Mendeleev Commun., 2011, 21, 137–139
oxidation of hydroxy groups at C-3 and C-7 can be reached by
Russia’(contract no. P715) and the Russian Foundation for Basic
Research (grant no. 10-03-00995-a).
the use of potassium permanganate in acidic media36 or in enzyme-
assisted synthesis.30 We obtained compound 9 by oxidation of
methyl cholate 4 with a twofold excess of IBX in 55% yield.
The reaction of diketone 9 with hydroxylamine proceeded
under milder conditions than the similar reaction of compound 6.
The yield of dioxime 10 was 51% after chromatographic puri-
fication. The reduction of compound 10 was carried out under
conditions similar to those for reduction of oxime 7. The struc-
ture of the target diamine 3 (45% yield after chromatographic
separation)¶ wasdeterminedbyNMRspectroscopy[1H, 13C{1H},
13C-DEPT-135, 1H,1H-COSY, 1H,13C-HSQC, 1H,13C-HMBC
(J 8 Hz) and 1H,13C-HMQC-COSY]. One-dimensional and two-
dimensional (1H,1H-COSY) proton spectra are not informative
since they contain overlapping groups of signals and cannot be
used for unambiguous assignment of proton signals. The use
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2011.04.007.
References
1 K. M. Bhattarai, A. P. Davis, J. J. Perry, C. J. Walter, S. Menser and
D. J. Williams, J. Org. Chem., 1997, 62, 8463.
2 L. Siracusa, F. M. Hurley, S. Dresen, L. J. Lawless, M. N. Pérez-Payán
and A. P. Davis, Org. Lett., 2002, 4, 4639.
3 A. J. Ayling, M. N. Pérez-Payán and A. P. Davis, J. Am. Chem. Soc.,
2001, 123, 12716.
4 J. P. Clare, A. J. Ayling, J.-B. Joos, A. L. Sisson, G. Magro, M. N. Pérez-
Payán, T. N. Lambert, R. Shukla, B. D. Smith and A. P. Davis, J. Am.
Chem. Soc., 2005, 127, 10739.
5 A. P. Davis, Coord. Chem. Rev., 2006, 250, 2939.
6 A. Iuliano, I. Pieraccini, G. Félix and P. Salvadori, Tetrahedron: Asymmetry,
2002, 13, 1265.
7 N. Tu, J. T. Link, B. K. Sorensen, M. Emery, M. Grynfarb, A. Goos-
Nilsson and B. Nguyen, Bioorg. Med. Chem. Lett., 2004, 14, 4179.
8 A. Kannan, E. De Clercq, C. Pannecouque, M. Witvrouw, T. L. Hartman,
J. A. Turpin, R. W. Buckheit and M. Cushman, Tetrahedron, 2001, 57,
9385.
9 R. Paschke, J. Kalbitz and C. Paetz, Inorg. Chim. Acta, 2000, 304, 241.
10 R. Paschke, J. Kalbitz, C. Paetz, M. Luckner, T. Mueller, H.-J. Schmoll,
H. Mueller, E. Sorkau and E. Sinn, J. Inorg. Biochem., 2003, 94, 335.
11 P. Bandyopadhyay, V. Janout, L. Zhang and S. L. Regen, J. Am. Chem.
Soc., 2001, 123, 7691.
1
of an advanced H,13C-HMQC-COSY technique allowed us to
observe cross-peaks between 13C and 1H attached to it, as well as
between 13C and 1H which have J-coupling with directly attached
1H, and thus, to determine all homonuclear correlations which
strongly overlapped in a simple COSY experiment. Assignment
of 1H, 13C{1H} spectra of compound 3 revealed that the signals
at d 3.10 (tt, J 11.6, 3.8 Hz, width 42.0 Hz) and d 3.50 (m, width
22.0 Hz) match those of the protons at C-3 and C-7 atoms of the
cholane framework. The coupling constant J 11.6 Hz of the
proton signal at C-3 suggests that it occupies an axial position,
while the width of the proton signal at C-7 suggests an equatorial
position. Thus, the resulting methyl 3a,7a-diamino-12a-hydroxy-
5b-cholan-24-oate 3 has the natural configuration.
