Synthesis of novel amide-linked dimers of lithocholic acid

Article abstract of DOI:10.3184/030823408X318325

An efficient synthesis of lithocholic amides and amide-linked dimers under mild conditions is described. New σ, m- and p-phenylenediamine-derived dimers of lithocholic acid were synthesised by the activation of the carboxyl group of the bile acid as a mixed anhydride resulting from the reaction of the acid with ethyl chloroformate. The reduction of lithocholic amides afforded the corresponding 24-amino-5β-cholane derivatives. All compounds were characterised by IR, ¹H and ¹³C NMR and mass spectra.

Full text of DOI:10.3184/030823408X318325

260 RESEARCH PAPER
MAY, 260–265
JOURNAL OF CHEMICAL RESEARCH 2008
Synthesis of novel amide-linked dimers of lithocholic acid
Roman Joachimiak, Monika Piasecka and Zdzisław Paryzek*
Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Pozna, Poland
An efficient synthesis of lithocholic amides and amide-linked dimers under mild conditions is described. New o-,
m- and p-phenylenediamine-derived dimers of lithocholic acid were synthesised by the activation of the carboxyl
group of the bile acid as a mixed anhydride resulting from the reaction of the acid with ethyl chloroformate.
The reduction of lithocholic amides afforded the corresponding 24-amino-5E-cholane derivatives. All compounds
were characterised by IR, 1H and 13C NMR and mass spectra.
Keywords: steroids, bile acid, steroid dimers, lithocholic amides
Bile acid amides exhibit various interesting properties.
Antibacterial1,2, antifungal1,3 and antiviral4ꢁDFWLYLW\ꢁRIꢁELOHꢁDFLGꢁ
amides have been reported. Metal complexing properties of
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other compounds of natural origin like amino acids, peptides
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acid amide9,10 and bile acid amidoalcohols11 have proved to
be effective organogelators.12
Amide and amine, derivatives of lithocholic acid have
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chloroformate under mild conditions. The method proved to
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E\ꢁ0F.HQQDꢁet al.13ꢁ,QꢁUHFHQWꢁ\HDUVꢅꢁGLPHULFꢁVWHURLGVꢁ±ꢁPDLQO\ꢁ
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dimers of bile acids has been reported.14-16 Some of these
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example, a piperazine linked dimer of lithocholic acid has
been used as the substrate for preparation of a cholaphane
VKRZLQJꢁ FRPSOH[LQJꢁ ELQGLQJꢁ SURSHUWLHVꢁ WRZDUGꢁ $J+.7,18
Various steroid dimers are also active as cation-transporting
trans-membrane channels.19,20 The head-to-head amide-linked
derivative of cholic acid has been reported as a host for the
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DFLGꢁDQGꢁJO\FLQHꢅ22 ester-linked lithocholic acid dimers linking
C-24 and C-3' carbon atoms and an oxalate diester linking
position 3–3' have also been reported.23ꢁ:KLOVWꢁWKLVꢁZRUNꢁZDVꢁ
LQꢁSURJUHVVꢁDꢁSDSHUꢁE\ꢁ+D]UDꢁDQGꢁFRꢃZRUNHUVꢁZDVꢁSXEOLVKHGꢁ
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preparation of bile acid amides have also been reported. These
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Results and discussion
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SUHSDUHGꢁ DFFRUGLQJꢁ WRꢁ Dꢁ SURFHGXUHꢁ GHVFULEHGꢁ E\ꢁ &KDSOLQꢁ et
al.40 Thus, 3DꢃDFHWR[\ꢃꢈEꢃFKRODQꢃꢆꢉꢃRLFꢁDFLGꢁZDVꢁWUHDWHGꢁZLWKꢁ
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experiment, 3DꢃDFHWR[\ꢃꢈEꢃFKRODQDPLGHꢅꢁ IRUꢁ H[DPSOHꢅꢁ ZDVꢁ
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under mild conditions.1 Under these conditions protection
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The reaction of lithocholic acid (1ꢏꢁZLWKꢁDꢁWZRꢁPRODUꢁH[FHVVꢁRIꢁ
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amides (4) and (5ꢏꢁLQꢁDOPRVWꢁTXDQWLWDWLYHꢁ\LHOGꢁꢐ6FKHPHꢁꢇꢏꢂꢁ
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The reaction of (2ꢏꢁ ZLWKꢁ DPPRQLXPꢁ K\GUR[LGHꢁ ꢐꢆꢈꢌꢏꢁ LQꢁ
dioxan afforded amide (3)42ꢁLQꢁꢑꢊꢌꢁ\LHOGꢂꢁ:KHQꢁWKHꢁDQK\GULGHꢁ
(2)ꢁZDVꢁWUHDWHGꢁZLWKꢁꢆꢉꢃDPLQRꢃꢈE-cholane-3D-ol (vide infra) a
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effective in transforming (2) to the anilide (6),37ꢁZKLFKꢁZDVꢁ
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diamines. Thus, the reaction of the intermediate (2)ꢁ ZLWKꢁ
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variable size.
The practical importance of bile acid amides and their
possible use as substrates for the preparation of cholaphanes
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preparation of unsubstituted amides33 and peptides.34,35
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JOURNAL OF CHEMICAL RESEARCH 2008 261
O
CO2H
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O
RO
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NH
dioxane, 0-10 o
C
X
HO
NH
H
RO
2
1
O
RNH2,
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10-20 o
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9
R = H, X = o-phenylene
10 R = Ac, X = o-phenylene
11 R = H, X = m-phenylene
12 R = Ac, X = m-phenylene
13 R = H, X = p-phenylene
14 R = Ac, X = p-phenylene
15 R = H, X = ethylene
CONHR
16 R = Ac, X = ethylene
Scheme 3
HO
H
3
4
5
6
R = H,
R = n-Bu
R = CH2C6H5
R = C6H5
O
O
RO
RO
N
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Scheme 1
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dimer (17ꢏꢅꢁDꢁGLFKRODQR\OꢁGHULYDWLYHꢁRIꢁSLSHUD]LQHꢅꢁZKLFKꢁZHꢁ
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amine at 90°C for 90 h18 or in another preparation in 51%
\LHOGꢂ7
17 R = H
18 R = Ac
Scheme 4
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amine (22).
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chloroform or benzene. Moreover, dimers (13) and (15ꢏꢁZHUHꢁ
QRWꢁ VROXEOHꢁ HYHQꢁ LQꢁ GLPHWK\OVXOIR[LGHꢃd6ꢁ DQGꢁ S\ULGLQHꢃd5,
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LPSURYHꢁWKHꢁVROXELOLW\ꢁRIꢁWKHꢁDPLGHVꢁꢐ9), (11), (13), (15) and
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afforded the corresponding 3,3'-bis-acetates (10), (12), (14),
(16) and (18).
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IR, H and 13C NMR and mass spectra (see Experimental).
