Synthesis of symmetrical C- and pseudo-symmetrical O-linked disaccharide analogs for arabinosyltransferase inhibitory activity in Mycobacterium tuberculosis

Article abstract of DOI:10.1016/j.bmcl.2007.05.099

Herein we report the synthesis of symmetrical C-linked and pseudo-symmetrical O-linked disaccharides structurally related to Araf motifs present in the cell wall of MTB. Their activity in a competition-based arabinosyltransferase assay using [¹⁴

Full text of DOI:10.1016/j.bmcl.2007.05.099

Bioorganic & Medicinal Chemistry Letters 17 (2007) 4527–4530
Synthesis of symmetrical C- and pseudo-symmetrical
O-linked disaccharide analogs for arabinosyltransferase
inhibitory activity in Mycobacterium tuberculosis
Ashish K. Pathak,a, Vibha Pathak,a, James R. Riordan,a William J. Suling,a
Sudagar S. Gurcha,b Gurdyal S. Besrab and Robert C. Reynoldsa,*
aDrug Discovery Division, Southern Research Institute, PO Box 55305, Birmingham, AL 35255, USA
bSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
Received 30 April 2007; revised 23 May 2007; accepted 30 May 2007
Available online 6 June 2007
Abstract—Herein we report the synthesis of symmetrical C-linked and pseudo-symmetrical O-linked disaccharides structurally
related to Araf motifs present in the cell wall of MTB. Their activity in a competition-based arabinosyltransferase assay using
[14C]-DPA as the glycosyl donor is also presented. In addition, in vitro inhibitory activity for the disaccharides was determined
in a colorimetric broth microdilution assay system against MTB H37Ra and Mycobacterium avium.
ꢀ 2007 Elsevier Ltd. All rights reserved.
The development of multi-drug resistant strains of
Mycobacterium tuberculosis (MTB)1,2 and co-infection
with HIV3 have limited TB treatment options, initiating
a worldwide effort to discover new biochemical targets
and selective inhibitors. The mycobacterial cell wall re-
mains an excellent target, focusing discovery efforts on
new proteins involved in the biogenesis of this critical
bacterial barrier.4 The cell wall of MTB allows the bac-
terium to elude cellular defenses and thrive within mac-
rophages of the host. Particular components of that
barrier, arabinofuranose (Araf), galactofuranose (galf),
and rhamnopyranose (rhaf), and several of the atten-
dant synthetic enzymes are not found in humans, and
they offer the potential for development of highly selec-
tive and potent new drugs.
quires several different sugar processing enzymes, or ara-
binosyltransferases (AraTs), for its complete genesis.5,6
Several synthetic O- and S-alkyl arabinofuranoside
acceptors have been prepared for the development of
arabinosyl-transferase assays7 and other biological and
structural studies based on the unbranched and highly
branched polysaccharides of AG and LAM.8–10
As part of ongoing programs to find carbohydrate-
based antimycobacterial agents targeting biogenesis of
the mycobacterial cell wall polysaccharides, we and oth-
ers have synthesized several analogs of a(1 ! 5) Araf
disaccharides.9b,11,12 We have reported the synthesis
and antimycobacterial activity of analogs (Fig. 1) with
substitution at the non-reducing terminus (ring B).
The major components of the mycobacterial integument
are the mycolyl arabinogalactan—peptidoglycan com-
plexes (mAGPs) and lipoarabino-mannan (LAM) asso-
ciated lipoglycans.5 The arabinan portion of the cell
wall is composed of Araf homopolymers with different
linkages viz. a(1 ! 5), a(1 ! 2), and a(1 ! 3), and re-
OH
O
X
B
OH
O
OH
N
O
O
OH
B
A
OH
O
O
OC8H17
OH
OH
A
1
Keywords: Tuberculosis; Glycosyltransferases; Inhibitors; Disaccharides.
