Organic Syntheses, Vol. 77, 162
Checked by Gilles Chambournier, Jane Djung, and David J. Hart.
1. Procedure
2. Notes
1. The
ribofuranose was obtained from Aldrich Chemical Company, Inc., and used as received.
2.
2,6-Lutidine (99%) was obtained from Aldrich Chemical Company, Inc., in a
Sure/Seal bottle and used as received.
5.
Silica gel (32-63 μm) was obtained from Fisher Scientific Company.
6. The physical properties are as follows:
[α]D21 +89.5° (CHCl
3,
c 0.1); IR (KBr) cm
−1: 1730;
1H NMR (CDCl
3) δ: 4.71 (ABX, 2 H, J
AB = 12.1, J
AX = 3.5, J
BX = 3.1, Δν
AB = 32.6), 4.93 (m, 1 H), 5.79 (dd, 1 H, J = 6.5, 4.4), 5.88 (dd, 1 H, J = 6.5, 2.1), 6.91 (d, 1 H, J = 4.3), 7.31-7.61 (m, 10 H), 7.72 (d, 1 H, J = 4.3), 8.0-8.11 (m, 8 H);
13C NMR (CDCl
3) δ: 64.0 (t), 70.7 (d), 71.5 (d), 82.8 (d), 94.9 (d), 126.3, 126.4, 128.4, 128.5, 128.6, 128.9, 129.2, 129.3, 129.5, 129.7, 129.8, 130.0, 133.0, 133.4, 133.6, 133.7, 163.5, 165.1, 165.6, 166.0 (s), several aromatic signals were not resolved; exact mass calcd. for C
34H
25F
2O
9 (M
+-F) m/z 615.1480. found m/z 615.1473. Anal. Calcd for C
34H
25F
3O
9: C, 64.34; H, 3.97. Found: C, 63.90; H, 3.97.
10. A plastic drying tube filled with Drierite was placed between the filter and the aspirator.
11. The product was stored under
argon in a
desiccator and appears to be stable for months. This material exhibited the following spectral characteristics:
1H NMR (C
6D
6) δ: 0.3 (s, 9 H), 0.4 (s, 9 H), 1.8 (s, 3 H), 7.8 (s, 1 H); exact mass calcd. for C
11H
19N
2O
2 Si
2 (M
+- CH
3) m/z 255.0918. found m/z 255.0963.
12. Anhydrous
acetonitrile was obtained from Aldrich Chemical Company, Inc. in a Sure/Seal bottle and used as received.
13. The white insoluble material is partially hydrolyzed
bis-TMS-thymine. The degree to which this suspension forms depends on the purity of the
bis-TMS-thymine and the water content of the flask and solvents.
14. Neat
tin(IV) chloride (99%) was obtained from Aldrich Chemical Company, Inc. in a Sure/Seal bottle and used as received.
15. The physical properties are as follows:
[α]D21 −78° (CHCl
3,
c 0.1);
1H NMR (CDCl
3) δ: 1.54 (s, 3 H), 4.65 (m, 1 H), 4.70 (ABX, 2 H, J
AB = 12.3, J
AX = 2.6, J
BX = 3.5, Δν
AB = 69.5), 5.75 (t, 1 H, J = 6.1), 5.84 (dd, 1 H, J = 3.8, 6.0), 6.33 (d, 1 H, J = 6.1), 7.33-7.63 (m, 8 H), 7.93 (d, 2 H, J = 7.3), 7.99-8.17 (m, 4 H), 8.78 (br s, 1 H);
13C NMR (CDCl
3) δ: 12.4, 64.2, 71.6, 74.0, 80.8, 87.3, 112.5, 127.0, 128.7, 128.9, 129.1, 129.4, 129.6, 129.9, 130.0, 130.6, 133.4, 134.0, 135.1, 150.6, 163.7, 164.4, 165.7, 166.2; IR (KBr) cm
−1: 3373, 3276, 3074, 1725, 1619, 1452, 1267, 1128, 1095, 713. Anal. Calcd for C
32H
25F
3N
2O
9: C, 60.17; H, 3.95. Found: C, 60.26; H, 4.06.