1
The complete assignment of 13C NMR spectra of amides and
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and summarised.41ꢁ$VꢁIRUꢁOLWKRFKROLFꢁDFLGꢅꢁRQO\ꢁWKHꢁGDWDꢁIRUꢁ
3-OꢃVXEVWLWXWHGꢁ FDUER[\OLFꢁ DFLGVꢁ DQGꢁ HVWHUVꢁ ZHUHꢁ SUHVHQWHGꢂꢁ
Therefore our spectral data for lithocholic amides and amide-
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Reduction of the amides (3–5) to the respective amines
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UHÀX[ꢂꢁ$PLQHVꢁꢐ19), (20) and (21ꢏꢁZHUHꢁLVRODWHGꢁLQꢁꢈꢊꢅꢁꢒꢊꢁDQGꢁ
O
NHR
H
H
N
H
HO
H
RO
RO
H
H
19 R = H,
20 R = n-Bu
21 R = CH2C6H5
22 R = C6H5
7 R = H
8 R = Ac
Scheme 2
Scheme 5

262 JOURNAL OF CHEMICAL RESEARCH 2008
Preparation of lithocholic amides and amide-linked dimers; general
procedure
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lithocholic amide-linked dimers, derived from isomeric
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preparation of diamides, derivatives of aromatic and aliphatic
SULPDU\ꢁDQGꢁVHFRQGDU\ꢁGLDPLQHVꢂꢁ7KHꢁV\QWKHVLVHGꢁGHULYDWLYHVꢁ
RIꢁOLWKRFKROLFꢁDFLGꢁZHUHꢁIXOO\ꢁFKDUDFWHULVHGꢁE\ꢁVSHFWURVFRSLFꢁ
methods. The lithocholic acid dimers are excellent substrates
IRUꢁ WKHꢁ SUHSDUDWLRQꢁ RIꢁ QHZꢁ OLWKLRFKRODSKDQHVꢁ ZKLFKꢁ LVꢁ WKHꢁ
subject of our further investigations.
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solution of lithocholic acid (1ꢏꢁꢐꢇꢍꢍꢁPJꢅꢁꢊꢂꢈꢁPPROHꢏꢁLQꢁDQK\GURXVꢁ
GLR[DQHꢁ ꢐꢇꢈꢁ POꢏꢁ DQGꢁ WKHꢁ VROXWLRQꢁ ZDVꢁ VWLUUHGꢁ DWꢁ ꢇꢊƒ&ꢁ IRUꢁ ꢇꢊꢁ PLQꢂꢁ
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VWLUULQJꢁFRQWLQXHGꢁIRUꢁꢇꢊꢁPLQꢂꢁDWꢁꢇꢊƒ&ꢂꢁ6XEVHTXHQWO\ꢁDꢁVROXWLRQꢁRIꢁ
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DWꢁURRPꢁWHPSHUDWXUHꢂꢁ:DWHUꢁꢐꢆꢊꢁPOꢏꢁZDVꢁDGGHGꢁDQGꢁWKHꢁSURGXFWꢁZDVꢁ
H[WUDFWHGꢁ ZLWKꢁ HWK\Oꢁ DFHWDWHꢁ RUꢁ FKORURIRUPꢂꢁ 7KHꢁ RUJDQLFꢁ OD\HUꢁ ZDVꢁ
ZDVKHGꢁZLWKꢁZDWHUꢅꢁGLOXWHꢁ+&OꢅꢁVRGLXPꢁK\GURJHQꢁFDUERQDWHꢁꢐꢈꢌꢏꢁDQGꢁ
ZDWHUꢁDQGꢁGULHGꢁRYHUꢁPDJQHVLXPꢁVXOIDWHꢂꢁ)LOWUDWLRQꢁDQGꢁHYDSRUDWLRQꢁ
RIꢁWKHꢁVROYHQWꢁXQGHUꢁUHGXFHGꢁSUHVVXUHꢁJDYHꢁWKHꢁFUXGHꢁDPLGHꢁZKLFKꢁ
ZDVꢁFU\VWDOOLVHGꢂ
3D-Hydroxy-5E-cholan-24-amide (3):1 Solution of NH4OH (25%)
ZDVꢁXVHGꢁꢐꢊꢂꢒꢈꢁPPROHꢏꢅꢁꢑꢍꢌꢁ\LHOGꢁRIꢁWKHꢁFUXGHꢁDPLGHꢅꢁꢑꢊꢌꢁ\LHOGꢁ
DIWHUꢁFU\VWDOOLVDWLRQꢂꢁ0ꢂSꢂꢁꢆꢇꢉ±ꢆꢇꢒƒ&ꢁꢐ&+&O3), lit.1 m.p. 208–210°C
1
(MeOH/H2O). H NMR (CDCl3): G = 5.36 (bs, 2 H, NH2), 3.62 (m,
Experimental
General
1 H, 3E-H), 0.92 (d, J = 6.3 Hz, 3 H, 21-CH3), 0.91 (s, 3 H, 19-CH3),
0.64 (s, 3 H, 18-CH3). IR (KBr pellets) Qmax: 3456, 3390, 3195, 1669,
1625 cm-1. MS (EI) m/z: 375 [M]+, 357 [M-H2O]+. MS (ESI) m/z:
773 [2M + Na]+, 751 [2M + H]+, 398 [M + Na]+, 376 [M + H]+, 358
[M + H-H2O]+.