*
2
OC8H17
Corresponding author. Tel.: +1 205 581 2454; fax: +1 205 581
2877; e-mail: reynolds@sri.org
X = OH, N3, NH2, NHCOR,
NHSO2R, NR2
OH
IC50 1.56 mM
MIC 8 μg/mL
Present address: Department of Chemistry, Western Illinois Univer-
sity, Macomb, IL, USA.
Figure 1. 50-Substituted Araf a(1 ! 5) Araf disaccharides.
0960-894X/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2007.05.099

4528
A. K. Pathak et al. / Bioorg. Med. Chem. Lett. 17 (2007) 4527–4530
OR1
We designed O-linked and C-linked disaccharide ana-
logs (3 and 4) that also possess C-substitution at the
anomeric center of the reducing terminus. This substitu-
tion is based on the N,N-dicyclohexyl-methylamino sub-
stitution of 2 at the 50-position that showed the best
activity among reported derivatives.11 C-sugars and
C-linked disaccharides offer advantages as enzyme
probes and inhibitors, and as drugs. Most importantly,
this linkage prevents glycosidase-mediated cleavage.
We report the synthesis and inhibitory data of pseudo-
symmetrical and symmetrical disaccharides 3 and 4,
respectively (Fig. 2).
6
OH
2
R2O
OH
HO
O
O
O
a
ref 17
5
HO
HO
OH
NH2.HCl
N3
N3
4
1
OH3
OR1
Glucosamine.HCl
5
6. R1 = R2 = TBDMS
b
7. R1 = TBDMS, R2 = H
Scheme 1. Reagents and conditions: (a) TBDMSCl, imidazole, DMF,
50 ꢁC, 18 h; (b) TFA/Water (1:1), THF, ꢀ4 ꢁC, 4 h, 85% (in 2 steps).
the presence of NIS and the Lewis acid promoter triflic
acid to produce 9 (Scheme 2). After several column puri-
fications, a slight trace of unreacted 8 was present necessi-
tating deacetylation to yield the diazido disaccharide 10 as
a pure, colorless oil. N,N-Dialkylation of 10 via reductive
alkylation with cyclohexane carboxyaldehyde in MeOH
over 10% Pd/C at room temperature under H2 atmo-
sphere gave 11 in 74% yield as a colorless oil after purifi-
cation. Desilylation of 11 in a trial reaction with
Bu4N+Fꢀ produced only a poor yield (48%) of 3. The syn-
thesis of 3 was achieved by desilylation of 11 using
Et4N+Fꢀ in THF in 88% yield after purification.
In our study of the Araf 1–5 linkages, it was noted that
the simple O-linked disaccharide core is pseudo-symmet-
rical around the central –O–C– bond. Hence, we tar-
geted 3 and 4 to incorporate the N,N-dicyclohexyl
group of the active compound 2 at both ends of the tar-
gets to take advantage of this symmetry to potentially
increase binding efficiency. Compound 4 contains a true
C2-symmetry axis as does the intermediate 17 that may
also offer the advantage of reduced degrees of freedom
around the disaccharide linkage that could further
improve binding efficiency.
The attempted synthesis of C-linked disaccharide 4 via
Wittig olefination18 to give a C-linked diazido disaccha-
ride similar to 9 was unsuccessful. Disaccharide 4 was
produced using Wittig olefination as shown in Scheme 3.
Azido saccharide 7 was first converted to the N,
N-dicyclohexylmethylamino derivative 12, ultimately
yielding 14 and 15 for coupling. Compound 12 was con-
verted to 6-iodomannitol derivative 13 by heating with
iodine, PhP3, and imidazole. After purification, 13 was
heated with neat Ph3P to produce the triphenylphos-
phonium iodide 14. Compound 12 was alternatively
oxidized with PCC in CH2Cl2 to aldehyde 15 that was
used directly in the coupling without purification.19
The two saccharides 14 and 15 were coupled in the
presence of BuLi at ꢀ30 ꢁC to give a mixture of olefin
16 (E/Z ratio 96:4 by NMR) after purification.
