Molecules 2015, 20
12661
toluene and finally a brown oil with was dried by co-evaporation with anhydrous pyridine (2 × 5 mL)
and dissolved in anhydrous pyridine (2.4 mL). To this solution 4,4′-dimethoxytrityl chloride (0.243 g,
0
.72 mmol) was added and the reaction was quenched after 3 h by adding saturated aqueous NaHCO
The resulting solution was extracted with DCM and the combined organic extracts were washed with
brine, dried over Na SO and concentrated under vacuum. The residual yellow oil was purified by
chromatography with 5% MeOH in DCM as the eluent to give 0.18 g (49%) 5 as a white foam.
1H-NMR (CDCl
): δ (ppm) 7.42–7.2 (m, 10H, Ph, NHCO), 7.04 (t, 1H, NHCO), 6.89 (m, 4H, Ph),
.82 (s, 3H, OCH ), 3.83–3.62 (m, 4H, OCH CCO), 3.43–3.23 (m, 4H, 2NHCH ), 1.4–1.8 (m, 4H,
CH , putrescine), 1.2 (s, 3H, CH ). C-NMR (CDCl ): δ (ppm) 174.4 (C=O), 158.5 (2C, COCH ),
58.4 (C=O, TFA), 144.6 (C, Ph), 135.5 (C, Ph), 130.0 (CH, Ph), 128.3 (CH, Ph), 128.0 (CH, Ph),
27.8 (CH, Ph), 126.8 (C, CF ), 113.1 (CH, Ph), 86.2 (C), 66.9 (CH ), 65.5 (CH ), 55.1 (CH ), 47.5 (C,
, putrescine), 18.7 (CH ); MS (ESI) m/z: calcd for
3
.
2
4
3
3
2
1
1
3
2
2
1
3
2
3
3
3
3
2
2
3
CMe), 43.2 (CH
2
, putrescine), 24.5 (CH
2
3
+
C
32
H
37
F
3
N O
2 6
603.2676 [M + H] , found 603.261.
3-[(4,4′-Dimethoxytrityl)-2-(hydroxymethyl)-2-methyl-N-(4-(2,2,2-trifluoroacetamido)butyl)propanamide]
phosphoramidite (6). 2-Cyanoethyl-N,N,N,N-tetraisopropylphosphoramidite (0.9 mL, 0.3 mmol) was
added to the solution of 5 (0.143 g, 0.234 mmol) and 5-(ethylthio)-1H-tetrazole (0.0273 g, 0.21 mmol)
in dichloromethane (1.2 mL) and the mixture was stirred at room temperature. After 2 h, TLC revealed
complete reaction. The mixture was diluted with dichloromethane, washed with saturated sodium
bicarbonate solution and the organic extracts were dried over Na
2
SO
4
. The product was purified by
silica gel chromatography with benzene–Et N (10%) and lyophilisation from benzene to give 6 (134 mg,
3
3
1
7
0% yield) as a white powder. P-NMR (C
6
H ): δ (ppm) 148.30; 148.54. MS (ESI) m/z: calcd for,
6
+
C
41
H
54
F
3
N O
4 7
P [M + H] 803.3755, found 803.371.
(
S)-N-(4,9,13-Triazatridecan-1-yl)-2,2-dimethyl-1,3-dioxolane-4-carboxyamide (8). The methyl
S)-2,2-dimethyl-1,3-dioxalane-4-carboxylate (7) (0.45 mL, 3 mmol), spermine (2.4 g, 12 mmol) were
(
dissolved in anhydrous methanol (1 mL) and the resulting solution was stirred at room temperature for
8–72 h at 25–35 °C. The solvent was evaporated under reduced pressure and the residue was purified
4
by column chromatography over silica gel (MeOH/MeNH
2
/H O) to give 8 (720 mg, 70% yield) as
2
1
yellow oil. H-NMR (CDCl
3
): δ (ppm) 7.22 (m, 1H, NHCO), 4.45 (q, 1H, J = 5.37 Hz, J = 2.44 Hz,
COCH), 4.25 (t, 1H, J =7.8, OCHCO), 4.05 (q, 1H, J = 5.37 Hz, J = 3.41 Hz, COCH), 3.38–3.24 (m,
H, CONHCH ), 2.53–2.65 (m, 6H, CH ), 2.05 (2H, NH), 1.66 (m, 2H, spermine), 1.49 (m, 2H,
spermine), 1.44 (s, 3H, CH ), 1.44 (s, 3H, CH
4.8 (C), 67.6 (C), 49.1 (CH ), 46.8 (CH
CH ). MS (ESI) m/z: calcd for C16
2
2
2
13
3
3
); C-NMR (CDCl
3
): δ (ppm) 171.3 (C=O), 110.6 (OCO),
7
2
2
), 37.1 (CH
2
), 28.6 (CH ), 27.1 (CH ), 26.0 (CH ), 24.8
2
2
2
+
(
3
H
34
N
4
O
3
[M + K] 369.2262, found 370.2801.
(R)-N-(4,9,13-Triazatridecan-1-yl)-2,2-dimethyl-1,3-dioxolane-4-carboxyamide (8a). The methyl
(
R)-2,2-dimethyl-1,3-dioxalane-4-carboxylate (7a) (0.45 mL, 3 mmol) was converted into compound 8a
1
following the above procedure (566 mg, 55% yield). H-NMR (CDCl
3
): δ (ppm) 7.19 (m, 1H, NHCO),
4
.45 (q, 1H, J = 5.37 Hz, J = 2.44 Hz, COCH), 4.26 (t, 1H, J = 7.8 Hz, OCHCO), 4.05 (q, 1H,
J = 5.37 Hz, J = 3.41 Hz, COCH), 3.43–3.3 (m, 2H, CONHCH
2
), 2.74–2.59 (m, 6H, CH
2
), 1.76 (m,
13
3
2H, spermine), 1.63 (m, 2H, spermine), 1.47 (s, 3H, CH ), 1.37 (s, 3H, CH
3
); C-NMR (CDCl ): δ
3