68.3 (C4), 62.1 (C6), 27.1 (NCH3), 20.7, 20.6, 20.6, 20.5 (one
signal obscured by overlapping, 4 acetate CH3). m/z (ESI) 920 (25%,
MK+), 905 (35, MNaH+), 802 (100, MH2 – 3CO).
s, 5ꢀtol CH3). δC ([D6]DMSO) 165.6, 165.3 (2 tol C=O), 163.5, 163.2
(2 naphth C=O), 161.4 (uridine C2), 149.4 (uridine C4), 144.6 (uridine
C6), 144.2 (3ꢀtol C4), 143.8 (5ꢀtol C4), 131.9 (naphth C5), 131.2 (naphth
C7), 130.8 (naphth C10), 130.0 (naphth C3), 129.9 (naphth C2), 129.5,
129.4, 129.3, 129.3 (tol C2, C3, C5, C6), 128.1 (naphth C6), 127.3
(naphth C9), 126.5 (tol C1a), 126.4 (tol C1b), 126.3 (naphth C4), 122.7
(naphth C8), 121.8 (naphth C1), 98.1 (uridine C5), 92.1 (C≡CH), 89.6
(C≡CH), 86.0 (sugar C1), 81.9 (sugar C4), 74.5 (sugar C3), 64.3 (sugar
C5), 36.9 (sugar C2), 26.8 (NCH3), 21.3 (5ꢀtol CH3), 21.0 (3ꢀtol CH3).
m/z (ESI) 698 (10% MH+), 579 (100, [M – tol+]), 534 (40, [(M – Otol –
NCH3)+]), 279 (98, [M – tol2 – naphth]+).
Preparation of 10 (5-(4-Ethynyl-N-ferrocenylundecylnaphthalimido)-
3ꢀ,5ꢀ-di-O-p-toluoyl-2ꢀ-deoxyuridine)
5-Iodo-3ꢀ,5ꢀ-di-O-p-toluoyl-2ꢀ-deoxyuridine (0.223 g, 0.38 mmol), CuI
(14 mg, 20%), and (PPh3)PdCl2 (27 mg, 10%) were stirred in a
Schlenk flask with 5 mL of dry DMF, and the yellow solution was
degassed with N2. 4-Ethynyl-N-ferrocenylundecylnaphthalimide[22]
(0.440 g, 0.79 mmol) followed by 104.5 µL of freshly distilled triethyl-
amine were added to the reaction mixture, producing an immediate
colour change from orange-red to dark red. The mixture was heated at
50◦C for 5 h at ambient temperature under an argon atmosphere while
being monitored by TLC (silica; CH2Cl2) in which a new yellow flu-
orescent spot (RF ≈ 0.6) appeared. The clear dark-green solution was
dried under vacuum to yield a dark red oil that was purified by SiO2
column chromatography. Impurities were removed by CH2Cl2 through
to CH2Cl2/Et2O 95 : 5 elution, and then the product was eluted with
CH2Cl2/Et2O 1 : 1, as a large orange/red band giving a dark yellow solu-
tion. Further purification by plate chromatography (SiO2; CH2Cl2/Et2O
9 : 1, RF ≈ 0.3) yielded the product as a yellow-orange powder (0.316 g,
82%) (Found: C 70.0, H 6.0, N 4.0, M+ 1022. C60H59N3FeO9 requires
C 70.6, H 5.8, N 4.1%, M+ 1022). vmax (KBr/cm−1) 2209 (C≡C), 1723
(tol CO), 1698 (naphth CO), 1659 (naphth CO). λabs/nm 406. λflu/nm
494. δH (CDCl3) 9.93 (1H, s, 4-OH), 8.72 (1H, d, J 8.4, naphth H5),
8.57 (1H, d, J 6.6, naphth H7), 8.41 (1H, d, J 7.5, naphth H2), 8.12 (1H,
s, uridine H6), 7.92 (4H, dd, J 8.1, tol H2,6), 7.80 (1H, dd, J 8.1, 7.5,
naphth H6), 7.50 (1H, d, J 7.2, naphth H3), 7.26 (2H, d, J 8.1, 3ꢀtol
H3,5), 7.09 (2H, d, J 8.0, 5ꢀtol H3,5), 6.44 (1H, dd, J 6.0, 8.0, sugar
H1), 5.63 (1H, d, J 6.3, sugar H3), 4.78 (2H, m, sugar H5), 4.63 (1H,
m, sugar H4), 4.15 (2H, m, NCH2), 4.07 (5H, s, C5H5), 4.02 (4H, m,
FcH), 2.88 (1H, m, sugar H2), 2.42 (3H, s, 3ꢀtol CH3), 2.38 (1H, m,