0HOWLQJꢁSRLQWVꢁZHUHꢁGHWHUPLQHGꢁRQꢁDꢁ.RÀHUꢁKRWꢃVWDJHꢁDSSDUDWXVꢁDQGꢁ
DUHꢁXQFRUUHFWHGꢂꢁ,5ꢁVSHFWUDꢁZHUHꢁGHWHUPLQHGꢁZLWKꢁDQꢁ)7ꢃ,5ꢁ%UXNHUꢁ
FS 113V spectrophotometer for solutions in chloroform or as KBr
pellets. 1H and 13&ꢁ105ꢁVSHFWUDꢁZHUHꢁUHFRUGHGꢁZLWKꢁDꢁ9DULDQꢁ*HPLQLꢁ
ꢎꢊꢊꢁ97ꢁVSHFWURPHWHUꢁꢐꢎꢊꢊꢁDQGꢁꢋꢈꢂꢈꢁ0+]ꢅꢁUHVSHFWLYHO\ꢏꢁRSHUDWLQJꢁLQꢁ
the Fourier transform mode using solutions in CDCl3/CD3OD (4:1)
RUꢁS\ULGLQHꢃd5. Chemical shifts (G) are expressed in ppm relative to
WHWUDPHWK\OVLODQHꢁDVꢁWKHꢁLQWHUQDOꢁVWDQGDUGꢂꢁ7KHꢁ'(37ꢁWHFKQLTXHꢁZDVꢁ
XVHGꢁIRUꢁWKHꢁDVVLJQPHQWꢁRIꢁPXOWLSOLFLW\ꢁRIꢁFDUERQꢁVLJQDOVꢁLQꢁ13C NMR
VSHFWUDꢂꢁ $GGLWLYLW\ꢁ UXOHVꢁ DQGꢁ FRPSDULVRQꢁ ZLWKꢁ GDWD41 reported for
FRPSRXQGVꢁRIꢁVLPLODUꢁVWUXFWXUHꢁZHUHꢁKHOSIXOꢁIRUꢁVLJQDOꢁDVVLJQPHQWꢂꢁ
(OHFWURQꢁLPSDFWꢁꢐLRQLVDWLRQꢁHQHUJ\ꢁRIꢁꢋꢊꢁH9ꢏꢁDQGꢁ)$%ꢁPDVVꢁVSHFWUDꢁ
ZHUHꢁ UHFRUGHGꢁ XVLQJꢁ DQꢁ $0'ꢁ ꢉꢊꢆꢁ RUꢁ $0'ꢁ ꢒꢊꢉꢁ VSHFWURPHWHUꢂꢁ
(OHFWURVSUD\ꢁ PDVVꢁ VSHFWUDꢁ ꢐ(6,ꢁ 06ꢏꢁ H[SHULPHQWVꢁ ZHUHꢁ SHUIRUPHGꢁ
XVLQJꢁDꢁ:DWHUVꢓ0LFURPDVVꢁ=4ꢁ(6ꢁPDVVꢁVSHFWURPHWHUꢁZLWKꢁPHWKDQROꢁ
VROYHQWꢁ V\VWHPꢂꢁ 6ROYHQWVꢁ ZHUHꢁ GULHGꢁ DQGꢁ GLVWLOOHGꢁ DFFRUGLQJꢁ WRꢁ WKHꢁ
VWDQGDUGꢁSURFHGXUHVꢂꢁ5HDFWLRQꢁSURJUHVVꢁDQGꢁSXULW\ꢁRIꢁFRPSRXQGVꢁZDVꢁ
PRQLWRUHGꢁ E\ꢁ 7/&ꢁ XVLQJꢁ SUHFRDWHGꢁ DOXPLQXPꢃEDFNHGꢁ VLOLFDꢁ SODWHVꢁ
(E. Merck, no. 5554). Silica gel 60 (Merck 70-230 mesh, no. 7734)
ZDVꢁXVHGꢁIRUꢁÀDVKꢁFKURPDWRJUDSK\ꢂ
N-n-Butyl-3D-hydroxy-5E-cholan-24-amide (4): Solution of
nꢃEXW\ODPLQHꢁꢐꢇ0ꢏꢁZDVꢁXVHGꢁꢐꢊꢂꢒꢈꢁPPROHꢏꢅꢁꢑꢍꢌꢁ\LHOGꢁRIꢁWKHꢁFUXGHꢁ
DPLGHꢁ ꢐSXUHꢁ RQꢁ 7/&ꢏꢅꢁ ꢍꢊꢌꢁ \LHOGꢁ DIWHUꢁ FU\VWDOOLVDWLRQꢂꢁ 0ꢂSꢂꢁ ꢆꢊꢊ±
202°C (AcOEt). 1H NMR (CDCl3): G = 5.38 (bs, 1 H, NH), 3.62 (m,
1 H, 3E-H), 3.25 (dd, J1 = 12.9 Hz, J2 = 7.1 Hz, 2 H, NHCH2), 2.41
(t, J = 7.1 Hz, 2 H, 23-CH2), 0.93 (d, J = 7.1 Hz, 3 H, 21-CH3), 0.91
(s, 3 H, 19-CH3), 0.63 (s, 3H, 18-CH3). IR (CHCl3) Qmax: 3607, 3450,
1660, 1518 cm-1. MS (EI) m/z: 431 [M]+, 374 [M-C4H9]+. Anal.
Calcd. for C28H49NO2: C, 77.9; H, 11.4; N, 3.2. Found: C, 77.25; H,
11.5; N, 3.1%.
N-Benzyl-3D-hydroxy-5E-cholan-24-amide
(5):1ꢁ %HQ]\ODPLQHꢁ
ꢐꢊꢂꢒꢈꢁ PPROHꢏꢓZDWHUꢁ ꢐꢇꢁꢄꢁꢇꢊꢏꢁ ZDVꢁ XVHGꢅꢁ ꢑꢍꢌꢁ \LHOGꢁ RIꢁ WKHꢁ FUXGHꢁ DPLGHꢁ
ꢐSXUHꢁ RQꢁ 7/&ꢏꢅꢁ ꢋꢈꢌꢁ \LHOGꢁ DIWHUꢁ FU\VWDOOLVDWLRQꢂꢁ 0ꢂSꢂꢁ ꢇꢑꢋ±ꢇꢑꢍƒ&ꢁ
(AcOEt); lit.1 m.p. 183–185°C (AcOEt/Et2O). 1H NMR (CDCl3):
G = 7.33–7.27 (m, 5 H, ArH), 5.74 (s, 1 H, NH), 4.44 (d, J = 5.8 Hz, 2 H,
NHCH2), 3.62 (m, 1 H, 3E-H), 2.33–2.23 (m, 1 H, 23-CH2), 2.15–2.05
(m, 1 H, 23-CH2), 0.91 (d, J = 6.0 Hz, 3 H, 21-CH3), 0.91 (s, 3 H, 19-
Table 1 13C NMR data of lithocholic amides (3–6) and 3D-hydroxy-5E-cholanyl-24-amine derivatives (19–22)
C
3a
4a
5a
6a
19a
20a
21a
22b
1
35.1
29.9
71.2
35.8
41.9
27.0
26.2
35.6
40.3
34.3
20.6
40.0
42.5
56.3
24.0
27.9
55.8
11.7
23.1
35.3
18.0
31.5
32.4
177.6
35.2
30.2
71.5
36.1
42.0
27.1
26.3
35.7
40.3
34.5
20.7
40.1
42.6
56.4
24.1
28.1
55.9
11.9
23.3
35.4
18.2
31.5c
33.5
174.0
13.6
20.0
31.8c
39.0
35.1
30.0
71.4
35.9
41.9
27.0
26.2
35.7
40.3
34.4
20.6
40.0
42.6
56.3
24.0
28.0
55.8
11.8
23.2
35.3
18.1
31.7
33.3
174.2
43.3
35.1
30.0
71.3
35.9
41.9
27.0
26.2
35.7
40.3
34.4
20.6
40.0
42.6
56.3
24.0
28.0
55.8
11.8
23.2
35.4
18.1
31.6
34.1
172.9
34.9
27.9
70.9
35.4
41.7
26.7
26.0
35.4
40.1
34.1
20.3
39.8
42.2
56.1
23.7
27.8
55.7
11.4
22.8
35.2
17.9
29.5
32.5
41.2
35.1
29.9
71.3
35.8
41.9
30.0
26.2
35.6
40.3
34.4
20.6
40.0
42.5
56.3
24.0
28.1
56.0
11.8
23.2
35.5
18.3
30.4
33.1
49.3
13.6
20.1
29.5
48.5
35.2
28.2
71.4
36.1
41.9
26.3
25.8
35.7
40.3
34.4
20.7
40.0
42.5
56.4
24.1
27.1
56.0
11.9
23.3
35.5
18.5
30.2
33.3
49.3
53.4
35.4
28.4
71.9
36.5
42.2
26.5
26.3
35.9
40.5
34.6
20.9
40.3
42.8
56.5
24.3
27.3
56.2
12.2
23.5
35.7
18.7
30.6
33.4
44.6
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1'
2'
3'
4'
ipso
ortho
meta
para
138.1
138.1
128.7
119.8
123.8
138.8
148.4
129.1
112.6
117.0
128.4c
127.5c
127.2c
128.4c
128.3c
127.1c
aFor solution in CDCl3/CD3OD (4:1); bfor solution in CDCl3; cthese signals may be interchanged.

