Amino steroids as antimalarial agents

Article abstract of DOI:10.1007/s00044-007-9068-x

Using easily accessible deoxycholic acid as the starting material, amino compounds 8a-e and 9a-c were prepared and screened against P. falciparum in vitro. Amino steroid 8d was the most active of the series with a minimum inhibiting concentration (MIC) of

Full text of DOI:10.1007/s00044-007-9068-x

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2008) 17:326–334
DOI 10.1007/s00044-007-9068-x
ORIGINAL RESEARCH
Amino steroids as antimalarial agents
Upasana Sharma Æ Kumkum Srivastava Æ
Sunil K. Puri Æ Chandan Singh
Received: 2 November 2007 / Accepted: 15 November 2007 / Published online: 29 December 2007
¨
Ó Birkhauser Boston 2007
Abstract Using easily accessible deoxycholic acid as the starting material, amino
compounds 8a-e and 9a-c were prepared and screened against P. falciparum in
vitro. Amino steroid 8d was the most active of the series with a minimum inhibiting
concentration (MIC) of 0.5 lg/mL.
Keywords Malaria Á Antimalarials Á Sarachine Á Deoxycholic acid Á
Amino steroids
Introduction
Malaria continues to be a major parasitic disease in many parts of the world.
Each year 300–500 million people suffer from malaria and about 2–2.5 million
die from the disease (WHO, 1999; Wiesner et al., 2003). The disease is caused
by Plasmodium sp., of which P. falciparum is the deadliest and is responsible for
over 85% cases and much of the mortality due to malaria. Commonly used
antimalarials such as chloroquine have become ineffective because of the
development of resistance by the parasite against these drugs (Bloland, 2001;
Wellems and Plowe, 2002). Thus there is an urgent need to develop new classes
of antimalarials.
U. Sharma Á C. Singh (&)
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow 226001,
India
e-mail: chandancdri@yahoo.com
K. Srivastava Á S. K. Puri
Division of Parasitology, Central Drug Research Institute, Lucknow 226001, India

Med Chem Res (2008) 17:326–334
327
Recently a new amino steroid, sarachine 1, isolated from the leaves of Saraca
punctata, has been reported to exhibit significant antimalarial activity (IC50 0.01 lg/
mL) against P. falciparum (Morreti et al., 1998).
N
H
H2N
1
Building on this lead and using deoxycholic acid as the starting material, we have
synthesized several new amino steroids (prototypes 8 and 9), some of which have
shown significant antimalarial activity against P. falciparum in vitro.
Chemistry
Oxidative decarboxylation of diacetyl deoxycholic acid 2 with Pb(OAc)4/Cu(OAc)2
furnished olefin 3 at 37% yield (Vaidya et al., 1968). Olefin 3 on treatment with m-
Chloroperbenzoic acid (m-CPBA) furnished epoxide 4 at 64% yield. Reaction of 4
with periodic acid furnished aldehyde 5 at 68% yield. Reductive amination of 5 with
benzyl amine 7a, isopropyl amine 7b, n-butyl amine 7c furnished compounds 8a-c
at 50–73% yields (Abdel-Magid et al., 1996). A similar reaction of aldehyde 5 with
4-aminoquinolines 7d,e furnished steroid-4-aminoquinoline hybrid compounds 8d
and 8e at 18–51% yields. (Scheme 1). Reaction of diacetyl deoxycholic acid 2 with
Pb(OAc)4/I2 furnished iodo compound 6 at 29% yield, which on reaction with
amines 7a-c furnished amino steroids 9a-c at 41–57% yields (Oishi et al., 2004)
(Scheme 2, Table 1, Fig. 1).
Antimalarial activity
Amino compounds 8a-e and 9a-c and the 4-aminoquinolines 7d and 7e were
evaluated against a chloroquine-sensitive strain of P. falciparum in vitro using
minor modifications to the technique of Rieckmann and co-workers (Reickmann
et al., 1978). Results are summarized in Table 2.
In vitro antimalarial efficacy
All the amino compounds 8a-e and 9a-c were evaluated in vitro against a chloroquine-
sensitive strain of P. falciparum (NF-54). The asynchronous parasites obtained from
cultures of P. falciparum were synchronized after 5% sorbitol treatment so as to
contain only ring-stage parasites (Lambros and Vanderverg, 1979). Parasite suspen-
sion in medium RPMI 1640 at 1–2% parasitaemia and 3% hematocrit was dispensed