sugar 2ꢀH), 2.30 (2H, m, CH2Fc), 2.12 (3H, s, 5ꢀtol CH3), 1.73 (2H, m,
NCH2CH2), 1.55–1.20(16H, m, 8CH2). δC (CDCl3)166.2(5ꢀtolC=O),
166.1 (3ꢀtol C=O), 164.0, 163.7 (2 naphth C=O), 161.4 (uridine C=O),
149.2(uridineC4), 144.8(3ꢀtolC4), 144.6(5ꢀtolC4), 142.1(uridineC6),
132.8 (naphth C5), 131.7 (naphth C7), 131.5 (naphth C10), 130.0, 129.9
(naphth C2, naphth C3), 129.6, 129.5, 129.4 (tol C2, C3, C5, C6, one
signal obscured by overlapping), 127.9 (naphth C6), 126.7 (naphth C9),
126.3 (5ꢀtol C1), 126.2 (3ꢀtol C1), 122.8 (naphth C8), 122.3 (naphth
C1), 100.3 (uridine C5), 91.5 (C≡C–naphth), 89.9 (–C≡C–naphth),
89.7 (FcH), 86.3 (sugar C1), 83.7 (sugar C4), 74.8 (sugar C3), 68.5
(C5H5), 68.1, 67.0, (2 signals, 4C, FcH), 64.3 (sugar C5), 40.6 (NCH2),
39.0 (sugar C2), 31.2, 29.7, 29.7, 29.6, 29.6, 29.4, 27.2 (10 CH2, three
signals obscured by overlapping), 21.8 (3ꢀtol CH3), 21.6 (5ꢀtol CH3).
m/z (APCI) 1022 (52%, [M+]), 957 (32, [(M – C5H5)+]), 670 (35,
[(M – N(CH2)11Fc)+]), 280 (88, [(M – 2tol – naphthalimide)+]), 263
(100, [(M – 2tol – naphthalimide – OH)+]). Fc0/+ (acetone, Bu4NClO4)
0.36 V.
Preparation of 8
Compound 6 (0.083 g, 0.14 mmol) was dissolved in benzene (10 mL),
Co2(CO)6dppm (0.093 g, 0.14 mmol) was added, and the solution
heated to reflux for 30 min. The dark brown solution was eva-
porated and the residue purified by column chromatography (SiO2;
CH2Cl2/MeOH 15 : 1). Compound 6 was obtained from the first frac-
tion as a dark brown oil (0.110 g, 65%) (Found: C 60.3, H 4.9, N 1.2,
C59H51Co2NO16P2·C6H6 requires C 60.6, H 4.5, N 1.1%, MH+ 1211).
vmax/cm−1 (CH2Cl2) 2028, 2001, 1974 (M–CO), 1757 (acetate CO),
1695 (naphth CO), 1656 (naphth CO). λabs/nm 270, 331. δH (CDCl3)
8.76 (1H, dd, J 1.0, 7.5, naphth H7), 8.60 (1H, dd, J 1.0, 7.2, naphth H5),
8.39 (1H, d, J 7.7, naphth H2), 7.85 (1H, d, J 7.8, naphth H3), 7.75 (1H,
dd, J 7.2, 8.4, naphth H6), 7.44–7.12 (20H, m, Ph), 5.35–5.26 (1H, m, 1
of OCH2), 5.20–5.03 (3H, m, H2, 3, 4), 4.98–4.90 (1H, m, 1 of OCH2),
4.76 (1H, d, J 8.1, H1), 4.21 (1H, dd, J 4.5, 12.0, H6), 4.05 (1H, dd, J 2.5,
12.0, H6ꢀ), 3.59 (3H, s, NCH3), 3.59–3.50 (2H, m, H5, 1 of PCH2P),
3.21 (1H, dt, J 10.0, 13.8, 1 of PCH2P) 2.04, 2.02, 2.00, 1.79 (4 × 3H,
4 s, 4 OAc). δC (CDCl3) 204.1 (Co–CO), 170.6, 170.3, 169.4, 169.3,
(4 acetate CO), 164.7, 164.6 (naphtha–CO), 137.1, 136.9, 136.5, 136.2
(4 × 4 Ph), 132.6, 132.1, 132.0, 131.7, 131.3, 131.2, 131.1, 130.9, 130.3,
130.1, 129.8, 129.7, 128.5, 128.4, 128.3, 125.8, 122.7, 119.8 (some sig-
nals obscured by overlapping, Ph and naphth), 99.8 (C1), 93.2 (C≡CH),
83.9 (C≡CH), 73.3 (C3), 71.8 (C5), 71.4 (C2), 68.4 (C4), 61.9 (C6), 56.9
(OCH2), 20.7, 20.6, 20.5 (one signal obscured by overlapping, 4 acetate
CH3). δP (CDCl3) 39.4. m/z (ESI) 1233 (50%, MNa+), 1249 (20, MK+);
(APCI) 386 (100, [sugarCH2C≡C]H+), 331 (5, sugar [C14H19O9]+).
