LETTER
2007, 13, 5566. (n) Okuda, K.; Hirota, T.; Kingery, D. A.;
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Voorhees, R. M.; Okuda, K.; Wohlgemuth, I.; Kitchen, D.
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Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 7897.
Synthesis of a Deoxyxylopuromycin Analogue
1057
J = 6.5 Hz, H1¢), 7.31–7.45 (m, 6 H, ar), 7.62–7.65 (m, 4 H,
ar), 8.02 (s, 1 H, H2), 8.29 (s, 1 H, H8). 13C NMR (70 MHz,
CDCl3 + CD3OD): d = 18.7 (SiC), 26.3 [(CH3)3], 40.6 (C2¢),
63.4 (C5¢5¢¢), 70.6 (C3¢), 84.0 (C1¢), 87.1 (C4¢), 118.8 (C5),
127.3 (p-ar), 129.4, 129.4 (o-ar), 132.1, 132.4 (i-ar), 134.9,
135.1 (m-ar), 138.2 (C2), 148.4 (C4), 152.1 (C6), 155.1
(C8). MS (ESI+): m/z = 490.1 [MH]+
6-N-[(di-n-Butylamino)methylene]-5¢-O-(tert-butyl-
diphenylsilyl)-2¢-deoxyadenosine (7)
Compound 6 (600 mg, 1.3 mmol) was dissolved in MeOH (5
mL). N,N-Di-n-butylformamide dimethylacetal (600 mg, 2.6
mmol) was added, and the solution was stirred for 2 h at r.t.
The volatiles were removed under reduced pressure, and the
residue was purified using silica gel column chromatog-
raphy (EtOAc–MeOH = 100:0 to 95:5 step gradient) to yield
7 (750 mg, 98%). Rf = 0.45 (CH2Cl2–MeOH = 9.5:0.5). 1H
NMR (300 MHz, CDCl3): d = 0.82–0.88 (m, 6 H, 2 ×
NCH2CH2CH2CH3), 0.96 [(s, 9 H, SiC(CH3)3], 1.23–133 (m,
4 H, 2 × NCH2CH2CH2CH3), 1.49–1.62 (m, 4 H, 2 ×
NCH2CH2CH2CH3), 2.46 (ddd, J = 13.2, 6.0, 3.5 Hz, 1 H,
HA2¢), 2.57–2.66 (m, 1 H, HB2¢), 3.28–3.34 (m, 2 H,
NCH2CH2CH2CH3), 3.59–3.65 (m, 2 H, NCH2CH2CH2CH3),
3.72–3.85 (m, 2 H, H5¢5¢¢), 4.05–4.09 (m, 1 H, H4¢), 4.64–
4.68 (m, 1 H, H3¢), 6.44 (t, J = 6.6 Hz, 1 H, H1¢), 7.25–7.32
(m, 6 H, ar), 7.53–7.58 (m, 4 H, ar), 8.02 (s, 1 H, H2), 8.41
(s, 1 H, H8), 8.91 (s, 1 H, CH=N). 13C NMR (70 MHz,
CDCl3): d = 13.6 (NCH2CH2CH2CH3), 13.8
(b) Schroeder, G. K.; Wolfenden, R. Biochemistry 2007, 46,
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Mol. Cell. 2008, 30, 589.
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1981, 70, 1169.
(8) Koch, M.; Huang, Y.; Spinzl, M. Angew. Chem. Int. Ed.
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S. A.; Steitz, T. A. Mol. Cell. 2005, 20, 437. (b) Schmeing,
T. M.; Huang, K. S.; Strobel, S. A.; Steitz, T. A. Nature
(London) 2005, 438, 520.
(10) Weinger, J. S.; Parnell, K. M.; Dorner, S.; Green, R.; Strobel,
S. A. Nat. Struct. Mol. Biol. 2004, 11, 1101.
(11) (a) Das, G. K.; Bhattacharyya, D.; Burma, D. P. J. Theor.
Biol. 1999, 200, 193. (b) Dorner, S.; Panuschka, C.; Schmid,
W.; Barta, A. Nucleic Acids Res. 2003, 31, 6536.
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Acharya, P.; Acharya, S.; Minakawa, N.; Foeldesi, A.;
Stoineva, I. B.; Yomtova, V. M.; Roussev, C. D.; Matsuda,
A.; Chattopadhyaya, J.; Petkov, D. D. ChemBioChem 2005,
6, 992. (d) Rodnina, M. V.; Beringer, M.; Wintermeyer, W.
Trends Biochem. Sci. 2007, 32, 20.
(12) (a) Nissen, P.; Hansen, J.; Ban, N.; Moore, P. B.; Steitz, T.
A. Science 2000, 289, 920. (b) Michel, B. Y.; Strazewski, P.
Chem. Eur. J. 2009, 15, 6244.
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1990, 54, 3093.
(NCH2CH2CH2CH3), 19.1 (SiC), 19.6 (NCH2CH2CH2CH3),
20.1 (NCH2CH2CH2CH3), 26.8 [(CH3)3], 29.1
(NCH2CH2CH2CH3), 30.9 (NCH2CH2CH2CH3), 40.6 (C2¢),
45.1 (NCH2CH2CH2CH3), 51.7 (NCH2CH2CH2CH3), 64.0
(C5¢5¢¢), 71.7 (C3¢), 84.01 (C1¢), 87.0 (C4¢), 126.1 (C5),
127.7, 129.7, 129.8, 132.7, 132.8, 135.4, 135.4 (Ar), 139.7
(C2), 151.0 (C4), 152.3 (C6), 158.3 (C8), 159.9 (CH=N).