16. The submitters report an
82% yield for this reaction. The checkers recovered 0.5 g (9%) of starting material (mp 108-110°C) after recrystallization of material from early fractions of the column.
17. The submitters purchased the reaction vessel from Ace Glass, Inc. (Catalog # 7841-15) and used a quartz immersion well purchased from Ace Glass, Inc. (Catalog # 7858-08) with a Pyrex filter and a Hanovia medium pressure, 450 W mercury lamp (Ace Glass, Inc. Catalog #7875). The checkers used the same apparatus except with a jacketed Pyrex immersion well in place of the quartz immersion well with a Pyrex filter.
18. The solvent was previously degassed by bubbling UHP
argon through the solvent for 30 min using a gas sparger.
HPLC grade 2-propanol was obtained from Aldrich Chemical Company, Inc., and used as received. The submitters used deionized water and the checkers used HPLC grade water from Aldrich Chemical Company, Inc.
19. The reaction assembly was immersed in a 5-gallon bucket of ice water. The reaction temperature was monitored and never went higher than 20°C. The checkers cooled the immersion well with recirculating water chilled to 10°C and used a 9-L bucket of ice water, and the internal temperature never went higher than 15°C.
21. The submitters indicate that synthetic
3',5'-di-O-benzoylthymidine was identical in all respects to an authentic sample prepared by the benzoylation of
thymidine: IR (KBr) cm
−1: 1695;
1H NMR (CDCl
3) δ: 1.62 (s, 3 H), 2.35-2.37 (m, 1 H), 2.67-2.73 (m, 1 H), 4.54 (d, 1 H, J = 2.0), 4.75 (ABX, 2 H, J
AB = 12.3, J
AX = 3.0, J
BX = 2.9, Δν
AB = 36.7), 5.66 (d, 1 H, J = 4.5), 6.47 (d, 1 H, J = 8.7, 5.6), 7.46-7.51 (m, 5 H), 7.60-7.65 (m, 2 H), 8.03-8.09 (m, 4 H), 8.50 (br s, 1 H);
13C NMR (CDCl
3) δ: 12.7 (q), 38.0 (t), 64.3 (t), 75.0 (d), 82.7 (d), 84.9 (d), 111.7 (s), 128.6 (d), 128.8 (d), 129.0 (s), 129.3 (s), 129.5 (d), 129.8 (d), 133.7 (d, 2C), 134.4 (d), 150.1 (s), 163.2 (s), 166.0 (s), 166.1 (s). Anal. Calcd for C
24H
22N
2O
7: C, 63.98; H, 4.93. Found: C, 64.07; H, 4.96.
22. Synthetic
5'-O-benzoyl-3'-deoxythymidine was identical in all respects to an authentic sample prepared by the benzoylation of
3'-deoxythymidine: IR (KBr) cm
−1: 1694;
1H NMR (CDCl
3) δ: 1.70 (d, 3 H, J = 0.9), 1.76-2.21 (m, 3 H), 2.44-2.51 (m, 1 H), 4.40-4.50 (m, 1 H), 4.53 (dd, 1 H, J = 12.2, 4.6), 4.65 (dd, 1 H, J = 12.2, 2.8), 6.1 (dd, 1 H, J = 6.4, 4.2), 7.35 (s, 1 H), 7.45 (t, 2 H, J = 7.5), 7.60 (t, 1 H, J = 7.4), 8.03 (d, 2 H, J = 7.1), 8.98 (br s, 1 H);
13C NMR (CDCl
3) δ: 12.4, 26.0, 32.3, 65.3, 78.4, 86.1, 110.7, 128.7, 129.6, 133.4, 133.5, 135.1, 150.3, 163.8, 166.0.
23. In one experiment, the checkers obtained 30%, 53%, and 1% of starting material (SM), monodeoxygenation product (MD) and dideoxygenation product (DD), respectively, after 7 hr of irradiation. In a second experiment, they obtained 3%, 57%, and 5% of SM, MD, and DD, respectively, after 10 hr of irradiation. The checkers also recovered
110 mg (
55%) of
9-ethyl-3,6-dimethylcarbazole (mp
56-58°C) from early fractions of the column.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Acknowledgment: This work was supported by Grant #DHP-172 from the American Cancer Society.
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