Stereospecific synthesis of oximes and oxime ethers of 3-azabicycles: A SAR study towards antimicrobial agents

Article abstract of DOI:10.1016/j.bmcl.2010.01.048

Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 1-14/15-28/29-42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 43-48/49-54/55-60 were synthesized and their stereochemistry was establis

Full text of DOI:10.1016/j.bmcl.2010.01.048

Bioorganic & Medicinal Chemistry Letters 20 (2010) 1642–1647
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Stereospecific synthesis of oximes and oxime ethers of 3-azabicycles:
A SAR study towards antimicrobial agents
Paramasivam Parthiban a, Paramasivam Rathika b, Venkatachalam Ramkumar c, Se Mo Son a,
Yeon Tae Jeong a,
*
a Division of Image Science and Information Engineering, Pukyong National University, Busan 608 739, Republic of Korea
b Department of Microbiology, Annamalai University, Annamalainagar 608 002, India
c Department of Chemistry, Indian Institute of Technology-Madras, Chennai 600 036, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 1–14/15–28/
29–42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 43–48/49–
54/55–60 were synthesized and their stereochemistry was established by 1D/2D NMR spectral and single
crystal XRD studies. All the synthesized oximes and oxime ethers were screened for their in vitro antimi-
crobial activity against a panel of pathogenic bacteria (Bacillus subtilis, Staphylococcus aureus, Klebsiella
pneumoniae and Pseudomonas aeruginosa) and fungi (Candida albicans, Candida parapsilosis, Aspergillus
niger and Cryptococcus neoformans) using Gentamicin and Fluconazole as standards, respectively. From
the SAR profile, the lead molecules were identified.
Received 11 November 2009
Revised 14 December 2009
Accepted 12 January 2010
Available online 20 January 2010
Keywords:
3-Azabicyclo[3.3.1]nonan-9-ones
Oximes
O-Methyloximes
2D NMR
Ó 2010 Elsevier Ltd. All rights reserved.
Single crystal XRD
Antibacterial activity
Antifungal activity
Molecules with the 3-azabicyclo[3.3.1]nonane nucleus are of
great interest due to their presence in a wide variety of naturally
occurring diterpenoid/norditerpenoid alkaloids and biological
activities.1 The 3-azabicyclo[3.3.1]nonane nucleus itself contains
an important class of piperidone pharmacophore2 and the SAR
studies on the piperidone heterocycle indicated that the nature
and position of substituents were important factors towards signif-
icantly effect the biological actions.3
Reports reveal the antimicrobial efficacy of oximes and oxime ethers
owing to the presence of AC@NAOAR functionality.4 An essential com-
ponent of the search for new leads in drug designing program is the syn-
thesis of molecules, which are novel, yet resembling known biologically
active molecules by virtue of the presence of some critical structural fea-
tures.5 Moreover, it would rather be achieved by an easier synthetic
strategy with stereo controlled product.
Altogether with an expectation of enhanced antimicrobial pro-
file, we synthesized new oximes and O-methyloximes of 2,4-dia-
ryl-3-azabicyclo[3.3.1]nonan-9-ones with CH3 group at C-1/C-7
and electron-withdrawing/donating F/Cl/Br/CH3/OCH3 substitu-
ents in ortho/meta/para positions of the phenyl at C-2 and C-4.
Synthetic strategy of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]-
nonan-9-ones 1–14 and their oximes/O-methyloximes 15–28/29–
42 is depicted in Scheme 1.