12 P. Bandyopadhyay, P. Bandyopadhyay and S. L. Regen, Bioconjugate
Chem., 2002, 13, 1314.
13 V. Janout, B. Jing and S. L. Regen, Bioconjugate Chem., 2002, 13, 351.
14 B. Jing, V. Janout and S. L. Regen, Bioconjugate Chem., 2003, 14, 1191.
15 V. Janout, B. Jing and S. L. Regen, J. Am. Chem. Soc., 2005, 127, 15862.
16 S. Walker, M. J. Sofia, R. Kakarla, N.A. Kogan, L. Wierichs, C. B. Longley,
K. Bruker, H. R. Axelrod, S. Midha, S. Babu and D. Kahne, Proc. Natl.
Acad. Sci. USA, 1996, 93, 1585.
In conclusion, we have synthesized mono- and diamino ana-
logues of cholic acid using reduction of oximes on treatment
with titanium(iii) chloride in the presence of sodium cyanoboro-
hydride. This method is not inferior to the catalytic hydrogena-
tion on platinum(iv) oxide.
17 U. Taotafa, D. B. McMullin, S. C. Lee, L. D. Hansen and P. B. Savage,
Org. Lett., 2000, 2, 4117.
18 Q. Guan, C. Li, E. J. Schmidt, J. S. Boswell, J. P. Walsh, G. W. Allman
and P. B. Savage, Org. Lett., 2000, 2, 2837.
ThisworkwassupportedbytheFederalgoal-orientedprogramme
‘Scientific and Scientific-Pedagogical Personnel of the Innovative
19 B. Ding, N.Yin,Y. Liu, J. Cardenas-Garcia, R. Evanson, T. Orsak, M. Fan,
G. Turin and P. B. Savage, J. Am. Chem. Soc., 2004, 126, 13642.
20 R. F. Epand, P. B. Savage and R. M. Epand, Biochim. Biophys. Acta,
2007, 1768, 2500.
Methyl 12a-amino-3a,7a-dihydroxy-5b-cholan-24-oate 2: [a]D20 –35
§
[c 1.0, CHCl3–MeOH (1:4)]. 1H NMR, d: 0.70 (s, 3H, 18-Me), 0.82 (s, 3H,
19-Me), 0.91 (d, 3H, 21-Me, J 5.8 Hz), 0.92–1.96 (m, 20H, steroid protons),
2.03–2.38 (m, 4H, steriod protons), 3.30 (br.t, 1H, 12b-H, J 3.0 Hz), 3.38
(tt, 1H, 3b-H, J 11.4, 4.4 Hz), 3.60 (s, 3H, OMe), 3.72–3.77 (m, 1H, 7b-
H). 13C NMR, d: 13.30, 17.21, 22.19, 23.40, 26.69, 28.01, 30.19, 30.70,
31.30, 34.81, 35.06, 35.24, 35.44, 35.68, 39.61, 39.73, 41.45, 42.00, 45.26,
48.08, 51.79, 55.76, 68.52, 72.08, 174.90. MS, m/z: 422.029 [M+H]+,
444.015 [M+Na]+. ESI HRMS (Bruker micrOTOF II), /z: 422.3269 (calc.
for C25H44NO4: 422.3265 [M+H]+), 444.3091 (calc. for C25H43NNaO4:
444.3084 [M+Na]+).
21 S. Broderick, A. P. Davis and R. P. Williams, Tetrahedron Lett., 1998,
39, 6083.
22 A. P. Davis and M. N. Pérez-Payán, Synlett., 1999, 991.
23 C. Li, A. Rehman, N. K. Dalley and P. B. Savage, Tetrahedron Lett.,
1999, 40, 1861.
24 X.-T. Zhou, A. Rehman, C. Li and P. B. Savage, Org. Lett., 2000, 2,
3015.
25 B. Ding, U. Taotofa, T. Orsak, M. Chadwell and P. B. Savage, Org. Lett.,
2004, 6, 3433.