JOURNAL OF CHEMICAL RESEARCH 2008 263
Table 2 13C NMR data of amide-linked lithocholic acid dimers (8), (9), (11), (14) and (16)
C
8a
9b
11b
14a
16a
1
34.6
35.1
29.9
71.3
35.8
41.8
27.0
26.3
35.6
40.2
34.4
20.6
40.0
42.6
56.3
24.0
28.1
55.8
11.8
23.2
35.4
18.1
31.7
33.8
173.6
35.1
30.0
71.3
35.9
41.9
27.0
26.2
35.6
40.3
34.4
20.6
40.0
42.5
56.3
24.0
28.0
55.8
11.8
23.2
35.4
18.1
31.6
34.0
173.1
34.5
28.3
74.4
35.0
41.8
26.6
26.3
35.8
40.4
34.5
20.8
40.1
42.7
56.5
24.2
27.0
56.1
12.1
23.3
35.5
18.4
31.6
32.2
171.8c
34.6
28.2
74.4
35.1
42.0
26.7
26.3
35.9
40.5
35.6
20.8
40.2
42.8
56.6
24.2
27.0
56.1
12.1
23.3
35.5
18.4
31.8
32.3
174.9
2
28.3 + 28.2d
74.4
3
4
35.0
5
41.9
6
26.6
7
26.3
8
35.8
9
40.4
10
34.6
11
20.8
12
40.2
13
42.73 + 42.69d
56.5
14
15
24.2
27.0
16
17
56.14 + 56.09d
12.0
18
19
23.3
20
35.49 + 35.44d
18.59 + 18.37d
31.9 + 32.2d
33.0 + 33.8d
173.4
21
22
23
24
24'
1'
39.9
40.2
ipso
ortho
meta
ortho'
CH3COO
CH3COO
130.4
125.9c
125.2c
138.6
111.0
115.3
129.0
134.2
120.5
21.4
170.6
21.5
21.4
170.5
170.7c
aFor solution in CDCl3; bfor solution in CDCl3/CD3OD (4:1); cthese signals may be interchanged; dfor unsymmetrical dimer two
signal were observed.
2 H, 23- and 23'-CH2), 0.97 (d, J = 5.9 Hz, 6 H, 21- and 21'-CH3),
0.91 (s, 6 H, 19- and 19'-CH3), 0.65 (s, 6 H, 18- and 18'-CH3). IR
(KBr pellets) Qmax: 3308, 3081, 1668, 1610, 784 cm-1. MS (FAB) m/z:
847 [M + Na]+, 575, 488, 186, 154, 128. HR MS: calcd. for [M + H]+
C54H85N2O4: 825.65094; found 825.65000.
H3), 0.63 (s, 3 H, 18-CH3). IR (KBr pellets) Qmax: 3413, 3334, 3060,
3038, 1652 cm-1. MS (ESI) m/z: 953 [2M + Na]+, 931 [2M + H]+, 488
[M + Na]+, 466 [M + H]+. Anal. Calcd. for C31H47NO2 u H2O: C, 77.0;
H, 10.2; N, 2.9. Found: C, 77.7; H, 10.5; N, 2.4%.
N-Phenyl-3D-hydroxy-5E-cholan-24-amide (6): Aniline (0.5 mmole)
N,N'-Bis(3D-hydroxy-5E-cholan-24-oyl)-p-phenylenediamine (13):
p-3KHQ\OHQHGLDPLQHꢁ ꢐꢊꢂꢆꢈꢁ PPROHꢏꢓGLR[DQHꢁ ꢐꢇꢄꢇꢊꢏꢁ ZDVꢁ XVHGꢅꢁ ꢑꢈꢌꢁ
\LHOGꢁRIꢁWKHꢁFUXGHꢁDPLGHꢁꢐSXUHꢁRQꢁ7/&ꢏꢂꢁ0ꢂSꢂꢁꢇꢍꢈ±ꢇꢍꢍƒ&ꢁꢐ&+2Cl2).
1+ꢁ105ꢁꢐS\ULGLQHꢃd5): G = 10.81 (s, 2 H, NH), 8.41 (s, 4 H, ArH), 3.90
(m, 2 H, 3E- and 3'E-H), 2.67–2.43 (m, 4 H, 23- and 23'-CH2), 0.91 (d,
J = 6.3 Hz, 6 H, 21- and 21'-CH3), 0.90 (s, 6 H, 19- and 19'-CH3), 0.56
(s, 6 H, 18- and 18'-CH3). IR (KBr pellets) Qmax: 3447, 3305, 3073,
1668, 1610, 838 cm-1. MS (ESI) m/z: 847 [M + Na]+, 186, 182, 151.
HR MS (FAB): calcd. for [M + H]+ C54H85N2O4: 825.65094; found
825.64710.
ZDVꢁXVHGꢅꢁꢍꢈꢌꢁ\LHOGꢁRIꢁWKHꢁFUXGHꢁDPLGHꢁꢐSXUHꢁRQꢁ7/&ꢏꢂꢁ0ꢂSꢂꢁꢆꢆꢈ±
1
227°C (AcOEt), 216–219°C (CHCl3). H NMR (CDCl3):
G = 7.56–7.06
(m, 6 H, NH and ArH), 3.63 (m, 1 H, 3E-H), 2.47–2.29 (m, 1 H, 23-CH2),
2.24–2.19 (m, 1 H, 23-CH2), 0.96 (d, J = 6.3 Hz, 3 H, 21-CH3), 0.92 (s,
3 H, 19-CH3), 0.65 (s, 3 H, 18-CH3). IR (KBr pellets) Qmax: 3433, 3307,
3198, 3137, 3059, 3021, 1664, 1600, 754, 693 cm-1. MS (FAB) m/z: 962
[2M + 2H2O + Na]+, 939 [2M + H + 2H2O]+, 903 [2M + Na]+, 488 [M + H
+ 2H2O]+, 452 [M + H]+, 434 [M + H-H2O]+. HR MS: calcd. for [M + H]+
C30H46NO2: 452.35284; found 452.35219.
