1
444
Y. Huang et al. / Tetrahedron Letters 44 (2003) 1441–1444
The reaction pattern of these silyl derivatives helps in
understanding the mechanism of this nucleosidation
reaction.
11. Birkofer, L.; Ritter, A.; Giessler, W. Angew. Chem. 1963,
75, 93–94.
12. Klebe, J. F.; Finkbeiner, H.; White, D. M. J. Am. Chem.
Soc. 1966, 88, 3391–3395.
1
3. Compound 1 (2.24 g, 10.6 mmol) was heated (90–95°C)
Acknowledgements
with HMDS (50 mL) and (NH ) SO (400 mg) under an
4
2
4
Ar atmosphere for 4 h whereupon a clear solution was
obtained. Upon distillation of excess HMDS under
reduced pressure at 95°C, a bright white solid was
obtained. The solid was dried under vacuum (0.5–1 mm
Hg, 95°C) and used directly in the next reaction.
This work was supported by grants from the National
Institutes of Health (GM54796) and CWRU Center for
AIDS Research (CFAR).
14. Vorbr u¨ ggen, H.; Ruh-Pohlenz, C. Handbook of
Nucleoside Synthesis; Wiley & Sons: New York, 2001; p.
References
91.
1
5. Pierce, A. E. Silylation of Organic Compounds: A Tech-
nique for Gas-Phase Analysis; Pierce Chemical Company:
Rockford, IL, 1968; pp. 63–71.
1
2
3
. Lukevics, E.; Zablocka, A. Nucleoside Synthesis:
Organosilicon Methods; Ellis Horwood Ltd: West Sussex,
UK, 1991.
. (a) Nishimura, T.; Shimizu, B.; Iwai, I. Chem. Pharm.
Bull. 1963, 11, 1470–1472; (b) Nishimura, T.; Iwai, I.
Chem. Pharm. Bull. Tokyo 1964, 12, 352–356.
. Selected changes: (a) Kim, H. O.; Schinazi, R. F.; Shan-
muganathan, K.; Jeong, L. S.; Beach, J. W.; Nampalli, S.;
Cannon, D. L.; Chu, C. K. J. Med. Chem. 1993, 36,
16. Kr u¨ ger, C.; Rochow, E. G.; Wannagat, U. Chem. Ber.
1
963, 96, 2138–2143.
4
1
7. Improved procedure for the preparation of N -Boc-
cytosine·TMS (2). A dry 250 mL, one-necked, round-bot-
tom flask, equipped with a magnetic stirring bar and a
4
rubber septum was charged with N -Boc-cytosine (1, 6.06
g, 28.7 mmol). After flushing this system with Ar,
5
19–528; (b) Mikhailov, S. N.; Pfleiderer, W. Synthesis
CH CN (121 mL) and BSA (7.10 mL, 28.7 mmol) were
3
1
985, 4, 397–399; (c) Okauchi, T.; Kubota, H.; Narasaka,
added. The resulting suspension was stirred at room
temperature for 2 h, when another 3.55 mL (14.4 mmol)
BSA was added. The reaction mixture became a clear
light-yellow solution after 15 min. Stirring was continued
at room temperature for another 2 h under an Ar atmo-
sphere, at which point the contents was transferred to a
flame-dried short-path distillation assembly (flushed with
K. Chem. Lett. 1989, 801–804; (d) Hangeland, J. J.; Voss,
J. J. De; Heath, J. A.; Townsend, C. A. J. Am. Chem.
Soc. 1992, 114, 9200–9202.
4
. (a) Jeong, L. S.; Schinazi, R. F.; Beach, J. W.; Kim, H.
O.; Shanmuganathan, K.; Nampalli, S.; Chun, M. W.;
Chung, W.-K.; Choi, B. G.; Chu, C. K. J. Med. Chem.
