The impact of sugar and fatty acid on the bioactivity of N-fatty acyl-L-tyrosine aglycone

Article abstract of DOI:10.1007/s12039-017-1298-y

Abstract: In the present study, a series of fatty acids-based (short, medium and long unsaturated chains) glycosylated N-fatty acyl-L-tyrosines and N-lipoyl-L-tyrosine methyl esters were synthesized and evaluated for their cytotoxic and antimicrobial activities. The aglycone moiety was synthesized using different chemical reagents. The glycosylation of aglycone moiety with different carbohydrates was performed using the Lewis acid, BF _3.Et ₂O. All the synthesized compounds were tested against a panel of four cancer cell lines. The glycosylated N-fatty acyl-L-tyrosines showed moderate activity against all the cell lines and the IC ₅₀ values were in the range of 15.6-45.6μM. However, the oleic acid analogues (10a, 10d) exhibited IC ₅₀ values of 15.6, 17.6μM, respectively, against MDA-MB-231 cell line. Glycosylated N-lipoyl-L-tyrosine methyl esters (6b–6d) showed promising activity against all the tested cell lines and the IC ₅₀ values ranged between 9.4-13.8μM. The compound 6d exhibited significant cytotoxicity and IC ₅₀ values were 10.5, 9.4, 10.9 and 12.1μM against A549, PC3, MDA-MB-231 and HepG2 cell lines, respectively. Moreover, the non-glycosylated N-fatty acyl-L-tyrosine and methyl N-fatty acyl-L-tyrosinate derivatives showed excellent and moderate antimicrobial activity against some of the tested bacterial strains. Graphical Abstract: The glycosylated N-fatty acyl-L-tyrosines with short, medium and long chain unsaturated fatty acids and glycosylated N-lipoyl-L-tyrosine methyl esters were synthesized and further evaluated for their biological activities to examine the impact of sugar and fatty acid on the bioactivity of N-fatty acyl-L-tyrosine derivatives. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s12039-017-1298-y

J. Chem. Sci. © Indian Academy of Sciences.
DOI 10.1007/s12039-017-1298-y
REGULAR ARTICLE
The impact of sugar and fatty acid on the bioactivity of N-fatty
acyl-L-tyrosine aglycone
SRIKANTH VUDHGIRIa,c, R B N PRASADa,c, Y POORNACHANDRAb,c,
C GANESH KUMARb,c, E ANJANEYULUa, K SIRISHAb,c and
RAM CHANDRA REDDY JALAa,c,∗
aCentre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
bMedicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500 007, India
cAcademy of Scientific and Innovative Research, New Delhi, India
E-mail: jrcreddy10@gmail.com; ramchandra@iict.res.in
MS received 4 January 2017; revised 17 March 2017; accepted 14 May 2017
Abstract. In the present study, a series of fatty acids-based (short, medium and long unsaturated chains)
glycosylated N-fatty acyl-L-tyrosines and N-lipoyl-L-tyrosine methyl esters were synthesized and evaluated
for their cytotoxic and antimicrobial activities. The aglycone moiety was synthesized using different chemical
reagents. The glycosylation of aglycone moiety with different carbohydrates was performed using the Lewis
acid, BF3.Et2O. All the synthesized compounds were tested against a panel of four cancer cell lines. The
glycosylated N-fatty acyl-L-tyrosines showed moderate activity against all the cell lines and the IC50 values
were in the range of 15.6−45.6 μM. However, the oleic acid analogues (10a, 10d) exhibited IC50 values of
15.6, 17.6 μM, respectively, against MDA-MB-231 cell line. Glycosylated N-lipoyl-L-tyrosine methyl esters
(6b–6d) showed promising activity against all the tested cell lines and the IC50 values ranged between
9.4−13.8 μM. The compound 6d exhibited significant cytotoxicity and IC50 values were 10.5, 9.4, 10.9
and 12.1 μM against A549, PC3, MDA-MB-231 and HepG2 cell lines, respectively. Moreover, the non-
glycosylated N-fatty acyl-L-tyrosine and methyl N-fatty acyl-L-tyrosinate derivatives showed excellent and
moderate antimicrobial activity against some of the tested bacterial strains.
Keywords. L-Tyrosine; N-fatty acyl-L-tyrosine; fatty acids; α-Lipioic acid; cytotoxicity; carbohydrates.
multiple biological activities9–12 such as analgesic,
anti-inflammatory and inhibition of cell proliferation.
1. Introduction
Further, a number of microbial secondary metabo-
lites carrying a carbohydrate moiety on the phenolic
hydroxyl group of tyrosine or hydroxy phenyl glycine
derivatives and phenolic glycosides and its deriva-
tives exhibited good cytotoxicity.13–17 Earlier, Brady
and Clardy isolated long-chain N-fatty acyl tyrosine
antibiotics from heterologously expressed environmen-
tal DNA,18,19 which exhibited anti-bacterial activities.
Further, there are some reports15,20,21 available on the
synthesis of glycosyl-tyrosine and their related deriva-
tives. However, there is a paucity of information on the
synthesis and biological activity of lipid derivatives of
glycosylated tyrosine.
In general, glycosides are biologically active com-
pounds and the glycosidic residue dictates their bio-
logical activity. In some cases, the glycosidic residue
also improves the pharmacokinetic parameters.1 In
some glycosides, the overall molecular structure1,2 con-
tributes to the biological activity. Especially, the com-
bination of carbohydrate moiety to aglycone plays a
functional role in the bioactivity, and to support this
statement, anotedexampleisvancomycin.1–4 Moreover,
most of the glycoprotein and glycolipid carbohydrate
antigens find application in the anticancer vaccine
research. These carbohydrate antigens are directed to
the cell surface either by lipid tail or by an amino acid
component linked to the oligosaccharide.5
Nevertheless, the biological activity of N-fatty acyl
tyrosines is dependent on the fatty acid moiety. Consid-
ering this fact, we have included an unusual fatty acid
On the other hand, many reports are available on bio-
logically active lipoamino acids and fatty amino acid
conjugates.6–8 These endogenous substances exhibit
α
-lipoic acid (1,2-dithiolane-3-valeric acid or thioctic
acid) in the present study. It is well-established that
*
α
-lipoic acid acts as an essential coenzyme in several
For correspondence

Srikanth Vudhgiri et al.
enzyme-catalyzed reactions and also exhibits antioxi- brought to pH of about 10 by adding saturated solution of
dant activity.22,23 A recent report on the lipoic acid-based
sodium carbonate and extracted with three portions of DCM.
The organic phase was evaporated to a white solid (6.03 g,
N-fatty acyl amino acids showed potential biological
◦
20
70% yield).; M.p.: 135−137 C, [ ]D = +26.98◦ (C=2.4
applications.22
α
◦
20
g/dL, MeOH) {Lit.24,25 M.p.: 135−136 C, [ ]D = +26.1◦
(C=2.4 g/dL, MeOH)}; 1H-NMR (CDCl3, 500MHz): δ 6.95
(d, J = 7.47 Hz, 2H), 6.7 (d, J = 8.24 Hz, 2H), 3.64
(s, 3H), 3.59 (t, J = 6.71 Hz, 1H), 2.88 (dd, J = 5.49,
13.58 Hz, 1H), 2.74 (dd, J = 7.17, 13.12 Hz, 1H); 13C-NMR
(CDCl3 +DMSO−d6, 100 MHz): 174.8(C=O), 155.7(Ar-C-
OH), 129.7(Ar-C), 127(Ar-CH), 115(Ar-CH), 55.4(NH-CH),
51.2(CH3), 39.7(Ar-CH2); IR(KBr): 3355, 3300, 2928, 1744,
1598, 1514, 1478, 1264, 1175, 1020, 837 cm−1; HRMS
(ESI) m/z [M+H]-calc. for C10H14O3N = 196.0968; Found
α
Based on the above facts, it was necessary to place
the amino acid acylated with fatty acids and glycosy-
lated with carbohydrates into a separate class of lipid
derivatives which are worthy to investigate. Hence,
in the present study, the glycosylated N-fatty acyl-L-
tyrosines with short, medium and long chain unsaturated
fatty acids and glycosylated N-lipoyl-L-tyrosinemethyl
esters were synthesized and further evaluated for their
biological activities to examine the impact of sugar and
fatty acid on the bioactivity of N-fatty acyl-L-tyrosine 196.0961.
derivatives.
2.3 General procedure for synthesis of methyl
N-fattyacyl-L-tyrosinate
2. Experimental
A mixture of 12.3 mmol of fatty acid, 12.3 mmol of EDC and
15.38 mmol of HOBt dissolved in ice-cold anhydrous DCM
(50 mL) was kept in ice for 20 min with stirring, followed by
the addition of 10.25 mmol of L-tyrosine methyl ester and the
mixture was left at room temperature for 12 h with stirring.
TLC (hexane/ethyl acetate 1:1, v/v) was used to monitor the
reaction. At the end of the reaction, the mixture was dissolved
in75mLofCHCl3, whichwas thenwashedwith5%NaHCO3
solution and saturated NaCl solution. The chloroform layer
was dried with anhydrous Na2SO4. The filtrate was then dried
under vaccum. Then, the crude mixture was purified by silica-
gel chromatography by using solvent mixture (hexane/ethyl
acetate 70:30, v/v), with 80-89% yield of the title compound
was obtained as a solid.
2.1 Materials and methods
All the chemicals used in these schemes were of analyti-
cal grade and they were obtained from different commercial
sources and were used without any further purification. All
the dry reactions were carried out under nitrogen atmo-
sphere using anhydrous freshly distilled solvents and 4 Å
molecular sieves in flame dried glassware using standard
gas-light syringes, cannulas and septa. Reactions were mon-
itored on micro TLC plates (coated with TLC grade silica
gel, obtained from Merck) and the spots were detected by
iodine vapor. Column chromatography was performed by
using silica gel (100–200 mesh) procured from Qualigens
(India) using freshly distilled solvents. All the 1H-NMR and
13C-NMR spectra were recorded with a Bruker Avance (oper-
ating for 1H-NMR at 300 MHz, 500 MHz, 600 MHz and for 2.3a Synthesis of methyl N-hexanoyl-L-tyrosinate (2):
13C-NMR at 75 MHz, 125 MHz, 175 MHz) spectrometer
The crude mixture was purified by silica-gel chromatogra-
using TMS (δ = 0 ppm) and δ 77.00 ppm as internal stan- phy by using solvent mixture (hexane/ethyl acetate 70:30,
dard for chemical shifts (δ) in CDCl3 at 25◦C. The chemical v/v), with 85% yield of the title compound, which was
1
shift values are presented in ppm (parts per million) units. obtained as a solid. H-NMR (CDCl3, 500 MHz): δ 7.14
Mass spectra were recorded with HRMS (Electron Spray Ion- (br s, 1H), 6.93 (d, J = 8.39 Hz, 2H), 6.73 (d, J = 8.54
ization Technique). IR spectra were recorded in chloroform Hz, 2H), 6.05 (d, J = 7.93 Hz, 1H), 4.86–4.9 (m, 1H),
on a Perkin-Elmer FT-IR spectrum BX. The melting points 3.73 (s, 3H), 3.08 (dd, J = 5.49, 14.03 Hz, 1H), 2.97 (dd,
were determined on a Barnstead Electro Thermal 9200 Instru-
J = 6.25, 14.03 Hz, 1H), 2.17 (t, J = 7.32 Hz, 2H), 1.54–
ment. Purity of the compounds was analyzed using HPLC 1.6 (m, 2H), 1.2–1.32 (m, 4H), 0.86 (t, J = 6.71 Hz, 3H);
(Agilent Technologies 1200 series with RI detector interfaced 13C-NMR (CDCl3, 125 MHz): δ 173.6(C=O), 172.3(C=O),
with Agilent Chemistation on a Rezex RPM-monosaccharide 155.7(Ar-C-OH), 130(Ar-C), 126.5(Ar-CH), 115.5(Ar-CH),
(Pb+2) column (300 × 7.8 mm), oven temperature at 65◦C, 53.1(NH-CH), 52.3(CH3), 37(Ar-CH2), 36.3(O = C-CH2),
100% water as mobile phase, flow rate at 0.6 mL/min, and 31.1(CH2), 25.1(CH2), 22.2(CH2), 13.7(CH3); IR(KBr):
optical unit temperature at 35◦C. All the purified compounds 3330, 2958, 2928, 1725, 1656, 1271, 1223, 829 cm−1; HRMS
were obtained with more than 98% purity.
(ESI) m/z [M+Na]-calc. for C16H23O4NNa = 316.1519;
Found: 316.1507.
2.2 Synthesis of methyl-L-tyrosinate (1)
2.3b Synthesis of methyl N-undec-10-enoyl-L-tyros-
Concentrated (96%) H2SO4 (9 mL) was added drop wise to inate(3): Thecrudemixturewaspurifiedbysilica-gelchro-
a heterogenic solution of L-tyrosine (8 g) in methanol (150 matography by using solvent mixture (hexane/ethyl acetate
mL). The mixture was refluxed for 4 h, and the solution was 70:30, v/v) (89% yield) of the title compound which was
1
concentrated by evaporating the methanol. The solution was obtained as a white solid. H-NMR (CDCl3, 300MHz): δ