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Med Chem Res (2008) 17:326–334
O
OAc
OAc
OAc
OAc
CHO
CO2H
(b)
AcO
(a)
AcO
(c)
AcO
AcO
3
4
2
5
OAc
NHR
(d)
5
AcO
8
Scheme 1 Reagents and conditions: (a) Pb(OAc)4, Cu(OAc)2, C5H5N (Cat.), C6H6, reflux, 10 h. (b) m-
CPBA, NaHCO3, CH2Cl2, 0°C-rt, 4.5 h. (c) HIO4.2H2O, THF, 0°C-rt, 4–5 h. (d) RNH2 (7a-e),
NaBH(OAc)3, AcOH, CH2Cl2, rt, 3–10 h
OAc
OAc
OAc
NHR
CO2H
AcO
I
(a)
(b)
AcO
AcO
9
6
2
Scheme 2 Reagents and conditions: (a) Pb(OAc)4, I2, CCl4, reflux, 30 min. (b) RNH2 (7a-c), K2CO3,
CH3CN, reflux, 0.5–1 h
Table 1 Yields of compounds 8a-e and 9a-c
general structure
Comp.
R
% yield
50%
CH2
8a
8b
8c
73%
53%
CH(CH3)2
CH2CH2CH2CH3
NHCH2CH2CH2
OAc
NHR
51%
8d
AcO
N
Cl
NHCH2CH2CH2CH2
18%
41%
8e
9a
N
Cl
OAc
CH2
NHR
57%
44%
CH(CH3)2
CH2CH2CH2CH3
9b
9c
AcO

Med Chem Res (2008) 17:326–334
329
NH2
HN
N
NH2
Cl
HN
N
CH2NH2
NH2
7b
NH2
Cl
7a
7c
7d
7e
Fig. 1 Structures of amines 7a-e
into the wells of sterile 96-well plates. Test compounds were serially diluted in
duplicate wells to obtain the final test concentration. Thin blood smears from each well
prepared at the end of the incubation period were microscopically examined and the
concentration that inhibited the maturation of rings into schizonts stage was recorded
as the MIC. The assay was performed at concentrations of 50, 10, 2, 1, and 0.5 lg/mL
and a few of them showed moderate activity.
Results and discussion
As seen from Table 2, the amino steroids 8a-e were more active than 9a-c.
Compound 8d with an MIC of 0.5 lg/mL was the most active compound of the
series and was several times more active than the corresponding 4-aminoquinoline
7d (MIC of 10 lg/mL). Compound 8e with an MIC of 1 lg/mL was the next most
active compound of the series and was twice as active as the corresponding 4-
aminoquinoline 7e (MIC of 2 lg/mL). Among the nonchloroquinoline amino
derivatives 8a-c, only 8a shows significant activity (MIC of 2 lg/mL). The fact that
quinoline-containing steroids 8d,e are more active than other amino steroids 8a-c
suggests that the quinoline moiety might be contributing towards biological activity.
All of the amino steroids 9a-c, which have one carbon more in their side chain as
compared with 8a-e, exhibited very poor activity. Thus amino steroids having side
chain similar to that of sarachine 1 show significant activity and increase in side
chain length even by one carbon has a deleterious effect on antimalarial activity.
Conclusion
Using sarachine 1, a naturally occurring amino steroid, as a lead and easily
accessible deoxycholic acid as the starting material, we prepared a new series of
amino steroids, some of which have shown significant antimalarial activity against
P. falciparum in vitro. Compound 8d with an MIC of 0.5 lg/mL was the most
active compound of the series.
Experimental section
All glass apparatus were properly cleaned and oven dried prior to use. Yields refer
to purified products and are not optimized. Infrared spectra (cm-1) were recorded on
a Perkin-Elmer RXI Fourier-transform (FT)-IR spectrophotometer. 1H nuclear
magnetic resonance (NMR) spectra were recorded on a Bruker Supercon Magnet
DPX-200/DRX-300 MHz using CDCl3 as solvent and tetramethylsilane (d 0.00

