Synthesis, Characterization, X-Ray Crystallography, and Antileishmanial Activities of N-Linked and O-Linked Glycopyranosides

Article abstract of DOI:10.1155/2018/9648710

Novel N-linked 5a-e and O-linked glycopyranosides 7a-e were synthesized in high yield from commercially available L-tartaric acid containing two asymmetric centers and C2 axis of symmetry. The compound L-tartaric acid was completely protected and then partially hydrolyzed to get the monoester, which upon treatment with different amino and hydroxyl derivatives of glycopyranoses gave the desired amides and esters. The synthesized derivatives were purified by chromatography and characterized by spectroanalytical techniques. The structure of compound 7c in the series was supported by X-ray analysis. Leishmanicidal activities of compounds 5a-e and 7a-e were investigated which showed moderate to good activities.

Full text of DOI:10.1155/2018/9648710

Hindawi
Journal of Chemistry
Volume 2018, Article ID 9648710, 9 pages
https://doi.org/10.1155/2018/9648710
Research Article
Synthesis, Characterization, X-Ray
Crystallography, and Antileishmanial Activities of
N-Linked and O-Linked Glycopyranosides
1
2
3,4
5
Haroon ur Rashid , Sher Wali Khan , Momin Khan, Akhtar Nadhman,
2
2
6
Noor Rehman, Muhammad Tariq, and Sammer Yousuf
1
Department of Chemistry, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan
Department of Chemistry, Shaheed BB University, Sheringal, Upper Dir, Khyber Pakhtunkhwa, Pakistan
Department of Biotechnology, Quaid-I-Azam University, Islamabad 45320, Pakistan
Department of Microbiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
Institute of Integrative Biosciences (IIB), CECOS University of Information Technology and Emerging Sciences, Peshawar,
Khyber Pakhtunkhwa, Pakistan
2
3
4
5
6
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi,
Karachi 75270, Pakistan
Correspondence should be addressed to Sher Wali Khan; sherwalikhn@yahoo.co.uk
Received 1 August 2017; Revised 14 November 2017; Accepted 7 December 2017; Published 30 January 2018
Academic Editor: Vinod Kumar Tiwari
Copyright © 2018 Haroon ur Rashid et al. ꢀis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Novel ꢀ-linked 5a–e and ꢁ-linked glycopyranosides 7a–e were synthesized in high yield from commercially available L-tartaric
acid containing two asymmetric centers and ꢂ axis of symmetry. ꢀe compound L-tartaric acid was completely protected
2
and then partially hydrolyzed to get the monoester, which upon treatment with diꢁerent amino and hydroxyl derivatives of
glycopyranoses gave the desired amides and esters. ꢀe synthesized derivatives were puriꢂed by chromatography and characterized
by spectroanalytical techniques. ꢀe structure of compound 7c in the series was supported by X-ray analysis. Leishmanicidal
activities of compounds 5a–e and 7a–e were investigated which showed moderate to good activities.
1
. Introduction
disease, the discovery of new potential drugs against it is
underway [8, 9].
Leishmania has long been known to human beings especially
in African and Indian populations since the mid eighteenth
century [1–3]. In 1903, Leishman and Donovan discovered
the protozoan in spleen tissues of patients in India, which
is now known as Leishmania donovani [4, 5]. Nicolle and
Comte reported infection by Leishmania in dogs in 1908 [6].
Leishmaniasis is a vector-borne disease carried by sand ꢃy
and caused by protozoa of the genus Leishmania. Recent
reports conꢂrm that people in about 88 countries are aꢁected
by Leishmania and 350 million are at risk, and more or less
Glycolipid and glycoprotein oligosaccharides present on
cell surfaces are known to play an important role in various
biological processes, that is, cellular recognition, adhesion,
tumor metastasis, and cell growth regulation [10]. One
major class of glycoprotein oligosaccharides consists of ꢀ-
oligosaccharides linked to asparagine by an amide bond [11,
12]. Amides are usually prepared by thermolysis of carboxylic
acids with amines, by coupling of carboxylic acids and
amines in the presence of a coupling reagent [13] or by prior
conversion of the carboxylic acid into a more electrophilic
derivative [14]. ꢀe concept to add a chiral aglycone moiety
such as tartaric acid to prepare glycosides is an active area
2
million new cases are reported each year [7]. In spite of
the socioeconomical signiꢂcance of this tropical infectious

2
Journal of Chemistry
of research. L-tartaric acid is cheap and readily available
starting material; it has two chiral centers with two carboxylic
acid groups which can be easily derivatized. Derivatives
of tartaric acid containing ester and amide linkages have
promisingly useful biological applications, for example, anti-
inꢃammatory, antifungal, thrombin inhibitors, antimicrobial,
and ꢃ-secretase inhibitory activities [15–20].
as matrix material. Optical rotations were measured on an
ATAGO, AP-100 Automatic polarimeter. Single crystal X-
ray diꢁraction data were collected on a Bruker Smart APEX
II, CCD detector diꢁractometer [21]. Data reductions were
performed using the SAINT program. ꢀe structures were
solved by direct methods [22] and reꢂned by full-matrix least
squares on F2 by using the SHELXTL-PC package [23]. ꢀe
ꢂgures were plotted with the aid of ORTEP program [24].
Hence, glyco derivatives of tartaric acid have potential
as curative agents for various infectious diseases. Herein, we
report an eꢄcient and scalable synthesis of ꢀ-linked (5a–e)
and ꢁ-linked glycopyranosides (7a–e) through anomeric ꢀ-
and ꢁ-acylation, respectively, using commercially available
L-tartaric acid as a starting material.
2
.1. General Procedure for the Synthesis of N-Linked Gly-
copyranosides (5a–e). In a round bottom ꢃask (100 mL),
monoester 1 (0.61 g, 3 mmol), EDC (0.74 g, 3 mmol × 1.3
eq.), and catalytic amount of DMAP were placed under
nitrogen. CH Cl (30 mL) was added as a solvent. Aꢅer
2
2
2
. Experimental
3
0 min glycopyranosyl amine 4a–e (3 mmol) was added and
the mixture was stirred for 18 h. ꢀe byproduct urea was
removed by extraction of the reaction mixture with ethyl
acetate or chloroform and water (30 mL × 2). ꢀe crude
product was puriꢂed by column chromatography using ethyl
acetate : hexane (3 : 7) as eluent.