Glycosylated N-fatty acyl-L-tyrosine derivatives
6.93 (d, J = 8.3 Hz, 2H), 6.83 (br s, 1H), 6.73 (d, J = 8.49 (chloroform/methanol 99:1, v/v) (89% yield) of the title
Hz, 2H), 6.02 (d, J = 7.93 Hz, 1H), 5.73–5.87 (m, 1H), compound which was obtained as a yellowish semi-solid.
4.94–5.01 (m, 2H), 4.84–4.91 (m, 1H), 3.73 (s, 3H), 3.08 1H-NMR (CDCl3, 500MHz): δ 6.94 (d, J = 8.54 Hz,
(dd, J = 5.66, 13.97 Hz, 1H), 2.98 (dd, J = 6.04, 13.97 2H), 6.73 (d, J = 8.34 Hz, 2H), 6.04 (m, 1H), 4.85–
Hz, 1H), 2.17 (t, J = 7.36 Hz, 2H), 1.57 (m, 2H), 1.25 4.9 (m, 1H), 3.75 (s, 3H), 3.48–3.55 (m, 1H), 3.07–3.19
(m, 10H); 13C-NMR (CDCl3, 100 MHz): δ 173.6(C=O), (m, 3H), 2.93–2.99 (m, 1H), 2.4–2.46 (m, 1H), 2.13–2.23
172.3(C=O), 155.7(Ar-C-OH), 139.1(H2C-CH = CH2), (m, 2H), 1.84–1.91 (m, 2H), 1.55–1.68 (m, 4H), 1.3–1.43
130.1(Ar-C), 126.5(Ar-CH), 115.5(Ar-CH), 114.1(CH = (m, 2H); 13C-NMR (CDCl3 + DMSO − d6, 100 MHz): δ
CH2), 53.2(NH-CH), 52.3(CH3), 37.1(Ar-CH2), 36.4(O = 171.3(C=O), 170.8(C=O), 154.6(Ar-C-OH), 128.5(Ar-C),
C-CH2), 33.7(H2C-CH = CH2), 29.2(CH2), 29(CH2), 125.6(Ar-CH), 113.7(Ar-CH), 54.7(S-CH), 52.2(NH-CH),
28.9(CH2), 28.8(CH2), 25.5(CH2); IR(KBr): 3413, 3317, 50.3(CH3), 38.5(S-CH-CH2), 36.7(Ar-CH2), 35(S-CH2),
2921, 2851, 1719, 1650, 1520, 1263, 1220, 1022, 913, 33.7(O = C-CH2), 32.9(S-CH-CH2), 26.9(CH2), 24.7(CH2),
824 cm−1; HRMS (ESI) m/z [M + Na]-calc. for C21H31O4 23.6(CH2); IR(Neat): 3309, 3016, 2931, 2858, 1739, 1647,
NNa = 384.2145; Found: 384.2135.
1615, 1515, 1441, 1368, 1220, 754 cm−1; HRMS (ESI) m/z
[M + Na]-calc. for C18H25O4NNaS2 = 406.1117; Found:
406.1104.
2.3c SynthesisofmethylN-tetradecanoyl-L-tyrosinate
(4): The crude mixture was purified by silica-gel chro-
matography by using a gradient of (hexane/ethyl acetate
70:30, v/v) (89% yield) of the title compound which was
obtained as a light brown solid. 1H-NMR (CDCl3, 500MHz):
δ 7.39 (br s, 1H), 6.92 (d, J = 8.54 Hz, 2H), 6.73 (d,
J = 8.39 Hz, 2H), 6.09 (d, J = 8.08 Hz, 1H), 4.85–4.89
(m, 1H), 3.72 (s, 3H), 3.07 (dd, J = 5.64, 14.03 Hz, 1H),
2.98 (dd, J = 6.1, 14.03 Hz, 1H), 2.18 (t, J = 7.47 Hz,
2H), 1.56–1.59 (m, 2H), 1.24 (m, 21H), 0.87 (t, J = 6.86
Hz, 3H); 13C-NMR (CDCl3, 100 MHz): δ 173.5(C=O),
172.3(C=O), 155.6(Ar-C-OH), 130.1(Ar-C), 126.6(Ar-CH),
115.5(Ar-CH), 53.1(NH-CH), 52.3(CH3), 37.1(Ar-CH2),
36.4(O = C-CH2), 31.8(O = C-CH2-CH2), 29.5(CH2),
29.4(CH2), 29.3(CH2), 29.2(CH2), 29.1(CH2), 25.5(CH2),
22.6(CH2), 14(CH3); IR(KBr): 3309, 2919, 2850, 1741,
1641, 1542, 1240, 1018, 825 cm−1; HRMS (ESI) m/z [M +
Na]-calc. for C24H39O4NNa = 428.2771; Found: 428.2745.
2.4 General procedure for synthesis of N-fatty acyl-
L-tyrosine
N-fatty acyl-L-tyrosine methyl esters (2–6) (1 eq.) were dis-
solved in THF: H2O (7:3) and LiOH added (3 eq.), stirred the
reaction mixture at RT for 16 h. After completion of the reac-
tion, the mixture was concentrated under vacuum to obtain a
white precipitate. This white precipitate was neutralized with
2 N HCl and the reaction mixture was extracted with ethyl
acetate. The organic layer was dried over sodium sulphate
and concentrated to yield a white solid. This solid with little
impurity was purified by silica gel chromatography using a
gradient of chloroform/methanol (95:5, v/v) to obtain a yield
(96 - 98%) of the title compound as a solid.
2.4a Synthesis of N-hexanoyl-L-tyrosine (7): The
crude mixture was purified by silica-gel chromatography by
using solvent mixture (chloroform/methanol 95:5, v/v), with
98% yield of the title compound which was obtained as a
2.3d Synthesis of methyl N-oleoyl-L-tyrosinate (5):
The crude mixture was purified by silica-gel chromatogra-
phy by using as gradient of (hexane/ethyl acetate 70:30, v/v)
(87% yield) of the title compound which was obtained as a
white solid. 1H-NMR (CDCl3, 500MHz): δ 6.94 (d, J = 8.39
Hz, 2H), 6.73 (d, J = 8.54 Hz, 2H), 6.38 (br s, 1H), 5.95
(d, J = 8.08 Hz, 1H), 5.30–5.37 (m, 2H), 4.86–4.9 (m,
1H), 3.73 (s, 3H), 2.96–3.1 (m, 2H), 2.17 (t, J = 7.47
Hz, 2H), 1.98–2.02 (m, 4H), 1.58 (m, 2H), 1.26 (m, 20H),
0.87 (t, J = 6.86 Hz, 3H); 13C-NMR (CDCl3, 125 MHz):
δ 173.3(C=O), 172.3(C=O), 155.5(Ar-C-OH), 130.1(Ar-C),
129.9(HC=CH), 129.6(HC=CH), 126.8(Ar-CH), 115.5(Ar-
CH), 53.1(NH-CH), 52.3(CH3), 37.2(Ar-CH2), 36.5(O =
1
solid. H-NMR (CDCl3 + CD3OD, 300 MHz): δ 7.00 (d,
J = 8.25 Hz, 2H), 6.74 (d, J = 8.25 Hz, 2H), 4.72 (t,
J = 6.05 Hz, 1H), 2.94–3.14 (m, 2H), 2.16 (t, J = 7.42
Hz, 2H), 1.51–1.60 (m, 2H), 1.21–1.33 (m, 4H), 0.86 (t,
J = 6.60 Hz, 3H); 13C-NMR (CDCl3 + CD3OD, 75 MHz):
δ 173.8(C=O), 173.7(C=O), 155.5(Ar-C-OH), 130.1(Ar-C),
126.9(Ar-CH), 115.1(Ar-CH), 53.1(NH-CH), 36.4(Ar-CH2),
36.1(O = C-CH2), 31.1(CH2), 25.1(CH2), 22.1(CH2),
13.5(CH3); IR (KBr): 3350, 2958, 2928, 1690, 1656, 1538,
1462, 1278, 1223, 829 cm−1; ESI m/z at 278 [M - H].
C-CH2), 31.8(O
=
C-CH2-CH2, H2C-CH
=
CH2),
2.4b Synthesis of N-undec-10-enoyl-L-tyrosine (8):
The crude mixture was purified by silica-gel chromatogra-
phy by using solvent mixture (chloroform/methanol 95:5,
v/v), with 98% yield of the title compound which was
obtained as a solid. 1H-NMR (CDCl3 + CD3OD, 500 MHz):
δ 7.02 (d, J = 8.54 Hz, 2H), 6.74 (d, J = 8.54 Hz,
2H), 5.76–5.84 (m, 1H), 4.90–4.99 (m, 2H), 4.69 (t, J =
29.7(CH2), 29.6(CH2), 29.4(CH2), 29.2(CH2), 29.1(CH2),
29(CH2), 25.5(CH2), 22.6(CH2), 14(CH3); IR(KBr): 3425,
3309, 2923, 2852, 1719, 1648, 1518, 1460, 1218, 1019,
825 cm−1; HRMS (ESI) m/z [M + Na]-calc for .C28H45O4
NNa = 482.3240; Found: 482.3221.
2.3e Synthesis of methyl N-(5-(1, 2-dithiolan-3-yl) 7.17 Hz, 1H), 2.93–3.12 (m, 2H), 2.17 (t, J = 7.32 Hz,
pentanoyl)-L-tyrosinate (6): The crude mixture was puri- 2H), 2.01–2.05 (m, 2H), 1.55 (m, 2H), 1.27–1.37 (m, 10H);
fied by silica-gel chromatography by using a gradient of 13C-NMR (CDCl3 + CD3OD, 75 MHz): δ 173.7(C=O),