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Med Chem Res (2008) 17:326–334
Table 2 In vitro antimalarial activity of compounds 8a-e, 9a-c, and 7d,e against a chloroquine-sensitive
strain of P. falciparum (NF-54)
a,bMIC
( g/mL)
general structure
Comp.
R
2.0
CH2
8a
8b
8c
10.0
CH(CH3)2
>10.0
CH2CH2CH2CH3
NHCH2CH2CH2
OAc
NHR
0.5
8d
AcO
N
Cl
NHCH2CH2CH2CH2
1.0
8e
9a
N
Cl
50.0
OAc
CH2
NHR
>50.0
>50.0
CH(CH3)2
9b
9c
CH2CH2CH2CH3
AcO
NHCH2CH2CH2NH2
10.0
7d
-
N
Cl
NHCH2CH2CH2CH2NH2
2.0
7e
-
-
N
Cl
Chloroquine
-
0.04
a
MIC is the minimum concentration inhibiting development of ring-stage parasites into the schizonts
b
50.00 lg/mL is the highest concentration used in this study
ppm) as an internal standard. Fast atom bombardment mass spectra (FAB-MS) were
obtained on a JEOL SX-102 spectrometer using glycerol or m-nitrobenzyl alcohol
as the matrix. Reactions were monitored on silica gel thin-layer chromatography
(TLC) plates. Column chromatography was performed over silica gel (60–120
Mesh) procured from Qualigens (India) using freshly distilled solvents. All the
chemicals and reagents were obtained from Aldrich (USA), Lancaster (England) or
Spectrochem (India) and were used without purification.
4-(3,12-Diacetoxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-
17-yl)-pentanoic acid (2)
Deoxycholic acid (5 g, 12.7 mmol) and acetic anhydride (6.5 g, 5 eq., 63.8 mmol) in
dry dichloromethane (75 mL) were reacted in the presence of triethysilyl triflurom-
ethanesulfonate(0.2 mL) at 0°C for 1 h. The reaction mixture was quenched with water

Med Chem Res (2008) 17:326–334
331
(50 mL) and extracted with dichloromethane (3 9 50 mL), dried over anhydrous
Na2SO4, and concentrated, and the crude product was purified by column chroma-
tography over silica gel to furnish compound 2 (5.5 g, 90.59% yield). IR (KBr, cm-1
)
3449, 1727; 1H NMR (200 MHz, CDCl3) d 0.73 (s, 3H), 0.81 (d, 3H, J = 5.9 Hz), 0.91
(s, 3H), 1.21–1.85 (m, 24H), 2.03 (s, 3H), 2.10 (s, 3H), 2.20–2.41 (m, 2H), 4.61–4.80
+
(m, 1H), 5.08 (bs, 1H); FAB-MS (m/z): 477 [M + H]
.
Acetic acid 3-acetoxy-10,13-dimethyl-17-(1-methyl-allyl)-hexadecahydro-
cyclopenta [a]phenanthren-12-yl ester (3)
To a refluxing mixture of diacetyl deoxycholic acid 2 (4.5 g, 9.45 mmol), Cu(OAc)2
(0.5 g, 0.25 eq.) and pyridine (0.3 g, 0.25 eq.) in benzene (50 mL) was added Pb(OAc)4
(8.86 g, 2 eq.) over 3 h and the reaction mixture was stirred at the same temperature for
6 h. It was cooled to room temperature and filtered through celite, the residue was
washed with benzene (75 mL), the combined organic layer was dried over anhydrous
Na2SO4, concentrated, and the crude product was purified by column chromatography
over silica gel to furnish compound 3 (1.5 g, 37% yield). FT-IR (KBr, cm-1) 1726; 1H
NMR (200 MHz, CDCl3) d 0.75 (s, 3H), 0.91 (s, 3H), 0.92 (d, 3H, J = 6.3 Hz), 1.08–
1.85 (m, 22H), 2.03 (s, 3H), 2.11 (s, 3H), 4.61–4.78 (m, 1H), 4.79–4.94 (m, 1H), 5.08
(bs, 1H), 5.52–5.75 (m, 1H); FAB-MS (m/z): 431 [M + H]+.
Acetic acid 3-acetoxy-10,13-dimethyl-17-(1-oxiranyl-ethyl)-hexadecahydro-
cyclo-penta[a]phenanthren-12-yl ester (4)
Olefin 3 (1.5 g, 3.5 mmol) and NaHCO3 (1.5 g, 5 eq.) in dry dichloromethane (50
mL) were stirred at 0°C and m-CPBA (1.5 g, 2.5 eq.) was added over 10 min. The
resulting mixture was stirred for an additional 4 h at room temperature. The mixture
was quenched with saturated Sodium bicarbonate (NaHCO3) solution (40 mL),
extracted with Dichloromethane (DCM) (3 9 25 mL), the solvent was removed
under reduced pressure, and the crude product was purified by column chromatog-
raphy over silica gel to furnish compound 4 (1 g, 64% yield). FT-IR (KBr, cm-1
)
1724; 1H NMR (200 MHz, CDCl3) d 0.73 (s, 3H), 0.85 (d, 3H, J = 6.8 Hz), 0.99 (s,
3H), 0.96–1.82 (m, 22H), 2.04 (s, 3H), 2.12 (s, 3H), 2.59–2.79 (m, 2H), 4.58–4.79
(m, 1H), 5.01 (bs, 1H); FAB-MS (m/z): 447 [M + H]+.
Acetic acid 3-acetoxy-10,13-dimethyl-17-(1-methyl-2-oxo-ethyl)-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (5)
To a magnetically stirred, ice-cooled solution of 4 (1 g, 2.24 mmol) in
Tetrahydrofuran (THF) (20 mL) was added a solution of periodic acid (0.5 g, 1
eq., 2.24 mmol) in THF (5 mL) dropwise over 5 min. The resulting mixture was
stirred for an additional 4 h at room temperature. The reaction mixture was
neutralized with saturated NaHCO3 solution (20 mL), water (50 mL) was added,

