2132
K. R. Bhushan
LETTER
3.42 (t, J = 5.2 Hz, 2 H, CH2), 3.25 (br s, 1 H, NH2), 3.10 (t,
J = 5.6 Hz, 2 H, CH2), 2.94 (br s, 1 H, NH2), 1.26 (d, J = 6.8
Hz, 3 H, CH3). MS (API-ES+): m/z = 268.1 [M + H+], 290.1
[M + Na+], 306.0 [M + K+].
References and Notes
(1) (a) Egholm, M.; Buchardt, O.; Christensen, L.; Behrens, C.;
Freier, S. M.; Driver, D. A.; Berg, R. H.; Kim, S. K.; Norden,
B.; Nielsen, P. E. Nature (London) 1993, 365, 566.
(b) Nielsen, P. E.; Egholm, M.; Berg, R. H.; Buchardt, O.
Science 1991, 254, 1497.
(2) (a) Ray, A.; Norden, B. FASEB J. 2000, 14, 1041.
(b) Cetojevic-Simin, D.; Dimitar, J.; Jasminka, M.; Visnja,
B.; Vesna, K.; Ljiljana, A.; Gordana, B. Arch. Oncol. 2001,
9, 33.
(3) Weiler, J.; Gausepohl, H.; Hauser, N.; Jensen, O. N.;
Hoheisel, J. D. Nucleic Acids Res. 1997, 25, 2792.
(4) Pirrung, M. C.; Wang, L.; Montague-Smith, M. P. Org. Lett.
2001, 3, 1105.
(5) (a) Fodor, S. P. A.; Read, J. L.; Pirrung, M. C.; Stryer, L.; Lu,
A. T.; Solas, D. Science 1991, 251, 767. (b) Pease, A. C.;
Solas, D.; Sullivan, E. J.; Cronin, M. T.; Holmes, C. P.;
Fodor, S. P. A. Proc. Natl. Acad. Sci. U.S.A. 1984, 91, 5022.
(6) (a) Lipshutz, R. J.; Fodor, S. P. A.; Gingeras, T. R.;
Lockhart, D. J. Nat. Genet. 1999, 21, 20. (b) Ramsay, G.
Nat. Biotechnol. 1998, 16, 40. (c) Gershon, D. Nature
(London) 2002, 416, 885.
(7) Singh-Gasson, S.; Green, R. D.; Yue, Y.; Nelson, C.;
Blattner, F.; Sussman, M. R.; Cerrina, F. Nat. Biotechnol.
1999, 17, 974.
(8) (a) Ohtsuka, E.; Tanaka, T.; Tanaka, S.; Ikehara, M. J. Am.
Chem. Soc. 1978, 100, 4580. (b) McCray, J. A.; Herbette,
L.; Kihara, T.; Trentham, D. R. Proc. Natl. Acad. Sci. U.S.A.
1980, 77, 7237. (c) Nerbonne, J. M.; Richard, S.; Nargeot,
J.; Lester, H. A. Nature (London) 1984, 310, 74. (d) Liu, Z.
C.; Shin, D. S.; Lee, K. T.; Jun, B. H.; Kim, Y. K.; Lee, Y.
S. Tetrahedron 2005, 61, 7967.
(9) Bhushan, K. R.; DeLisi, C.; Laursen, R. A. Tetrahedron Lett.
2003, 44, 8585.
(10) Atwell, G. J.; Denny, W. A. Synthesis 1984, 1032.
(11) Fader, L. D.; Boyd, M.; Tsantrizos, Y. S. J. Org. Chem.
2001, 66, 3372.
Compound 5: 1H NMR (400 MHz, CDCl3): d = 7.72 (d,
J = 8.0 Hz, 1 H, ArH), 7.54 (t, J = 7.4 Hz, 1 H, ArH), 7.45
(d, J = 7.6 Hz, 1 H, ArH), 7.31 (t, J = 7.8 Hz, 1 H, ArH), 5.09
(s, 1 H, NH), 4.02–4.21 (m, 2 H, CH2), 4.09 (q, J = 7.2 Hz,
2 H, CH2), 3.70 (m, 1 H, CH), 3.38 (s, 2 H, CH2), 3.20 (t,
J = 5.2 Hz, 2 H, CH2), 2.76 (t, J = 5.6 Hz, 2 H, CH2), 2.21 (br
s, 1 H, NH), 1.27 (d, J = 6.8 Hz, 3 H, CH3), 1.21 (t, J = 7.0
Hz, 3 H, CH3). MS (API-ES+): m/z = 354.1 [M + H+], 376.1
[M + Na+], 392.1 [M + K+].