Srikanth Vudhgiri et al.
173.6(C=O), 155.5(Ar-C-OH), 138.9(H2C-CH = CH2), 2.5 General procedure for synthesis of β-D-glucose
and β-D-galactose penta acetates26
130.1(Ar-C), 126.8(Ar-CH), 115.1(Ar-CH), 113.8(CH =
CH2), 53.1(NH-CH), 36.4(Ar-CH2), 36.1(O = C-CH2),
33.5(O
=
C-CH2-CH2, H2C-CH
=
CH2), 29(CH2), A mixture of dextrose/galactose (6.0 g, 33.32 mmol) and
28.9(CH2), 28.8(CH2), 28.6(CH2), 25.3(CH2); IR(KBr): sodium acetate (8.196 g, 99.99 mmol) were dissolved in acetic
3452, 2958, 2922, 1692, 1654, 1278, 1234, 816 cm−1; ESI anhydride (51.6 mL, 549.6 mmol). The reaction mixture was
m/z at 346 [M - H].
refluxed for 2.5 h at 90◦C. After the reaction time, the reac-
tion mixture was cooled to room temperature and poured into
a beaker containing crushed ice (250 mL) under stirring con-
ditions. The penta-acetate was precipitated. The precipitation
was filtered and washed with ice-cold water until the odor of
the acetic acid disappeared. The crude product was purified
by recrystallization from MeOH to afford the title compound
(11.95 g, 92%) as a white crystalline solid.
2.4c Synthesis of N-tetradecanoyl-L-tyrosine (9):
The crude mixture was purified by silica-gel chromatography
by using solvent mixture (chloroform/methanol 95:5, v/v),
with 96% yield of the title compound which was obtained
1
as a solid. H-NMR (CDCl3 + CD3OD, 500 MHz): δ 6.99
(d, J = 8.54 Hz, 2H), 6.74 (d, J = 8.54 Hz, 2H), 4.71 (t,
J = 6.25 Hz, 1H), 2.96–3.11 (m, 2H), 2.16 (t, J = 7.47
Hz, 2H), 1.55 (m, 2H), 1.25 (m, 20H), 0.88 (t, J = 6.86 Hz,
3H); 13C-NMR (CDCl3 +CD3OD, 75 MHz): δ 173.7(C=O),
173.5(C=O), 155.5(Ar-C-OH), 130(Ar-C), 126.8(Ar-CH),
115(Ar-CH), 53(NH-CH), 36.3(Ar-CH2), 36(O = C-CH2),
31.6(O = C-CH2-CH2), 29.3(CH2), 29.2(CH2), 29(CH2),
28.9(CH2), 25.3(CH2), 22.3(CH2), 13.7(CH3); IR(KBr):
2.5a Synthesis of 1,2,3,4,6 penta-O-acetyl-β-D-glu
copyranose26 (a): M.p. 130−135◦C, lit. 132−133.5◦C.
1H-NMR (500 MHz, CDCl3) δ 5.72 (d, J = 8.3 Hz, 1H),
5.26 (t, J = 9.3 Hz, 1H), 5.11−5.16 (m, 2H), 4.29 (dd, J =
4.5, 12.5 Hz, 1H), 4.11 (dd, J = 2.1, 12.5 Hz, 1H), 3.83–3.86
(m, 1H), 2.11 (s, 3H), 2.09 (s, 3H), 2.03 (s, 6H), 2.01 (s, 3H);
13C-NMR (125 MHz, CDCl3) δ 170.4(C=O),169.9(C=O),
169.2(C=O), 169(C=O), 168.7(C=O), 91.5(C1), 72.6(C3),
72.5(C5), 70(C2), 67.5(C4), 61.3(C6), 20.6(CH3),
20.5(CH3), 20.4(CH3). IR (CHCl3) 3027, 2969, 2951,
2907,1756, 1743, 1422, 1371, 1322, 1225, 1067,1048, 912,
756, 704, 641, 599 cm−1. HRMS (ESI) m/z [M + Na]-calc
for C16H22O11Na 413.10543 Found: 413.10449.
3250, 2942, 2926, 1678, 1662, 1278, 1245, 736 cm−1
ESI m/z at 390 [M - H].
;
2.4d Synthesis of N-oleoyl-L-tyrosine (10): The crude
mixture was purified by silica-gel chromatography by using
solvent mixture (chloroform/methanol 95:5, v/v), with 98%
yield of the title compound which was obtained as a solid.
1H-NMR (CDCl3,500 MHz): δ 6.93 (d, J = 7.62 Hz,
2H), 6.68 (d, J = 7.62 Hz, 2H), 6.34 (s, 1H),5.29–
5.37 (m, 2H), 4.82 (m, 1H), 3.04 (m, 2H), 2.17 (t, J =
7.62 Hz, 2H), 1.98–2.00 (m, 4H), 1.54 (m, 2H), 1.25 (m,
20H), 0.87 (t, J = 6.71 Hz, 3H); 13C-NMR (CDCl3,
100 MHz): δ 174.8(C=O), 174.5(C=O), 155.2(Ar-C-OH),
130.3(HC=CH), 130(HC=CH), 129.6(Ar-C), 126.9(Ar-CH),
115.6(Ar-CH), 53.4(NH-CH), 36.7(HC = CH-CH2), 36.3
2.5b Synthesis of 1, 2, 3, 4, 6 penta-O-acetyl-β-D-
galactopyranose (b): M.p. 142−145◦C, lit. 143−144◦C.
1H-NMR (400 MHz, CDCl3) δ 5.71 (d, J = 8.31 Hz, 1H),
5.42–5.43 (m, 1H), 5.31–5.36 (m, 1H), 5.1 (dd, J = 3.42,
10.39 Hz, 1H), 4.1–4.19 (m, 2H), 4.05–4.06 (m, 1H), 2.17
(s, 3H), 2.12 (s, 3H), 2.05 (s, 6H), 2.0 (s, 3H); 13C-NMR
(100 MHz, CDCl3) δ 170(C=O), 169.8(C=O), 169.6(C=O),
169.1(C=O), 168.7(C=O), 91.9(C1), 71.4(C3), 70.5(C5),
67.6(C2), 66.6(C4), 60.8(C6), 20.5(CH3), 20.4(CH3),
20.3(CH3); IR (CHCl3) 3029, 2969, 2946, 2852,1752, 1748,
1424, 1368, 1322, 1228, 1060,1048, 912, 756, 704, 641,
599 cm−1. ESI-MS: m/z at 413 [M + Na].
(O
=
C-CH2), 31.8(O
=
C-CH2-CH2), 29.7(CH2),
29.5(CH2), 29.2(CH2), 29.1(CH2), 27.2(CH2), 25.5(CH2),
22.6(CH2), 14.1(CH3); IR(KBr): 3342, 2947, 2929, 1692,
1670, 1278, 1236, 832 cm−1; ESI m/z at 444 [M - H].
2.4e SynthesisofN-(5-(1, 2-dithiolan-3-yl)pentanoyl)-
L-tyrosine (11): The crude mixture was purified by
silica-gel chromatography by using solvent mixture (chlo-
roform/methanol 92:8, v/v), with 96% yield of the title
compound which was obtained as a solid. 1H-NMR (CDCl3+
2.6 General procedure for synthesis of D-mannose,
L-rhamnose penta and tetra acetates27
CD3OD, 300 MHz): δ 7.02 (d, J
=
8.25 Hz, 2H),
L-rhamnose monohydrate/mannose (22 mmol) was dissolved
in pyridine (30 mL) and followed by acetic anhydride (30
mL) was added slowly to the reaction mixture. The reaction
mixture was stirred for 12 h at RT. After completion of the
consumption of the starting material, the reaction mixture was
quenched with 1 M HCl. Then, the reaction mixture was dis-
solved in EtOAc and the organic layer was extracted with 1 M
HCl and water. The organic layer was dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The crude
product was purified by silica gel chromatography using sol-
vent mixture hexane: EtOAc (60: 40, v/v) to semi-solid.
6.74 (d, J = 8.25 Hz, 2H), 4.69 (t, J = 5.77 Hz,
1H), 2.91–3.19 (m, 3H), 2.79 (m, 1H), 2.19 (t, J
=
7.42 Hz, 2H), 1.87–2.05 (m, 2H), 1.56–1.68 (m, 4H),
1.40 (m, 2H); 13C-NMR (CDCl3 + CD3OD, 75 MHz): δ
173.5(C=O), 155.3(Ar-C-OH), 129.9(Ar-C), 127(Ar-CH),
114.9(Ar-CH), 56(S-CH), 53.1(NH-CH), 39.8(S-CH-CH2),
38(Ar-CH2), 36.2(S-CH2), 35.5(S-CH-CH2), 34.1(O
C-CH2), 29.2(CH2), 24.9(CH2); IR(KBr): 3332, 3022, 2945,
=
2884, 1695, 1647, 1615, 1515, 1441, 1368, 1220, 754 cm−1
ESI m/z at 368 [M - H].
;

Glycosylated N-fatty acyl-L-tyrosine derivatives
2.6a Synthesis of 1, 2, 3, 4, 6 penta-O-acetate-D- 2H), 4.84 (d, J = 7.36 Hz, 1H), 4.60–4.65 (m, 1H), 3.85–
mannopyranose (c): 1H-NMR (500 MHz, CDCl3) δ 6.09 3.89 (m, 1H), 3.71 (m, 1H), 3.67 (s, 3H), 3.51 (m, 1H),
(m, 1H), 5.14–5.34 (m, 3H), 3.82–4.29 (m, 3H), 2.2 (s, 3.40–3.45 (m, 3H), 3.04–3.19 (m, 3H), 2.85–2.92 (m, 1H),
3H), 2.18 (s, 3H), 2.1 (s. 3H), 2.06 (s, 3H), 2.0 (s, 3H); 2.37–2.48 (m, 1H), 2.16 (t, J = 7.17 Hz, 2H), 1.80–1.88
13C-NMR (100 MHz, CDCl3) δ 170.3(C=O), 169.7(C=O), (m, 1H), 1.50–1.67 (m, 4H), 1.31–1.38 (m, 2H), 1.25 (m,
169.4(C=O), 169.2(C=O), 167.8(C=O), 90.3(C1), 90.1(C1), 1H); 13C-NMR (CDCl3 +CD3OD, 75 MHz): δ 175.6(C=O),
72.9(C3), 70.3(C5), 68.5(C2), 68(C2), 65.2(C4), 65.1(C4), 173.4(C=O), 157.7(Ar-C-OH), 131.7(Ar-C), 130.9(Ar-CH),
61.8(C6), 20.6(CH3), 20.5(CH3), 20.4(CH3), 20.2(CH3); IR 117.6(Ar-CH), 102.1(C1), 77.7(C3), 77.6 (C5), 74.6(C2),
(CHCl3) 3018, 2932, 2872, 1752, 1734, 1456, 1376, 1321, 71.1(C4), 62.3(C6), 57.3(S-CH), 54.9(NH-CH), 52.7(CH3),
1225, 1074,1052, 916, 756, 704, 641, 599 cm−1; ESI-MS: 41.1(S-CH-CH2), 39.2(Ar-CH2), 37.4(S-CH2), 36.3(S-CH-
m/z at 413 [M + Na].
CH2), 35.5(O = C-CH2), 29.5(CH2), 26.3(CH2); IR(KBr):
3404, 2924, 2855, 1742, 1647, 1512, 1233, 1077, 830 cm−1
;
HRMS (ESI) m/z [M+Na]-calc. for C24H35O9NS2
568.1645; Found: 568.1659.
=
2.6b Synthesis of 1, 2, 3, 4 tetra-O-acetate-L-rhamno-
pyranose27 (d): 1H-NMR (300 MHz, CDCl3) δ 6.01 (d,
J = 1.7 Hz, 1H), 5.84 (d, J = 0.94 Hz, 1H), 5.24–5.33
(m, 1H), 5.07–5.15 (m, 1H), 3.64–4.15 (m, 1H), 2.23 (s, 3H),
2.16 (s, 3H), 2.07 (s, 3H), 2.01 (s, 3H), 1.22–1.28 (m, 3H);
13C-NMR (75 MHz, CDCl3) δ 170.1(C=O), 169.9(C=O),
169.6(C=O), 168.3(C=O), 90.5(C1), 90.2(C1), 71.3(C3),
70.5(C4), 70.3(C4), 68.7(C5), 68.6(C5), 68.5(C2), 68.4(C2),
20.7(CH3), 20.6(CH3), 20.5(CH3), 20.4(CH3), 17.2(C6);
IR(Neat) 1752.3, 1433.8, 1371.6, 1222, 1150.1, 1087.8,
1055.5, 973.6 cm−1; HRMS (ESI) m/z [M + Na]-calc for
C14H20O9Na = 355.0999; Found: 355.0994.
2.7b Synthesis of methyl N-(5-(1, 2-dithiolan-3-yl)
pentanoyl)-O-β-D-galactopyranosyl-(S)-tyrosinate
(6b): This solid was purified by silica gel chromatogra-
phy using a gradient of chloroform/methanol (92:8, v/v) to
obtain a yield of 72%, as a yellow solid. 1H-NMR (CD3OD,
300MHz): δ 7.12 (d, J = 8.49 Hz, 2H), 7.03 (d, J = 8.68
Hz, 2H), 6.70 (d, J = 7.93 Hz, 1H), 4.82 (d, J = 7.74, 1H),
4.60–4.64 (m, 1H), 3.88–3.96 (m, 2H), 3.74–3.80 (m, 2H),
3.67 (s, 3H), 3.49–3.59 (m, 2H), 3.04–3.20 (m, 2H), 2.84–
2.92 (m, 2H), 2.38–2.48 (m, 1H), 2.16 (t, J = 6.98 Hz, 2H),
1.80–1.91 (m, 1H), 1.49–1.67 (m, 4H), 1.30–1.38 (m, 2H),
1.27 (m, 1H); 13C-NMR (CD3OD, 75 MHz): δ 175.8(C=O),
173.6(C=O), 158(Ar-C-OH), 131.8(Ar-C), 131.1(Ar-CH),
117.7(Ar-CH), 102.9(C1), 76.7(C3), 74.7(C5), 72.2(C2),
70.1(C4), 62.3(C6), 57.5(S-CH), 55.1(NH-CH), 52.7(CH3),
41.2(S-CH-CH2), 39.3(Ar-CH2), 37.5(S-CH2), 36.7
(S-CH-CH2), 35.6(O = C-CH2), 29.6(CH2), 26.5(CH2);
IR(KBr): 3402, 2928, 2848, 1748, 1632, 1522, 1223, 1072,
830 cm−1;HRMS(ESI)m/z [M+Na]-calc. forC24H35O9NS2
= 568.1645; Found: 568.1659.
2.7 General procedure for synthesis of methyl
N-(5-(1,2-dithiolan-3-yl) pentanoyl)-O-α/β-D/L-
glycopyranosyl-(S)-tyrosinates
To a solution of hexose penta acetate (2.56 mmol) in
dichloromethane (10 mL) was added methyl lipoyl tyrosi-
nate (3.704 mmol) and borontrifloride etherate (3.84 mmol)
at 0◦C and the reaction mixture was stirred at room tem-
perature for overnight. The reaction mixture was dissolved
in CHCl3 and washed with NaHCO3 solution and water
(2 × 150 mL). The organic phase was dried over sodium
sulphate and concentrated to a yield a liquid. The crude
compound was directly used for the next step. This crude
mixture was dissolved in dry methanol that contained a cat-
alytic amount of sodium methoxide. The reaction mixture
was allowed to stir at ambient temperature for 30 min under
nitrogen. After total consumption of the starting material, the
reaction mixture was neutralized by the addition of Amberlite
IR-120 (H+) resin. Then, the reaction mixture was filtered
and concentrated under reduced pressure to obtain a crude
product. This crude product was purified by silica gel chro-
matography using a gradient of chloroform: methanol (92:8,
v/v) to give title compounds (6a–6d) as yellow solids with
70–75% yields.
2.7c Synthesis of methyl N-(5-(1, 2-dithiolan-3-yl)
pentanoyl)-O-α-D-mannopyranosyl-(S)-tyrosinate
(6c): This solid was purified by silica gel chromatogra-
phy using a gradient of chloroform/methanol (92:8, v/v) to
obtain a yield of 70%, as a yellow solid. 1H-NMR (CD3OD,
300MHz): δ 8.29 (d, J = 7.74 Hz, 1H), 7.13 (d, J = 8.49
Hz, 2H), 7.03 (d, J = 7.93 Hz, 2H), 5.43 (br s, 1H), 4.62 (m,
1H), 3.98 (m, 1H), 3.85–3.89 (m, 1H), 3.71–3.75 (m, 3H),
3.68 (s, 3H), 3.50–3.58 (m, 1H), 3.06–3.17 (m, 2H), 2.83–
2.91 (m, 2H), 2.39–2.48 (m, 1H), 2.16 (t, J = 6.98 Hz, 2H),
1.81–1.90 (m, 1H), 1.48–1.63 (m, 4H), 1.27–1.36 (m, 3H);
13C-NMR (CD3OD, 75 MHz): δ 175.9(C=O), 173.6(C=O),
156.9(Ar-C-OH), 132(Ar-C), 131.2(Ar-CH), 117.8(Ar-CH),
100.2(C1), 75.3(C3), 72.4(C5), 72(C2), 68.3(C4), 62.6(C6),
57.5(S-CH), 55.2(NH-CH), 52.7(CH3), 41.3(S-CH-CH2),
39.3(Ar-CH2), 37.6(S-CH2), 36.4(S-CH-CH2), 35.7(O =
C-CH2), 29.6(CH2), 26.5(CH2); IR(KBr): 3398, 2964, 2854,
2.7a Synthesis of methyl N-(5-(1,2-dithiolan-3-yl)
pentanoyl)-O-β-D-glucopyranosyl-(S)-tyrosinate (6a):
This solid was purified by silica gel chromatography using a
gradient of chloroform/methanol (92:8, v/v) to obtain a yield 1740, 1642, 1532, 1233, 1072, 830 cm−1; HRMS (ESI)
1
of 71%, as a yellow solid. H-NMR (CD3OD, 300MHz): m/z [M+Na]-calc. for C24H35O9NS2 = 568.1645; Found:
δ 7.10 (d, J = 8.49 Hz, 2H), 6.99 (d, J = 8.49 Hz, 568.1657.