1
993, 36, 2627–2638; (b) Forestier, M. A.; Ayi, A. I.;
Ar). The CH CN was first distilled under reduced pres-
3
Condom, R.; Boyode, B. P.; Colin, J. N.; Selway, J.;
Challand, R.; Guedj, R. Nucleosides Nucleotides 1993, 12,
sure at room temperature and then the residual liquid
was heated at 40–50°C under reduced pressure (0.5–1.0
mm Hg) for another 2 h to afford a white solid. This
white solid was dried under vacuum (0.5–1.0 mm Hg) at
9
15–924; (c) Ozerov, A. A.; Novikov, M. S.; Brel%, A. K.;
Andreeva, O. T.; Vladykov, G. V.; Boreko, E. I.;
Korobchenko, L. V.; Vervetchenko, S. G. Pharm. Chem.
J. (Engl. Transl.) 1991, 25, 560–565.
40–50°C overnight during which time colorless needles
formed on the condenser and eventually converted to a
white solid after continued heating under vacuum. The
5
6
. Sugiura, Y.; Furuya, S.; Furukawa, Y. Chem. Pharm.
Bull. 1988, 36, 3253–3256.
white solid (8.13 g, 100 %) in the flask was used directly
. (a) Lau, J.; Walczak, K.; Pupek, K.; Buch, C.; Nielsen, C.
M.; Pedersen, E. B. Arch. Pharm. (Weinheim) 1991, 324,
1
in the next reaction without further purification.
H
NMR (300 MHz, benzene-d ) l 8.54 (s, N–H), 8.30 (d,
6
9
53–958; (b) Lau, J.; Wengel, J.; Pedersen, E. B.; Vester-
J=11.3 Hz, 1H, H-6), 7.67 (d, J=11.4 Hz, 1H, H-5),
gaard, B. F. Synthesis 1991, 1183–1190; (c) Dueholm, K.
L.; Motawia, M. S.; Pedersen, E. B.; Nielsen, C.; Lundt,
I. Arch. Pharm. (Weinheim) 1992, 325, 597–601; (d)
Kofoed, T.; Aleem, A. A. H.; Jørgensen, P. T.; Pedersen,
T. R.; Pedersen, E. B. Acta Chem. Scand. 1995, 49,
1
.30 (s, 9H, (CH ) C-OC-), 0.34 (s, 9H, (CH ) SiO).
3 3
3 3
CBoc
1
8. Revised procedure for synthesis of Fmoc-S
serine, O-[[4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-oxo-
(2H)-pyrimidinyl]methyl]-N-[(9H-fluoren-9-ylmethoxy)-ca
rbonyl]-phenylmethyl ester (4)). A flask containing 0.63 g
of crushed 3 A MS was flame-dried under vacuum,
flushed with Ar, then cooled to room temperature. A
-OBn (L-
1
2
91–296.
. (a) Breipohl, G.; Uhlmann, E.; Knolle, J. Eur. Pat. Appl.
72701, Sep. 20, 1995; (b) Breipohl, G.; Uhlmann, E.;
,
7
6
MTM
solution of Fmoc-Ser
mL dry THF, 0.44 M) was transferred to the flask,
-OBn (3, 0.628 g, 1.32 mmol in
Knolle, J. Eur. Pat. Appl. 672661, Sep. 20, 1995.
3
8. Garner, P.; Dey, S.; Huang, Y.; Zhang, X. Org. Lett.
4
followed by the addition of a solution of N -Boc-
cytosine·TMS (2, 0.701 g, 2.47 mmol in 1.4 mL dry THF,
1
999, 1, 403–405.
9
. (a) Ogilvie, K. K.; Nguyen-ba, N.; Hamilton, R. G. Can.
J. Chem. 1984, 62, 1622–1627; (b) Tsantrizos, Y. S.;
Lunetta, J. F.; Boyd, M.; Fader, L. D.; Wilson, M.-C. J.
Org. Chem. 1997, 62, 5451–5457.
1
4
.25 M) and a solution of iodine (0.334 g, 1.32 mmol in
mL of dry THF). The reaction mixture was stirred at
room temperature under Ar atmosphere for 48 h, where-
upon TLC analysis showed only the presence of the
product 4 and some unconverted 3. Workup and purifica-
tion was similar to that described in Ref. 8.
1
0. Huang, Y. Development of Antisense Alpha-Helical Pep-
tide Nucleic Acids. Ph. D., Thesis, Case Western Reserve
University, Cleveland, OH, May 2002.