All chemicals were of highest purity available and used as sup-
plied. D-glucose, D-mannose, D-galactose, D-glucosamine,
and D-galactosamine hydrochloride were purchased from
Fluka and Sigma Aldrich. Dry solvents like methanol,
dichloromethane, chloroform, and n-hexane were obtained
by distillation using standard procedures or by passage
through a column of anhydrous alumina using equipment
from anhydrous engineering (University of Bristol, UK)
based on Grubbs’ design. Reactions under anhydrous con-
ditions were carried out under nitrogen gas using three-way
stopcock and rubber septa.
Liquid reagents, solutions, or solvents were added via
syringe or cannula through rubber septa. Solid reagents were
added via Schlenk type adapters. All reactions were moni-
tored by TLC on Kieselgel 60 F254 (Merck); ethyl acetate/n-
hexane and methanol/chloroform were used as eluent. Chro-
2.2. (2R,3R,5R,6R)-2-(Acetoxymethyl)-6-((4R,5R)-5-(methox-
ycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxamido)tetra-
hydro-2H-pyran-3,4,5-triyl Triacetate 5a. Yield: 72%. Color-
2
5
−1
less oil [ꢇ] = 12.5. (IR ꢈ cm ): 3347 (NH), 2955 (CH),
D
1
1
742 (COOCH ), 1701 (CONH), 1299 (C-O-C). HNMR
3
(
400 MHz, CDCl ): ꢉ (ppm): 7.18 (d, J = 9.3 Hz, NH), 5.23,
3
5
.18, 5.05, 4.96 (pseudo t, J ∼ 9.2 Hz in each, CH), 4.65 (d,
J = 5.4 Hz, CH), 4.59 (d, J = 5.4 Hz, CH), 4.30 (dd, J = 12.5,
3
1
.6 Hz, CH), 4.21 (ddd, J = 10.4, 3.6, 2.1 Hz, CH), 3.95 (dd, J =
2.5, 2.1 Hz, CH), 3.75 (s, OCH ), 1.94, 1.92, 1.91, 1.89 (s, CH ),
3
3
matograms were detected under UV light (ꢄ
254 and
13
max
1.56 (s, CH ), 1.50 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ
3
3
3
3
65 nm) and by charring with 10% sulfuric acid in ethanol,
(
ppm): 171.2 (CONH), 170.7 (COOCH ), 170.0, 169.9, 169.5,
3
ninhydrin, and vanillin, respectively. Column chromatogra-
1
69.2 (CO), 113.3 (qt C), 81.8 (CH), 76.3 (CH), 75.2 (CH), 73.3,
phy was performed using silica gel [Merck, 230−400 mesh
7
2
2.5, 70.0, 67.8 (CH), 61.2 (CH), 52.4 (OCH ), 25.9, (CH ),
3
3
(
40−63 ꢅm)]. Extracts were concentrated under reduced
5.2 (CH ), 20.2, 20.1 (3), (CH ). HRMS-ESI for C H NO
3
3
22 31
14
pressure using both rotary evaporator (bath temperature up
+
Na: [M + Na] calcd: 556.1745, found: 556.1621. Anal. Calc.
∘
to 40 C) at a pressure of either 15 mmHg (diaphragm pump)
For C H NO : C, 49.53; H, 5.86; N, 2.63; O, 41.99 Found
22
31
14
or 0.1 mmHg (oil pump), as appropriate and a high vacuum
line at room temperature. Melting points were determined in
C, 49.43; H, 5.56; N, 2.78; O, 42.10.
∘
degree Celsius ( C) using Gallenkamp digital melting point
2
.3. (2R,3R,5R,6R)-2-(Acetoxymethyl)-6-((4R,5R)-5-(methox-
apparatus and are uncorrected. IR spectra were recorded on
a Bruker IFS 66 (FT-IR), Nicolet 205 FT-IR; Nicolet 360
smart orbit (ATR); ꢀermo Scientiꢂc Nicolet 6700 FT-IR and
Shimadzu Fourier Transform Infrared Spectrophotometer
Model 270. Solid samples were taken in KBr pellets and
oils were used in NaCl cells for recording their spectra.
ycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxamido)tetra-
hydro-2H-pyran-3,4,5-triyl Triacetate 5b. Yield: 69%. Color-
2
5
−1
less oil [ꢇ] = 13.3. (IR ꢈ cm ): 3337 (NH), 2925 (CH),
D
1
1732 (COOCH ), 1703 (CONH), 1292 (C-O-C). HNMR
3
(400 MHz, CDCl ): ꢉ (ppm): 7.47 (d, J = 9.3 Hz, NH), 5.34,
3
1
HNMR spectra were recorded on an NMR Bruker apparatus
5.31, 5.24 (pseudo t, J = 10.0, Hz in each, CH), 4.95 (t, J =
3.9 Hz, CH), 4.93 (d, J = 5.5 Hz, CH), 4.80 (d, J = 5.5 Hz,
CH), 4.28 (dd, J = 12.4, 3.5 Hz, CH), 4.10 (ddd, J = 10.3, 3.6,
13
at 300 MHz and Varian 400 MHz INOVA instrument.
C
NMR spectra were recorded on NMR Bruker apparatus at
7
5 MHz and Varian 100 MHz INOVA instrument. Chemical
2.1 Hz, CH), 3.95 (dd, J = 12.4, 3.5 Hz, CH), 3.77 (s, OCH ),
3
shiꢅs are quoted in parts per million from SiMe or residual
2.34, 2.23, 2.13, 1.99 (s, CH ), 1.52 (s, CH ), 1.46 (s, CH ).
4
3
3
3
13
solvent proton signals and coupling constants (ꢆ) given in
Hertz. Multiplicities are abbreviated as b (broad), s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), or combina-
tions thereof. Positive ion Matrix Assisted Laser Desorption
Ionization Time-of-Flight (MALDI-TOF) mass spectra were
recorded using an HP-MALDI instrument using gentisic acid
C NMR (100 MHz, CDCl ): ꢉ (ppm): 172.2 (CONH), 170.9
3
(COOCH ), 170.1, 169.6, 169.3, 169.1 (CO), 114.3 (qt C), 81.4
3
(CH), 76.5 (CH), 75.1 (CH), 73.1, 72.3, 70.1, 67.9 (CH), 61.8
(CH), 52.9 (OCH ), 25.5 (CH ), 25.1 (CH ), 20.1, 20.0 (3)
3
3
3
+
(CH ). HRMS-ESI for C H NO Na: [M + Na] calcd:
3
22 31
14
556.1745, found: 556.1627. Anal. Calc. For C H NO : C,
22
31
14

Journal of Chemistry
3
4
9.53; H, 5.86; N, 2.63; O, 41.99 Found C, 49.43; H, 5.56; N,
72.3, 70.1, 67.3, (CH), 62.4 (CH), 53.2 (OCH ), 26.2 (CH ),
3
3
2
.78; O, 42.10.