Deblocking of 16 with Et4N+Fꢀ in THF and purifica-
tion produced 17 in 86% yield as an E/Z mixture.
Reduction of 17 produced the symmetrical C-linked
disaccharide 4 in 62% yield.
Several groups have reported C-linked glycoside analogs
of the a-D-Araf-(1 ! 5)-a-D-Araf motif found in the cell
wall of mycobacteria using various approaches.13–16 We
describe the synthesis of targets 3 and 4 through
coupling of a 5-azidoarabinosyl donor with a 1-azido
D-mannitol derivative and C–C bond formation by
Wittig olefination,14 respectively. These syntheses
began with 2,5-anhydro-1-azido-1-deoxy-D-mannitol (5)
prepared from D-glucosamine hydrochloride by diazoti-
zation-mediated ring contraction and selective monotosy-
lation followed by introduction of the azido group using
NaN3.17 Compound 5 was persilylated to produce 6
which on selective desilylation at the 6-position using a
trifluoroacetic acid/water mixture (1:1) in dry THF at
ꢀ4 ꢁC produced 7 as shown in Scheme 1.
The synthesis of disaccharide 3 was achieved by coupling
of p-thiotolyl 1,5-dideoxy-5-azido-2,3-di-O-acetyl-a-D-
arabinofuranoside (8)11 with 2,5-anhydro-1-azido-3,
4-di-O-tert-butyldimethylsilyl-1-deoxy-D-mannitol (7) in
OAc
N3
O
OAc
N3
O
OTBDMS
O
a
O
7
+
STol
OAc
OAc
N3
OTBDMS
12
OH
N
8
O
8
11
Tol = p-tolyl
9. R = OAc
10. R = H
B
6
OH
b
O
10
O
OH9
2
7
c
5
A
C6H11
C6H11
N
OH
O
4
N
1
OH3
3
d
12
3
OTBDMS
OH
N
O
O
O
B
8
OH
11
C6H11
C6H11
11
10
6
OH
2
N
O
A
OH9
7
OTBDMS
5
N
4
1
OH3
Scheme 2. Reagents and conditions: (a) NIS, TfOH, CH2Cl2, ꢀ20 ꢁC,
15 min; (b) 7N NH3/MeOH, MeOH, rt, overnight, 85% (in 2 steps); (c)
C6H11CHO, 10% Pd/C, MeOH, rt, 4 h, 74%; (d) Et4N+Fꢀ, THF, rt,
overnight, 88%.
4
Figure 2. Target O- and C-linked disaccharides.

A. K. Pathak et al. / Bioorg. Med. Chem. Lett. 17 (2007) 4527–4530
4529
OTBDMS
Acknowledgments
OTBDMS
HO
HO
O
O
C6H11
C6H11
a
RCR acknowledges NIH/NIAID Grant R01AI45317.
GSB acknowledges support from Mr. James Bardrick,
The Wellcome Trust, and MRC.
N3
OTBDMS
N
OTBDMS
7
12
b
c
H
OTBDMS
References and notes
OTBDMS
O
I
O
O
C6H11
C6H11
C6H11
C6H11
1. WHO http://www.who.int/tb/en/.
N
N
2. Collins, F. M. Crit. Rev. Microbiol. 1993, 19, 1.
3. Dolin, P. J.; Raviglione, M. C.; Kochi, A. Bull. World
Health Org. 1994, 72, 213.
OTBDMS
OTBDMS
15
13
d
4. Basso, L. A.; Blanchard, J. S. Adv. Exp. Med. Biol. 1998,
456, 115.
5. (a) Brennan, P. J. Annu. Rev. Biochem. 1995, 64, 29; (b)
Chatterjee, D. Curr. Opin. Chem. Biol. 1997, 1, 579; (c)
Daffe, M.; Draper, P. Adv. Microb. Physiol. 1998, 39, 131.