N-(3D-Hydroxy-5E-cholan-24-yl)-3D-hydroxy-5E-cholan-24-amide
(7): 24-Amino-5E-cholan-3DꢃROꢁꢐꢊꢂꢒꢆꢁPPROHꢏꢁZDVꢁXVHGꢅꢁꢑꢍꢌꢁ\LHOGꢁRIꢁ
WKHꢁFUXGHꢁDPLGHꢁꢐSXUHꢁRQꢁ7/&ꢏꢅꢁZKLFKꢁZDVꢁSXUL¿HGꢁE\ꢁZDVKLQJꢁWKHꢁ
SUHFLSLWDWHꢁZLWKꢁHWK\OꢁDFHWDWHꢁWRꢁJLYHꢁSURGXFWꢁꢐꢋꢏꢁLQꢁꢒꢍꢌꢁ\LHOGꢂꢁ1H NMR
ꢐS\ULGLQHꢃd5): G = 8.49 (t, J = 5.5 Hz, 1 H, NH), 3.91 (m, 2 H, 3E- and
3'E-H), 3.56 (dd, J1 = 12.8 Hz, J2 = 6.0 Hz, 2 H, 24'-CH2), 2.57–2.43
(m, 2 H, 23-CH2ꢏꢅꢁꢊꢂꢑꢈꢁDQGꢁꢊꢂꢑꢍꢁꢐWZRꢁGꢅꢁJ = 6.6 Hz, 6 H, 21- and 21'-
CH3ꢏꢅꢁꢊꢂꢑꢆꢁDQGꢁꢊꢂꢑꢇꢁꢐWZRꢁVꢅꢁꢒꢁ+ꢅꢁꢇꢑꢃꢁDQGꢁꢇꢑꢔꢃ&+3), 0.612 and 0.619
ꢐWZRꢁVꢅꢁꢒꢁ+ꢅꢁꢇꢍꢃꢁDQGꢁꢇꢍꢔꢃ&+3). IR (KBr pellets) Qmax: 3298, 1645, 1553
cm-1. MS (ESI) m/z: 742 [M + Na]+, 720 [M + H]+. HR MS (FAB):
calcd. for [M-OH]+ C48H80NO2: 702.61890; found 702.62125.
N,N'-Bis(3D-hydroxy-5E-cholan-24-oyl)-o-phenylenediamine (9):
o-3KHQ\OHQHGLDPLQHꢁ ꢐꢊꢂꢆꢈꢁ PPROHꢏꢓGLR[DQHꢁ ꢐꢇꢄꢇꢊꢏꢁ ZDVꢁ XVHGꢅꢁ ꢑꢈꢌꢁ
\LHOGꢁ RIꢁ WKHꢁ FUXGHꢁ DPLGHꢁ ꢐSXUHꢁ RQꢁ 7/&ꢏꢂꢁ 0ꢂSꢂꢁ !ꢁ ꢆꢈꢊƒ&ꢁ ꢐ$F2(Wꢏꢂꢁ
1H NMR (CDCl3): G = 7.98 (s, 2 H, NH), 7.41–7.34 and 7.28–7.25
ꢐWZRꢁPꢅꢁꢉꢁ+ꢅꢁ$U+ꢏꢅꢁꢎꢂꢒꢆꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎE- and 3'E-H), 2.45–2.23 (m, 4 H,
23- and 23'-CH2), 0.97 (d, J = 6.0 Hz, 6 H, 21- and 21'-CH3), 0.92
(s, 6 H, 19- and 19'-CH3), 0.66 (s, 6 H, 18- and 18'-CH3). IR (KBr
pellets) Qmax: 3291, 3129, 3064, 1668, 751 cm-1. MS (ESI) m/z: 847
[M + Na]+, 848 [M + Na + H], 186, 151. HR MS: calcd. for [M + H]+
C54H85N2O4: 825.65094; found 825.65017.
N,N'-Bis(3D-hydroxy-5E-cholan-24-oyl)-ethylenediamine
(15):
(WK\OHQHGLDPLQHꢁ ꢐꢊꢂꢆꢈꢁ PPROHꢏꢁ ZDVꢁ XVHGꢅꢁ ꢍꢉꢌꢁ \LHOGꢁ RIꢁ WKHꢁ FUXGHꢁ
amide (pure on TLC). M.p. 202–205°C. IR (KBr pellets) Qmax: 3442,
1660, 1558 cm-1. MS (FAB) m/z: 831 [M + H + 3H2O]+, 813 [M + H
+ 2H2O]+, 777 [M + H]+, 740 [M–2H2O]+ꢂꢁ&RPSRXQGꢁꢐꢇꢈꢏꢁZDVꢁQRWꢁ
soluble in CDCl3, DMSO-d6ꢁDQGꢁS\ULGLQHꢃd5. HR MS: calcd. for [M
+ H]+ C50H85N2O4: 777.65094; found 777.64824.
N,N'-Bis(3D-hydroxy-5E-cholan-24-oyl)-piperazine
(17):7,18
3LSHUD]LQHꢁ ꢐꢊꢂꢆꢈꢁ PPROHꢏꢓGLR[DQHꢁ ꢐꢇꢁꢄꢁꢈꢏꢁ ZDVꢁ XVHGꢅꢁ ꢍꢒꢌꢁ \LHOGꢁ RIꢁ WKHꢁ
crude amide (pure on TLC). M.p. 120–123°C (AcOEt). 1H NMR
(CDCl3): Gꢁ ꢁꢎꢂꢒꢎ±ꢎꢂꢉꢒꢁꢐPꢅꢁꢇꢊꢁ+ꢅꢁꢎȕꢃꢁDQGꢁꢎꢔE-H and N(CH2)2(CH2)2N),
2.44–2.18 (m, 4 H, 23- and 23'-CH2), 0.94 (d, J = 6.5 Hz, 6 H, 21- and
21'-CH3), 0.91 (s, 6 H, 19- and 19'-CH3), 0.64 (s, 6 H, 18- and 18'-
CH3). IR (KBr pellets) Qmax: 3385, 1634, 1601 cm-1. MS (FAB) m/z:
826 [M + Na]+, 803 [M + H]+, 767 [M–2H2O]+. HR MS: calcd. for
[M + H]+ C52H87N2O4: 803.66656; found 803.66692.