25.7 (CH ), 20.7, 19.5 (3) (CH ). HRMS-ESI for C H NO
3
3
22 31
14
+
Na: [M + Na] calcd: 555.1904, found: 555.1719. Anal. Calc.
For C H N O : C, 49.62; H, 6.06; N, 5.26; O, 39.06 Found
2
2
32
2
13
2
.4. (2R,3R,5R,6R)-2-(Acetoxymethyl)-6-((4R,5R)-5-(methox-
C, 49.32; H, 6.16; N, 5.21; O, 39.16.
ycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxamido)tetra-
hydro-2H-pyran-3,4,5-triyl Triacetate 5c. Yield: 65%. Color-
2
5
−1
2
.7. General Procedure for the Synthesis of ꢁ-Linked Glycopy-
less oil [ꢇ] = 27.1. (IR ꢈ cm ): 3339 (NH), 2928 (CH),
D
1
ranosides (7a–e). Hydrazinium acetate (1.10 g, 12 mmol) was
added to a stirred solution of anomeric mixture of acetylated
monosaccharides 1a–e (3.12 g, 8 mmol) in DMF (40 mL). ꢀe
1
736 (COOCH ), 1700 (CONH), 1290 (C-O-C). HNMR
3
(
400 MHz, CDCl ): ꢉ (ppm): 7.37 (d, J = 9.3 Hz, NH), 5.42,
3
5
.40, 5.36 (pseudo t, J ∼ 6.5 Hz in each, CH), 4.98 (t, J =
∘
reaction mixture was heated at 55 C for 30 min under a
1
1.9 Hz, CH), 4.97 (d, J = 5.6 Hz, CH), 4.90 (d, J = 5.6 Hz,
nitrogen atmosphere. Aꢅer completion, the reaction mixture
CH), 4.48 (dd, J = 12.7, 3.4 Hz, CH), 4.12 (ddd, J = 10.4, 3.6,
was diluted with H O (100 mL) and extracted with EtOAc
2
.1 Hz, CH), 3.92 (dd, J = 12.4, 3.5 Hz, CH), 3.84 (s, OCH ),
2
3
(
40 mL × 3). ꢀe combined organic layers were washed with
2
.11, 2.10, 2.09, 1.99 (s, CH ), 1.54 (s, CH ), 1.48 (s, CH ).
3
3
3
1
3
water and brine (40 × 2), dried over anhydrous MgSO .
C NMR (100 MHz, CDCl ): ꢉ (ppm): 171.8 (CONH), 170.2
4
3
ꢀ
e solvent was removed under reduced pressure and the
(
COOCH ), 170.3, 169.5, 169.4, 169.2 (CO), 114.2 (qt C), 81.5
3
crude product was used without further puriꢂcation. To the
resulting hemiacetal (1.04 g, 3 mmol), monoester 1 (0.61 g,
3 mmol), EDC (0.74 g, 3 mmol × 1.3 eq.), and catalytic amount
of DMAP were added under nitrogen with CH Cl (30 mL).
(
CH), 76.1 (CH), 75.2 (CH), 73.3, 72.2, 70.1, 67.5 (CH), 61.9
(
CH), 52.5 (OCH ), 26.5 (CH ), 25.7 (CH ), 20.4, 19.5 (3)
3
3
3
+
(
CH ). HRMS-ESI for C H NO Na: [M + Na] calcd:
3
22 31
14
5
56.1745, found: 556.1643. Anal. Calc. For C H NO : C,
2
2
22
31
14
ꢀ
e reaction mixture was stirred for 18 h; the byproduct urea
4
9.53; H, 5.86; N, 2.63; O, 41.99 Found C, 49.43; H, 5.56; N,
was removed by extraction of the reaction mixture with ethyl
acetate or chloroform and water (30 mL × 3). ꢀe crude
product was puriꢂed by column chromatography using ethyl
acetate: n-hexane (3 : 7) as eluent.
2
.78; O, 42.10.
2
.5. (2R,3S,5R,6R)-5-Acetamido-2-(acetoxymethyl)-6-((4R,
R)-5-(methoxycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-car-
5
boxamido)tetrahydro-2H-pyran-3,4-diyl Diacetate 5d. Yield:
2
5
−1
2.8. (4R,5R)-4-Methyl-5-((2S,3R,5R,6R)-3,4,5-triacetoxy-6-
6
7%. Gel like. [ꢇ] = 43.3. (IR ꢈ cm ): 3343 (NH), 2948
D
(
acetoxymethyl)tetrahydro-2H-pyran-2-yl)-2,2-dimethyl-1,3-
(
CH), 1746 (COOCH ), 1710 (CONH), 1293 (C-O-C).
3
1
dioxolane-4,5-dicarboxylate 7a. Yield: 72%. Colorless oil
HNMR (400 MHz, CDCl ): ꢉ (ppm): 7.69 (d, J = 9.5 Hz,
3
25
−1
[
ꢇ] = 26.5. (IR ꢈ cm ): 2991 (CH), 1742 (CO), 1366 (C-O-
NH), 7.57 (d, J = 9.3 Hz, NH), 5.43 (t, J = 10.0 Hz, 1H), 5.41-5.32
D
1
C). HNMR (400 MHz, CDCl ): ꢉ (ppm): 6.45 (d, J = 4.0 Hz,
(
m, CH), 5.37, 4.99 (pseudo t, J ∼ 10.0 Hz in each, CH), 4.96
3
ꢀ
ꢁ
(
d, J = 5.5 Hz, CH), 4.94 (d, J = 5.5 Hz, CH), 4.44 (dd, J = 12.7,
1H, H-1 ), 5.56 (d, J = 8.0 Hz, 1H, H-1 ), 5.48, 5.45, 4.93
(pseudo t, J ∼ 9.8 Hz in each, CH), 4.91 (d, J = 6.3 Hz, CH),
4.88 (d, J = 6.3 Hz, CH), 4.32 (dd, J = 12.5, 3.6 Hz, CH), 4.12
(ddd, J = 10.4, 3.6, 2.1 Hz, CH), 3.93 (dd, J = 12.5, 2.1 Hz, CH),
3.86 (s, OCH ), 2.19, 2.17, 2.12, 2.04 (s, CH ), 1.55 (s, CH ),
3
.4 Hz, CH), 4.22 (ddd, J = 10.4, 3.6, 2.1 Hz, CH), 3.91 (dd, J =
1
1
(
1
2.4, 3.5 Hz, CH), 3.86 (s, OCH ), 2.21, 2.20, 2.19, 2.13 (s, CH ),
3
3
13
.57 (s, CH ), 1.49 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ
3
3
3
3
13
ppm): 172.8 (CONH), 171.2 (COOCH ), 170.2, 169.8, 169.5,
3
3
3
3
1
3
69.1 (CO), 114.1 (qt C), 81.8 (CH), 76.1 (CH), 75.3 (CH), 73.2,
1.46 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ (ppm): 172.6
3
3
7
2.1, 70.0, 67.8 (CH), 61.4 (CH), 52.2 (OCH ), 26.2 (CH ), 25.8
(COOCH ), 171.2, 169.5, 169.3, 169.0 (CO), 113.4 (qt C), 92.3
3
3
3
(
CH ), 20.3, 19.3 (3) (CH ). HRMS-ESI for C H N O Na:
(CH), 92.1 (CH), 76.3 (CH), 75.4 (CH), 74.2, 73.3, 72.1, 70.3
3
22 32
2
+
[
M + Na] calcd: 555.1904, found: 555.1619. Anal. Calc. For
(CH), 56.6 (CH), 53.4 (OCH ), 26.6 (CH ), 25.9 (CH ), 20.3
3
3
3
+
C H N O : C, 49.62; H, 6.06; N, 5.26; O, 39.06 Found C,
(2), 19.8, 19.3 (CH ). HRMS-ESI for C H O Na: [M + Na]
22
32
2
13
3
22 30 15
4
9.32; H, 6.16; N, 5.21; O, 39.16.