6. Lee, R. E.; Mikusova, K.; Brennan, P. J.; Besra, G. S.
J. Am. Chem. Soc. 1995, 117, 11829.
OTBDMS
IPh3P
O
C6H11
C6H11
N
e
OTBDMS
7. Lee, R. E.; Brennan, P. J.; Besra, G. S. Glycobiology 1997,
7, 1121.
8. (a) Lowary, T. L. J. Carbohydr. Res. 2000, 21, 691, and
references therein; (b) Sanchez, S.; Bamhaoud, T.; Prandi,
J. Tetrahedron Lett. 2000, 41, 7447.
9. (a) Pathak, A. K.; Pathak, V.; Khare, N. K.; Maddry, J.
A.; Reynolds, R. C. Carbohydr. Lett. 2001, 4, 117; (b)
Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.;
Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med.
Chem. 2001, 9, 3145.
14
C6H11
C6H11
OR
O
N
OR
O
4
OR
C6H11
N
g
C6H11
OR
16. R = TBDMS
17. R = H
f
10. (a) Pathak, A. K.; Pathak, V.; Bansal, N.; Maddry, J. A.;
Reynolds, R. C. Tetrahedron Lett. 2001, 42, 979; (b)
Pathak, A. K.; Pathak, V.; Gurcha, S. S.; Besra, G. S.;
Reynolds, R. C. Bioorg. Med. Chem. Lett. 2002, 12, 2749.
11. Pathak, A. K.; Pathak, V.; Kulshrestha, M.; Kinnaird, D.;
Suling, W. J.; Gurcha, S. S.; Besra, G. S.; Reynolds, R. C.
Tetrahedron 2003, 59, 10239.
Scheme 3. Reagents and conditions: (a) C6H11CHO, Pd/C, MeOH, rt,
4 h, 95%; (b) I2, imidazole, Ph3P, toluene, 80 ꢁC, 1 h, 56%; (c) PCC,
CH2Cl2, rt, 4 h, 85%; (d) PPh3, 120 ꢁC, 4 h, 67%; (e) THF–HMPA,
BuLi, ꢀ30 ꢁC, 2 h, 55%; (f) Et4N+Fꢀ, THF, rt, overnight, 86%; (g)
Pd(OH)2, H2, EtOAc–MeOH (1:1), rt, 4 h, 62%.
12. Cociorva, O. M.; Lowary, T. L. Carbohydr. Res. 2004,
339, 853, and reference therein.
13. Gurjar, M. K.; Nagaprasad, R.; Ramana, C. V. Tetrahe-
dron Lett. 2002, 43, 7577.
14. Dondoni, A.; Marra, A. Tetrahedron Lett. 2003, 44, 4067.
15. Aslam, T.; Fuchs, M. G. G.; Le Formal, A.; Wightman,
R. H. Tetrahedron Lett. 2005, 46, 3249.
All compounds were characterized by ESIMS analysis
1
and H NMR spectroscopy.20 NOE and D2O exchange
experiments were performed as needed to confirm NMR
assignments.
Activity was determined in the cell-free enzymatic arabi-
nosyltransferase acceptor assay7 in the presence of mem-
branes and is based on inhibition of [14C]Araf
incorporation from [14C]DPA by the control a(1 ! 5)-
linked 1-O-octyl arabinofuranosyl disaccharide.11
Disaccharide analogs 3, 4, and 17 showed inhibitory
activity at a concentration of 3.6 mM (with control
acceptor at 0.4 mM) and specific IC50 values were
2.80, 3.44 and 4.15 mM, respectively. Bacterial growth
inhibition was determined versus MTB H37Ra (ATCC
25177) and Mycobacterium avium (NJ 211) at the initial
concentrations of 1.28 and 12.8 lg/mL.21 Initial activity
was confirmed using half-log dilutions at 16, 8, and 4 lg/
mL to determine an MIC as reported.21 Ethambutol
showed a MIC in the range 2–4 lg/mL. Compounds 3
and 17 showed a modest MIC of 8 lg/mL, 4 and 10 gave
an MIC of 16 lg/mL, and 11 a MIC of >12.8 lg/mL
against MTB. Against M. avium, however, compound
17 showed a MIC of 8 lg/mL, and 3 and 4 a MIC of
16 lg/mL. The blocked analogs 10 and 11 were inactive
at 12.8 lg/mL. In conclusion, we report efficient synthe-
ses of O- and C-linked disaccharides 3, 4, and 17, and
their inhibitory activity against MTB.