All 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones 1–14
were synthesized as single isomer with good yields in one-pot by
a modified and an optimized Mannich reaction.1a,6 Stereochemis-
try of the compounds were established by use of their H,H-COSY,
NOESY, HSQC and HMBC spectral data. The long-range couplings
by means of ‘W’ arrangement from the H,H-COSY as well as NOE
(Fig. 1) indicate the twin-chair conformation for the 3-azabicycle
with equatorial orientation of the aryl groups at C-2 and C-4. The
bridge-head proton H-5 appeared as a quintet in the most of the
compounds. However, in some compounds, it appeared as a broad
singlet/unresolved multiplet with a half-width ‘‘W1/2” of about
8 Hz, supporting the twin-chair conformation.7
E/Z isomerism is obvious while synthesizing the oximes or
oxime ethers from unsymmetrical ketones. However, in all cases,
only E isomer was achieved with >90% yields. The effect of oxima-
tion/oximination on 1H/13C NMR spectra was significant by the
allylic (A1,3) interaction between the N–O and C(5)–H bonds be-
sides the decrease in electronegativity at C-9 by the reduction of
C@O as C@N. In fact, A1,3 interaction is noteworthy (Fig. 2a) as
deshielded H-5 (syn a-proton) >1 ppm and shielded C-5 (syn a-car-
bon) about 7 ppm besides the electronegativity (oximation) effect
on that proton/carbon. Thus, the effect of A1,3 interaction domi-
nated the electronegativity effect on consecutive (syn) b position
and affect the
ethers, due to the presence of electron-donating CH3 group at
oxime functionality, the oximino carbon C-9 and syn -proton
c
-carbon. Although, A1,3 effect was similar in oxime
*
Corresponding author. Tel.: +82 51 629 6411; fax: +82 51 629 6408.
a
E-mail address: ytjeong@pknu.ac.kr (Y.T. Jeong).
0960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.01.048

P. Parthiban et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1642–1647
1643
O
H-5 were shielded by ꢀ1 and 0.15 ppm, respectively. On the basis
of NMR studies, we conceived that the oximes 15–28 and oxime
ethers 29–42 are exist in the twin-chair conformation with equato-
rial disposition of the aryl groups at C-2 and C-4 (Figs. 1a and 2),
which was further proved by XRD analysis (Fig. 3). Refer Supple-
mentary data for detailed NMR/XRD analysis.
H3C
7
8
1
O
9
6
H3C
R1
5
4
R1
a
H
O
O
H
2'
2
2''
R2
R3
R2
R3
3
1'
3'
1''
N
H
3''
R1
R2
R1
R2
4'
6''
6'
4''
1-14
5'
5''
c
b
R3
R3
NH4OAc
H3C
7
7
OH
O
N
9
8
1
8
1
N
9
6
6
H3C
H3C
R1
R1
R1
5
4
R1
5
4
2'
2
2'
2
2''
2''
R2
R3
3
R2
3''
R2
R3
R2
R3
3
3'
1'
1'
1''
3'
1''
N
H
N
H
3''
4'
4'
6''
6''
6'
6'
4''
4''
R3
R3
29-42
15-28
5'
5'
5''
5''
R3
R1
R2
Compound
R1
R2
Compound
8, 22, 36
9, 23, 37
10, 24, 38
11, 25, 39
12, 26, 40
13, 27, 41
14, 28, 42
Br
H
H
H
H
H
OCH3
H
H
Br
H
CH3
H
H
1, 15, 29
2, 16, 30
3, 17, 31
4, 18, 32
5, 19, 33
6, 20, 34
7, 21, 35
H
F
H
H
Cl
H
H
H
H
F
H
H
Cl
H
H
H
H
F
H
H
Cl
H
CH3
H
OCH3
H
H
OCH3
Figure 3. ORTEP of compound 16 with atoms represented as 30% probability
ellipsoids. Single crystal XRD analysis proved that the bicycle exists in a twin-chair
conformation with equatorial orientation of the ortho-fluorophenyl groups on both
sides of the secondary amino group. The compound exists in E configuration.
Scheme 1. Reagents and conditions: (a) EtOH, warm, stirring; (b) HO–NH2.HCl,
CH3COONaÁ3H2O, EtOH, reflux; (c) CH3–O–NH2ÁHCl, CH3COONaÁ3H2O, EtOH, reflux.