calcd: 557.1585, found: 557.1452. Anal. Calc. For C H O : C,
2
2
30 15
4
9.44; H, 5.66; O, 44.90 Found C, 49.39; H, 5.70; O, 44.81.
2
.6. (2R,3S,5R,6R)-5-Acetamido-2-(acetoxymethyl)-6-((4R,
R)-5-(methoxycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-car-
5
2.9. (4R,5R)-4-Methyl-5-((2S,3R,5R,6R)-3,4,5-triacetoxy-6-
(acetoxymethyl)tetrahydro-2H-pyran-2-yl)-2,2-dimethyl-1,3-
dioxolane-4,5-dicarboxylate 7b. Yield: 74%. Colorless gel
boxamido)tetrahydro-2H-pyran-3,4-diyl Diacetate 5e. Yield:
2
5
−1
6
8%. Gel like. [ꢇ] = 47.1. (IR ꢈ cm ): 3341 (NH), 2942 (CH),
D
2
5
−1
1
[
ꢇ] = 21.6. (IR ꢈ cm ): 2993 (CH), 1744 (CO), 1361 (C-O-
1
(
(
745 (COOCH ), 1711 (CONH), 1290 (C-O-C). HNMR
D
3
1
400 MHz, CDCl ): ꢉ (ppm): 7.67 (d, J = 9.6 Hz, NH), 7.55
C). HNMR (400 MHz, CDCl3): ꢉ (ppm): 6.47 (d, J = 3.9 Hz,
3
ꢀ
ꢁ
d, J = 9.3 Hz, NH), 5.41 (t, J = 10.8 Hz, CH), 5.40 (m, CH),
1H, H-1 ), 5.53 (d, J = 8.3 Hz, 1H, H-1 ), 5.47, 4.93 (pseudo
t, J ∼ 6.9 Hz in each, CH), 5.50 (t, J = 8.9 Hz, CH), 4.94 (d,
J = 6.3 Hz, CH), 4.88 (d, J = 6.3 Hz, CH), 4.27 (dd, J = 12.5,
3.6 Hz, CH), 4.14 (ddd, J = 10.4, 3.6, 2.1 Hz, CH), 3.96 (dd, J =
12.5, 2.1 Hz, CH), 3.86 (s, OCH ), 2.19, 2.17, 2.12, 2.04 (s, CH ),
5
.38, 4.97 (pseudo t, J ∼ 6.9 Hz in each, CH), 4.93 (d, J =
5
.6 Hz, CH), 4.91 (d, J = 5.5 Hz, CH), 4.41 (dd, J = 12.7, 3.4 Hz,
CH), 4.21 (ddd, J = 10.4, 3.6, 2.1 Hz, CH), 3.90 (dd, J = 12.4,
3
.5 Hz, CH), 3.83 (s, OCH ), 2.23, 2.22, 2.20, 2.16 (s, CH ),
3
3
3
3
13
13
1
(
1
.56 (s, CH ), 1.46 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ
1.55 (s, CH ), 1.45 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ
3
3
3
3
3
3
ppm): 172.2 (CONH), 171.3 (COOCH ), 170.5, 169.5, 169.2,
(ppm): 172.3 (COOCH ), 171.7, 169.4, 169.3, 169.1 (CO), 113.3
3
3
69.1 (CO), 113.4 (qt C), 81.6 (CH), 76.4 (CH), 75.2 (CH), 73.4,
(qt C), 92.7 (CH), 92.4 (CH), 76.2 (CH), 75.6 (CH), 74.4, 73.5,

4
Journal of Chemistry
7
2.2, 70.2, (CH), 56.5 (CH), 53.2 (OCH ), 25.6 (CH ), 24.9
171.4 (COOCH ), 170.3, 169.5, 169.4, 169.2 (CO), 114.4 (qt C),
3
3
3
(
CH ), 20.6 (2), 19.7, 19.5 (CH ). HRMS-ESI for C H O
93.4 (CH), 92.7 (CH), 76.3 (CH), 75.2 (CH), 74.5, 73.4, 72.6,
70.1 (CH), 58.7 (CH), 53.5 (OCH ), 26.6 (CH ), 25.6 (CH ),
3
3
22 30 15
+
Na: [M + Na] calcd: 557.1585, found: 557.1466. Anal. Calc.
For C H O : C, 49.44; H, 5.66; O, 44.90 Found C, 49.39;
H, 5.70; O, 44.81.
3
3
3
20.1 (2), 19.4, 19.1 (CH ). HRMS-ESI for C H NO Na:
22
30 15
3
22 31
14
+
[M + Na] calcd: 556.1745, found: 556.1616. Anal. Calc. For
C H NO : C, 49.53; H, 5.86; N, 2.63; O, 41.99 Found C,
22
31
14
4
9.55; H, 5.81; N, 2.60; O, 41.91.