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Med Chem Res (2008) 17:326–334
extracted with ether (4 9 25 mL), solvent was distilled off, and the crude product
was purified by column chromatography over silica gel to furnish compound 5 (660
mg, 68% yield). IR (KBr, cm-1) 1727; 1H NMR (200 MHz, CDCl3) d 0.78 (s, 3H),
0.88 (s, 3H), 1.01 (d, 3H, J = 6.8 Hz), 1.26–1.85 (m, 21H), 2.04 (s, 3H), 2.12 (s,
3H), 2.18–2.31 (m, 1H), 4.07–4.09 (m, 1H), 5.06 (bs, 1H), 9.55 (d, 1H, J = 2.9 Hz),
FAB-MS (m/z): 433 [M + H]+.
Acetic acid 3-acetoxy-17-(3-iodo-1-methyl-propyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (6)
A solution of diacetyl deoxycholic acid 2 (0.5 g, 1.1 mmol), Pb(OAc)4 (0.6 g, 1.2
eq.) and iodine (0.66 g, 2.5 eq.) in CCl4 (15 mL) was irradiated with a 500-W
tungsten-halogen lamp for 30 min. The reaction mixture was quenched by adding
saturated Na2S2O3 solution and extracted with dichloromethane (3 9 25 mL), dried
over Na2SO4, concentrated, and the crude product was purified by column
chromatography over silica gel to furnish compound 6 (0.2 g, 29% yield). IR (KBr,
cm-1) 1727; 1H NMR (200 MHz, CDCl3) d 0.75 (s, 3H), 0.81 (d, 3H, J = 5.8 Hz),
0.91 (s, 3H), 1.01–1.95 (m, 24H), 2.03 (s, 3H), 2.09 (s, 3H), 3.01–3.13 (m, 1H),
3.24–3.33 (m, 1H), 4.65–4.76 (m, 1H), 5.08 (bs, 1H); FAB-MS (m/z): 559 [M + H]+,
497 [M + H - AcOH]+, 439 [M + H – 2 AcOH]+.
General procedure for the preparation of compounds 8a–e (preparation of 8d as
representative)
Aldehyde 5 (300 mg, 0.7 mmol), 4-aminoquinoline 7d (330 mg, 1.4 mmol), and glacial
acetic acid (0.1 mL) in CH2Cl2 (50 mL) were stirred at room temperature for 30 min.
NaBH(OAc)3 (330 mg, 1.03 mmol) was added portionwise for over 3 h and the
reaction mixture was stirred for another 6 h. The reaction mixture was quenched with
water (50 mL) and extracted with CH2Cl2 (3 9 30 mL), solvent was removed under
reduced pressure, and the crude product was purified by column chromatography over
silica gel to furnish compound 8d (230 mg, 51% yield). mp 113–115°C. IR (KBr, cm-
1) 3399; 1H NMR (200 MHz, CDCl3) d 0.72 (s, 3H), 0.91 (s, 3H), 0.99 (d, 3H, J = 6.0
Hz), 1.08–1.84 (m, 25H), 2.03 (s, 3H), 2.09 (s, 3H), 2.48 (t, 1H, J = 8.0 Hz), 2.81 (t,
1H, J = 8.0 Hz), 3.01 (bs, 2H), 3.46 (bs, 2H), 4.70 (m, 1H), 5.07 (bs, 1H), 5.96 (bs, 1H,
NH), 6.27 (d, 1H, J = 5.8 Hz), 7.34 (dd, 1H, J = 8.8 and 1.4 Hz), 7.89 (d, 1H, J = 1.4
Hz), 8.11 (d, 1H, J = 8.8 Hz), 8.31 (d, 1H, J = 5.8 Hz); FAB-MS (m/z): 652 [M + H]+,
592 [M + H - AcOH]+, 532 [M + H – 2 AcOH]+.
Compounds 8a-c and 8e were prepared by the above procedure.
Acetic acid 12-acetoxy-10,13-dimethyl-17-(1-methyl-2-phenylamino-ethyl)-
hexadecahydro-cyclopenta[a]phenanthren-3-yl ester (8a)
1
IR (KBr, cm-1) 3433; H NMR (300 MHz, CDCl3) d: 0.73 (s, 3H), 0.89 (d, 3H,
J = 5.4 Hz), 0.90 (s, 3H), 1.01–1.88 (m, 23H), 2.03 (s, 3H), 2.09 (s, 3H), 2.29 (dd,