X
O
H
H3C
H
H3C
5
5
1
1
Ha
Ha
Ha
Ha
Ha
Ha
Ar
Ha
Ha
6
2
6
2
F
8
4
8
4
2''
He
He
He
He
He
He
Ar
H
3
6'
F
2'
3
H6''
N
7
N
7
Ha
Ha
H
H
2
: Ar = 2-F phenyl, X = O
16: Ar = 2-F phenyl, X = NOH
31: Ar = 3-F phenyl, X = NOCH
(a)
(b)
3
Figure 1. (a) Long-range couplings between the protons that are in ‘W’ arrangement. Accordingly, the compounds exist in the twin-chair conformation with equatorial
orientation of the aryl groups at C-2 and C-4 of the 1-methyl-3-azabicycle. All compounds exhibited a weak correlation between H-4a and H-6a comparing to H-2a and H-8a;
(b) Meaningful NOE observed in the NOESY spectrum of compound 2.
H3C
N
R
O
O
A1,3 interaction
N
9
H
H3C
Ha
δ
H
H3C
δ
5
5
1
syn
1
anti
Ha
4
Ha
He
He
H
Ha
6
2
4
8
2''
8
2
6
H
6'
F
Ar
Ar
2'
3
3
6''
7
N
N
H
7
Ha
H
(a)
(b)
F
Figure 2. (a) Non-bonded 1,3-allylic interaction between the N–O and C(5)–H bonds; (b) significant NOE observed in the NOESY spectrum of compound 31.

1644
P. Parthiban et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1642–1647
CH3
Of the synthesized bicyclic ketones 43–48, the para-F (45),
meta-Cl (47) and para-Cl (48) compounds were achieved as single
isomer in good yields, whereas, ortho-F (43a, 43b), meta-F (44a,
44b) and ortho-Cl (46a, 46b) compounds were obtained as mix-
tures of two conformational isomers. Stereochemistry of the bicy-
clic ketones 43–48 were established on the basis of the observed
long-range couplings, NOE and W1/2 of the bridge-head protons
by H,H-COSY and NOESY spectra (Figs. 4 and 5). Accordingly, com-
pounds 43a, 44a, 45, 46a and 48 exist in the twin-chair conforma-
tion with equatorial orientation of all substituents, whereas 43b,
44b, 46b and 47 exist in the chair-boat conformation with equato-
rial orientation of the aryl groups at C-2/C-4 and exocyclic orienta-
tion of the CH3 group at C-7. The bridge-head protons in 43a, 44a,
45, 46a and 48 appeared as broad singlets, whereas, in 43b, 44b,
46b and 47, they observed as doublets with J of 9–10 Hz. According
O
CH3
H
7
8
1
O
6
9
R1
5
4
R1
a
H
O
O
2'
2
2''
R2
R3
R2
R3
3
1'
3'
1''
N
H
3''
R1
R2
R1
R2
4'
6''
6'
4''
5'
43-48
5''
c
b
R3
R3
NH4OAc
CH3
O
CH3
CH3
7
OH
7
8
1
N
9
6
N
8
6
9
R1
5
4
R1
R1
R1
5
4
1
to the a-effect by the introduction of CH3 at C-7, it was deshielded
2'
2
2''
R2
R3
R2
3''
2'
2
R2
R3
3
R2
R3
2''
3
about 6 ppm in 43–48, whereas, the effect reversed at C-1 by the
CH3 at C-1 in 1–14. The C-1 was shielded by 1–3 ppm depends
on the nature and position of the substituents in phenyl.
1'
3'
1''
6''
1'
3'
1''
6''
N
H
N
H
3''
4'
4'
6'
4''
6'
4''
R3
5'
5''
5'
5''
49-54
55-60
According to NMR data, it is clear that all 7-methyl-2,4-diaryl-
3-azabicyclo[3.3.1]nonan-9-ones 43–48 afforded the correspond-
ing oximes 49–54 and oxime ethers 55–60 with syn orientation
of the N–O to C(5)–H bond. Owing to this phenomenon, a non-
bonded interaction established between them, and as a conse-
Compound
R1
R2
R3
Compound
43a, 49a, 55a
44a, 50a, 56a
45, 51, 57
46a, 52a, 58a
47, 53, 59
48, 54, 60
F
H
H
Cl
H
H
H
F
H
H
H
H
F
H
H
43b, 49b, 55b
44b, 50b, 56b
46b, 52b, 58b
quence, the syn-
the anti- proton H-1 shielded by 0.05–0.1 ppm. Thus in oximes,
the d5,1 was P1.05 ppm, however, reduced to 0.90–0.95 ppm by
a proton H-5 deshielded about 1 ppm, whereas
Cl
H
a
Cl
D
"a"and"b"areconformationalisomers
O-methylation. Stereochemistry of the oximes and oxime ethers
are shown in Figure 6 as witnessed by NMR studies, which were
further witnessed by XRD analysis of 53 and 54 (Figs. 7 and 8). Re-
fer Supplementary data for detailed NMR/XRD analysis.
