Selective Synthesis of Glycoside Fatty Acid Esters and Their Antibacterial Structure-activity Relationship against Bacterial Staphylococcus Aureus and Salmonella Agona

Article abstract of DOI:10.1002/jccs.201500261

Fatty acid esters of glycosides and glucopyranosiduronides were regioselectively synthesized with tin-mediated method using dibutyltin dimethoxide as the stannylating agent, these novel esters were investigated for their antibacterial activities against bacterial Staphylococcus Aureus and Salmonella Agona, the essential structural feature as antibacterial agents was probed. Antimicrobial tests showed that some laurates of trans-ol glycosides are effective inhibitors against S. Aureus, while some laurates and myristates of cis-ol glycosides are moderate inhibitors against both S. Aureus and S. Agona. Studies on antimicrobial structure-activity relationship of sugar fatty acid esters showed that both the carbohydrate moiety and the length of fatty acid played a vital role on the antibacterial effect. Fatty acid esters of glycosides and glucopyranosiduronides were regioselectively synthesized with tin-mediated method, the structure-activity relationship against bacterial Staphylococcus Aureus and Salmonella Agona of these glycoside fatty acid esters was investigated, and the essential structural feature of carbohydrate fatty acid esters as antibacterial agent was described in this work.

Full text of DOI:10.1002/jccs.201500261

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Selective Synthesis of Glycoside Fatty Acid Esters and Their Antibacterial
Structure-activity Relationship against Bacterial Staphylococcus Aureus and
Salmonella Agona
Xin Loua* and Seamas Cassidyb
aSchool of Material Science and Chemical Engineering, Chuzhou Uniersity, Chuzhou 23900, China
bSchool of Food Science and Environmental Health, Dublin Institute of Technology, Dublin 1, Ireland
(Received: Jul. 4, 2015; Accepted: Sept. 23, 2015; Published Online: Oct. 30, 2015; DOI: 10.1002/jccs.201500261)
Fatty acid esters of glycosides and glucopyranosiduronides were regioselectively synthesized with
tin-mediated method using dibutyltin dimethoxide as the stannylating agent, these novel esters were in-
vestigated for their antibacterial activities against bacterial Staphylococcus Aureus and Salmonella
Agona, the essential structural feature as antibacterial agents was probed. Antimicrobial tests showed that
some laurates of trans-ol glycosides are effective inhibitors against S. Aureus, while some laurates and
myristates of cis-ol glycosides are moderate inhibitors against both S. Aureus and S. Agona. Studies on
antimicrobial structure-activity relationship of sugar fatty acid esters showed that both the carbohydrate
moiety and the length of fatty acid played a vital role on the antibacterial effect.
Keywords: Glycoside fatty acid esters; Tin-mediated method; Structure-activity relationship;
Antibacterial.
INTRODUCTION
Sugar fatty acid esters have been reported to show
cosyltransferases of Streptococcus sobrinus and Bacillus
species. However with enzyme method in most cases only
6-OH positions of sugar moiety were acylated to produce
6-acyl isomers, which lead into limited isomers of sugar es-
ters and hinder the elucidation of structure-activity rela-
tionship.
antibacterial activity, particularly against gram-positive
bacteria.1 Among the first fatty acid esters of sugars re-
ported to display antimicrobial activity were sucrose di-
caprylate and sucrose monolaurate, which were shown to
be active against some gram-negative and gram-positive
bacteria, as well as fungi.2,3 Fatty acid esters of sucrose
have also been reported to inhibit the growth of Vibrio
parahaemolyticus.4 However these earlier studies were
carried out using commercial preparations that contained a
mixture of sugar ester compounds. Thus, it was difficult to
correlate antimicrobial activity with chemical structure of
sugar esters. Structure-defined carbohydrate fatty acid es-
ters used to be chemically synthesized by direct esteri-
fication and transesterification, however an issue regarding
the chemical synthesis of these esters is related to the high
functionality of the carbohydrate molecule with many
hydroxyl groups, which compete during the derivatization
step, leading to produce mixtures of mono-, di- and polyes-
ters;5 Enzymatic synthesis of sugar fatty acid esters has
been reported regioselective,6-9 this novel type of fatty acid
esters of carbohydrates were also reported to show antibac-
terial activity, for instance Devulapalle10 and Ferrer11 had
regioselectively synthesized a series of fatty acid esters of
sucrose and maltose for the use as inhibitors of the glu-
Organic-tin method was ever used to regioselectively
introduce substituted group on the sugar moiety, 1,6-di-
butylstannylene acetals are reactive intermediates which
have been treated with acylating and alkylating agents to
provide mono-substituted derivatives of diols or polyols
with high regioselectivity.12-16 Hence this chemical method
can be used to regioselectively synthesize carbohydrate
fatty acid esters, producing some sugar esters isomers
which couldn’t be prepared with enzyme method. The pro-
duction of pure and regiochemically defined sugar fatty