Srikanth Vudhgiri et al.
2.7d Synthesis of methyl N-(5-(1, 2-dithiolan-3-yl) 36.6(O = C-CH2), 32.1(CH2), 26.2(CH2), 23.1(CH2),
pentanoyl)-O-α-L-rhamnopyranosyl-(S)-tyrosinate
14.2(CH3); IR(KBr): 3399, 3303, 2928, 1735, 1647, 1538,
(6d): This solid was purified by silica gel chromatogra- 1232, 1082, 830 cm−1; HRMS (ESI) m/z [M - H]-calc. for
phy using a gradient of chloroform/methanol (92:8, v/v) to C21H30O9N = 440.1915; Found: 440.1924.
obtain a yield of 74%, as a yellow solid. 1H-NMR (CD3OD,
300MHz): δ 7.13 (d, J = 8.49 Hz, 2H), 6.98 (d, J =
2.8b Synthesis of N-(hexanoyl)-O-β-D-galactopyran
8.30 Hz, 2H), 6.69 (d, J = 8.30 Hz, 1H), 5.38 (br s,
osyl-(S)-tyrosine (7b): This solid had a little impurity
1H), 4.61–4.66 (m, 1H), 3.98 (m, 1H), 3.79–3.84 (m, 1H),
3.69 (s, 3H), 3.34–3.64 (m, 4H), 3.03–3.19 (m, 3H), 2.83–
2.91 (m, 2H), 2.37–2.47 (m, 1H), 2.16 (t, J = 6.98 Hz,
2H), 1.79–1.90 (m, 1H), 1.48–1.63 (m, 4H), 1.27–1.36 (m,
3H), 1.2 (s, 3H); 13C-NMR (CD3OD + CDCl3, 75 MHz):
δ 175.6(C=O), 173.5(C=O), 156.5(Ar-C-OH), 131.6(Ar-C),
131.1(Ar-CH), 117.4(Ar-CH), 99.6(C1), 73.6(C3), 72(C4),
71.8(C5), 70.4(C2), 57.3(S-CH), 54.9(NH-CH), 52.7(CH3),
41.1(S-CH-CH2), 39.2(Ar-CH2), 37.5(S-CH2), 36.3(S-CH-
CH2), 35.5(O = C-CH2), 29.5(CH2), 26.4(CH2), 18(C6);
IR(KBr): 3379, 2927, 1736, 1647, 1512, 1229, 1016, 831
cm−1; HRMS (ESI) m/z [M+Na]-calc. for C24H35O8NS2 =
552.1696; Found: 552.1707.
which was purified by silica gel chromatography using a gra-
dient of chloroform/methanol (75:25, v/v) to obtain a yield of
65%,as a white solid. H-NMR (CD3OD, 300MHz): δ 7.14
1
(d, J = 8.52 Hz, 2H), 7.01 (d, J = 8.52 Hz, 2H), 4.84 (d,
J = 7.42 Hz, 1H), 4.58–4.62 (m, 1H), 3.85–3.89 (m, 1H),
3.69 (dd, J = 4.67, 11.82 Hz, 1H), 3.39–3.45 (m, 4H), 3.11–
3.17 (m, 1H), 2.84–2.92 (m, 1H), 2.14 (t, J = 7.42 Hz, 2H),
1.46–1.56 (m, 2H), 1.16–1.37 (m, 4H), 0.88 (t, J = 6.87
Hz, 3H); 13C-NMR (CD3OD, 75 MHz): δ 176.1(C=O),
175.0(C=O), 158.0(Ar-C-OH), 132.4(Ar-C), 131.2(Ar-CH),
117.7(Ar-CH), 102.5(C1), 78.1(C3), 77.9(C5), 74.9(C2),
71.4(C4), 62.5(C6), 55.1(NH-CH), 37.6(Ar-CH2), 36.7(O =
C-CH2), 32.4(CH2), 30.7(CH2), 26.5(CH2), 23.4(CH2),
14.3(CH3); IR(KBr): 3418, 3301, 2929, 1732, 1647, 1542,
1262, 1082, 830 cm−1; HRMS (ESI) m/z [M - H]-calc. for
C21H30O9N = 440.1915; Found: 440.1923.
2.8 General procedure for synthesis of N-(fatty
acyl)-O-α/β-D/L-glycopyranosyl-(S)-tyrosines
To a solution of hexose penta acetate (2.56 mmol) in
dichloromethane (10 mL) was added methyl N-acyl tyrosi-
nate(3.704 mmol) andborontriflorideetherate(3.84 mmol) at
0◦C and the reaction mixture was stirred at room temperature
for overnight. The reaction mixture was dissolved in CHCl3
and washed with NaHCO3 solution and water (2 × 150 mL).
The organic phase was dried over sodium sulphate and con-
centrated to yield a liquid. The crude compound was directly
used for the next step. Methyl ester (1 eq.) was dissolved in
THF: H2O (7:3) and added (3 eq.) of LiOH, stirred the reac-
tion mixture at RT for 16 h. After completion of reaction, the
mixture was concentrated under vaccum to obtain a white pre-
cipitate. This white precipitate was neutralized with 2 N HCl
and the reaction mixture was extracted with ethyl acetate. The
organic layer was dried over sodium sulphate. This organic
layer was concentrated to yield a white solid. This solid was
purified by silica gel chromatography using a gradient of chlo-
roform/methanol (75:25, v/v) to obtain a yield (65–77%) of
the title compound as a solid.
2.8c Synthesis of N-(hexanoyl)-O-α-D-mannopyrano
syl-(S)-tyrosine (7c): This solid was purified by silica
gel chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 66%, as a white solid.
1H-NMR (CD3OD, 300MHz): δ 7.17 (d, J = 8.52 Hz,
2H), 6.99 (d, J = 8.80 Hz, 2H), 5.38 (d, J = 1.65
Hz, 1H), 4.62–4.67 (m, 1H), 3.97–3.99 (m, 1H), 3.84 (dd,
J = 3.30, 9.35 Hz, 1H), 3.59–3.66 (m, 3H), 3.45 (t, J = 9.62
Hz, 1H), 3.14–3.21 (m, 1H), 2.85–2.92 (m, 1H), 2.15 (t,
J = 7.70 Hz, 2H), 1.45–1.55 (m, 2H), 1.8–1.29 (m, 4H),
0.87 (t, J = 7.42 Hz, 3H); 13C-NMR (CD3OD, 75 MHz):
δ 176.1(C=O), 174.8(C=O), 156.7(Ar-C-OH), 132.1(Ar-C),
131.3(Ar-CH), 117.4(Ar-CH), 99.9(C1), 73.8(C3), 72.2(C5),
72.1(C2), 70.5(C4), 62.5(C6), 54.9(NH-CH), 37.6(Ar-CH2),
36.7(O = C-CH2), 32.3(CH2), 26.5(CH2), 23.4(CH2),
14.3(CH2); IR(KBr): 3372, 3318, 2918, 1738, 1652, 1530,
1231, 1081, 830 cm−1; HRMS (ESI) m/z [M - H]-calc. for
C21H30O9N = 440.1915; Found: 440.1924.
2.8d Synthesis of N-(hexanoyl)-O-α-L-rhamnopyran
2.8a Synthesis of N-(hexanoyl)-O-β-D-glucopyrano osyl-(S)-tyrosine (7d): This solid was purified by silica
syl-(S)-tyrosine (7a): This solid was purified by silica gel chromatography using a gradient of chloroform/methanol
gel chromatography using a gradient of chloroform/methanol (75:25, v/v) to obtain a yield of 65%, as a white solid.
(75:25, v/v) to obtain a yield of 65%, as a white solid. 1H-NMR (CD3OD, 300MHz): δ 7.17 (d, J = 8.49 Hz,
1H-NMR (CD3OD, 300MHz): δ 7.15 (d, J = 8.49 Hz, 2H), 2H), 6.99 (d, J = 8.30 Hz, 2H), 6.7 (d, J = 8.3 Hz,
7.01 (d, J = 8.68 Hz, 2H), 4.84 (d, J = 7.36 Hz, 1H), 4.58– 1H), 5.38 (br s, 1H), 4.63–4.67 (m, 1H), 3.98 (m, 1H), 3.85
4.62 (m, 1H), 3.85–3.89 (m, 1H), 3.66–3.71 (m, 1H), 3.39– (dd, J = 3.02, 9.25 Hz, 1H), 3.59–3.66 (m, 1H), 3.46 (t,
3.45 (m, 4H), 3.11–3.17 (m, 1H), 2.85–2.92 (m, 1H), 2.14 (t,
J = 9.44 Hz, 1H), 3.15–3.2 (m, 1H), 2.85–2.93 (m, 1H), 2.16
J = 7.36 Hz, 2H), 1.46–1.56 (m, 2H), 1.21–1.33 (m, 4H), (t, J = 7.36 Hz, 2H), 1.46–1.56 (m, 2H), 1.8–1.3 (m, 4H),
0.87 (t, J = 6.79 Hz, 3H); 13C-NMR (CD3OD, 125 MHz): 0.87 (t, J = 6.79 Hz, 3H); 13C-NMR (CD3OD, 75 MHz):
δ 175.6(C=O), 174.7(C=O), 157.5(Ar-C-OH), 131.9(Ar-C), δ 176.1(C=O), 156.7(Ar-C-OH), 132.1(Ar-C), 131.3(Ar-
131(Ar-CH), 117.4(Ar-CH), 102.1(C1), 77.6(C3), 77.5(C5), CH), 117.4(Ar-CH), 99.9(C1), 73.8(C3), 72.2(C4), 72.1(C5),
74.4(C2), 71(C4), 62.3(C6), 54.7(NH-CH), 37.4(Ar-CH2), 70.5(C2), 54.9(NH-CH), 37.6(Ar-CH2), 36.7(O = C-CH2),