2
.10. (4R,5R)-4-Methyl-5-((2R,3R,5R,6R)-3,4,5-triacetoxy-6-
(
acetoxymethyl)tetrahydro-2H-pyran-2-yl)-2,2-dimethyl-1,3-
dioxolane-4,5-dicarboxylate 7c. Yield: 70%. White foam m.p
3. Results and Discussion
∘
25
−1
=
151–153 C. [ꢇ] = 17.3. (IR ꢈ cm ): 2995 (CH), 1745 (CO),
D
1
As outlined in synthetic Schemes 1 and 2, our proposed
strategy was to transform ꢂve diꢁerent glycopyranoses to
glycopyranosyl amines 4a–e which would serve as nucle-
ophiles. In sugars, the anomeric position is comparatively
more reactive due to the presence of the endocyclic oxygen
atom. Owing to its higher reactivity, microwave assisted
Kochetkov amination was tried. ꢀe Kochetkov amination
is used to introduce amino functionality at the anomeric
position in unprotected sugars [25]. However, when glucose
was reacted under microwave with Kochetkov reagents,
that is, ammonium carbonate in DMSO, a mixture of
amino and untreated glucose was obtained aꢅer prolonged
lipophilization. In the case of glucosamine and galactosamine
hydrochlorides, which already contain amino functionality,
to ensure chemoselectivity in coupling with tartaric acid,
a relative long route was adopted involving protecting the
entire hydroxyl and amino functionalities on these sugars.
1
336 (C-O-C). HNMR (400 MHz, CDCl ): ꢉ (ppm): 6.42
3
ꢀ
ꢁ
(
d, J = 3.7 Hz, 1H, H-1 ), 5.51 (d, J = 4.0 Hz, 1H, H-1 ), 5.46,
5
.43 (pseudo t, J ∼ 5.6 Hz in each, CH), 4.96 (t, J = 9.8 Hz,
CH), 4.93 (d, J = 5.3 Hz, CH), 4.89 (d, J = 5.3 Hz, CH), 4.26
(
dd, J = 12.5, 3.6 Hz, CH), 4.13 (ddd, J = 10.4, 3.6, 2.1 Hz,
CH), 3.93 (dd, J = 12.5, 2.1 Hz, CH), 3.76 (s, OCH ), 2.15,
3
13
2
.14, 2.12, 2.11 (s, CH ), 1.56 (s, CH ), 1.46 (s, CH ). C NMR
3
3
3
(
1
(
(
100 MHz, CDCl ): ꢉ (ppm): 171.3 (COOCH , 170.7, 169.6,
3
3
69.3, 169.1 (CO), 113.4 (qt C), 92.4 (CH), 92.1 (CH), 76.1
CH), 75.6 (CH), 74.2, 73.2, 72.1, 70.5 (CH), 56.7 (CH), 53.3
OCH ), 26.6 (CH ), 25.8 (CH ), 20.2 (2), 19.8, 19.4 (CH ).
3
3
3
3
+
HRMS-ESI for C H O Na: [M + Na] calcd: 557.1585,
22
30 15
found: 557.1475. Anal. Calc. For C H O : C, 49.44; H, 5.66;
22
30 15
O, 44.90 Found C, 49.39; H, 5.70; O, 44.88.
2
.11. (4R,5R)-4-((2S,3R,5S,6R)-3-Acetamido-4,5-diacetoxy-6-
(
acetoxymethyl)tetrahydro-2H-pyran-2-yl)-5-methyl-2,2-dim-
ꢀ
us per acetylation [26], followed by anomeric bromination
ethyl-1,3-dioxolane-4,5-dicarboxylate 7d. Yield: 67%. Color-
2
5
−1
[27], azide formation [28] and reduction of azides aꢁorded
the target acetylated glycopyranosyl amines 4a–e.
less oil [ꢇ] = 45.0. (IR ꢈ cm ): 3342 (NH), 2981 (CH), 1739
D
1
(
CO), 1360 (C-O-C). HNMR (400 MHz, CDCl ): ꢉ (ppm):
3
ꢀ
Following the same coupling procedure with increased
time (Table 2), ꢁ-linked glycopyranosides 7a–e were also
prepared in 63–74% yields, starting from acetylated monosac-
charides 1a–e, Scheme 3.
7
.87 (d, J = 9.5 Hz, NH), 6.49 (d, J = 3.7 Hz, 1H, H-1 ), 5.57
ꢁ
(
d, J = 8.3 Hz, 1H, H-1 ), 5.46 (m, CH) 5.43, 4.96 (pseudo t,
J ∼ 7.4 Hz in each, CH), 4.94 (d, J = 6.3 Hz, CH), 4.83 (d, J =
6
.3 Hz, CH), 4.37 (dd, J = 12.5, 3.6 Hz, CH), 4.23 (ddd, J = 10.4,
It was observed that during per acetylation, a mixture
of both ꢇ and ꢃ anomers is formed in a 3 : 1 ratio. In
the bromination step, the thermodynamically more stable
ꢇ anomer was obtained exclusively. In the resultant bromo
analogue when leꢅ for longer time (two days), slight decom-
position was observed. ꢀerefore the product was used in
the next step immediately. ꢀe reaction of bromide 3a with
sodium azide in DMF proceeded in low yield; however under
sonication, the azide analogue was produced in excellent
yield. ꢀe substitution involves inversion of conꢂguration at
3
.6, 2.1 Hz, CH), 3.93 (dd, J = 12.5, 2.1 Hz, CH), 3.87 (s, OCH ),
3
2
.13, 2.11, 2.10, 2.04 (s, CH ), 1.57 (s, CH ), 1.49 (s, CH ).
3
3
3
1
3
C NMR (100 MHz, CDCl ): ꢉ (ppm): 171.6 (COOCH ),
3
3
1
(
(
70.3, 169.3, 169.2, 169.0 (CO), 113.6 (qt C), 92.6 (CH), 92.2
CH), 76.2 (CH), 75.1 (CH), 74.5, 73.3, 72.6, 70.1 (CH), 57.9
CH), 53.5 (OCH ), 26.4 (CH ), 25.6 (CH ), 20.1 (2), 19.5,
3
3
3
+
1
9.2, (CH ). HRMS-ESI for C H NO Na: [M + Na] calcd:
3
22 31
14
5
4
56.1745, found: 556.1614. Anal. Calc. For C H NO : C,
22
31
14
9.53; H, 5.86; N, 2.63; O, 41.99 Found C, 49.55; H, 5.76; N,
.60; O, 41.90.