Acetylation of lithocholic amides and amide dimers; general procedure
7KHꢁ OLWKRFKROLFꢁ DPLGHVꢁ ZHUHꢁ DFHW\ODWHGꢁ XQGHUꢁ VWDQGDUGꢁ FRQGLWLRQVꢁ
LQꢁS\ULGLQHꢓDFHWLFꢁDQK\GULGHꢁꢐꢇꢊꢄꢇꢏꢁPL[WXUHꢁDWꢁURRPꢁWHPSHUDWXUHꢁIRUꢁ
ꢆꢉꢁKꢂꢁ7KHꢁXVXDOꢁZRUNXSꢁꢐH[WUDFWLRQꢁZLWKꢁEHQ]HQHꢁRUꢁDGGLWLRQꢁRIꢁZDWHUꢁ
DQGꢁ¿OWUDWLRQꢁRIꢁWKHꢁSUHFLSLWDWHꢏꢁJDYHꢁDꢁFUXGHꢁSURGXFWꢂ
N-(3D-Acetoxy-5E-cholan-24-yl)-3D-acetoxy-5E-cholan-24-amide
(8): Yield 72% of the crude compound (pure on TLC), oil. 1H NMR
(CDCl3): G = 5.35 (t, Jꢁ ꢁꢈꢂꢈꢁ+]ꢅꢁꢇꢁ+ꢅꢁ1+ꢏꢅꢁꢉꢂꢋꢇꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎȕꢃꢁDQGꢁ
N,N'-Bis(3D-hydroxy-5E-cholan-24-oyl)-m-phenylenediamine(11):
m-3KHQ\OHQHGLDPLQHꢁ ꢐꢊꢂꢆꢈꢁ PPROHꢏꢓGLR[DQHꢁ ꢐꢇꢄꢇꢊꢏꢁ ZDVꢁ XVHGꢅꢁ ꢑꢊꢌꢁ
\LHOGꢁRIꢁWKHꢁFUXGHꢁDPLGHꢁꢐSXUHꢁRQꢁ7/&ꢏꢂꢁ0ꢂSꢂꢁꢇꢈꢆ±ꢇꢈꢎƒ&ꢁꢐ$F2(Wꢏꢂꢁ
1H NMR (CDCl3): G = 7.25–7.17 (6 H, NH and ArH), 3.62 (m, 2 H,
3E- and 3'E-H), 2.41–2.36 (m, 2 H, 23- and 23'-CH2), 2.54–2.20 (m,

264 JOURNAL OF CHEMICAL RESEARCH 2008
NHCH2ArH), 3.59 (m, 1 H, 3E-H), 2.61–2.53 (m, 2 H, 24-CH2), 0.94
(d, J = 6.6 Hz, 3 H, 21-CH3), 0.90 (s, 3 H, 19-CH3), 0.62 (s, 3 H, 18-
CH3). IR (KBr pellets) Qmax: 3319, 3085, 3062, 3027, 1645, 754, 698
cm-1. MS (ESI) m/z: 474 [M + Na]+, 452 [M + H]+.
3'E-H), 3.21 (m, 2 H, 24'-CH2ꢏꢅꢁꢆꢂꢊꢎꢁꢐVꢅꢁꢒꢁ+ꢅꢁWZRꢁ&+3CO2), 0.90 (d,
J = 6.6 Hz, 6 H, 21- and 21'-CH3), 0.92 (s, 6 H, 19- and 19'-CH3),
ꢊꢂꢒꢉꢁDQGꢁꢊꢂꢒꢎꢁꢐWZRꢁVꢅꢁꢒꢁ+ꢅꢁꢇꢍꢃꢁDQGꢁꢇꢍꢔꢃ&+3). IR (KBr pellets) Qmax
:
3307, 1737, 1647, 1544 cm-1. MS (ESI) m/z: 826 [M + Na]+, 744
[M–CH3COO-]+. HR MS (FAB): calcd. for [M + H]+ C52H86NO5:
804.65057; found 804.64244.
24-Phenylamino-5E-cholan-3D-ol (22): A solution of diborane–
GLPHWK\OVXO¿GHꢁ FRPSOH[ꢁ ꢐꢇꢊ0ꢅꢁ ꢇꢊꢊꢁ POꢅꢁ ꢊꢂꢒꢉꢑꢁ PPROHꢏꢁ ZDVꢁ DGGHGꢁ
GURSZLVHꢁWRꢁDꢁERLOLQJꢁVROXWLRQꢁRIꢁDPLGHꢁꢐꢒꢏꢁꢐꢇꢊꢊꢁPJꢅꢁꢊꢂꢆꢊꢎꢁPPROHꢏꢁ
XQGHUꢁ DUJRQꢁ LQꢁ DQK\GURXVꢁ WHWUDK\GURIXUDQꢁ ꢐꢎꢁ POꢏꢁ DQGꢁ WKHꢁ VROXWLRQꢁ
ZDVꢁ UHÀX[HGꢁ IRUꢁ ꢇꢂꢈꢁ Kꢂꢁ7KHꢁ VROXWLRQꢁ ZDVꢁ DFLGL¿HGꢁ E\ꢁ WKHꢁ DGGLWLRQꢁ
RIꢁ PHWKDQROLFꢁ K\GURJHQꢁ FKORULGHꢁ DQGꢁ WKHꢁ VROYHQWꢁ ZDVꢁ HYDSRUDWHGꢂꢁ
7KHꢁ UHVLGXHꢁ ZDVꢁ GLVVROYHGꢁ LQꢁ EHQ]HQHꢓPHWKDQROꢁ ꢐꢇꢄꢇꢏꢅꢁ WKHꢁ VROXWLRQꢁ
ZDVꢁ ZDVKHGꢁ ZLWKꢁ VRGLXPꢁ FDUERQDWHꢁ ꢐꢇꢊꢌꢏꢅꢁ EULQHꢁ DQGꢁ WKHꢁ VROYHQWꢁ
HYDSRUDWHGꢁWRꢁJLYHꢁ\HOORZꢁRLOꢁꢐꢍꢆꢁPJꢏꢁZKLFKꢁZDVꢁFKURPDWRJUDSKHGꢁ
RQꢁDꢁVLOLFDꢁJHOꢁFROXPQꢁWRꢁJLYHꢁꢐꢆꢆꢏꢁꢐꢈꢒꢁPJꢅꢁꢒꢎꢌꢁ\LHOGꢏꢂ
N,N'-Bis(3D-acetoxy-5E-cholan-24-oyl)-o-phenylenediamine (10):
Yield 82% of the crude compound (pure on TLC). M.p. 156–158°C
(AcOEt). 1H NMR (CDCl3): Gꢁ ꢁꢍꢂꢇꢆꢁꢐVꢅꢁꢆꢁ+ꢅꢁWZRꢁ1+ꢏꢅꢁꢋꢂꢉꢇ±ꢋꢂꢎꢈꢁDQGꢁ
ꢋꢂꢆꢉ±ꢋꢂꢇꢈꢁꢐWZRꢁPꢅꢁꢉꢁ+ꢅꢁ$U+ꢏꢅꢁꢉꢂꢋꢆꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎȕꢃꢁDQGꢁꢎꢔE-H), 2.03 (s,
ꢒꢁ+ꢅꢁWZRꢁ&+3CO2), 0.98 (d, J = 6.0 Hz, 6 H, 21- and 21'-CH3), 0.93
(s, 6 H, 19- and 19'-CH3), 0.66 (s, 6 H, 18- and 18'-CH3). IR (KBr
pellets) Qmax: 3291, 3131, 3064, 1737, 1667, 753 cm-1. MS (ESI) m/z:
931 [M + Na]+, 573, 552, 496. Anal. Calcd. for C58H88N2O6 u 1.5
H2O: C, 74.4; H, 9.8; N, 3.0. Found: C, 74.3; H, 10.1; N, 2.8%.
