3244
N. Oka et al. / Bioorg. Med. Chem. Lett. 14 (2004) 3241–3244
8. For a review, see: (a) Seliger, H. In Current Protocols in
J ¼ 8:0 Hz, 1H), 4.32–4.30 (m, 1H), 4.18 (dd, J ¼ 6:6,
4.6 Hz, 1H), 3.79 (s, 6H), 3.76 (s, 6H), 3.56 (dd, 11.2,
1.2 Hz, 1H), 3.12 (dd, J ¼ 11:2, 3.6 Hz, 1H), 2.63 (m, 1H),
2.40 (br s, 1H). 13C NMR (100 MHz, CDCl3) d 162.9,
159.6, 158.2, 158.2, 158.1, 156.9, 156.5, 149.7, 144.9, 142.7,
140.0, 137.8, 137.5, 133.7, 133.5, 131.6, 129.9, 129.4, 129.3,
128.3, 127.7, 125.0, 124.2, 119.6, 118.8, 118.1, 117.8, 113.3,
113.2, 90.7, 87.6, 86.9, 81.4, 74.3, 72.7, 62.4, 55.4, 55.2.
HRMS: calcd for C51H47N2O11 (M+Hþ) 863.3174, found
Nucleic Acid Chemistry; Beaucage, S. L., Bergstrom, D.
E., Glick, G. D., Jones, R. A., Eds.; Wiley, 2000; pp 2.3.1–
2.3.34; (b) Successful use of trityl groups as acid-labile
50-protecting groups was originally reported by Khorana
et al., in Gilman, P. T.; Khorana, H. G. J. Am. Chem.
Soc.. p 6212; Smith, M.; Rammler, D. H.; Goldberg, I.
H.; Khorana, H. G. J. Am. Chem. Soc. 1962, 84, 430.
9. To the best of our knowledge, there is only one report of
bis(trityl chloride)s which are applied to protect nucleo-
sides. In this case the 2-trityl units are connected via an
1
863.3169; 10a H NMR (400 MHz, CDCl3) d 8.53 (br s,
1H), 7.64 (s, 1H), 7.47 (d, J ¼ 8:0 Hz, 1H), 7.48–6.53 (m,
23H), 6.44 (m, 1H), 5.28 (d, J ¼ 8:0 Hz, 1H), 4.51 (m, 1H),
4.09 (m, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.76 (s, 3H), 3.72 (s,
3H), 3.30 (m, 1H), 3.14 (dd, J ¼ 10:2, 4.4 Hz, 1H), 2.93 (d,
J ¼ 10:2 Hz, 1H), 2.63 (br s, 1H). 13C NMR (100 MHz,
CDCl3) d 162.9, 158.7, 158.4, 158.2, 158.1, 157.3, 153.7,
150.4, 146.4, 142.7, 140.1, 137.6, 134.5, 134.4, 131.4, 130.7,
129.8, 129.7, 128.2, 127.6, 127.3, 122.6, 122.4, 122.1, 115.8,
113.7, 113.4, 113.1, 113.1, 110.3, 102.9, 87.6, 86.7, 85.8,
76.1, 64.0, 55.2, 55.2, 55.2. HRMS: calcd for C51H47N2O11
(M+Hþ) 863.3174, found 863.3144; 9c 1H NMR
(400 MHz, CDCl3) d 8.87 (br s, 1H), 8.76 (s, 1H), 8.12 (s,
1H), 8.01 (d, J ¼ 7:6 Hz, 2H), 7.61 (m, 1H), 7.53 (t,
J ¼ 7:6 Hz, 2H), 7.35–7.28 (m, 8H), 7.11–7.00 (m, 8H),
6.80–6.70 (m, 8H), 6.00 (d, J ¼ 2:4 Hz, 1H), 4.56 (dd,
J ¼ 6:8, 4.8 Hz, 1H), 4.37 (m, 1H), 3.77 (s, 3H), 3.76 (s,
3H), 3.73 (s, 3H), 3.70 (s, 3H), 3.61 (dd, J ¼ 10:8, 1.6 Hz,
1H), 3.24–3.20 (m, 2H), 2.57 (d, J ¼ 2:8 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 164.2, 159.6, 158.1, 158.0, 158.0,
157.3, 156.1, 152.3, 150.9, 149.2, 145.1, 143.1, 141.5, 138.0,
136.8, 134.9, 133.5, 132.9, 132.6, 132.0, 129.7, 129.5, 128.8,
128.7, 128.5, 127.6, 127.5, 124.9, 124.4, 123.2, 119.6, 119.3,
119.0, 116.5, 113.3, 113.3, 113.3, 113.1, 90.0, 87.5, 86.5,
82.0, 73.5, 73.4, 62.7, 55.3, 55.2, 55.2. HRMS: calcd for
€
ester linkage. Biernat, J.; Wolter, A.; Koster, H. Tetrahe-
dron Lett. 1983, 24, 751–754.
10. Hirai, H.; Baba, S. Jpn. Kokai Tokkyo Koho. 1987; 5 pp
JP 62161741.