2
the anomeric site and thus the ꢇ-glycopyranosyl bromide
gave the corresponding ꢃ-glycopyranosyl azide. ꢀe azide
intermediates were reduced immediately under catalytic
hydrogenation in the next step. ꢀe hydrogenation reaction
furnished the desired amines in quantitative yield, which
were stable when completely dried under vacuum. Once a
series of glycopyranosyl amines 4a–e were generated, the
next step was to synthesize the monoester 1 starting from
commercially available L-tartaric acid. Both the hydroxyl and
carboxyl groups were protected followed by partial hydrolysis
with one equivalent of lithium hydroxide; however the yield
was variable. By the use of a stronger base sodium hydroxide,
the yield was improved. It is important to mention that the
formation of monoester 1 from the diester does not depend
2
.12. (4R,5R)-4-((2S,3R,5S,6R)-3-Acetamido-4,5-diacetoxy-6-
(
acetoxymethyl)tetrahydro-2H-pyran-2-yl)-5-methyl-2,2-dim-
ethyl-1,3-dioxolane-4,5-dicarboxylate 7e. Yield: 63%. Color-
2
5
−1
less oil [ꢇ] = 33.3. (IR ꢈ cm ): 3348 (NH), 2990 (CH), 1741
D
1
(
CO), 1356 (C-O-C). HNMR (400 MHz, CDCl ): ꢉ (ppm):
3
ꢀ
7
.86 (d, ꢆ = 9.7 Hz, NH), 6.52 (d, ꢆ = 3.9 Hz, 1H, H-1 ), 5.67
ꢁ
(
d, ꢆ = 8.7 Hz, 1H, H-1 ), 5.46 (m, CH), 5.43, 4.96 (pseudo
t, ꢆ ∼ 6.0 Hz in each, CH), 4.93 (d, J = 5.4 Hz, CH), 4.82
(
d, ꢆ = 5.3 Hz, CH), 4.38 (dd, ꢆ = 12.5, 3.6 Hz, CH), 4.33
ddd, ꢆ = 10.4, 3.6, 2.1 Hz, CH), 3.93 (dd, ꢆ = 12.5, 2.1 Hz,
(
CH), 3.85 (s, OCH ), 2.14, 2.12, 2.10, 2.06 (s, CH ), 1.56 (s,
3
3
13
CH ), 1.46 (s, CH ). C NMR (100 MHz, CDCl ): ꢉ (ppm):
3
3
3

Journal of Chemistry
5
２1
OH
２1 OAc
２3
２1 OAc
２1 OAc
２3
２3
２3
(d)
(a)
(b)
(e)
(c)
２2
AcO
O
2
2
2
O
O
O
２
２
２
HO
OAc
AcO
AcO
．3
OH
２4
２4
２4
２4
Br
ꢀ
a–ꢀe
2a–2e
ꢁa–ꢁe
O
２1
O
２1
OAc
OAc
２3
２3
O
O
O
O
2
O
２
2
O
２
O
+
H
AcO
N
AcO
．（2
HO
O
２4
２4
O
O
ꢂa–ꢂe
ꢃa–ꢃe
1
3
2
4
1
3
2
4
(
a) D-Glucose ２ , ２ = H; ２ , ２ = OH
(d) D-Glucosamine·HCl ２ , ２ = H; ２ = OH; ２ = N（ ·HCl
2
1
4
2
3
1
2
3
4
(
b) D-Galactose ２ , ２ = OH; ２ , ２ = H
(e) D-Galactosamine·HCl ２ = OH; ２ , ２ = H; ２ = N（ ·HCl
2
1
4
2
3
(
c) D-Mannose ２ , ２ = H; ２ , ２ = OH
Sꢆꢇꢈꢉꢈ 1: Reagents and conditions: (a) Ac O, pyridine, cat. DMAP, N , r.t., overnight; (b) HBr/AcOH (30%), CH Cl , N , r.t., 2 h; (c) NaN ,
2
2
2
2
2
3
DMF, sonication, r.t., 15 min; (d) Pd/C (10%), H , MeOH, 30 min; (e) EDC, CH Cl , cat. DMAP, N , r.t., 18 h.
2
2
2
2
O
O
OH
OH
O
OH
O
O
(b)
O
O
(a)
O
O
O
O
HO
OH
O
O
(
1)
+
Sꢆꢇꢈꢉꢈ 2: Reagents and conditions: (a) MeOH, H , reꢃux, 2 h, 2-methoxypropene, CSA, DMF, N , r.t., overnight; (b) NaOH (1 eq), MeOH,
2
r.t., 2 h.
on which ester group of the two is cleaved as both groups
are homotopic and therefore monohydrolysis of any of these
groups will lead to identical molecules. ꢀe same strategy was
then used for all of the compounds in the series.
With glycopyranosyl amines and monoester in hand, it
was decided to use coupling reagents to form peptides 5a–e.
Diꢁerent coupling conditions were tried to generate the target
amides, Table 1. DCC in the presence of a DMAP catalyst
furnished the target amide in low yield. EDC when used in 1.3
equivalents for 12 h aꢁorded the amides in good yield and the
reaction was reproducible. Once coupling conditions were
optimized, the same coupling conditions were used for the
rest of the series to furnish the respective amides, Table 1.
and 170.9–170.2 ppm to C=O (ester), respectively. Elemental
analysis of the glycopyranosyl amides 5a–e conꢂrmed the
structures of the compounds. ꢀe exact mass of the com-
pounds was conꢂrmed by HRMS-ESI.
ꢀe anomeric acetyl group was hydrolyzed selectively
using hydrazinium acetate, in DMF [29–31]; the resulting
hemiacetal was washed with water and brine and used with-
out further puriꢂcation. To the crude hemiacetal, monoester
was added using EDC as a coupling agent. When compound
6a was coupled with monoester 1 using 1.3 eq. EDC, DMAP
with increased reaction time aꢁorded compound 7a in 72%
yield. Once the reaction conditions were optimized, the same
conditions were used for the rest of the series to furnish the
respective esters, Table 2.
ꢀ
e coupling reaction was high yielding and the com-
pounds were puriꢂed by column chromatography. IR spec-
tral data of the compounds 5a–e exhibited the appearance
of characteristic (NH) stretching bands in the range of
ꢀe synthesized compounds were puriꢂed by column
chromatography and characterized by spectroscopic tech-
niques. IR spectral data of the compounds 7a–e showed
characteristic (C=O) stretching bands ranging from 1745 to
−1
3
347–3331 cm and disappearance of NH stretching. Two
2
−
1
C=O stretching bands ranging from 1742 to 1736 and 1701
1739 cm in addition to C-O-C stretching in 1366–1356.