Glycosylated N-fatty acyl-L-tyrosine derivatives
32.3(CH2), 26.5(CH2), 23.3(CH2), 18(C6), 14.3(CH2); 170.5(C=O), 153.3(Ar-C-OH), 137.1(H2C-CH = CH2),
IR(KBr): 3383, 2926, 2856, 1735, 1640, 1536, 1514, 1236, 128.6(Ar-C), 114.6(Ar-CH), 112.6(CH = CH2, Ar-CH),
1025, 817 cm−1; HRMS (ESI) m/z [M - H]-calc. for 97.4(C1), 72.5(C3), 69.2(C5), 68.6(C2), 65.3(C4), 59.5(C6),
C21H30O8N = 424.1965; Found: 424.1978.
52.9(NH-CH), 34.8(Ar-CH2), 34.1(O = C-CH2), 31.733.2
(H2C-CH = CH2), 27.5(O = C-CH2-CH2), 27.3(CH2),
27.03(CH2), 26.8(CH2), 23.7(CH2); IR(KBr): 3356, 2928,
2858, 1728, 1622, 1462, 1228, 1078, 765 cm−1; HRMS
(ESI) m/z [M - H]-calc. for C26H38O9N = 508.2541; Found:
508.2551.
2.8e Synthesis of N-(10-undecenoyl)-O-β-D-gluco
pyranosyl-(S)-tyrosine (8a): This solid was purified by
silica gel chromatography using solvent mixture of chloro-
form/methanol (75:25, v/v) to obtain a yield of 72%, as a
white solid. 1H-NMR (CDCl3+CD3OD, 300MHz): δ 7.13 (d,
J = 8.12 Hz, 2H), 7.0 (d, J = 7.55 Hz, 2H), 6.73 (d, J = 8.3 2.8h Synthesis of N-(10-undecenoyl)-O-α-L−rhamno
Hz, 1H), 5.72–5.86 (m, 1H), 4.92–5.0 (m, 2H), 4.89 (m, 1H), pyranosyl-(S)-tyrosine (8d): This solid was purified
4.52 (d, J = 7.55 Hz, 1H), 3.67–3.92 (m, 4H), 3.45–3.5 (m, by silica gel chromatography using a gradient of chloro-
2H), 2.93–3.21 (m, 2H), 2.18 (t, J = 6.8 Hz, 2H), 2.0 – 2.06 form/methanol (75:25, v/v) to obtain a yield of 70%, as
(m, 2H), 1.56 (m, 2H), 1.29 (m, 10H); 13C-NMR (CDCl3 + a white solid. 1H-NMR (CDCl3 + CD3OD, 300MHz): δ
CD3OD, 75 MHz): δ 174(C=O), 171.9(C=O), 155.8(Ar-C- 7.13 (d, J = 8.49 Hz, 2H), 6.98 (d, J = 8.68 Hz, 2H),
OH), 138.3(H2C-CH = CH2), 129.4(Ar-C), 115.9(Ar-CH), 6.73 (d, J = 6.49 Hz, 1H), 5.73–5.86 (m, 1H), 5.40 (br s,
113.2(CH = CH2, Ar-CH), 100.3(C1), 76.2(C3), 75.7(C5), 1H), 4.89–5.0 (m, 2H), 4.69 (m, 1H), 4.02 (m, 1H), 3.88
72.7(C2), 69.3(C4), 60.8(C6), 52.9(NH-CH), 36(Ar-CH2), (dd, J = 3.39, 9.44 Hz, 1H), 3.63–3.73 (m, 1H), 3.47 (t,
35.9(O = C-CH2), 35.333.5(H2C-CH = CH2), 33(O =
J = 9.44 Hz, 1H), 2.93–3.19 (m, 2H), 2.18 (t, J = 7.36
C-CH2-CH2), 28.5(CH2), 28.4(CH2), 28.3(CH2), 28.2(CH2), Hz, 2H), 2.0–2.07 (m, 2H), 1.55 (m, 2H), 1.24 - 1.28 (m,
24.9(CH2); IR(KBr): 3414, 2924, 2854, 1730, 1600, 1459, 13H);13C-NMR(CDCl3+CD3OD, 75MHz):δ 175.1(C=O),
1220, 1089, 765 cm−1; HRMS (ESI) m/z [M - H]-calc. for 174.2(C=O), 150.6(Ar-C-OH), 139.5(H2C-CH = CH2),
C26H38O9N = 508.2541; Found: 508.2553.
130.8(Ar-C), 116.9(Ar-CH), 114.4(CH = CH2, Ar-CH),
99(C1), 73.2(C3), 71.7(C4), 71.2(C5), 69.7(C2), 54.08(NH-
CH), 37.1(Ar-CH2), 36.6(O = C-CH2), 34.3(H2C-CH =
CH2), 29.8(O = C-CH2 − CH2), 29.6(CH2), 29.5(CH2),
29.4(CH2), 26.2(CH2), 17.8(C6); IR(KBr): 3514, 3334,
2.8f Synthesis of N-(10-undecenoyl)-O-β-D-galacto
pyranosyl-(S)-tyrosine (8b): This solid was purified
by silica gel chromatography using a gradient of chloro-
form/methanol (75:25, v/v) to obtain a yield of 70%, as a
white solid. 1H-NMR (CDCl3 + CD3OD, 300MHz): δ 7.09
(d, J = 8.49 Hz, 2H), 7.04 (d, J = 8.87 Hz, 1H), 6.99 (d,
J = 8.68 Hz, 2H), 5.73–5.87 (m, 1H), 4.90–5.01 (m, 2H),
2920, 2850, 1735, 1645, 1514, 1235, 1068, 1015, 663 cm−1
;
HRMS (ESI) m/z [M - H]-calc. for C26H38O8N = 492.2591;
Found: 492.2603.
4.84 (d, J = 7.74 Hz, 1H), 4.71 (t, J = 5.85, 1H), 3.90–3.96 2.8i Synthesis of N-(tetradecanoyl)-O-β-D-glucopy
(m, 2H), 3.78–3.84 (m, 2H), 3.57–3.66 (m, 2H), 2.98–3.15 ranosyl-(S)-tyrosine (9a): This solid had a little impu-
(m, 2H), 2.18 (t, J = 7.17 Hz, 2H), 2.0–2.06 (m, 2H), 1.57 rity which was purified by silica gel chromatography using
(m, 2H), 1.28 (m, 10H); 13C-NMR (CDCl3 + DMSO-d6, a gradient of chloroform/methanol (75:25, v/v) to obtain a
125 MHz): δ 172.9(C=O), 172.5(C=O), 155.8(Ar-C-OH), yield of 75%, as a white solid. 1H-NMR (CD3OD, 300MHz):
138.6(H2C-CH
= CH2), 129.9(Ar-C), 116.05(Ar-CH), δ 7.12 (d, J = 8.49 Hz, 2H), 7.01 (d, J = 8.49 Hz, 2H), 5.39
113.7(CH = CH2, Ar-CH), 100.7(C1), 74.5(C3), 73.2(C5), (d, J = 3.55 Hz, 1H), 4.82 (d, J = 7.36 Hz, 1H), 4.46–4.50
70.6(C2), 68.2(C4), 60.8(C6), 52.7(NH-CH), 36.2(Ar-CH2), (m, 1H), 3.79–3.88 (m, 1H), 3.60–3.69 (m, 2H), 3.49–3.54
35.8(O = C-CH2), 33.2(H2C-CH = CH2), 33(O = (m, 1H), 3.38–3.44 (m, 2H), 3.1–3.6 (m, 1H), 2.85–2.92 (m,
C-CH2-CH2), 28.7(CH2), 28.5(CH2), 28.3(CH2), 25.08 1H), 2.12 (t, J = 7.35 Hz, 2H), 1.49 (m, 2H), 1.26 (m, 20H),
(CH2); IR(KBr): 3398, 2934, 2862, 1728, 1618, 1438, 1230, 0.88 (t, J = 6.23 Hz, 3H); 13C-NMR (CD3OD, 75 MHz):
1081, 765 cm−1; HRMS (ESI) m/z [M - H]-calc. for δ 177.8(C=O), 175.6(C=O), 157.8(Ar-C-OH), 131.4(Ar-C),
C26H38O9N = 508.2541; Found: 508.2550.
117.9(Ar-CH)„ 102.5(Ar-CH), 99.5(C1), 78(C3), 74.9(C5),
73.3(C2), 71.4(C4), 62.5(C6), 56.8(NH-CH), 38.2(O =
C-CH2), 37.1(O = C-CH2-CH2), 33(CH2), 31.8(CH2),
30.7(CH2), 30.3(CH2), 30.4(CH2), 26.9(CH2), 23.7(CH2),
21.1(CH2), 14.5(CH3); IR(KBr): 3421, 2921, 2850, 1728,
1650, 1511, 1228, 1064, 839 cm−1; HRMS (ESI) m/z [M -
H]-calc. for C29H46O9N = 552.3167; Found: 552.3180.
2.8g SynthesisofN-(10-undecenoyl)-O-α-D-mannopy
ranosyl-(S)-tyrosine (8c): This solid was purified by silica
gel chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 70%, as a white solid.
1H-NMR (CDCl3 + CD3OD, 300MHz): δ 7.13 (d, J =
7.74 Hz, 2H), 6.98 (d, J = 7.74 Hz, 2H), 5.73–5.86
(m, 1H), 5.46 (br s, 1H), 4.89–5.0 (m, 2H), 4.57 (m, 1H), 2.8j Synthesis of N-(tetradecanoyl)-O-β-D-galactopy
4.03 (m, 1H), 3.93–3.97 (m, 1H), 3.71–3.86 (m, 4H), 3.59– ranosyl-(S)-tyrosine(9b): Thissolidwaspurifiedbysilica
3.63 (m, 1H), 2.94–3.16 (m, 2H), 2.16 (t, J = 6.98 Hz, gel chromatography using a gradient of chloroform/methanol
2H), 2.02 – 2.04 (m, 2H), 1.54 (m, 2H), 1.27 (m, 10H); (75:25, v/v) to obtain a yield of 75%, as a white solid.
13C-NMR (CDCl3 + DMSO-d6, 75 MHz): δ 172.7(C=O), 1H-NMR (CD3OD, 300MHz): δ 7.13 (d, J = 8.49 Hz, 2H),