HRMS (ESI+): m/z calcd: 629.3635 [MH]+; found:
629.3636.
9-[3¢-Azido-5¢-O-(tert-butyldiphenylsilyl)-2¢,3¢-dideoxy-
b-D-xylofuranosyl)-6-N-[(di-n-butylamino)methylene]-
adenine (8)
(14) Chladek, S.; Sprinzl, M. Angew. Chem., Int. Ed. Engl. 1985,
To a THF (1.9 mL) solution of 7 (69 mg, 0.11 mmol) and
Ph3P (90 mg, 0.33 mmol), a mixture of DIAD (71 mL, 0.33
mmol) and DPPA (65 mL, 0.33 mmol) in THF (500 mL) was
added dropwise at 0 °C under Ar. After 7 h of stirring at r.t.,
EtOH (1 mL) was added, and the solution was stirred for 30
min. After evaporation of all the volatiles, the oily residue
was purified by silica gel column chromatography (EtOAc–
cyclohexane = 3:7 to 8:2 step gradient). Ph3PO contained in
the chromatographed product was removed by precipitation
from cold Et2O (3 h, 4 °C). After the second precipitation the
filtrate was evaporated to yield 8 (61 mg, 85%). Rf = 0.4
(CH2Cl2–MeOH = 9.5:0.5). 1H NMR (300 MHz, CDCl3):
d = 0.94 (2 t, J = 7.3, 7.3 Hz, 6 H, 2 × NCH2CH2CH2CH3),
1.09 [s, 9 H, SiC(CH3)3], 1.21–1.45 (m, 4 H, 2 ×
24, 371.
(15) Michel, B. Y.; Krishnakumar, K. S.; Strazewski, P. Synlett
2008, 2461.
(16) (a) Mitsunobu, O.; Yamada, Y. Bull. Chem. Soc. Jpn. 1967,
40, 2380. (b) Mitsunobu, O. Synthesis 1981, 1.
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Watanabe, M.; Miura, S.; Sakata, S.; Sasaki, T.; Matsuda, A.
J. Org. Chem. 1997, 62, 3140. (d) Broggi, J.; Kumamoto,
H.; Berteina-Raboin, S.; Nolan, S. P.; Agrofoglio, L. A. Eur.
J. Org. Chem. 2009, 1880.
(17) Kim, J.; Yoon, D.; Lee, S. H.; Ko, S.; Lee, Y.; Zong, K. Bull.
Korean Chem. Soc. 2006, 27, 1910.
(18) 5¢-O-(tert-Butyldiphenylsilyl)-2¢-deoxyadenosine (6)
TBDPSCl (1.6 g, 5.7 mmol) was added to 5 (1.2 g, 4.8
mmol) in dry pyridine (24 mL), and the solution was stirred
for 18 h at r.t. under N2. H2O (2 mL) was added, stirring was
continued for 30 min, and the volatiles were evaporated. The
residue was partitioned (H2O–EtOAc), and the organic
phase was washed with H2O (2 × 50 mL) and brine, then
dried (Na2SO4). The volatiles were evaporated, and the
residue was column chromatographed (step gradient from
EtOAc–cyclohexane = 1:1 to 1:0 and then to EtOAc–MeOH
= 95:5) to yield 6 (2.0 g, 88%). Rf = 0.33 (EtOAc–MeOH =
9:1). 1H NMR (300 MHz, CDCl3): d = 1.06 [s, 9 H,
SiC(CH3)3], 2.53 (ddd, 1 H, J = 13.4, 6.2, 4.0 Hz, HA2¢), 2.75
(td, 1 H, J = 13.1, 6.4 Hz, HB2¢), 3.79–3.98 (m, 2 H, H5¢5¢¢),
4.71–4.75 (m, 1 H, H3¢), 5.84 (s, 2 H, NH2), 6.46 (t, 1 H,
NCH2CH2CH2CH3), 1.58–1.71 (m, 4 H, 2 ×
NCH2CH2CH2CH3), 2.54 (dd, J = 14.8, 0.9 Hz, 1 H, HA2¢),
2.83 (ddd, J = 14.0, 7.9, 6.0 Hz, 1 H, HB2¢¢), 3.38 (t, J = 7.3
Hz, 2 H, NCH2CH2CH2CH3), 3.67–3.75 (m, 2 H,
NCH2CH2CH2CH3), 3.96–4.07 (m, 2 H, H5¢5¢¢), 4.19–4.24
(m, 1 H, H4¢), 4.41–4.44 (m, 1 H, H3¢), 6.41 (dd, J = 7.9, 2.1
Hz, 1 H, H1¢), 7.42–7.70 (m, 10 H, ar), 8.19 (s, 1 H, H2),
8.52 (s, 1 H, H8), 9.02 (s, 1 H, CH=N). 13C NMR (70 MHz,
CDCl3): d = 13.6 (NCH2CH2CH2CH3), 13.9
(NCH2CH2CH2CH3), 19.1 (SiC), 19.7 (NCH2CH2CH2CH3),
20.1 (NCH2CH2CH2CH3), 26.8 [(CH3)3], 29.2
(NCH2CH2CH2CH3), 30.9 (NCH2CH2CH2CH3), 39.0 (C2¢),
45.1 (NCH2CH2CH2CH3), 51.8 (NCH2CH2CH2CH3), 61.5
(C3¢), 61.9 (C5¢5¢¢), 83.1 (C1¢), 83.1 (C4¢), 125.8 (C5),
Synlett 2010, No. 7, 1055–1058 © Thieme Stuttgart · New York