Med Chem Res (2008) 17:326–334
333
1H, J = 11.7 and 8.4 Hz), 2.65 (dd, 1H, J = 11.7 and 3.0 Hz), 3.72 (d, 1H,
J = 13.2 Hz), 3.81 (d, 1H, J = 13.2 Hz), 4.68 (m, 1H), 5.08 (bs, 1H), 7.24–7.33 (m,
5H); FAB-MS: (m/z): 524 [M + H]+, 464 [M + H - AcOH]+, 404 [M + H – 2
AcOH]+.
Acetic acid 12-acetoxy-17-(2-isopropylamino-1-methyl-ethyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-3-yl ester (8b)
1
IR (KBr, cm-1) 3342; H NMR (300 MHz, CDCl3) d: 0.75 (s, 3H), 0.91 (s, 3H),
0.96 (d, 3H, J = 5.4 Hz), 1.18 (d, 6H, J = 6.3 Hz), 1.20–1.88 (m, 23H), 2.03 (s,
3H), 2.10 (s, 3H), 2.33 (dd, 1H, J = 12.0 and 9.0 Hz), 2.76 (bd, 1H, J = 12.0 Hz),
2.97 (septate, 1H, J = 6.3 Hz), 4.70 (m, 1H), 5.08 (bs, 1H), FAB-MS (m/z): 476 [M
+ H]+, 416 [M + H - AcOH]+, 356 [M + H – 2 AcOH]+.
Acetic acid 3-acetoxy-17-(2-butylamino-1-methyl-ethyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (8c)
IR (KBr, cm-1) 3342; 1H NMR (300 MHz, CDCl3) d: 0.79 (s, 3H), 0.91 (s, 3H), 0.99
(d, 3H, J = 7.2 Hz), 1.06–1.83 (m, 30H), 2.03 (s, 3H), 2.10 (s, 3H), 2.37 (t, 2H,
J = 10.0 Hz), 2.80 (bd, 1H, J = 11.4 Hz), 3.02–3.09 (m, 1H), 4.70 (m, 1H), 5.07 (bs,
1H); FAB-MS (m/z): 490 [M + H]+, 430 [M + H - AcOH]+, 370 [M + H – 2 AcOH]+.
Acetic acid 3-acetoxy-17-{2-[4-(7-chloro-quinolin-4-ylamino)-butylamino]-1-
methyl-ethyl}-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-12-yl
ester (8e)
IR (KBr, cm-1) 3279; 1H NMR (200 MHz, CDCl3) d: 0.78 (s, 3H), 0.90 (s, 3H), 0.99
(d, 3H, J = 6.0 Hz), 1.09–1.90 (m, 27H), 2.03 (s, 3H), 2.11 (s, 3H), 2.65–2.81 (m, 1H),
2.92–3.80 (m, 3H), 3.50 (bs, 2H), 4.67 (m, 1H), 5.01 (bs, 1H), 5.97 (bs, 1H, NH), 6.52
(d, 1H, J = 5.6 Hz), 7.10 (d, 1H, J = 8.4 Hz), 7.45 (bs, 1H), 8.12–8.17 (m, 2H); FAB-
MS (m/z): 666 [M + H]+, 606 [M + H - AcOH]+, 546 [M + H – 2 AcOH]+.
General procedure for the preparation of compounds 9a–c (preparation of 9a as
representative).
Compound 6 (50 mg, 0.09 mmol), benzyl amine 7a (24 mg, 2.5 eq., 0.22 mmol) and
K2CO3 (5.0 mg, 0.035 mmol) in CH3CN (20 mL) were refluxed for 2 h. The
reaction mixture was cooled to room temperature and solvent was removed under
reduced pressure. Residue was taken in CH2Cl2 (50 mL) and washed with water
(2 9 25 mL), dried and concentrated, and the crude product was purified by column
chromatography over silica gel to furnish compound 9a (20 mg, 41% yield). IR
(KBr, cm-1) 3471; 1H NMR (300 MHz, CDCl3) d 0.71 (s, 3H), 0.80 (d, 3H, J = 6.0