16. Chang, G. X.; Lowary, T. L. Tetrahedron Lett. 2006, 47,
4561.
17. Reynolds, R. C.; Bansal, N.; Rose, J.; Friedrich, J.;
Suiling, W. J.; Maddry, J. A. Carbohydr. Res. 1999, 317,
164.
18. Dondoni, A.; Zuurmond, H. M.; Boscarato, A. J. Org.
Chem. 1997, 62, 8114.
19. Compound formation was monitored by ESI-MS that
showed m/z at 583 [M+H]+.
20. Selected data: Compound 6: 1H NMR (CDCl3): d 4.13 (s,
1H, H-3), 3.97–4.04 (m, 3H, H-2, H-4, H-5), 3.66 (d, 2H,
J = 7.4 Hz H2-6), 3.46 (dd, 1H, J = 7.0, 12.3 Hz, H-1a),
3.32 (dd, 1H, J = 6.7, 12.3 Hz, H-1b), 0.893 (s, 9H, 3·
CH3), 0.890 (s, 9H, 3· CH3), 0.89 (s, 9H, 3· CH3), 0.10
(12H, s, 4· CH3), 0.05 (6H, s, 2· CH3). ESIMS: m/z calcd
for C24H53N3O4Si3 532.3422, found: 532.3418 [M+H]+.
1
Compound 7: H NMR (CDCl3): d 4.10–4.06 (m, 2H,
H-2, H-5), 4.05–4.00 (m, 2H, H-3, H-4), 3.71 (dd, 2H,
J = 4.5, 5.7 Hz, H2-6), 3.50 (dd, 1H, J = 7.0, 12.4 Hz,
H-1a), 3.36 (dd, 1H, J = 6.8, 12.4 Hz, H-1b), 2.38 (t, 1H,
J = 5.7 Hz, 6-OH), 0.91, 0.90 (s, 9H, 3· CH3), 0.90 (s, 9H,
3· CH3), 0.12 (3H, s, CH3), 0.11 (3H, s, CH3), 0.10 (3H, s,
CH3), 0.09 (3H, s, CH3). ESI-MS: m/z calcd for
C18H39N3O4Si2 418.2557, found: 418.2551 [M+H]+.

4530
A. K. Pathak et al. / Bioorg. Med. Chem. Lett. 17 (2007) 4527–4530
Compound 11: 1H NMR (CDCl3): d 5.01 (1H, s, H-10),
7.55–7.52 (1H, m, Ar), 7.49–7.43 (2H, m, Ar), 4.68 (1H,
m, H-6a), 4.42 (1H, s, H-4), 4.29 (1H, m, H-5), 3.39
(1H, s, H-3), 3.85 (1H, m, H-6b), 3.71 (1H, dd, J = 5.6,
7.1 Hz, H-2), 2.46 (1H, dd, J = 7.1, 13.8 Hz, H-1a), 2.39
(1H, dd, J = 5.6, 13.8 Hz, H-1b), 1.95 (1H, dd, J = 6.3,
12.0 Hz, NCH2), 2.46 (1H, dd, J = 7.4, 12.0 Hz, NCH2),
1.71–1.56 (10H, m, cyclohexyl), 1.31–1.03 (10H, m,
cyclohexyl), 0.93 (9H, s, 3· CH3), 0.82 (9H, s, 3· CH3),
0.71–0.61 (2H, m, cyclohexyl), 0.23 (3H, s, CH3),
0.21 (3H, s, CH3), 0.18 (6H, s, 2· CH3). ESIMS: m/z
calcd for C50H79NO3IPSi2 825.5335, found: 825.5330
[M-I]+.