26 Y. R. Vandenburg, B. D. Smith, M. N. Pérez-Payán and A. P. Davis,
Methyl 3a,7a-diamino-12a-hydroxy-5b-cholan-24-oate 3: 1H NMR
¶
(Bruker Avance-600, 600.13 MHz, CD3OD) d: 0.75 (s, 3H, 18-Me), 1.02
(d, 3H, 21-Me, J 6.5 Hz), 1.03 (s, 3H, 19-Me), 1.13–1.23 (m, 2H, Ha-1,
Ha-15), 1.32–1.41 (m, 2H, Ha-16, Ha-22), 1.41–1.50 (m, 1H, H-20),
1.56–1.62 (m, 1H, Ha-2), 1.63–1.71 (m, 3H, H-5, Ha-11, Hb-11), 1.72–1.93
(m, 7H, Ha-4, Ha-6, Hb-2, Hb-15, Hb-22, H-14, H-17), 1.93–2.04 (m, 4H,
Hb-1, Hb-4, Hb-16, H-8), 2.31–2.24 (ddd, 1H, Ha-23, J 6.9, 9.3, 15.4 Hz),
2.31–2.37 (m, 2H, Hb-6, H-9), 2.39 (ddd, 1H, Hb-23, J 5.3, 9.8, 15.4 Hz),
3.10 (tt, 1H, H-3, J 11.8, 3.8 Hz), 3.49–3.52 (m, 1H, H-7), 3.61 (s, 3H, OMe),
3.98 (br.t, 1H, H-12, J 3.1 Hz). 13C NMR (150.90 MHz) d: 12.75 (C-18, +),
17.69 (C-21, +), 22.41 (C-19, +), 23.92 (C-15, –), 26.61 (C-2, –), 28.17
(C-9, +), 28.36 (C-16, –), 28.87 (C-11, –), 31.42 (C-6, –), 31.79 (C-23, –),
32.12 (C-22, –), 41.69 (C-3, +), 34.77 (C-4, +), 35.83 (C-10, –), 35.85
(C-1, –), 36.53 (C-20, +), 37.87 (C-8, +), 41.81 (C-5, +), 42.23 (C-14, +),
47.88 (C-17, +), 48.04 (C-13, –), 51.02 (C-7, +), 52.07 (OMe, +), 52.56 (C-3,
+), 73.87 (C-12, +), 176.47 (C-24, +). MS, m/z: 420.970 [M]+. ESI HRMS
(Bruker micrOTOF II), m/z: 421.3409 (calc. for C25H45N2O3: 421.3425
[M+H]+), 459.2980 (calc. for C25H44N2O3K: 459.2984 [M+K]+).
For characteristics of compounds 4, 5, 7, 8b,c, 9 and 10, see Online
Supplementary Materials.
J. Am. Chem. Soc., 2000, 122, 3252.
27 A. Anikin, M. Maslov, J. Sieler, S. Blaurock, J. Baldamus, L. Hennig,
M. Findeisen, G. Reinhardt, R. Oehme and P. Welzel, Tetrahedron, 2003,
59, 5295.
28 H. Tohma and Y. Kita, Adv. Synth. Catal., 2004, 346, 111.
29 A. F. Hofmann, Acta Chem. Scand., 1963, 17, 173.
30 S. Riva, R. Bovara, P. Pasta and G. Carrea, J. Org. Chem., 1986, 51, 2902.
31 O. Bortolini, U. Cova, G. Fantin and A. Medici, Chem. Lett., 1996, 5, 335.
32 J. P. Leeds and H. A. Kirst, Synth. Commun., 1988, 18, 777.
33 T. F. Gallagher and W. P. Long, J. Biol. Chem., 1943, 147, 131.
34 L. F. Fieser and S. Rajagopalan, J. Am. Chem. Soc., 1950, 72, 5530.
35 K. Kuhajda, S. Kevresan, J. Kandrac, J. P. Fawcett and M. Mikov, Eur.
J. Drug Metab. Ph., 2006, 31, 179.
36 S. Kuwada, S. Furushiro and M. Kawashima, Ann. Rep. Takeda Res.
Lab., 1949, 8, 50.
37 F. C. Chang, J. Org. Chem., 1979, 44, 4567.
Received: 21st October 2010; Com. 10/3615
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