11. Characterization data of 7: 1H NMR (400 MHz, CDCl3) d
7.21 (t, J ¼ 8:2 Hz, 2H), 7.14 (dt, J ¼ 9:0, 2.6 Hz, 8H),
6.98–6.95 (m, 4H), 6.85–6.81 (m, 2H), 6.81 (dt, J ¼ 9:0,
4.2 Hz, 8H), 3.79 (s, 12H), 2.64 (s, 2H). 13C NMR
(100 MHz, CDCl3) d 158.4, 156.5, 149.2, 138.9, 128.9,
128.9, 122.6, 118.3, 117.0, 113.1, 81.2, 55.3. ESI-MASS
m=z for C42H38NaO7 (M+Naþ) 677.
12. Genaral procedure for the reaction of 2 with 8a–d: 0.1 M
solution of 7 in dry CH2Cl2–toluene (1:1, v/v) (11.0 mL,
1.1 mmol) was treated with (COCl)2 (1.74 mL, 20 mmol) for
2 h at rt, then the mixture was concentrated under reduced
pressure in an argon atmosphere. Dry pyridine (10.0 mL),
2,4,6-collidine (0.66 mL, 5.0 mmol), and a 1 M solution of
AgClO4 in pyridine (2.2 mL, 2.2 mmol), which was dried
over MS 4A for 12 h prior to use, were added to the residue.
A solution of 8 in dry pyridine (0.1 M for 8a, c, d; 0.033 M
for 8b) was added dropwise to the mixture over 2 h at 65 ꢁC
and the mixture was stirred for 1 h at the same temperature.
The mixture was cooled to rt and pored into an ice-cold
saturated NaHCO3 aqueous solution (100 mL). The mix-
ture was extracted with CH2Cl2 (3 · 100 mL), and the
combined organic layers were dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residue was
purified by column chromatography [treated with CH2Cl2–
Et3N (100:1, v/v) prior to use; eluent: CH2Cl2–MeOH–
Et3N (100:0:1 to 100:2:1, v/v)]. The fractions containing 9
and 10 were collected and concentrated under reduced
pressure. The residue was dissolved in CH2Cl2 (50 mL),
washed with 0.2 M phosphate buffer (pH 7.0, 50 mL), dried
over Na2SO4, filtered, and concentrated under reduced
pressure to give a mixture of 9 and 10 (70–78% yield, see,
Table 1). One-fifth of the mixture of 9a and 10a was
purified by preparative TLC [treated with CH2Cl2–Et3N
(100:1, v/v) prior to use; eluent: AcOEt–hexane–MeOH–
Et3N (60:40:1:1, v/v)] to give 9a (44.0 mg, 51 lmol, 25%)
and 10a (71.6 mg, 83 lmol, 41%); the mixture of 9c and 10c
was purified by column chromatography [treated with
CH2Cl2–Et3N (100:1, v/v) prior to use; eluent: CH2Cl2–
MeOH–Et3N (100:0:1 to 97:3:1, v/v)] to give 9c (0.25 g,
0.25 mmol, 25%) and 10c (0.52 g, 0.53 mol, 53%).
1
C59H52N5O10 (M+Hþ) 990.3709, found 990.3679; 10c H
NMR (400 MHz, CDCl3) d 8.92 (s, 1H), 8.29 (br s, 1H),
8.03 (m, 3H), 7.62–7.52 (m, 4H), 7.34–6.63 (m, 21H), 6.31–
6.25 (m, 3H), 5.66 (m, 1H), 4.25 (m, 1H), 3.78 (s, 3H), 3.77
(s, 3H), 3.71 (s, 3H), 3.55 (s, 3H), 3.53–3.49 (m, 1H), 3.42
(m, 1H), 2.83 (dd, J ¼ 9:4, 3.0 Hz, 1H), 2.70 (br s, 1H). 13
C
NMR (100 MHz, CDCl3) d 164.1, 158.6, 158.6, 158.3,
158.1, 158.0, 157.8, 154.2, 151.9, 151.2, 149.1, 146.3, 142.8,
142.6, 138.1, 136.7, 134.1, 133.5, 132.6, 131.2, 130.9, 129.7,
129.2, 129.0, 128.8, 127.9, 127.6, 127.3, 123.4, 123.3, 122.8,
122.7, 116.2, 113.3, 113.0, 112.9, 112.8, 112.6, 112.5, 87.5,
87.3, 84.6, 74.9, 71.7, 62.8, 55.2, 55.2, 55.2, 55.1. HRMS:
calcd for C59H52N5O10 (M+Hþ) 990.3709, found 990.3669.
14. Reddy, M. P.; Rampal, J. B.; Beaucage, S. L. Tetrahedron
Lett. 1987, 28, 23.
15. Pon, R. T. In Current Protocols in Nucleic Acid Chemistry;
Beaucage, S. L., Bergstrom, D. E., Glick, G. D., Jones, R.
A., Eds.; Wiley, 2000; pp 3.2.12–3.2.13.
16. For synthesis of an analogous reagent and its application
in DNA chemistry see: Oka, N.; Sanghvi, Y. S.; Theodo-
rakis, E. A. Synlett 2004, 823.
13. Characterization data for 9a, 9c, 10a, and 10c: 9a 1H NMR
(400 MHz, CDCl3) d 8.37 (br s, 1H), 7.70 (d, J ¼ 8:0 Hz,
1H), 7.37–6.75 (m, 24 H), 5.79 (d, J ¼ 1:6 Hz, 1H), 5.58 (d,
17. 7 is commercially available from Sai Dru Syn