4.76 (1H, d, J = 1.4 Hz, H-1), 4.17 (1H, br s, H-40), 4.03–
3.97 (3H, m, H-2, H-4, H-20), 3.83–3.76 (3H, m, H-3, H-
5a, H-30), 3.68–3.58 (1H, m, OCH2), 3.59 (1H, dd,
J = 3.2 Hz, J = 10.4 Hz, H-5b), 3.35–3.28 (1H, m,
OCH2), 2.71–2.60 (2H, m, H2-50), 2.44 (2H, dd, J = 7.7,
12.6 Hz, NCH2), 2.16 (2H, dd, J = 5.2, 12.6 Hz, NCH2),
0
1.87–1.60 (4H, m, cyclohexyl CH2 s), 1.57–1.50 (10H, m,
cyclohexyl), 1.46–1.41 (2H, m, CH2), 1.37 (10H, br s, 5·
CH2), 1.20–1.08 (8H, m, cyclohexyl), 0.90–0.86 (21H, m,
7· CH3), 0.09, 0.07, 0.06 (each s, 4· CH3). ESIMS: m/z
calcd for C51H98N2O7Si2 907.6990, found: 907.6998
[M+H]+.
Compound 16: 1H NMR (CDCl3): d 5.66 (2H, dd,
J = 2.0, 6.6 Hz, H-6, H-7), 4.54 (2H, d, J = 6.6, 13.2 Hz,
H-5, H-8), 3.99 (2H, s, H-3, H-10), 3.97 (2H, dd,
J = 4.5, 8.7 Hz, H-2, H-11), 3.91 (2H, s, H-4, H-9), 2.76
(2H, dd, J = 8.7, 13.4 Hz, H-1a, H-12a), 2.34 (2H, dd,
J = 4.6, 13.4 Hz, H-1b, H-12b), 2.20 (2H, dd J = 8.6,
12.6 Hz, NCH2), 2.12 (2H, dd J = 5.7, 12.6 Hz, NCH2),
1.91–1.11 (40H, m, cyclohexyl), 0.93 (18H, s, 6· CH3),
0.87 (18H, s, 6· CH3), 0.92–0.75 (4H, m, cyclohexyl),
0.11 (6H, s, 2· CH3), 0.10 (6H, s, 2· CH3), 0.073 (6H,
s, 2· CH3), 0.070 (6H, s, 2· CH3). ESIMS: m/z calcd
for C64H126N2O6Si4 1131.8765, found: 1131.8756
[M+H]+.
Compound 3: 1H NMR (CD3OD): d 4.95 (1H, dd,
J = 1.6 Hz, H-10), 4.83 (1H, d, J = 1.7 Hz, H-1), 4.04 (1H,
ddd, J = 3.5, 6.2, 6.6 Hz, H-40), 4.00 (1H, dd, J = 1.6 Hz,
J = 3.8 Hz, H-20), 4.03–3.99 (1H, m, H-4), 3.94 (1H, dd,
J = 1.7, 3.9 Hz, H-2), 3.87 (1H, dd,J = 3.8, 6.6 Hz, H-30),
3.86–3.79 (2H, m, H-3, H-5a), 3.73–3.65 (1H, m, OCH2),
3.65 (1H, dd, J = 3.6, 11.1 Hz, H-5b), 3.50 (1H, dd,
J = 3.3, 13.3 Hz, H-50a), 3.44–3.36 (2H, m, OCH2), 3.37
(1H, dd, J = 6.2, 13.3 Hz, H-50b), 1.62–1.53 (2H, m, CH2),
1.30 (10H, br s, 5· CH2), 0.92–0.87 (3H, m, CH3). ESIMS:
m/z calcd for C18H33N3O8Na 442.2165, found: 442.2176
[M+Na]+.