Compound 6a: 1H NMR (400 MHz, CDCl3): d = 8.52 and
8.50 (2 s, 1 H, NH), 7.67 (d, J = 8.0 Hz, 1 H, ArH), 7.52 (t,
J = 7.4 Hz, 1 H, ArH), 7.43 (d, J = 7.6 Hz, 1 H, ArH), 7.30
(t, J = 7.8 Hz, 1 H, ArH), 7.01 and 6.98 (2 s, 1 H, CH), 5.63
and 5.05 (2 s, 1 H, NH), 4.38 and 4.32 (2 s, 2 H, CH2), 4.03–
4.20 (m, 2 H, CH2), 4.08 (q, J = 7.2 Hz, 2 H, CH2), 4.01 (s,
2 H, CH2), 3.64 (m, 1 H, CH), 3.50 (t, J = 5.2 Hz, 2 H, CH2),
3.32 (t, J = 5.6 Hz, 2 H, CH2), 1.89 (s, 3 H, CH3), 1.35 (d,
J = 6.8 Hz, 3 H, CH3), 1.25 (t, J = 7.0 Hz, 3 H, CH3). MS
(API-ES+): m/z = 520.1 [M + H+], 542.1 [M + Na+], 558.1
[M + K+].
Compound 7a: 1H NMR (400 MHz, CDCl3): d = 9.81 and
9.79 (2 br s, 1 H, NH), 7.70 (d, J = 8.0 Hz, 1 H, ArH), 7.54
(t, J = 7.4 Hz, 1 H, ArH), 7.45 (d, J = 7.6 Hz, 1 H, ArH), 7.33
(t, J = 7.8 Hz, 1 H, ArH), 7.06 and 7.01 (2 s, 1 H, CH), 5.88
and 5.39 (2 s, 1 H, NH), 4.40 and 4.38 (2 s, 2 H, CH2), 4.07–
4.25 (m, 2 H, CH2), 4.02 (s, 2 H, CH2), 3.62 (m, 1 H, CH),
3.49 (t, J = 5.2 Hz, 2 H, CH2), 3.35 (t, J = 5.6 Hz, 2 H, CH2),
1.82 and 1.80 (2 s, 3 H, CH3), 1.32 (d, J = 6.8 Hz, 3 H, CH3).
MS (API-ES+): m/z = 492.1 [M + H+], 514.1 [M + Na+],
530.0 [M + K+].
(16) McGall, H. G.; Barone, A. D.; Diggelmann, M.; Fodor, S. P.
A.; Gentalen, E.; Ngo, N. J. Am. Chem. Soc. 1997, 119,
5081.
(17) In a typical procedure to attach photolabile PNA to an
amino-glass slide, NPPOC-T was attached to the amino-
glass slide mounted in a flow cell by activation of the
carboxyl groups of NPPOC-T (14.7 mg, 0.03 mmol) in DMF
(0.25 mL). After 20 min, excess NPPOC-T was flushed out
with MeCN and specific areas (pixels) were irradiated at 365
nm in MeCN using DMD for varying period of time to
remove the photolabile protecting groups at specific
locations. The amino groups exposed by this treatment were
visualized by being covalently coupled to a BODIPY dye
(100 mg) in DMF (0.25 mL) for 10 min followed by scanning
on a GenPix Scanner.
(12) Will, D. W.; Breipohl, G.; Langner, D.; Knolle, J.; Uhlmann,
E. Tetrahedron 1995, 51, 12069.
(13) (a) Dueholm, K. L.; Egholm, M.; Behrens, C.; Christensen,
L.; Hansen, H. F.; Vulpius, T.; Petersen, K. H.; Berg, R. H.;
Nielsen, P. E.; Buchardt, O. J. Org. Chem. 1994, 59, 5767.
(b) Coull, J. M.; Egholm, M.; Hodge, R. P.; Ismail, M.;
Rajur, S. B. US Patent 6 133 444, 2000.
(14) Puschl, A.; Sforza, S.; Haaima, G.; Dahl, O.; Nielsen, P. E.
Tetrahedron Lett. 1998, 39, 4707.
(15) Spectroscopic Data for Selected Compounds.
Compound 4: 1H NMR (400 MHz, CDCl3): d = 7.66 (d,
J = 8.0 Hz, 1 H, ArH), 7.51 (t, J = 7.4 Hz, 1 H, ArH), 7.41
(d, J = 7.6 Hz, 1 H, ArH), 7.30 (t, J = 7.8 Hz, 1 H, ArH), 6.14
(s, 1 H, NH), 4.05–4.25 (m, 2 H, CH2), 3.59 (m, 1 H, CH),
(18) Stewart, J. M.; Young, J. D. Solid Phase Peptide Synthesis;
Pierce Chemical Co.: Rockford IL, 1984.
Synlett 2006, No. 13, 2130–2132 © Thieme Stuttgart · New York