Scheme 2. Reagents and conditions: (a) EtOH, warm, stirring; (b) HO–NH2ÁHCl,
CH3COONaÁ3H2O, EtOH, reflux; (c) CH3–O–NH2ÁHCl, CH3COONaÁ3H2O, EtOH, reflux.
All the synthesized oximes/oxime ethers were evaluated for
their in vitro antimicrobial activity against a panel of pathogenic
bacteria and fungi by standard broth micro-dilution technique
Synthesis of 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-
ones 43–48 and their oximes/O-methyloximes 49–54/55–60 are
illustrated in Scheme 2.
O
O
H
H
H
H
5
1
Ha
1
5
Ha
Ha
Ha
H
Ha
Ha
6
Ha
2
6
Ha
Ar
8
2''
4
2
H
8
4
He
6'
F
He
H3C
H
He
He
H3C
3
Ar
2'
3
6''
7
N
N
7
Ha
H
Ha
H
F
(a)
(b)
Figure 4. (a) Long-range couplings between the protons that are in ‘W’ arrangement, according to the H,H-COSY spectrum of compound 44a; (b) significant NOE observed in
the NOESY spectrum of 44a. Both H,H-COSY and NOESY suggest that the bicycle exists in a twin-chair conformation with equatorial orientation of all substituents.
O
O
H
H
H
H
H
H
7
7
5
5
H3C
47
H3C
1
1
Ha
Ha
H
H
Ha
Ha
6
6
2
2
8
2''
8
2''
4
4
H
H
6'
He
He
Cl
6'
F
H
H
eHa
Ha
eHa
Ha
H
H
3
3
6''
6''
N
N
H
H
44b
Cl
F
Figure 5. Significant NOE observed in the compounds 44b and 47, suggesting the chair-boat conformation. Also, the absence of long-range couplings in the H,H-COSY
spectrum of 44b and 47 support the non-existence of the bicycle in the twin-chair conformation. The NOE between H-7 and H-1 indicates the exocyclic orientation of the CH3
group at C-7.

P. Parthiban et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1642–1647
1645
R
N
R
N
O
O
'W' correlation
by H,H-COSY
A1,3 interaction
A1,3 interaction
'W' correlations
by H,H-COSY
NOE
'W'
'W'
δ
δ
H
H
H
H
H
δ
5
δ
NOE
NOE
7
NOE
1
5
H3C
1
Ha
Ha
Ha
Ha
Ha
Ha
Ar
6
2
6
2
8
4
8
4
He
He
He
H
eHa
Ar
Ar
Ha
Ar
3
3
H3C
7
N
N
NOE
Ha
H
H
(a)
(b)
Figure 6. (a) Chair–chair conformation of compounds 49a, 50a, 51, 52a, 54, 55a, 56a, 57, 58a and 60 with equatorial orientation of the aryl groups at C-2 and C-4 and
exocyclic as well as equatorial orientation of the CH3 at C-7. NOE and ‘W’ correlations (between H-1 and H-5, H-2a and H-8a, H-4a and H-6a; because H-6e and H-8e were
merged, we could not get the correlation between them) strongly support the proposed stereochemistry; (b) chair–boat conformation of compounds 49b, 50b, 52b, 53, 55b,
56b, 58b and 59 with equatorial orientation of the aryl groups at C-2/C-4 and exocyclic orientation of the CH3 at C-7. Observed NOE and the absence of ‘W’ correlations
(except H-1 and H-5 from H,H-COSY) insist that the compounds exist in chair–boat conformation. NOE between the H-7 and H-1 indicates the exocyclic orientation of the CH3
at C-7.