N,N'-Bis(3D-acetoxy-5E-cholan-24-oyl)-m-phenylenediamine
(12): Yield 64% of the crude compound (pure on TLC), oil. 1H NMR
(CDCl3): Gꢁ ꢁꢋꢂꢍꢉ±ꢋꢂꢇꢍꢁꢐPꢅꢁꢒꢁ+ꢅꢁWZRꢁ1+ꢁDQGꢁ$U+ꢏꢅꢁꢉꢂꢋꢆꢁꢐPꢅꢁꢆꢁ+ꢅꢁ
ꢎȕꢃꢁ DQGꢁ ꢎꢔEꢃ+ꢏꢅꢁ ꢆꢂꢊꢎꢁ ꢐVꢅꢁ ꢒꢁ +ꢅꢁ WZRꢁ &+3CO2), 0.96 (d, J = 6.0 Hz,
6 H, 21- and 21'-CH3), 0.92 (s, 6 H, 19- and 19'-CH3), 0.64 (s, 6
H, 18- and 18'-CH3). IR (KBr pellets) Qmax: 3317, 3152, 3086, 1736,
1667, 1609, 732 cm-1. MS (ESI) m/z: 931 [M + Na]+, 573, 552, 496.
HR MS (FAB): calcd. for [M + H]+ C58H89N2O6: 909.67206; found
909.67454.
1HNMR(CDCl3):G=7.16(t,J=7.4Hz,2H,ArH),6.67(t,J=7.3Hz,
1 H, ArH), 6.59 (d, J = 7.7 Hz, 2 H, ArH), 3.66 (m, 1 H, 3E-H), 3.05
(m, 2 H, 24-CH2), 0.92 (d, J = 6.8 Hz, 3 H, 21-CH3), 0.91 (s, 3 H, 19-
CH3), 0.64 (s, 3 H, 18-CH3). IR (KBr pellets) Qmax: 3315, 3083, 3050,
3019, 2932, 2862, 1603, 1506, 1465, 1447, 1373, 1365, 1321, 1260,
1176, 1069, 1040, 746, 691 cm-1. MS (ESI) m/z: 439 [M + H]+. Anal.
Calcd. for C30H47NOꢀuꢀ0.5 H2O: C, 80.7; H, 10.8; N, 3.1. Found: C,
80.3; H, 10.6; N, 3.1%.
)LQDQFLDOꢁ VXSSRUWꢁ E\ꢁ WKHꢁ 0LQLVWU\ꢁ RIꢁ 6FLHQFHꢁ DQGꢁ +LJKHUꢁ
(GXFDWLRQꢁ ꢐSURMHFWꢁ 1Rꢂꢁ ꢎꢁ 7ꢊꢑ$ꢁ ꢊꢍꢈꢁ ꢆꢍꢏꢁ LVꢁ JUDWHIXOO\ꢁ
DFNQRZOHGJHGꢂ
N,N'-Bis(3D-acetoxy-5E-cholan-24-oyl)-p-phenylenediamine (14):
Yield 78% of the crude compound (pure on TLC). M.p. 135–136°C
1
(AcOEt). H NMR (CDCl3): G = 7.46 (s, 4 H, ArH), 7.16 (s, 2 H,
WZRꢁ1+ꢏꢅꢁꢉꢂꢋꢆꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎȕꢃꢁDQGꢁꢎꢔEꢃ+ꢏꢅꢁꢆꢂꢊꢎꢁꢐVꢅꢁꢒꢁ+ꢅꢁWZRꢁ&+3CO2),
0.96 (d, J = 6.0 Hz, 6 H, 21- and 21'-CH3), 0.92 (s, 6 H, 19- and 19'-
CH3), 0.65 (s, 6 H, 18- and 18'-CH3). IR (KBr pellets) Qmax: 3355,
3161, 3062, 1736, 1718, 1689, 1667, 1609, 838 cm-1. MS (ESI) m/z:
931 [M + Na]+, 573, 552, 496. HR MS (FAB): calcd. for [M + H]+
C58H89N2O6: 909.67206; found 909.67475.
Received 23 February 2008; accepted 27 April 2008
Paper 08/5231
doi: 10.3184/030823408X318325
References
N,N'-Bis(3D-acetoxy-5E-cholan-24-oyl)-ethylenediamine
(16):
<LHOGꢁ ꢑꢆꢌꢁ RIꢁ WKHꢁ FUXGHꢁ FRPSRXQGꢅꢁ FKURPDWRJUDSK\ꢁ RQꢁ VLOLFDꢁ JHOꢁ
FROXPQꢅꢁ ꢋꢒꢌꢁ \LHOGꢂꢁ 0ꢂSꢂꢁ ꢇꢍꢈ±ꢇꢍꢒƒ&ꢁ ꢐ$F2(Wꢏꢂꢁ 1H NMR (CDCl3):
Gꢁ ꢁꢒꢂꢇꢒꢁꢐVꢅꢁꢆꢁ+ꢅꢁWZRꢁ1+ꢏꢅꢁꢉꢂꢋꢇꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎȕꢃꢁDQGꢁꢎꢔE-H), 3.38 (s,
4 H, NCH2CH21ꢏꢅꢁꢆꢂꢊꢎꢁꢐVꢅꢁꢒꢁ+ꢅꢁWZRꢁ&+3CO2), 0.92 (s, 6 H, 19- and
19'-CH3), 0.64 (s, 6 H, 18- and 18'-CH3). IR (KBr pellets) Qmax: 3323,
3275, 1739, 1652, 1640, 1550 cm-1. MS (FAB) m/z: 883 [M + Na]+,
861 [M + H]+, 801 [M–CH3COO-]+, 741 [M–2CH3COOH]+. HR
MS: calcd. for [M + H]+ C54H89N2O6: 861.67206; found 861.67422.
N,N'-Bis(3D-acetoxy-5E-cholan-24-oyl)-piperazine (18): Yield
91% of the crude compound (pure on TLC). M.p. 203–205°C
(AcOEt). 1H NMR (CDCl3): Gꢁ ꢁꢉꢂꢋꢆꢁꢐPꢅꢁꢆꢁ+ꢅꢁꢎȕꢃꢁDQGꢁꢎꢔE-H), 3.70–
ꢎꢂꢉꢒꢁꢐWZRꢁEVꢅꢁꢍꢁ+ꢅꢁ1ꢐ&H2)2(CH2)2N), 2.44–2.18 (m, 4 H, 23- and 23'-
CH3ꢏꢅꢁꢆꢂꢊꢎꢁꢐVꢅꢁꢒꢁ+ꢅꢁWZRꢁ&+3CO2), 0.96 (d, J = 5.8 Hz, 6 H, 21- and
21'-CH3), 0.92 (s, 6 H, 19- and 19'-CH3), 0.64 (s, 6 H, 18- and 18'-
CH3). IR (KBr pellets) Qmax: 3446, 1734, 1650 cm-1. MS (ESI) m/z:
909 [M + Na]+, 887 [M + H]+, 826 [M-CH3COOH]+. Anal. Calcd. for
C56H90N2O6ꢀuꢀ1.5 H2O: C, 73.6; H, 10.25; N, 3.1. Found: C, 73.3; H,
10.6; N, 2.7%.