−1
−1
to 1692 cm were assigned to ester and amide, respec-
ꢀe NH stretching bands 7d-e appeared in 3348–3342 cm .
1
1
tively. HNMR spectral data shows characteristic doublets
HNMR spectral data showed doublets 7d-e, for the NH
for the NH protons in the range of 7.69–7.18 ppm with
protons in the range of 7.87–7.86 ppm with coupling con-
a coupling constant of 9.6–9.3 Hz. ꢀe anomeric protons
appeared as pseudotriplets in the range of 5.42–5.36 ppm
with coupling constant of 12.2–6.5 Hz which conꢂrms the
stant of 9.7–9.5 Hz. Both ꢇ- and ꢃ-anomers were found
to be 1 : 3 except compound 7c where ꢇ and ꢃ ratio was
1
1 : 1 as conꢂrmed by HNMR spectroscopy. ꢀe anomeric
formation of the ꢃ-anomer. In 13C NMR spectra, peaks
protons appeared as doublets in the range of 5.67–5.43 ppm
ranging from 172.8–171.2 ppm were assigned to C=O (amide)
with coupling constant of 8.3–8.0 Hz for the ꢃ-anomers

6
Journal of Chemistry
O
O
２1
２1 OAc
OAc
２1
OAc
２3
２3
２3
O
O
(
a)
O
(b)
O
O
2
O
2
O
+
２
２
2
O
O
O
AcO
OAc
AcO
OH
HO
２
O
AcO
２4
ꢅa–ꢅe
２4
２4
O
ꢀ
a–ꢀe
ꢄa–ꢄe
∘
Sꢆꢇꢈꢉꢈ 3: Reagents and conditions: (a) N H /AcOH (1.5 eq.), DMF, 55 C, N , 30 min; (b) EDC, CH Cl , cat. DMAP, N , rt, 18 h.
2
4
2
2
2
2
Tꢊꢋꢌꢈ 1: Diꢁerent coupling condition for amide synthesis.
Entry
1
2
3
4
5
6
Starting material
HA
HA
Reagents/conditions
Product (isolated yield%)
4a
4a
4a
4a
5a
6a
1.2 eq. DCC, cat. DMAP, CH Cl , r.t., 8 h
46
36
70
76
61
2
2
1 eq. EDC, cat. DMAP, CH Cl r.t., 8 h
2
2
HA
HA
HA
HA
1.1 eq. EDC, cat. DMAP, CH Cl r.t., 12 h
2
2
1.3 eq. EDC, cat. DMAP, CH Cl r.t., 12 h
2
2
1.3 eq. EDC, cat. DMAP, CH Cl r.t., 12 h
2
2
1.3 eq. EDC, cat. DMAP, CH Cl r.t., 18 h
79
2
2
and in 6.52–6.42 ppm with coupling constant of 4.0–3.7 Hz
for the ꢇ-anomers, respectively. ꢀe coupling constant of
anomeric hydrogen for mannopyranosyl 7c was 4.0 Hz in
both the anomers. Finally the synthesis of glycopyrano-
sides was supported by one of the crystal structure for
ꢇ-anomer, O-(2,3,4,6-tetra-O-acetyl-ꢇ-D-mannopyranosyl)-
C12
C14
C11 O5
O9
O6
C9
O4
C10
C13
(
4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate 7c by
O7
C4
X-ray crystallography (Figure 1).
C3
O8
Crystal system = monoclinic. Torsion angles for com-
C2
∘
pound 7c are C5-O1-C1-O13 = −62.9(2) , C5-O1-C1-C2
∘
∘
=
54.9(2) , C15-O13-C1-O1 = −76.4(2) (2) , C15-O13-C1-
C5
∘
∘
O1
C2 = 160.28(19) , C13-O8-C2-C3 = −103.8(2) , C13-O8-
C6
O2
C22
∘
∘
C2-C1 = 136.00(19) , O1-C1-C2-O8 = 73.3(2) , O13-C1-
C1
∘
∘
O3
O13
C2-O8 = −165.60(16) , O1-C1-C2-C3 = −46.9(2) , O13-C1-
∘
∘
C2-C3 = 74.2(2) , C11-O6-C3-C4 = −149.8(2) , C11-O6-
O11
C18
∘
∘
C3-C2 = 88.7(3) , O8-C2-C3-O6 = 49.8(2) , C1-C2-C3-
C7
∘
∘
O6 = 167.17(17) , O8-C2-C3-C4 = −69.0(2) , C1-C2-C3-
C15
∘
∘
∘
C8
C16
C4 = 48.4(3) , C9-O4-C4-C3 = −119.6(3) , C9-O4-C4-
∘
∘
O10
O12
C5 = 123.8(3) , O6-C3-C4-O4 = 67.2(2) , C2-C3-C4-O4
∘
∘
C17
=
−172.34(18) , O6-C3-C4-C5 = −176.24(17) , C2-C3-C4-
∘
∘
C5 = −55.8(2) , C1-O1-C5-C6 = 176.43(19) , C1-O1-C5-
∘
C4 = −61.4(2) , O4-C4-C5-O1 = 176.08(18) , C3-C4-C5-
O14
∘
∘
O1 = 60.3(2) , O4-C4-C5-C6 = −65.2(3) , C3-C4-C5-C6
O15
∘
∘
=
179.0(2) , C7-O2-C6-C5 = −153.1(2) , O1-C5-C6-O2 =
C19
∘
∘
∘
−
68.2(3) , C4-C5-C6-O2 = 172.1(2) , C6-O2-C7-O3 = 1.9(5) ,
∘
∘
C6-O2-C7-C8 = −175.2(3) , C4-O4-C9-O5 = −7. 1(6) , C4-
C20
∘
∘
C21
O4-C9-C10 = 174.8(3) , C3-O6-C11-O7 = 3.7(4) , C3-O6-C11-
∘
∘
C12 = −175.5(2) , C2-O8-C13-O9 = 6.4(3) , C2-O8-C13-C14
Fꢍꢎꢏꢐꢈ 1: Crystal structure of ꢇ-anomer, O-(2,3,4,6-tetra-O-acetyl-
ꢇ-D-mannopyranosyl)-(4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-
dicarboxylate 7c.