Srikanth Vudhgiri et al.
7.06 (d, J = 8.87 Hz, 1H), 7.0 (d, J = 8.49 Hz, 2H), 4.8 (d, 1H-NMR (CD3OD, 300MHz): δ 7.13 (d, J = 8.30 Hz,
J = 7.55 Hz, 1H), 4.54–4.58 (m, 1H), 3.87–3.88 (m, 1H), 2H), 6.98 (d, J = 8.30 Hz, 2H), 5.28–5.38 (m, 2H),
3.64–3.78 (m, 4H), 3.55 (dd, J = 3.39, 9.82 Hz, 1H), 3.09– 4.88 (d, J = 7.36 Hz, 1H), 4.55 (m, 1H), 3.87–3.91
3.15 (m, 1H), 2.84–2.92 (m, 1H), 2.13 (t, J = 6.6 Hz, 2H), 1.5 (m, 1H), 3.73–3.76 (m, 1H), 3.44–3.50 (m, 4H), 3.10–3.16
(m, 2H), 1.26 (m, 20H), 0.87 (t, J = 6.23 Hz, 3H); 13C-NMR (m, 1H), 2.94–3.01 (m, 1H), 2.17 (t, J = 7.36 Hz, 2H),
(CD3OD, 75 MHz): δ 176(C=O), 175.7(C=O), 158(Ar-C- 2.01–2.08 (m, 4H), 1.56 (m, 2H), 1.28 (m, 20H), 0.88
OH), 132.4(Ar-C), 131.2(Ar-CH), 117.7(Ar-CH), 103(C1), (t, J = 6.6 Hz, 3H); 13C-NMR (CDCl3 + DMSO-d6,
76.7(C3), 74.8(C5), 72.2(C2), 70.1(C4), 62.3(C6), 55.5(NH- 75 MHz): δ 172.4(C=O), 155.8(Ar-C-OH), 131.3(Ar-C),
CH), 37.7(O = C-CH2), 36.8(O = C-CH2-CH2), 33(CH2), 130.1(HC=CH), 129.9(HC=CH), 129.4(Ar-CH), 115.6(Ar-
30.7(CH2), 30.6(CH2), 30.4(CH2), 30.2(CH2), 26.8(CH2), CH), 100.4(C1), 78.7(C3), 76.7(C5), 73.1(C2), 69.6(C4),
23.7(CH2), 14.5(CH3); IR(KBr): 3408, 2928, 2852, 1730, 60.7(C6), 48.8(NH-CH), 36.3(HC = CH-CH2), 35.6(O =
1656, 1518, 1218, 1064, 839 cm−1; HRMS (ESI) m/z [M - C-CH2), 31.3(O = C-CH2-CH2), 29.2(CH2), 29(CH2),
H]-calc .for C29H46O9N = 552.3167; Found: 552.3183.
28.9(CH2), 28.8(CH2), 28.7(CH2), 26.7(CH2), 25.3(CH2),
22.1(CH2), 13.9(CH3); IR(KBr) 3323, 2925, 2853, 1722,
1644, 1512, 1238, 1080, 695 cm−1; HRMS (ESI) m/z [M
- H]-calc. for C33H52O9N = 606.3636; Found: 606.3660.
2.8k Synthesis of N-(tetradecanoyl)-O-α-D-mannopy
ranosyl-(S)-tyrosine (9c): This solid was purified by silica
gel chromatography using a gradient of chloroform/methanol
(75:25, v/v) (71 % yield) to obtain as a white solid. 1H-NMR
(CD3OD, 300MHz): δ 7.13 (d, J = 8.49 Hz, 2H), 6.99 (d,
J = 8.68 Hz, 2H), 5.41 (br s, 1H), 4.52–4.56 (m, 1H), 3.95–
3.97 (m, 1H), 3.85–3.89 (m, 1H), 3.7–3.76 (m, 3H), 3.53–3.59
(m, 1H), 3.1–3.16 (m, 1H), 2.83–2.91 (m, 1H), 2.13 (t, J =
7.36 Hz, 2H), 1.48 (m, 2H), 1.26 (m, 20H), 0.87 (t, J = 6.23
Hz, 3H); 13C-NMR (CD3OD, 75 MHz): δ 176.5(C=O),
175.9(C=O), 156.7(Ar-C-OH), 132.7(Ar-C), 131.4(Ar-CH),
117.6(Ar-CH), 100.2(C1), 75.2(C3), 72.4(C5), 72(C2), 68.3
(C4), 62.5(C6), 55.9(NH-CH), 37.9(O = C-CH2), 37(O =
C-CH2-CH2), 33(CH2), 30.7(CH2), 30.6(CH2), 30.4(CH2),
30.2(CH2), 26.9(CH2), 23.7(CH2), 14.5(CH3); IR(KBr):
2.8n SynthesisofN-(oleoyl)-O-β-D-galactopyranosyl-
(S)-tyrosine (10b): This solid was purified by silica gel
chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 76%, as a white solid.
1H-NMR (CD3OD, 300MHz): δ 7.10 (d, J = 7.74 Hz,
2H), 7.02 (d, J = 8.87 Hz, 1H), 6.98 (d, J = 7.93 Hz,
2H), 5.29–5.38 (m, 2H), 4.83 (d, J = 7.55 Hz, 1H), 4.59
(m, 1H), 3.94–4.04 (m, 2H), 3.72–3.84 (m, 2H), 3.58–3.64
(m, 2H), 3.14–2.97 (m, 2H), 2.17 (t, J = 7.36 Hz, 2H),
2.0–2.02 (m, 4H), 1.57 (m, 2H), 1.27 (m, 20H), 0.88 (t,
J = 6.42 Hz, 3H); 13C-NMR (CDCl3 + CD3OD, 75 MHz):
δ 175.6(C=O), 174.3(C=O), 156.4(Ar-C-OH), 131.3(Ar-C),
130.6(HC=CH), 130.1(HC=CH), 129.9(Ar-CH), 117.2(Ar-
CH), 101.5(C1), 75.2(C3), 73.5(C5), 71.1(C2), 69.02(C4),
61.7(C6), 54.8(NH-CH), 37.1(HC = CH-CH2), 36.5(O =
C-CH2), 32.7(O = C-CH2-CH2), 29.9(CH2), 29.8(CH2),
29.7(CH2), 29.5(CH2), 29.4(CH2), 27.4(CH2), 25.8(CH2),
22.8(CH2), 14.1(CH3); IR(KBr) 3300, 2935, 2826, 1732,
1634, 1522, 1238, 1080, 695 cm−1; HRMS (ESI) m/z [M
- H]-calc. for C33H52O9N = 606.3636; Found: 606.3655.
3402, 2962, 2863, 1738, 1642, 1552, 1238, 1060, 839 cm−1
;
HRMS (ESI) m/z [M - H]-calc. for C29H46O9N = 552.3167;
Found: 552.3182.
2.8l Synthesis of N-(tetradecanoyl)-O-α-L-rhamnopy
ranosyl-(S)-tyrosine(9d): Thissolidwaspurifiedbysilica
gel chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 71% as a white solid. 1H-NMR
(CD3OD, 300MHz): δ 7.14 (d, J = 8.68 Hz, 2H), 6.96 (d,
J = 8.49 Hz, 2H), 6.67 (d, J = 8.3 Hz, 1H), 5.36 (br s,
1H), 4.59 – 4.64 (m, 1H), 3.95 (m, 1H), 3.81 (dd, J = 3.39,
9.44 Hz, 1H), 3.56–3.67 (m, 1H), 3.43 (t, J = 9.44 Hz, 1H),
3.11–3.17 (m, 1H), 2.83–2.91 (m, 1H), 2.13 (t, J = 7.36
Hz, 2H), 1.46–1.53 (m, 2H), 1.18 - 1.26 (m, 23H), 0.88
(t, J = 6.23 Hz, 3H); 13C-NMR (CD3OD, 75 MHz): δ
176.1(C=O), 174.8(C=O), 156.7(Ar-C-OH), 132.1(Ar-C),
131.3(Ar-CH), 117.4(Ar-CH), 99.9(C1), 73.8(C3), 72.2(C4),
72(C5), 70.5(C2), 54.9(NH-CH), 37.6(O = C-CH2), 36.8
2.8o SynthesisofN-(oleoyl)-O-α-D-mannopyranosyl-
(S)-tyrosine (10c): This solid was purified by silica gel
chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 76%, as a white solid.
1H-NMR (CD3OD, 300MHz): δ 7.12 (d, J = 8.12 Hz,
2H), 6.98 (d, J = 8.12 Hz, 2H), 5.46 (br s, 1H), 5.28–
5.38 (m, 2H), 4.58 (m, 1H), 4.02 (m, 1H), 3.92–3.96 (m,
1H), 3.71 – 3.84 (m, 3H), 3.59–3.62 (m, 1H), 2.93–3.17
(m, 2H), 2.17 (t, J = 7.36 Hz, 2H), 2.01–2.02 (m, 4H),
1.55 (m, 2H), 1.28 (m, 20H), 0.88 (t, J = 6.79 Hz, 3H);
13C-NMR (CDCl3 + CD3OD + DMSO-d6, 75 MHz): δ
174.5(C=O), 172.6(C=O), 155.2(Ar-C-OH), 131.8(Ar-C),
130.3(HC=CH), 130.1(HC=CH), 129.7(Ar-CH), 116.4(Ar-
CH), 99.1(C1), 74.4(C3), 70.9(C5), 70.3(C2), 66.8(C4),
(O
=
C-CH2-CH2), 33(CH2), 30.7(CH2), 30.5(CH2),
30.4(CH2), 30.1(CH2), 26.8(CH2), 23.7(CH2), 18(C6),
14.5(CH3); IR(KBr): 3445, 3321, 2850, 1734, 1647, 1607,
15551, 1234, 1058, 1016, 838 cm−1; HRMS (ESI) m/z [M -
H]-calc. for C29H46O8N = 536.3217; Found: 536.3229.
2.8m Synthesis of N-(oleoyl)-O-β-D-glucopyra 61.1(C6), 54.5(NH-CH), 36.6(HC = CH-CH2), 35.7(O =
nosyl-(S)-tyrosine (10a): This solid was purified by silica C-CH2), 32.2(O = C-CH2-CH2), 31.5(CH2), 29.4(CH2),
gel chromatography using a gradient of chloroform/methanol 29.2(CH2), 29.1(CH2), 28.9(CH2), 26.9(CH2), 25.5(CH2),
(75:25, v/v) to obtain a yield of 76%, as a white solid. 22.3(CH2), 14.0(CH3); IR(KBr) 3312, 2918, 2842, 1736,

Glycosylated N-fatty acyl-L-tyrosine derivatives
1640, 1532, 1238, 1080, 695 cm−1; HRMS (ESI) m/z [M plotted absorbance data for the dose response curves. IC50
- H]-calc. for C33H52O9N = 606.3636; Found: 606.3651.
values (in μM) are expressed as the average of two indepen-
dent experiments.
2.8p SynthesisofN-(oleoyl)-O-α-L-rhamnopyranosyl-
(S)-tyrosine (10d): This solid was purified by silica gel
chromatography using a gradient of chloroform/methanol
(75:25, v/v) to obtain a yield of 76%, as a white solid.
1H-NMR (CD3OD, 300MHz): δ 7.10 (d, J = 8.49 Hz,
2H), 6.97 (d, J = 8.49 Hz, 2H), 5.42 (br s, 1H), 5.29–
5.38 (m, 2H), 4.73 (m, 1H), 4.03 (m, 1H), 3.89 (dd, J =
3.39, 9.44 Hz, 1H), 3.65–3.74 (m, 1H), 3.47 (t, J = 9.44
Hz, 1H), 2.98–3.17 (m, 2H), 2.18 (t, J = 7.36 Hz, 2H),
2.0–2.02 (m, 4H), 1.57 (m, 2H), 1.25–1.27 (m, 23H), 0.88
(t, J = 6.42 Hz, 3H); 13C-NMR (CDCl3 + CD3OD,
75 MHz): δ 174.3(C=O), 173.8(C=O), 155.7(Ar-C-OH),
130.6(Ar-C), 130.3(HC=CH), 130.2(HC=CH), 129.9(Ar-
CH), 116.6(Ar-CH), 98.6(C1), 73(C3), 71.5(C4), 70.9(C5),
69.3(C2), 53.5(NH-CH), 36.9(HC = CH-CH2), 36.5(O =
C-CH2), 32.8(O = C-CH2-CH2), 30(CH2), 29.9(CH2),
29.7(CH2), 29.5(CH2), 29.4(CH2), 27.4(CH2), 25.9(CH2),
22.9(CH2), 17.6(C6), 14.2(CH3); IR(KBr): 3416, 3322,
2923, 2852, 1725, 1650, 1229, 1011, 668 cm−1; HRMS
(ESI) m/z [M - H]-calc. for C33H52O8N = 590.3700; Found:
590.3687.
2.10 Antimicrobial activity
Antimicrobial activity of the prepared glycosylated N-fatty
acyl-L-tyrosine derivatives was determined using well diffu-
sion method29 against a panel of pathogenic bacterial strains,
including Micrococcus luteus MTCC 2470, Staphylococcus
aureus MTCC 96, Staphylococcus aureus MLS16 MTCC
2940, Bacillus subtilis MTCC 121, Escherichia coli MTCC
739, Klebsiella planticola MTCC 530, Pseudomonas aerugi-
nosa MTCC 2453 and Candida albicans MTCC 3017 which
were procured from the Microbial Type Culture Collection
(MTCC), CSIR-Institute of Microbial Technology, Chandi-
garh, India. The pathogenic reference strains were seeded on
the surface of the medium Petri plates, containing Muller-
Hinton agar with 0.1 mL of previously prepared microbial
suspensions individually containing 1.5 × 108 cfu mL−1
(equal to 0.5 McFarland standard). Wells of 6.0 mm diam-
eter were prepared in the media plates using a cork borer
and the glycosylated N-fatty acyl-L-tyrosine derivatives at
a dose range of 125−0.48 μg well−1 were added in each
well under sterile conditions in a laminar air flow chamber.
Standard antibiotic solutions of Ciprofloxacin and Micona-
zole at a dose range of 125−0.48 μg well−1 and the well
containing methanol served as positive and negative controls,
respectively. The plates were incubated for 24 h at 37◦C for
bacterial and 30◦C for Candida albicans and the well con-
taining the least concentration showing the inhibition zone
was considered as the minimum inhibitory concentration. All
experiments were carried out in duplicates and mean values
are represented.
2.9 In vitro cytotoxicity evaluation
The cytotoxicity of the prepared glycosylated N-fatty acyl-
L-tyrosine derivatives was evaluated on the basis of mea-
surement of in vitro growth of tumor cell lines in 96 well
plates by cell-mediated reduction of tetrazolium salt to water
insoluble formazan crystals using doxorubicin as a standard
control. The cytotoxicity was assessed against a panel of four
different tumor cell lines: A549 derived from human alve-
olar adenocarcinoma epithelial cells (ATCC No. CCL-185),
PC3 derived from human prostate cancer cells (ATCC No.
CRL-1435), MDA-MB-231 derived from human breast ade-
nocarcinoma cells (ATCC No. HTB-26), HepG2 derived from
human liver adenocarcinoma cells (ATCC No HB-8065) and
HUVEC derived from human umbilical vein endothelial cells
(ATCC No. CRL-1730) using the MTT assay.28 The IC50 val-
3. Results and Discussion
3.1 Synthesis and characterization
As per Scheme 1, the synthesis of glycosylated N-fatty
acyl-L-tyrosine derivatives initiated with the prepara-
ues (50% inhibitory concentration) were calculated from the tion of methyl-L-tyrosinate24,25,30 (1) from L-tyrosine
O
H
N
O
O
R
O
ii
OH
i
O
O
NH2
NH2
HO
HO
OH
1
-
2
6
O
H
N
R
iii, iv
OH
R
2, 7
3, 8
),
= Hexanoyl (
Myristoyl (
Lipoyl (
), Undecenoyl (
5, 10
),
O
4, 9
), Oleoyl (
6, 11
)
OH
-
7
11
Scheme 1. Reagents and conditions: i) H2SO4-MeOH, 4 h, Reflux, 70%; ii) Fatty acid, EDC.HCl,
HOBT, DCM, rt, 12 h, 80–89%; iii) LiOH, THF, rt, 16 h; iv) 2N HCl, 96–98%.