Figure 8. ORTEP of compound 54 with atoms represented as 30% probability
ellipsoids. According to XRD analysis, the bicycle exists in a twin-chair conforma-
Figure 7. ORTEP of compound 53 with atoms represented as 30% probability
tion with equatorial orientation of the para-chlorophenyl groups. Also, the analysis
ellipsoids. The bicycle exists in a chair–boat conformation with equatorial orien-
witnessed the equatorial as well as exocyclic orientation of the CH3 group at C-7
tation of the meta-chlorophenyl groups on both sides of the secondary amino group.
and E configuration of the molecule.
The molecule exists in E configuration with exocyclic orientation of the CH3 group
at C-7. Chlorine atom in one of the phenyl rings and oxygen atom of the oxime
functionally are disordered over two positions with site occupancy factors of 0.5.
One of the disordered oxygen atoms is omitted for clarity.
Careful analysis of the MICs in Table 2 provides the lead mole-
cules with good antifungal profile. Despite the position of CH3 in
according to NCCLS guidelines,8 using Gentamicin and Fluconazole
as standards.
the bicycle, all oxime ethers exhibited comparatively better activ-
ity than their oximes. Both 1- and 7-methyl substituted oxime
ethers with F/Cl substituents at ortho/para positions (30, 32, 33,
35, 55a, 55b, 57, 58a, 58b and 60) expressed promising antifungal
profile. Particularly, 7-methyl oxime ethers 55b and 58b registered
Data of the Table 1 describe the antibacterial activity of the syn-
thesized oximes/oxime ethers against pathogenic bacteria and sug-
gest the lead molecules. Among the oxime derivatives, compounds
with electron-withdrawing F/Cl/Br substituents at phenyl ex-
pressed moderate to good activity. Especially, the F and Cl substit-
uents at ortho or para positions of the phenyl showed maximum
activity. Among the 1-methyl oximes 15–28, 16, 18, 19 and 21
exhibited moderate activity against all strains and enhanced by
the introduction of a CH3 group at oxime functionality. Thus, 30,
32, 33 and 35 expressed a good activity profile against all strains
their best MIC in the range of 2–4
addition, analogous oximes 49b and 52b exhibited their best MIC
at g/mL against Aspergillus niger and Candida albicans,
lg/mL against all tested fungi. In
4
l
respectively.
In summary, libraries of 3-azabicyclo[3.3.1]nonan-9-ones/oxi-
mes/O-methyloximes with F/Cl/Br/CH3/OCH3 substituents at
ortho/meta/para position of the phenyl groups at C-2/C-4 and CH3
group at C-1/C-7 were synthesized in a stereospecific manner by
an easier strategy with high yield. All oximes and oxime ethers
were achieved only as E-isomers. Among the oxime derivatives,
irrespective of the nature and position of the substituents, all 1-
methyl compounds 15–42 exist in the twin-chair conformation
with the MIC range of 4–16
16 g/mL). Likewise, the oxime ethers 55a, 57, 58a and 60 also
exhibited broad-spectrum antibacterial activity, their MIC lies in
the range of 2–16 g/mL against all strains, except 60 against Pseu-
domonas aeruginosa.