∘
∘
=
=
=
−171.9(2) , C1-O13-C15-O12 = −5.2(4) , C1-O13-C15-C16
∘
∘
173.8(2) , C19-O15-C16-C15 = 131.8(4) , C19-O15-C16-C17
∘
∘
11.0(5) , O12-C15-C16-O15 = −7. 6(4) , O13-C15-C16-O15 =
∘
∘
173.5(2) , O12-C15-C16-C17 = 108.9(4) , O13-C15-C16-C17 =
∘
∘
−
70.1(3) , C19-O14-C17-C18 = 130.6(5) , C19-O14-C17-C16 =
∘
∘
1
1.5(6) , O15-C16-C17-O14 = −13.4(5) , C15-C16-C17-O14 =
∘
∘
∘
∘
−
=
=
=
133.2(4) , O15-C16-C17-C18 = −131.8(3) , C15-C16-C17-C18
−97.4(4) , C17-O14-C19-O15 = −5.3(7) , C17-O14-C19-C21 =
∘
∘
∘
∘
108.4(3) , C22-O11-C18-O10 = −2.3(9) , C22-O11-C18-C17
109.3(8) , C17-O14-C19-C20 = −123.6(6) , C16-O15-C19-O14
∘
∘
∘
∘
178.0(4) , O14-C17-C18-O10 = −31.2(7) , C16-C17-C18-O10
= −4.3(6) , C16-O15-C19-C21 = −121.1(8) , and C16-O15-C19-
∘
∘
∘
82.9(6) , O14-C17-C18-O11 = 148.5(4) , C16-C17-C18-O11 =
C20 = 113.7(6) .

Journal of Chemistry
7
Tꢊꢋꢌꢈ 2: Coupling conditions and isolated yield for 5a–e and 7a–e.
ꢇ : ꢃ
25
Entry
Starting material
Reagents/conditions
Product (isolated yield%)
[ꢇ]
D
ratio
1
4a
4b
4c
4d
4e
6a
6b
6c
6d
6e
HA
HA
HA
HA
HA
HA
HA
HA
HA
HA
1.3 eq. EDC, cat. DMAP, r.t., 12 h
1.3 eq. EDC, cat. DMAP, r.t., 12 h
1.3 eq. EDC, cat. DMAP, r.t., 12 h
1.3 eq. EDC, cat. DMAP, r.t., 12 h
1.3 eq. EDC, cat. DMAP, r.t., 12 h
1.3 eq. EDC, cat. DMAP, r.t., 18 h
1.3 eq. EDC, cat. DMAP, r.t., 18 h
1.3 eq. EDC, cat. DMAP, r.t., 18 h
1.3 eq. EDC, cat. DMAP, r.t., 18 h
1.3 eq. EDC, cat. DMAP, r.t., 18 h
72
69
65
67
68
72
74
70
67
63
0 : 1
0 : 1
0 : 1
0 : 1
0 : 1
1 : 3
1 : 3
1 : 1
1 : 3
1 : 3
12.5
13.3
27.1
2
3
4
5
6
7
8
9
43.3
47.1
26.5
21.6
17.3
45.0
33.3
10
ꢂ = 24 mg/2 mL in dichloromethane.
Tꢊꢋꢌꢈ 3: % inhibition of compounds 5a–e and 7a–e against L. tropica leishmania.
a
a
Compound
ꢊ. ꢋꢌꢍꢎꢏꢐꢑ
Compound
7a
7b
7c
7d
ꢊ. ꢋꢌꢍꢎꢏꢐꢑ
5a
0.65 ± 0.01
1.35 ± 0.04
5b
0.68 ± 0.09
0.73 ± 0.12
5c
0.81 ± 0.16
0.63 ± 0.18
5
5
d
e
0.68 ± 0.27
0.77 ± 0.08
0.66 ± 0.18
0.89 ± 0.11
7e
Standard drug IC
(ꢅg/mL ± SD)
50
Amphotericin B
0.56 ± 0.20
a
Percentage inhibition activity: 100 = (nonsigniꢂcant; 0.95−0.80 = low; 0.79−0.70 = moderate; 0.69−0.60 = good; below 0.59−0.56 = signiꢂcant activity).
4
. Material and Methods
using Leishmania tropica KWH23 promastigotes for in vitro
screening. ꢀe results are shown in Table 3. Compounds 5a,
4
.1. Antileishmanial Activity. Antileishmanial activities of
5
5
b, and 5d showed good activity while the compounds 5c and
e exhibited low activity.
compounds 5a–e and 7a–e were assayed by Zhai et al .’ s
method (1999) [32] using a preestablished culture ofLeishma-
nia. Triple-N media slants were overlaid with 199 media for
leishmanial growth. NNN medium was prepared by mixing
Among the synthesized O-linked glycopyranosides
a–7e, compounds 7c and 7e showed good activity; 7b
7
and 7d showed moderate activity. Compound 7a showed
4
g of agar in 100 mL of distilled water. ꢀe mixture was
nonsigniꢂcant activity.
∘
then dissolved and sterilized by autoclaving at 121 C and then
∘
allowed to cool to 55 C. 15–20 mL of deꢂbrinated sheep blood
6
. Conclusion
was aseptically added to the mixture with gentle rolling with
glass beads; 1 ampoule of gentamicin was mixed in blood and
mixed with the agar mixture. Slopes of culture medium were
prepared by dispensing 2-3 mL of the blood agar mixture into
sterile tubes that were then set in a slant position until the
agar completely solidiꢂed. To prepare 199 medium diꢁerent
constituents were mixed in 1000 mL of distilled water. ꢀe pH
was adjusted to 7.4 and medium was ꢂltered, sterilized, and
Most of the synthesized compounds 5a–e and 7a–e showed
moderate to good activities against Leishmania tropica
KWH23 promastigotes. Compounds 5a, 5b, and 5d were the
most active. Among the synthesized compounds, 7a–7e, 7c,
and 7e were more active than 7a, 7b, and 7d. Drug resistance
has been reported in various species of Leishmania against
various antileishmanial drugs like antimonials, amphotericin
B, pentamidine, miltefosine, and so forth. In this scenario
these synthetic compounds may be further explored for
research in medicinal chemistry and drug designing. ꢀese
compounds may prove to be good candidates against leish-
maniasis. A number of other new compounds can also be
synthesized while following the same N- and O-acylation
synthetic routes. Such compounds can act as valuable gly-
codrugs as many of the glycosides and their derivatives have
been reported to be biologically active compounds.
∘
kept at 37 C for 24 h to check sterility. Preestablished culture
of Leishmania tropica KWH23 was inoculated in 199 medium
∘
in Triple-N medium slants and incubated at 24 C for 6-7 days
and the results are summarized in Table 3.
5
. Results
All the synthesized N-linked 5a–e and O-linked glycopyra-
nosides 7a–e were tested for their antileishmanial activity

8
Journal of Chemistry
Conflicts of Interest
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