1
Compound 12: H NMR (CDCl3): d 4.00 (3H, m, H-3,
Compound 17: 1H NMR (CDCl3): d 5.84 (2H, dd,
J = 1.1, 4.7 Hz, H-6, H-7), 4.59 (2H, dd, J = 4.7,
13.4 Hz, H-5, H-8), 3.99 (2H, dd, J = 3.9, 6.7 Hz, H-2,
H-11), 3.98 (4H, s, H-3, H-4, H-9, H-10), 2.67 (2H, dd,
J = 6.7, 13.2 Hz, H-1a, H-12a), 2.56 (2H, dd, J = 2.9,
13.2 Hz, H-1b, H-12b), 2.28 (2H, dd, J = 8.3, 12.8 Hz,
NCH2), 2.14 (2H, dd, J = 5.4, 12.8 Hz, NCH2), 1.82–
1.09 (44H, m, cyclohexyl, 4· OH), 0.91–0.78 (4H, m,
cyclohexyl). ESIMS: m/z calcd for C40H70N2O6
675.5306, found: 675.5317 [M+H]+.
H-4, H-5), 3.96 (1H, dd, J = 5.5, 8.1 Hz, H-2), 3.68 (1H, d,
J = 4.1 Hz, H-6a), 2.72 (1H, dd, J = 8.1, 13.6 Hz, H-1a),
2.43 (1H, dd, J = 5.5, 13.6 Hz, H-1b), 2.18 (2H, m,
NCH2), 1.93–1.10 (22H, m, Cyclohexyl), 0.90, 0.89 (each
9H, s, 6· CH3), 0.12 (3H, s, CH3), 0.11 (6H, s, 2· CH3),
0.80 (3H, s, CH3). ESIMS: m/z calcd for C32H65NO4Si2
584.4530, found: 584.4534 [M+H]+.
Compound 13: 1H NMR (CDCl3): d 4.24 (1H, s,
H-4), 4.14 (1H, dd, J = 5.3, 10.4 Hz, H-5), 4.04 (1H, dd,
J = 5.1, 8.5 Hz, H-2), 3.96 (1H, s, H-3), 3.44 (1H, dd,
J = 9.4, 10.4 Hz, H-6a), 3.22 (1H, dd, J = 5.3, 9.4 Hz,
H-6b), 2.67 (1H, dd, J = 8.5, 13.4Hz, H-1a), 2.39 (1H,
dd, J = 5.1, 13.4 Hz, H-1b), 2.19 (1H, dd, J = 8.1,
12.6 Hz, NCH2), 2.12 (1H, dd, J = 5.7, 12.8 Hz,
NCH2), 1.85–1.10 (20H, m, cyclohexyl) 0.92–0.76 (4H,
m, cyclohexyl), 0.91 (9H, s, 3· CH3), 0.89 (9H, s, 3·
CH3), ESIMS: m/z calcd for C32H64INO3Si2 694.3549,
found: 694.3539 [M+H]+.
1
Compound 4: H NMR (DMSO-d6, D2O exchanged):
d 3.75 (8H, m, H-2, H-3, H-4, H-5, H-8, H-9, H-10, H-
11), 2.53 (2H, m, H-1a, H-12a), 2.35 (2H, dd, J = 7.6,
13.6 Hz, H-1b, H-12b), 2.20 (2H, dd, J = 8.2, 12.5 Hz,
NCH2), 2.12 (2H, dd, J = 6.6, 12.5 Hz, NCH2), 1.85–
1.08 (40H, m, cyclohexyl), 0.88–0.71 (4H, m, cyclo-
hexyl). ESIMS: m/z calcd for C40H72N2O6 677.5463,
found: 677.5466 [M+H]+.
21. Suling, W. J.; Reynolds, R. C.; Barrow, E. W.; Wilson, L.
N.; Piper, J. R.; Barrow, W. W. J. Antimicrob. Chemother.
1998, 42, 811.
Compound 14: 1H NMR (CDCl3): d 7.89–7.82 (4H,
m, Ar), 7.76–7.74 (2H, m, Ar), 7.71–7.62 (6H, m, Ar),