1
A.M. Bellini, M.P. Quaglio, G. Cavazzini and R. Ceccherini. Farmaco
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2
A. Finni, G. Fazio, A. Roda, A.M. Bellini, E. Mencini and M. Guarneri.
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ꢁ ꢎꢁ %ꢂ*ꢂꢁ +D]UDꢅꢁ 9ꢂ6ꢂꢁ 3RUHꢅꢁ 6ꢂ.ꢂꢁ 'H\ꢅꢁ 6ꢂꢁ 'DWWDꢅꢁ 0ꢂ3ꢂꢁ 'DURNDUꢅꢁ 'ꢂꢁ 6DLNLDꢅꢁ
S.P.S. Khanujab and A.P. Thakura. Bioorg. Med. Chem. Lett., 2004, 14,
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4
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6
7
A. Kreutzberger, J.E. Herz, R.E. Mantecón and A. Murillo. Arch. Pharm.,
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J. Tamminen, E. Kolehmainen, J. Linnanto, P. Vainiotalo and
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M. Haapala, E. Kolehmainen, J. Tamminen, R. Kauppinen, J. Linnanto,
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E. Virtanen, J. Koivukorpi, J. Tamminen, P. Mänttäri and E. Kolehmainen.
J. Organomet. Chem., 2003, 668, 43-50.
ꢁ ꢍꢁ 6ꢂꢁ 0XNKRSDGK\D\ꢅꢁ 8ꢂꢁ 0DLWUDꢅꢁ ,UDꢅꢁ *ꢂꢁ .ULVKQDPRRUWK\ꢅꢁ -ꢂꢁ 6FKPLGWꢁ DQGꢁ
Y. Talmon. J. Am. Chem. Soc., 2004, 126, 15905.
H.M. Willemen, T. Vermonden, A.T.M. Marcelis and E.J.R.Sudhölter.
Langmuir, 2002, 18, 7102.
9
10 H.M. Willemen, T. Vermonden, A.T.M. Marcelis and E.J.R.Sudhölter.
Preparation of amines (19–21); general procedure
Eur. J. Org. Chem., 2001, 12, 2329.
/LWKLXPꢁ DOXPLQRK\GULGHꢁ ꢐꢇꢊꢊꢁ PJꢅꢁ ꢆꢂꢒꢁ PPROHꢏꢁ ZDVꢁ DGGHGꢁ WRꢁ Dꢁ
VROXWLRQꢁRIꢁDQꢁDPLGHꢁꢐꢊꢂꢎꢁPPROHꢏꢁLQꢁDQK\GURXVꢁWHWUDK\GURIXUDQꢁDQGꢁ
WKHꢁPL[WXUHꢁZDVꢁUHÀX[HGꢁIRUꢁꢆꢉꢁKꢂꢁ7KHꢁH[FHVVꢁUHGXFLQJꢁDJHQWꢁZDVꢁ
GHFRPSRVHGꢁ E\ꢁ FDUHIXOꢁ DGGLWLRQꢁ RIꢁ HWK\Oꢁ DFHWDWHꢁ DQGꢁ Dꢁ VDWXUDWHGꢁ
VROXWLRQꢁ RIꢁ PDJQHVLXPꢁ VXOIDWHꢂꢁ 7KHꢁ VROXWLRQꢁ ZDVꢁ GULHGꢁ RYHUꢁ
DQK\GURXVꢁPDJQHVLXPꢁVXOIDWHꢁDQGꢁWKHꢁVROYHQWꢁHYDSRUDWHGꢁWRꢁJLYHꢁDꢁ
crude product.
11 A. Valkonen, M. Lahtinen, E. Virtanen, S. Kaikkonen and E. Kolehmainen.
Biosens. Bioelectr., 2004, 20, 1233.
12 N.M. Sangeetha and U. Maitra. Chem. Soc. Rev., 2005, 34, 821.
ꢁꢇꢎꢁ -ꢂꢁ0F.HQQDꢅꢁ-ꢂ0ꢂꢁ0F.HQQDꢁDQGꢁ'ꢂ:ꢂꢁ7KRUQWKZDLWHꢂꢁJ. Chem. Soc. Chem.
Commun., 1977, 809.
14 Y. Li and J.R. Dias. Chem. Rev., 1997, 97, 283.
24-Amino-5E-cholan-3D-ol (19):1 Yield 69% of the crude amine,
FKURPDWRJUDSK\ꢁRQꢁDꢁVLOLFDꢁJHOꢁFROXPQꢁJDYHꢁWKHꢁDPLQHꢁLQꢁꢈꢊꢌꢁ\LHOGꢂꢁ
M.p. 145–148°C (EtOH), lit. [1] m.p. 148–150°C (MeOH). 1H NMR
(CDCl3): G = 3.57 (m, 1 H, 3E-H), 2.63 (m, 2 H, 24-CH2), 0.91 (d,
J = 6.6 Hz, 3 H, 21-CH3), 0.91 (s, 3 H, 19-CH3), 0.64 (s, 3 H, 18-
CH3). IR (KBr pellets) Qmax: 3362, 1561 cm-1. MS (ESI) m/z: 362
[M + H]+, 343 [M-H2O]+, 242, 133.
15 P. Wallimann, T. Marti, A. Fürer and F. Diederich. Chem. Rev., 1997, 97,
1567.
16 E. Virtanen and E. Kolehmainen. Eur. J. Org. Chem., 2004, 3385.
17 J. Tamminen and E. Kolehmainen. Molecules, 2001, 6, 21.
18 J. Tamminen, E. Kolehmainen, M. Haapala and J. Linnanto. Synthesis,
2000, 1464.
19 M. Di Filippo, I. Izzo, L. Savignano, P. Tecillab and F. De Riccardisa.
Tetrahedron, 2003, 59, 1711.
24-n-Butylamino-5E-cholan-3D-ol (20): Yield 98% of the crude
DPLQHꢅꢁ SXUL¿HGꢁ DVꢁ WKHꢁ K\GURFKORULGHꢅꢁ ꢒꢊꢌꢁ \LHOGꢂꢁ 0ꢂSꢂꢁ ꢍꢑ±ꢑꢇƒ&ꢁ
20 C. Goto, M. Yamamura, A. Satake and Y. Kobuke. J. Am. Chem. Soc.,
1
2001, 123, 12152.
(EtOH). H NMR (CDCl3): G = 3.61 (m, 1 H, 3E-H), 2.51–2.62 (m,
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4H, CH2NHCH2), 0.94 (d, J = 6.6 Hz, 3 H, 21-CH3), 0.91 (s, 3 H,
19-CH3), 0.63 (s, 3 H, 18-CH3). IR (KBr pellets) Qmax: 3405, 1645
cm-1. MS (ESI) m/z: 419[M + 2H], 418 [M + H]+. Anal. Calcd. for
C28H51NOꢀuꢀ1.5 H2O: C, 75.6; H, 12.2; N, 3.1. Found: C, 75.9; H,
12.4; N, 3.0%.
24 D.B. Salunke, B.G. Hazra, V.S. Pore, M.K. Bhat, P.B. Nahar and
24-Benzylamino-5E-cholan-3D-ol (21):1 Yield 98% of the crude
compound (pure on TLC). M.p. 74–75°C (EtOH), lit.1 m.p. 193–
195°C. 1H NMR (CDCl3): G = 7.41–7.23 (m, 5 H, ArH), 3.77 (s, 2H,
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JOURNAL OF CHEMICAL RESEARCH 2008 265
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