lg/mL as Gentamicin (MIC range 2–
l
l

1646
P. Parthiban et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1642–1647
Table 1
Table 2
Antibacterial activity of compounds 15–42 and 49–60
Antifungal activity of compounds 15–42 and 49–60
a
Compounds
Minimum inhibitory concentration (MIC90
)
in
lg/mL
Compounds
Minimum inhibitory concentration (MIC90) in lg/mL
B. Subtilis
S. aureus
K. pneumoniae
P. aeruginosa
C. albicans
C. parapsilosis
A. niger
C. neoformans
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
>128
32
128
64
128
8
64
16
8
64
64
64
64
128
128
64
128
32
64
4
>128
16
32
32
16
64
16
128
>128
128
>128
128
>128
64
128
4
>128
32
128
64
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
>128
8
>128
8
64
32
8
64
64
64
>128
>128
>128
128
>128
>128
>128
8
>128
64
128
64
16
>128
64
128
128
64
>128
64
>128
32
8
128
32
>128
128
>128
128
64
128
>128
>128
8
32
16
64
64
32
64
>128
128
128
>128
>128
128
128
4
64
32
>128
>128
128
>128
64
128
64
128
128
>128
16
>128
>128
>128
>128
>128
>128
128
>128
>128
>128
8
64
128
>128
128
>128
16
31
32
33
34
35
36
37
38
39
40
41
42
49a
49b
50a
50b
51
52a
52b
53
128
32
32
128
64
64
64
32
32
32
64
64
16
32
128
>128
64
32
64
32
32
4
8
16
32
16
8
32
64
16
16
16
8
4
32
16
8
32
16
8
64
31
32
33
34
35
36
37
38
39
40
41
42
49a
49b
50a
50b
51
52a
52b
53
16
8
64
8
4
32
16
32
128
128
>128
64
64
32
16
128
8
32
32
64
32
128
>128
128
64
4
64
32
64
>128
32
64
128
16
4
64
8
128
64
128
64
128
128
>128
64
16
>128
64
32
32
64
>128
64
16
4
32
32
16
64
64
64
128
64
>128
64
64
16
128
64
32
16
4
64
64
8
2
32
8
16
8
4
16
32
1
64
32
64
32
32
64
32
32
16
8
32
32
32
8
16
16
64
32
2
16
16
32
4
4
8
32
16
4
32
16
64
32
128
64
32
128
64
16
64
32
64
32
32
32
32
16
2
64
128
>128
128
128
64
>128
128
32
128
64
32
64
32
>128
64
32
8
32
64
64
16
4
64
128
128
32
64
32
64
32
16
128
64
32
2
32
16
64
16
4
8
54
54
32
16
2
64
16
16
32
2
55a
55b
56a
56b
57
58a
58b
59
55a
55b
56a
56b
57
58a
58b
59
16
64
64
8
64
32
8
16
2
32
16
2
4
16
32
8
16
128
32
32
64
4
60
60
16
2
Gentamicin
2
16
Fluconazole
a
MIC90 is the lowest concentration of an antimicrobial agent to significantly
inhibit the 90% growth of a pathogen after a period of incubation; MIC values are
represented in micrograms per millilitre.
Acknowledgement
Corporate-affiliated Research Institute of Academic-Industrial-
Institutional Cooperation Improvement (Business No.
S7080008110) supported this work.
with equatorial orientation of the aryl substituents at C-2 and C-4
of the 3-azabicycle. Of the 7-methyl compounds 49–60, 49a/50a/
51/52a/54/55a/56a/57/58a/60 and 49b/50b/52b/53/55b/56b/58b/
59, respectively, adopted the chair–chair and chair–boat conforma-
tions with exocyclic substitution of the methyl at C-7 along with
equatorial orientation of the aryl groups at C-2 and C-4. Among
the synthesized compounds, oximes with electron-withdrawing
F/Cl substituents at ortho/para positions of the phenyl exhibited
remarkable antibacterial as well as antifungal activity. Further,
the activity was enhanced by the introduction of a methyl group
at oxime functionality. Thus, the present SAR provides some lead
molecules with worthy antibacterial and antifungal activities. Fur-
thermore, to optimize the lead molecules and to develop better
antimicrobial agents, toxicity and mechanistic studies are planned
to carry out.
Supplementary data
Complete experimental details, IR, 1H and 13C NMR data of all
compounds, 2D NMR data of the representative compounds, and
single crystal XRD data of 16, 53 and 54 were provided as supple-
mentary material. Supplementary crystallographic data for 16
(CCDC No. 753535), 53 (CCDC No. 753536) and 54 (CCDC No.
753537) can be obtained free of charge at www.ccdc.cam.ac.uk/
conts/retrieving.html. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.bmcl.2010.01.048.

P. Parthiban et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1642–1647
1647
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Rameshkumar, N.; Veena, A.; Ilavarasan, R.; Adiraj, M.; Shanmugapandiyan, P.;
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