Srikanth Vudhgiri et al.
OH
OAc
O
X
X
O
i
Y
OH
Y
OAc
HO
AcO
OH
OAc
X = H, Y= OH, Glucose
X = OH, Y= H, Galactose
a
X = H, Y= OAc, Glucose pentaacetate ( )
b
X = OAc, Y= H, Galactose pentaacetate ( )
OAc
OH
HO
O
AcO
O
HO
HO
OH
AcO
AcO
OAc
Mannose
OH
ii
c
Mannose pentaacetate ( )
OAc
O
O
HO
AcO
HO
OH
AcO
OAc
L- Rhamnose
d
L-Rhamnose tetraacetate ( )
Scheme 2. Regents and conditions: i) NaOAc, Ac2O, 90◦C, Reflux, 2.5 h, 92%; ii) Pyridine/Ac2O, rt, 12 h, 98%.
using methanol-sulfuric acid solution. This methyl- N-lipoyl-L-tyrosine as compared to the other series of
L-tyrosinate (1) was further derivatized to afford N- compounds (7a–7d, 8a–8d, 9a–9d, 10a–10d), which
fatty acyl-L- tyrosine methyl esters (2–6) with differ- is due to the presence of sulfur-containing shorter acyl
ent fatty acids using EDC-HCl and HOBt coupling chain lipoic acid. Hence, we restricted the synthesis up
reagents.
to N-lipoyl-L-tyrosine methyl esters (6a–6d) and in the
Further, to obtain fattyacyl-L-tyrosine (7–11), N- final step, only sugar acetate groups were deprotected
fatty acyl-L-tyrosine methyl esters (2–6) were hydroly- by using NaOMe/MeOH instead of LiOH.H2O reagent
zed with LiOH.H2O in THF-H2O solvent mixture and (Scheme 4).
this was followed by acidification of lithium salts
The glucose and galactose N-fatty acyl-L-tyrosines
with 2N HCl. The penta-O-acetyl-β-D-glucose (a) were formed in β–configuration and the mannose and
α
and penta-O-acetyl-β-D-galactose (b) were prepared rhamnose N-fatty acyl-L-tyrosines were formed in –
by employing NaOAc/Ac2O method as per our pre- configuration due to neighboring group participation
vious report26 and penta-O-acetyl-α-D-mannose (c) of C2-acetate group of the sugar during the glycosy-
1
α
and tetra-O-acetyl- -L-rhamnose (d) were prepared lation. The data on the H-NMR chemical shifts and
by adopting pyridine/Ac2O method27 as indicated in J1,2 coupling constants corroborate with the published
Scheme 2.
reports;32,33 for glucose and galactose derivatives the
As depicted in Scheme 3, glycosylation of N-fatty coupling constant of J1,2 is ≥ 7 Hz indicating the β-
acyl-L-tyrosine methyl esters (2–5) with sugar acetates configurationandformannoseandrhamnosederivatives
(a–d) was achieved with the Lewis acid BF3-Et2O31 and the coupling constant of J1,2 is < 3 Hz representing -
α
simultaneous deacylation and methyl ester hydrolysis configuration.
was accomplished with LiOH.H2O in THF-H2O sol-
vent mixture and this was followed by acidification of
lithium salts with 2N HCl to obtain the final glycosy-
3.2 Biological studies
lated N-fatty acyl-L-tyrosines (7a–7d, 8a–8d, 9a–9d, 3.2a Cytotoxicity: The amino acid acylated and gly-
10a–10d). Attempts were made to prepare glycosylated cosylated with fatty acids and carbohydrates represent
N-lipoyl-L-tyrosines using the same synthetic protocol
as mentioned in Scheme 3.
However, we observed that the extraction of the gly-
cosylated N-lipoyl-L-tyrosine from the reaction mix-
ture was very difficult. The plausible reason may be
attributable to the more polar nature of glycosylated
a separate class of lipid derivatives which demand a
detailed investigation. In this context, glycosylated N-
fatty acyl-L-tyrosines and N-lipoyl-L-tyrosine methyl
ester derivatives were synthesized and evaluated to
examine the impact of sugar and fatty acid on the biolog-
ical activity of this aglycone moiety. All the synthesized

Glycosylated N-fatty acyl-L-tyrosine derivatives
X
OH
X
OAc
X
OH
O
Y
O
O
iii
O
i, ii
Y
HO
Y
OAc
O
OH
HO
AcO
OH
OAc
O
HN
O
a
X = H, Y= OAc ( )
OH
HN
R
O
b
X = OAc, Y= H ( )
OLi
R
O
7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b
Compounds (
)
OH
HO
OH
HO
OAc
O
O
HO
HO
HO
AcO
HO
O
iii
i, ii
AcO
AcO
OAc
O
O
c
Mannose pentaacetate ( )
O
HN
O
HN
OH
R
O
OLi
R
O
7c, 8c, 9c, 10c
Compounds (
)
R
O
R
O
Li
O
OH
HN
HN
O
O
O
OAc
O
O
O
ii
O
iii
i,
AcO
AcO
HO
AcO
OAc
AcO
HO
OAc
OH
7d, 8d, 9d, 10d
d
L - Rhamnose tetraacetate ( )
Compounds (
)
Scheme 3. Reagents and conditions: i) Compounds 2–5, BF3.Et2O, DCM, rt, Overnight; ii) LiOH,
THF, rt, 16 h; iii) 2N HCl, 65-77 %.
glycosylated N-fatty acyl-L-tyrosines (7a–7d, 8a–8d, undecenoic acid (8a–8d) derivatives showed a poor
9a–9d and 10a–10d) were tested against a panel of four cytotoxicity. These results demonstrate that the sugar
cancer cell lines, namely A549, PC3, MDA-MB-231, and fatty acid both substituents enhance the activity.
and HepG2.28
Further, the non-glycosylated N-fatty acyl-L-tyrosine
Based on the results depicted in Table 1, compounds methyl esters (2–6) and N-fatty acyl-L-tyrosines (7–11)
7a–7c, 8c, 9c and 10c exhibited moderate cytotoxicity showed poor cytotoxicity against all the tested cell lines
against all the tested cancer cell lines irrespective of the as compared to the glycosylated N-fatty acyl derivatives
carbohydrate and lipid (saturated and short to medium (Table 1).
chain) moieties and the IC50 values ranged between
Similarly, glycosylated N-lipoyl-L-tyrosine methyl
19.5−45.6 μM. However, in case of oleic (unsatu- esters (6a–6d) were evaluated for cytotoxicity against
rated) acid, the compounds 10a (IC50 value of 15.6 μM) the same panel of cancer cell lines. Based on the results
and 10d (IC50 value of 17.6 μM) showed promis- shown in Table 1, the compounds (6b–6d) bearing
α
ing cytotoxicity against MDA-MB-231, and compound an unusual, highly active -lipoic acid moiety exhib-
10b (IC50 value of 18.7 μM) showed significant activ- ited good cytotoxicity against all the cell lines and the
ity against A549 cell line. The compounds 10a,10b IC50 values ranged between 9.4−13.8 μM. Among
and 10d also showed good to moderate cytotoxicity them, the compound 6d exhibited promising activity
against all the other tested cancer cell lines. Here, with IC50 values of 10.5, 9.4, 10.9 and 12.1 against
the respective non-glycosylated free carboxylic acid A549, PC3, MDA-MB-231 and HepG2, respectively.
derivative (10) showed poor cytotoxicity and excellent However, the compound 6a did not exhibit any cyto-
antimicrobial activity when compared to glycosylated toxicity. Whereas in non-glycosylated free carboxylic
one. In addition to that when compared to other fatty acid derivative (11) and non-glycosylated methyl ester
acid derivatives like saturated (7a–7d, 9a–9d) and compound 6 showed very poor cytotoxicity and good

Srikanth Vudhgiri et al.
OH
O
X
Y
O
HO
OH
O
O
i
S
N
H
S
O
6a, 6b
Compounds (
)
OH
HO
O
HO
O
HO
S
S
ii
O
O
HN
HO
O
O
O
N
O
S
S
H
6c
Compound (
)
O
iii
H
N
S
S
O
O
6d
Compound (
)
O
O
HO
HO
HO
Scheme 4. Reagents and conditions: i) A) a or b, BF3.Et2O, DCM, rt, Over night; B) NaOMe, MeOH,
70-75%; ii) A) c, BF3.Et2O, DCM, rt, Over night; B) NaOMe, MeOH, 70-75%; iii) A) d, BF3.Et2O,
DCM, rt, Over night; B) NaOMe, MeOH, 70-75%.
antimicrobial activity when compared to glycosylated 3.2b Antimicrobial activity: The antimicrobial activ-
derivative. It is also noteworthy to mention that all ities29 of N-fatty acyl-L-tyrosine methyl esters (2–6)
the synthesized compounds (7a–7d, 8a–8d, 9a–9d, and N-fatty acyl-L-tyrosines (7–11) were examined
10a–10d and 6b–6d) did not exhibit any antimicrobial against seven bacterial and one fungal strain and the
activity; however, they showed promising cytotoxic- results to this regard are shown in Table 2. It was
ity. These results again proved that the fatty acid and observed that among all the synthesized compounds,
sugar play significant role in enhancing or affecting N-fatty acyl-L-tyrosine methyl esters (2–6) showed a
the biological activity of these compounds. Moreover, poor antimicrobial activity against both bacterial and
irrespective of the lipid moiety all the mannose ana- fungal strains. However, N-fatty acyl-L-tyrosines (7–
logues (7c, 8c, 9c, 10c and 6c) exhibited moderate 11) exhibited promising antimicrobial activity against
cytotoxicity against all the tested cell lines. From a both bacterial and fungal strains. Among these N-
mechanistic perspective, it is presumed that these glyco- fatty acyl-L-tyrosines (7–11), specifically compound 9,
sides may be causing cell cycle arrest in the S and G2/M showed promising antimicrobial activity against four
phases, enabling the activation of the caspase cascade Gram positive bacterial strains and two Gram neg-
and thus inducing the apoptosis in the cancerous cell ative bacterial strain, such as Staphylococcus aureus
lines.17,34,35 In addition, these phenolic glycosides from MTCC 96, Bacillus subtilis MTCC 121, S. aureus
natural sources have been reported to exhibit diverse MLS16 MTCC 2940, Micrococcus luteus MTCC 2470
biological activities and have been claimed to function and Klebsiella planticola MTCC 530, Escherichia coli
as pro-drugs.36,37
MTCC 739 with MIC values of 1.9, 1.9, 3.9, 3.9 and
Based on the cytotoxicity results, the cytotoxicity 3.9, 3.9 μg/mL, respectively. Similarly compound 10
of aglycone moiety depends on the fatty acid nature exhibited good antimicrobial activity against two Gram
(oleic acid and lipoic acid) and sugar moiety. These two positive bacterial strains and three Gram negative bac-
substituents in combination enhance the cytotoxicity of terial strain, such as Bacillus subtilis MTCC 121, S.
aglycone as well as the sugar moiety inversely affects aureus MLS16 MTCC 2940 andKlebsiella planticola
the antimicrobial activity of aglycone.
MTCC 530, Pseudomonas aeruginosa MTCC 2453,