Preparation of 9 (5-(4-Ethynyl-N-methylnaphthalimido)-
3ꢀ,5ꢀ-di-O-p-toluoyl-2ꢀ-deoxyuridine)
5-Iodo-3ꢀ,5ꢀ-di-O-p-toluoyl-2ꢀ-deoxyuridine (0.200 g, 0.34 mmol), CuI
(13 mg, 20%), and (PPh3)PdCl2 (23.8 mg, 10%) were stirred in a
Schlenk flask in 13 mL of dry DMF, and the pale yellow solution was
degassed with Ar. After some minutes, the solution turned orange, then
back to pale yellow upon the addition of 93.9 µL of freshly distilled
triethylamine. 4-Ethynyl-N-methylnaphthalimide (0.199 g, 0.85 mmol)
was added to the mixture and the colour changed to dark brown and a
grey/black precipitate was deposited. The reaction mixture was stirred
for 5 h at ambient temperature under an argon atmosphere while being
monitored by TLC (silica; CH2Cl2) in which a new yellow fluores-
cent spot (RF ≈ 0.45) appeared. The reaction mixture was filtered to
remove the grey solid and the dark green filtrate was dried under vac-
uum to obtain a sticky brown/yellow solid. The product was purified by
column chromatography (SiO2; CH2Cl2/Et2O 1 : 1) and by plate chro-
matography (SiO2; CH2Cl2/MeOH 9 : 1) to obtain 9 as a yellow powder
(0.090 g, 38%) (Found: MH+ 698. C40H31N3O9 requires MH+ 698).
vmax/cm−1 (KBr) 2209w (C≡C), 1721 (tol CO), 1700 (naphth CO),
1659(naphthCO). λabs/nm356. λflu/nm(CH2Cl2)442. δH([D6]DMSO)
8.70 (1H, dd, J 8.8, 1.0, naphth H5), 8.54 (1H, dd, J 7.5, 1.0, naphth
H7), 8.43 (1H, d, J 8.0, naphth H2), 8.34 (1H, s, uridine H6), 7.92
(3H, m, naphth H6, 3ꢀtol H2, H6), 7.86 (2H, d, J 8.0, 5ꢀtol H2, H6),
7.75 (1H, d, J 7.5, naphth H3), 7.36 (2H, d, J 8.0, 3ꢀtol H3, H5), 7.18
(2H, d, J 8.5, 5ꢀtol H3, H5), 6.30 (1H, t, J 7.0, sugar H1), 5.63 (1H, m,
sugar H3), 4.65 (2H, m, sugar H5), 4.59 (1H, m, sugar H4), 3.35 (3H, s,
NCH3), 2.80–2.60 (2H, m, sugar H2), 2.40 (3H, s, 3ꢀtol CH3), 2.15 (3H,
Preparation of 11
Compound 6 (23 mg, 0.039 mmol) was dissolved in methanol (5 mL)
and 100 mg of IRA 400 (OH) resin was added. The mixture was left for
20 h without stirring, filtered, and the methanol was removed to obtain
11 as a yellow oil (15 mg, 88%) (Found: M 427. C22H21NO8 requires
M427). vmax/cm−1 (KBr)2128(C≡C), 1699(naphthCO), 1653(naphth
CO). λabs/nm 353. δH ([D6]DMSO) 8.62 (1H, dd, J 1.2, 8.4, naphth H7),
8.50 (1H, dd, J 1.2, 7.2, naphth H5), 8.39 (1H, d, J 1.5, 7.2, naphth H2),
7.95 (1H, d, J 7.2, naphth H3), 7.91 (1H, dd, J 7.8, 8.4, naphth H6),
5.27 (1H, d, J 4.8, 2-OH), 5.05 (1H, d, J 4.2, 3-OH), 4.98 (1H, d, J 4.8,