184
T. Ruman et al. / Bioorganic Chemistry 37 (2009) 180–184
used in the last step of reaction procedure. Final yield was 121 mg
of 4. Analytical data for 4: MS (electrospray ionization, m/z): 204
(100%). Elemental Anal. Calcd for C10H13BN2O2: C, 58.87%; H,
6.42%; N, 13.73%. Found: C, 58.81; H, 6.47; N, 13.70. 1H NMR (ace-
tone-d6, ppm): 8.52 (br, B–OH, 1H); 7.28–7.45 (m, Ph, 5H); 5.85
(br, NH, 1H); 4.30 (m, N–CH, 1H); 2.88 (s, Me, 3H); 1.45 (m, B–
CH2, 2H). 13C NMR (acetone-d6, ppm): 156.0 (C@O); 127.1, 122.4,
123.2 (Ph); 42.2 (N–CH); 27.1 (Me); 19.3 (B–CH2). 11B NMR (ace-
tone-d6, ppm): 26.0. 11B NMR (methanol-d4, ppm): 1.7.
CH2); 27.4 (B–CH). 11B NMR (acetone-d6, ppm): 29.2. 11B NMR
(methanol-d4, ppm): 5.1.
4.9. Preparation of 8 (4-hydroxy-3-N-methyl-5-phenyl-5,6-
dihydroborauracil)
Preparation procedure for 8 is analogical to that presented for 1,
but for phenylacetonitrile (0.44 ml, 3.8 mmol) used in the first
reaction step instead of acetonitrile. Additionally, methyl isocya-
nate (2:1 methyl isocyanate to boronic amino acid molar ratio)
was used in the last step of the reaction procedure. Yield was
69 mg of 8. Analytical data for 8: MS (electrospray ionization, m/
z): 204 (100%). Elemental Anal. Calcd for C4H9BN2O2: C, 58.87%;
H, 6.42%; N, 13.73%. Found: C, 58.80; H, 6.45; N, 13.71. 1H NMR
(acetone-d6, ppm): 8.75 (br, B–OH, 1H); 7.33–7.52 (m, Ph, 5H);
5.84 (br, NH, 1H); 3.59 (m, N–CH2, 2H); 2.90 (s, Me, 3H); 2.83
(m, B–CH, 1H). 13C NMR (acetone-d6, ppm): 154.8 (C@O); 126.2,
125.7, 124.1 (Ph); 39.6 (N–CH2); 27.1 (Me); 27.9 (B–CH). 11B
NMR (acetone-d6, ppm): 29.5. 11B NMR (methanol-d4, ppm): 5.2.
4.6. Preparation of 5 (4-hydroxy-5,6-dihydroborathymine)
Preparation procedure for 5 is analogical to that presented for 1,
but for priopionitrile (0.27 ml, 3.8 mmol) used in the first reaction
step instead of acetonitrile. Final yield was 82 mg of 5. Analytical
data for 5: MS (electrospray ionization, m/z): 127–128 (100%). Ele-
mental Anal. Calcd for C4H9BN2O2: C, 37.55%; H, 7.09%; N, 21.90%.
Found: C, 37.53; H, 7.11; N, 21.88. 1H NMR (acetone-d6, ppm): 8.36
(br, B–OH, 1H); 5.92, 5.75 (br, NH, 2H); 3.38 (m, N–CH2, 2H); 1.34
(m, B–CH, 1H); 1.24 (d, Me, 3H). 13C NMR (acetone-d6, ppm): 153.4
(C@O); 34.7 (N–CH2); 17.0 (B–CH); 12.1 (Me). 11B NMR (acetone-
d6, ppm): 24.6. 11B NMR (methanol-d4, ppm): 1.5.
4.10. Interactions of 1–8 with pyridine and n-butylamine
Approx. 2 mg of a given cyclic compound was dissolved in
0.5 ml of acetone-d6, containing pyridine or n-butylamine (1:1
pyridine or n-butylamine to 5,6-dihydroborauracil molar ratios).
The NMR results are presented in Table 1.
4.7. Preparation of 6 (4-hydroxy-3-N-methyl-5,6-dihydroborathymine)
Preparation procedure for 6 is analogical to that presented for 1,
but for priopionitrile (0.27 ml, 3.8 mmol) used in the first reaction
step instead of acetonitrile. Additionally, methyl isocyanate (2:1
methyl isocyanate to boronic amino acid molar ratio) was used
in the last step of the reaction procedure. Final yield was 65 mg
of 6. Analytical data for 6: MS (electrospray ionization, m/z):
141–142 (100%). Elemental Anal. Calcd for C5H11BN2O2: C,
42.30%; H, 7.81%; N, 19.73%. Found: C, 42.27; H, 7.88; N, 19.68.