Glycosylated N-fatty acyl-L-tyrosine derivatives
Table 1. Cytotoxicity evaluation of the glycosylated N-fatty acyl-L-tyrosines (7a–7d, 8a–8d, 9a–
9d, 10a–10d), glycosylated N-fatty acyl-L-tyrosines methyl esters (6a–6d), N-fatty acyl-L-tyrosine
methyl esters (2–6) and N-fatty acyl-L-tyrosines (7–11).
Test compound
IC50 values (μM)*
A549
PC3
MDA-MB-231
HepG2
HUVEC
7a
7b
7c
7d
40.7 0.26
31.2 0.28
45.6 0.17
19.5 0.11
31.3 0.29
44.4 0.36
25.9 0.36
32.5 0.52
32.6 0.41
29.2 0.29
38.4 0.48
33.7 0.22
89.6 0.32
92.3 0.36
100.6 0.44
a
–
–
–
–
–
8a
8b
8c
8d
–
–
–
–
–
–
–
–
–
–
29.2 0.35
–
25.2 0.42
21.6 0.32
–
33.3 0.36
–
121.5 0.18
–
–
9a
9b
–
–
–
–
–
–
–
–
–
–
9c
9d
38.9 0.22
–
25.6 0.17
–
38.6 0.44
–
31.9 0.52
–
99.5 0.28
–
10a
10b
10c
10d
23.1 0.37
18.7 0.32
25.1 0.36
22.8 0.15
–
18.6 0.35
19.6 0.26
25.5 0.24
18.9 0.18
–
15.6 0.11
19.2 0.22
25.1 0.18
17.6 0.31
–
19.1 0.14
22.9 0.35
22.6 0.32
19.8 0.22
–
112 0.52
125 0.26
98.5 0.32
102.3 0.38
–
6a
6b
6c
6d
2
10.7 0.19
11.0 0.26
10.5 0.28
–
11.2 0.14
10.6 0.09
9.4 0.11
215.6 0.22
–
11.7 0.22
13.8 0.25
10.9 0.22
–
13.2 0.16
12.5 0.15
12.1 0.19
236.9 0.28
–
99.2 0.42
101.2 0.36
110.5 0.32
–
3
–
–
–
4
5
6
7
8
9
10
11
152.1 0.44 129.8 0.38
156.3 0.38
–
143.2 0.44 201.3 0.42
–
185.6 0.55
201.3 0.42
30.2 0.33
50.1 0.42
37.5 0.18
36.9 0.22
50.5 0.15
0.6 0.11
–
–
–
–
172.3 0.36 210.5 0.18
29.8 0.56
45.6 0.32
36.6 0.28
40.2 0.24
45.5 0.18
0.8 0.12
35.6 0.19
51.6 0.22
48.9 0.14
39.2 0.16
29.6 0.38
0.9 0.07
29.6 0.22
39.9 0.28
40.5 0.37
38.6 0.26
37.2 0.15
0.8 0.09
98.2 0.55
90.4 0.48
99.9 0.42
101.2 0.36
89.6 0.51
68.2 0.22
Doxorubicin
* Micro Molar
A549: human alveolar adenocarcinoma epithelial cells (ATCC No. CCL-185), PC3: human prostate
cancer cells (ATCC No. CRL-1435), MDA-MB-231: human breast adenocarcinoma cells (ATCC
No. HTB-26), HepG2: human liver adenocarcinoma cells (ATCC No. HB-8065), HUVEC: Normal
human umbilical vein endothelial cells (ATCC No. CRL-1730); a–: No activity.
Escherichia coli MTCC 739 with MIC values of 1.9, 4. Conclusions
1.9, and 1.9, 3.9, 3.9 μg/mL, respectively.
In conclusion, glycosylated N-fatty acyl-L-tyrosines
and N-lipoyl-L-tyrosine methyl esters were synthesized
and evaluated for their cytotoxicity antimicrobial activ-
ity in the present study. All the N-fatty acyl-L-tyrosines
were glycosylated with four sugar moieties in presence
of the Lewis acid, BF3.Et2O. All the synthesized gly-
cosylated N-fatty acyl-L-tyrosines and esters (7a–7d,
8a–8d, 9a–9d, 10a–10d and 6a–6d) were further tested
for cytotoxicity against A549, PC3, MDA-MB-231 and
HepG2 cell lines. Among the tested compounds, 7a–7c,
8c, 9c and 10c exhibited moderate activity against all the
In addition to that, compounds 9 and 10 exhibited
excellent antifungal activity against Candida albicans
MTCC 3017 fungal strain with MIC values 3.9 and
3.9 μg/mL, respectively. While all the other compounds
showedmoderatetopoorantimicrobialactivitiesagainst
seven bacterial and one fungal strain with MIC val-
ues of 7.8 and > 125 μg/mL. Based on the above
results, medium-chain saturated myristic acid (9) and
unsaturated oleic acid (10) derivatives exhibited excel-
lent antimicrobial activity against bacterial and fungal
strains.

Srikanth Vudhgiri et al.
tested cell lines. However, in case of oleic (unsaturated)
acid, the compounds 10a and 10d exhibited good cyto-
toxicity against MDA-MB-231 cell line and compound
10b showed promising activity against A549 cell line.
Whereas in case of N-lipoyl-L-tyrosine methyl esters
α
(6a–6d), due to the presence of -lipoic acid moiety, the
compounds (6b–6d) exhibited good cytotoxicity against
all the tested cell lines. The compound 6d (IC50 value
of 9.4 μM) exhibited promising cytotoxicity against
PC3 cell line. All the glycosylated compounds did not
show antimicrobial activity. Further, the N-fatty acyl-L-
tyrosine methyl ester (2–6) and N-fatty acyl-L-tyrosine
(7–11) aglycone moieties showed poor cytotoxicity,
when compared to glycosylated compounds. Moreover,
the N-fatty acyl-L-tyrosines (7–11) exhibited promis-
ingantimicrobialactivityagainstsomeofthepathogenic
bacterial strains. Based on the above results, it can be
concluded that the carbohydrate and fatty acid moieties
play a significant role in determining the cytotoxicity
of aglycone and the sugar moiety inversely affects the
antimicrobial activity of aglycone.
Supplementary Information (SI)
1H-NMR, 13C-NMR and HRMS spectral data for the synthe-
sized compounds and HPLC results of Compounds 10a–10d
and 6a–6d are presented in the Supplementary Information
which is available at www.ias.ac.in/chemsci.
Acknowledgements
VS and YP acknowledge the Council of Scientific and Indus-
trial Research, Government of India for financial support in
the form of Fellowships.
References
1. Kren V and Martinkova L 2001 Glycosides in medicine:
the role of glycosidic residue in biological activity Curr.
Med. Chem. 11 1303
2. Varki A 1993 Biological roles of oligosaccharides: All
of the theories are correct Glycobiology 3 97
3. Dondoni A and Marra A 2000 Methods for anomeric
carbon-linked and fused sugar amino acid synthesis: the
gateway to artificial glycopeptides Chem. Rev. 100 4395
4. Liu B, Cui C, Duan W, Zhao M, Peng S, Wang L, Liu H
and Cui G 2009 Synthesis and evaluation of anti-tumor
activities of N4 fatty acyl amino acid derivatives of 1-β-
arabinofuranosylcytosine Eur. J. Med. Chem. 44 3596
5. Galonic D P and Gin D Y 2007 Chemical glycosylation
in the synthesis of glycoconjugate antitumour vaccines
Nature 446 1000
6. Burstein S 2008 The elmiric acids: Biologically active
anandamide analogs Neuropharmacology 55 1259
7. Georgiades S N and Clardy J 2008 Synthetic libraries
of tyrosine-derived bacterial metabolites Bioorg. Med.
Chem. Lett. 18 3117

Glycosylated N-fatty acyl-L-tyrosine derivatives
8. Brady S F and Clardy J 2005 N-Acyl derivatives of argi- cancer cells with concomitant autophagy induction Car-
nine and tryptophan isolated from environmental DNA
expressed in Esch. Coli.Org. Lett. 7 3613
9. Yao L Y, Lin Q, Niu Y Y, Deng K M, Zhang J H and Lu
Y 2009 Synthesis of Lipoamino acids and their activity
against cerebral ischemic injury Molecules 14 4051
cinogenesis 36 817
24. Abdolmaleki A, Mallakpour S, Borandeh S and Sabza-
lian M R 2012 Fabrication of biodegradable poly(ester-
amide)s based on tyrosine natural amino acid Amino
Acids Amino Acids 42 1997
10. Burstein S, McQuain C, Salmonsen R and Seicol B 2012 25. Atsushi N, Junichi I, Hiroto K and Takeshi E 2004
N-Amino acid linoleoyl conjugates: anti-inflammatory
activities Bioorg. Med. Chem. Lett. 22 872
11. Kaki S S, Arukali S, Korlipara P V, Prasad R B N, Yedla P
Synthesis of optically active polyurethanes by self-
polyaddition of tyrosine-based monomers J. Polym. Sci.
Part A: Polym. Chem. 42 1143
and Kumar C G 2016 Synthesis and biological evaluation 26. Srikanth V, Prasad R B N, Poornachandra Y, Phani Babu
of novel lipoamino acid derivatives Bioorg. Med. Chem.
Lett. 26 209
12. Burstein S and Salmonsen R 2008 Acylamido analogs
of endocannabinoids selectively inhibit cancer cell pro-
liferation Bioorg. Med. Chem. 16 9644
13. Takahashi S, Hasumi K, Ohnishi A, Koshino H and Mat-
sumoto S 2007 Synthesis and biological activities of
analogs of D-glucosyl-L-tyrosine, a humoral factor that
stimulates transcription of the acyl-CoA binding protein
V S, Ganesh Kumar C, Jagadeesh B and Jala R C 2016
Synthesis of dihydrosterculic acid-based monoglucosyl
diacylglycerol and its analogues and their biological
evaluation Eur. J. Med. Chem. 109 134
27. Vudhgiri S, Prasad R B N, Kota A, Poornachandra Y,
Kumar C G, Sistla R and Reddy Jala R C 2016 Synthesis
andbiologicalevaluationofMarumosideAisolatedfrom
Moringa oleifera and its lipid derivatives Int. J. Pharm.
Sci. Res. 7 607
in the pheromone gland of the Silkmoth, Bombyx mori 28. Mosmann T J 1983 Rapid colorimetric assay for cellu-
Bioorg. Med. Chem. 15 97
14. Schuler P, Fischer S N, Marsch M and Oberthur M
lar growth and survival: application to proliferation and
cytotoxicity assays Immunol. Methods 65 55
α
2013 Efficient -mannosylation of phenols: the role of 29. Amsterdam D 1996 Susceptibility testing of antimicro-
carbamates as scavengers for activated glycosyl donors
Synthesis 45 27
15. Fahmi N E, Dedkova L, Wang B, Golovine S and Hecht S
bialinliquidmedia InAntibioticsinlaboratorymedicine
V Loman (Ed). 4th ed. (Baltimore: Williams & Wilkins)
p. 52
M 2007 Site-specific incorporation of glycosylated ser- 30. Jacob V and Snait T 2006 Exogenous markers for
ine and tyrosine derivatives into proteins J. Am. Chem.
Soc. 129 3586
oxidative stress PCT WO 2006/103677 A2 and PCT/IL
2006/000409
16. Perry N B and Brennan N J 1997 Antimicrobial and cyto- 31. Wang Z D, Mo Y, Chiou C L and Liu M 2010 A sim-
toxic phenolic glycoside esters from the New Zealand
tree Toronia Toru J. Nat. Prod. 60 623
17. Wang T, Chen F and Wu Y 2009 The use of pheno-
ple preparation of 2,3,4,6-tetra-o-acyl-gluco-, galacto-
and mannopyranoses and relevant theoretical study
Molecules 15 374
lic glycosides derivatives in the manufacture of com- 32. Bunyapaiboonsri T, Yoiprommarat S, Khonsanit A and
positions for treating cell proliferation diseases PCT
WO2009/105936 A1 and PCT/CN 2008/070373
18. Brady S F and Clardy J 2000 Long-chain N-acyl amino
Komwijit S 2008 Phenolic glycosides from the filamen-
tous fungus Acremonium sp. BCC 14080 J. Nat. Prod. 71
891
acid antibiotics isolated from heterologously expressed 33. Shin B, Ahn S, Noh M, Shin J and Oh D C 2015
environmental DNA J. Am. Chem. Soc. 122 12903
19. Brady S F, Chao C J and Clardy J 2002 New natural
Suncheonosides A-D, Benzothioate glycosides from a
marine-derived Streptomyces sp. J. Nat. Prod. 78 1390
product families from an environmental DNA (eDNA) 34. Ghate N B, Chaudhuri D, Sarkar R, Sajem A L, Panja
gene cluster J. Am. Chem. Soc. 124 9968
S, Rout J and Mandal N 2013 An antioxidant extract
of tropical lichen, Parmotrema reticulatum, induces cell
cycle arrest and apoptosis in breast carcinoma cell line
MCF-7 PLoS One 8 e82293
20. Wang L X, Pavlova N V, Yang M, Li S C, Li Y T and
Lee Y C 1998 Synthesis of aryl 3’-sulfo-beta-lactosides
as fluorogenic and chromogenic substrates for ceramide
glycanases Carbohydr Res. 306 341
21. Jiao Z Z, Yue S, Sun H X, Jin T Y, Wang H N, Zhu
R X and Xiang L 2015 Indoline amide glucosides from
portulaca oleracea: isolation structure, and DPPH radical
scavenging activity J. Nat. Prod. 78 2588
35. Milutinovic M, Stankovic M, Cvetkovic D, Maksimovic
V, Smit B, Pavlovic R and Markovic S 2015 The molec-
ular mechanisms of apoptosis induced by Allium flavum
L. and synergistic effects with new-synthesized Pd(II)
complex on colon cancer cells J. Food Biochem. 39
238
22. Kates S A, Casale R A, Baguisi A and Beeuwkes III R
2014 Lipoic acid analogs with enhanced pharmacologi- 36. Kim D H, Jung E A, Sohng I S, Han J A, Kim T H
cal activity Bioorg. Med. Chem. 22 505
23. Goder A, Nagel G, Kraus A, Dorsam B, Seiwert N,
Kaina B and Fahrer J 2015 Lipoic acid inhibits the DNA
and Han M J 1998 Intestinal bacterial metabolism of
flavonoids and its relation to some biological activities
Arch. Pharm. Res. 21 17
repair protein-O-6-methylguanine-DNA methyltrans- 37. Kim D H 2002 Herbal medicines are activated by intesti-
ferase (MGMT) and triggers its depletion in colorectal nal microflora Nat. Prod. Sci. 8 35