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Med Chem Res (2008) 17:326–334
Hz), 0.90 (s, 3H), 1.00–1.87 (m, 26H), 2.03 (s, 3H), 2.09 (s, 3H), 2.55–2.57 (m, 1H),
3.75 (d, 1H, J = 13.5 Hz), 3.76 (d, 1H, J = 13.5 Hz), 4.70–4.71 (m, 1H), 5.08 (bs,
1H), 7.24–7.41 (m, 5H); FAB-MS: (m/z) 538 [M + H]+, 478 [M + H - AcOH]+, 418
[M + H – 2 AcOH]+.
Compounds 9b and 9c were prepared by the above procedure.
Acetic acid 3-acetoxy-17-(3-benzylamino-1-methyl-propyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (9b)
1
IR (KBr, cm-1) 3420; H NMR (300 MHz, CDCl3) d 0.73 (s, 3H), 0.84 (d, 3H,
J = 6.0 Hz), 0.91 (s, 3H), 1.02–1.87 (m, 31H ), 2.03 (s, 3H), 2.11 (s, 3H), 2.74–2.88
(m, 1H), 2.91–3.11 (m, 1H), 3.32–3.43 (m, 1H), 4.69 (m, 1H), 5.07 (bs, 1H), FAB-
MS (m/z): 490 [M + H]+, 430 [M + H - AcOH]+, 370 [M + H – 2 AcOH]+.
Acetic acid 3-acetoxy-17-(3-butylamino-1-methyl-propyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (9c)
1
IR (KBr, cm-1) 3358; H NMR (300 MHz, CDCl3) d: 0.73 (s, 3H), 0.83 (d, 3H,
J = 5.9 Hz), 0.91 (s, 3H), 1.08–1.90 (m, 32H), 2.03 (s, 3H), 2.11 (s, 3H), 2.81–3.32
(m, 4H), 4.69 (m, 1H), 5.07 (bs, 1H); FAB-MS (m/z): 504 [M + H]+.
Acknowledgment Upasana Sharma is grateful to the Council of Scientific and Industrial Research
(CSIR), New Delhi for the award of a Senior Research Fellowship.
References
Abdel-Magid AF, Carson KG, Harris BD, Maryanoff CA, Shah RD (1996) Reductive amination of
aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive
amination procedures. J Org Chem 61:3849–3862
Bloland BP (2001) Drug Resistance in Malaria, WHO, Geneva. Report no. WHO/CDS/CSR/DRS/2001.4
Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum erythrocytic stages in
culture. J Parasitol 65:418–420
Moretti C, Sauvain M, Lavaud C, Massiot G, Bravo JA, Munoz V (1998) A novel antiprotozoal
aminosteroid from Saracha punctata. J Nat Prod 61:1390–1393
Oishi T, Tsuchikawa H, Murata M, Yoshida M, Morisawa M (2004) Synthesis and identification of an
endogenous sperm activating and attracting factor isolated from eggs of the ascidian Ciona
intestinalis, an example of nanomolar-level structure elucidation of novel natural compound.
Tetrahedron 60:6971–6980
Ridley RG (2002) Medical need, scientific opportunity and the drive for antimalarial drugs. Nature
415:686–693
Rieckmann KH, Campbell GH, Sax LJ, Mrema JE (1978) Drug sensitivity of plasmodium falciparum. An
in-vitro microtechnique. Lancet 1:22–23
Vaidya AS, Dixit SM, Rao AS (1968) Degradation of bile acid side chain with lead tetraacetate. Tet Lett
50:5173–5174
Wellems J, Plowe C (2001) Chloroquine-resistant malaria. J Infec Dis 184:770–776
Wiesner J, Ortmann R, Jomaa H, Schlitzer M (2003) New antimalarial drugs. Angew Chem Int Ed 42:
5274–5293
WHO (1999) Drug Information Bulletin 13:9