1H NMR (acetone-d6, ppm): 8.47 (br, B–OH, 1H); 5.90 (br, NH,
1H); 3.41 (m, N–CH2, 2H); 2.85 (s, 3-Me, 3H); 1.37 (m, B–CH,
1H); 1.22 (d, 5-Me, 3H). 13C NMR (acetone-d6, ppm): 157.0
(C@O); 34.8 (N–CH2); 26.1 (3-Me); 17.9 (B–CH); 12.3 (5-Me). 11B
NMR (acetone-d6, ppm): 25.1. 11B NMR (methanol-d4, ppm): 2.1.
Acknowledgment
This work was supported by the Ministry of Education and Sci-
ence, Poland, Grant No. N204 088 31/2052 2006–2009.
References
[1] J.-C. Zhuo, A.H. Soloway, J.C. Beeson, W. Ji, B.A. Barnum, F.-G. Rong, W. Tjarks,
G.T. Jordan IV, J. Liu, S.G. Shore, J. Org. Chem. 64 (1999) 9566–9574.
[2] T. Ruman, K. Dlugopolska, A. Kusnierz, A. Jurkiewicz, A. Les´, W. Rode, Bioorg.
Chem. 37 (2009) 65–69.
[3] V.J. Reddy, S. Chandra, M.V. Ram Reddy, Org. Biomol. Chem. 5 (2007) 889–891.
[4] W. Yang, X. Gao, B. Wang, Med. Res. Rev. 23 (2003) 346–368.
[5] R.R. Wolfenden, Annu. Rev. Biophys. Bioeng. 5 (1976) 271.
[6] A.H. Soloway, W. Tjarks, B.A. Barnum, F.-G. Rong, R.F. Barth, I.M. Codogni, J.G.
Wilson, Chem. Rev. 98 (1998) 1515–1562.
4.8. Preparation of 7 (4-hydroxy-5-phenyl-5,6-dihydroborauracil)
[7] M. Groll, C. Berkers, H. Ploegh, H. Ovaa, Structure 14 (3) (2006) 451–456.
[8] T.R. Transue, J.M. Krahn, S.A. Gabel, E.F. DeRose, R.E. London, Biochemistry 43
(2004) 2829–2839.
[9] J.E. DeMoor, G.P.J. Van der Kelen, Organomet. Chem. 6 (1966) 235.
[10] W.D. Phillips, H.C. Miller, E.L.J. Mutterties, Am. Chem. Soc. 81 (1959) 4496.
[11] H. Nöth, H. Vahrenkamp, Chem. Ber. 99 (1966) 1049.
[12] H.C. Brown, J.B. Campbell Jr., J. Org. Chem. 45 (1980) 389.
[13] K.J. Maruyama, Org. Chem. 42 (1977) 3252.
[14] H. Landesman, R.E. Willams, J. Am. Chem. Soc. 83 (1961) 2663.
[15] C.D. Good, D.M. Ritter, Ritter J. Am. Chem. Soc. 84 (1962) 1162.
[16] T.P. Onak, H. Landesman, R.E. Willams, J. Phys. Chem. 63 (1959) 1533.
[17] C.A. Brown, S. Krishnamurthy, J. Org. Chem. 43 (1978) 2731.
Preparation procedure for 7 is analogical to that presented for 1,
but for phenylacetonitrile (0.44 ml, 3.8 mmol) used in the first
reaction step instead of acetonitrile. Yield was 55 mg of 7. Analyt-
ical data for 7: MS (electrospray ionization, m/z): 190 (100%). Ele-
mental Anal. Calcd for C9H11BN2O2: C, 56.89%; H, 5.83%; N,
14.74%. Found: C, 56.84; H, 5.87; N, 14.69. 1H NMR (acetone-d6,
ppm): 8.63 (br, B–OH, 1H); 7.31–7.46 (m, Ph, 5H); 5.79, 5.71 (br,
NH, 2H); 3.57 (m, N–CH2, 2H); 2.81 (m, B–CH, 1H). 13C NMR (ace-
tone-d6, ppm): 155.9 (C@O); 126.3, 125.0 121.2 (Ph); 39.2 (N–