acid esters makes it possible to provide insights into struc-
ture/activity relationships of antibacterial effect for these
compounds.
The antibacterial mechanism of action of carbohy-
drate esters has not yet been elucidated, but the cytoplasmic
membrane is thought to be the primary site of action for
fatty acid esters.17-18 The toxic action of the esters might be
due to fatty acid induced membrane disruption or due to in-
teraction with specific processes in the bacterium. An
abundance of pure carbohydrate ester isomers with varying
* Corresponding author. Email: franklinee@hotmail.com
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Tin-mediated Regioselective Synthesis of Carbohydrate Fatty Acid Esters as Antibacterial Agents
structure will help to elucidate the working mechanism of
these esters, this prompt us to use tin-mediated method to
regioselectively prepare carbohydrate fatty acid esters.
The aim of this study was (a) to syntheses series of
glycoside fatty acid esters using tin-mediated method, and
(b) to address the antimicrobial structure-activity relation-
ships of this novel type of carbohydrate fatty acid esters,
meanwhile the regioselectivity of tin-mediated method on
acylation of fatty acid and glycosides was also probed.
Stereoselective synthesis of methyl(azide)
a-D-glucopyranosiduronic acid via 1, 6-
lactone
Scheme 1
RESULTS AND DISCUSSION
Synthesis of fatty acid esters of glycosides
To probe the antimicrobial structure-activity relation-
ship of sugar fatty acid esters, various sugar esters with di-
verse structure are needed to be synthesized. Carbohy-
drates, which will be selectively acylated with tin-mediated
method, have to meet certain structural requirement for re-
gion-selective substitution, hence some structurally similar
cis-ol and trans-ol glycosides were chosen to be selectively
acylated to give fatty acid esters. Beside commercially
available glycosides, a-glucuronides were also tried as
sugar substrates in order to probe the sugar substrate scope
suitable for tin-mediated method. Stanylene acetal method
insofar was only applied into the sugar substrates without
active groups, whether this method can work on sugar sub-
strates bearing active COOH groups is an issue of interest.
However, the a configuration of glucuronide, which is pos-
sibly to be regioselectively acylated with stannylene me-
thod, need to be stereoselectively synthesized from glu-
curonic acid. Many methods were documented to convert
glucuronic acid into a-D-glucuronides, among reported
methods the one by TMSR mediated ring opening of 1,6-
anhydro sugars is rather effective with high selectivity,19-21
as shown in Scheme 1. With this method two substrates
methyl a-D-glucopyranosiduronide and azido a-D-gluco
pyranosiduronide were prepared.
acetals with poly-hydroxyl groups at room temperature and
easier handle of workup for acylation and alkylation reac-
tions.22-24
The factors governing regioselectivity of this reac-
tion were intensively investigated. For reaction solvent,
dioxane was found to be optimal one among various sol-
vents tested, in which regioselective reaction can proceed
smoothly and judged with HPLC. Surprisingly, the regio-
selectivity was not observed by the replacement of dioxane
with toulene or acetonitrile, etc. The effect of temperature
was also probed on regioselectivity of acylation reaction. It
was found that the selective reaction preferred to occur at
0-5 °C. Long-chained fatty acid were selectively intro-
duced into glycoside and glucuronide on optimized condi-
tion giving corresponding esters.
Using the optimal conditions mentioned above, a se-
ries of fatty acid esters of glycosides and glucopyrano-
siduronides were prepared and separated with flash chro-
matography and preparative HPLC method. The synthe-
sized esters were methyl 2-O-acyl-a-D-glucopyranoides
(1-6), methyl 2-O-acyl-a-D-mannopyranosides (7-12),
methyl 3-O-acyl-a-D-manopyranosides (13-18), methyl
3-O-acyl-b-D-galacto-pyranosides (19-24), methyl 2-O-
acyl-a-D-glucuronic acids (25-27) and azido 2-O-acyl-a-
D-glucuronic acids (28-30) as shown in Figure 1. The
yields of corresponding esters are listed in Table 1.
Tin-mediated regioselective acylation of glycosides
and glucopyranosiduronides
Tin-mediated method has proved to introduce substi-
tuted group on the sugar moiety as benzoyl, acetyl group
with high regioselectivity. It is of interest whether this
tin-mediated acylation is suitable for long-chained acy-
lating agents. In this work, different length of fatty acids,
from octanoic acid (C8) to stearic acid (C18), were tested to
be introduced into glycosides and a-D-glucopyranosi-
duronic acids with stannylene acetal method. Dibutyltin
dimethoxide (DBDM), instead of more common dibutyltin
oxide (DBO), was used as stannylating agent. DBDM was
documented to show rapid formation of dibutylstannylene
The tin-mediated regioselective acylation of various
glycosides and glucopyranosiduronides with fatty acid
chloride was probed. In most cases, the satisfactory re-
gioselectivity was observed on optimized conditions ex-
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Table 1. The given yields of glycoside fatty acid esters on
optimized conditions
Compounds Yields (%)
Methyl 2-acyl-a-D- octanoyl (1) 73 Methyl a-D-gluco
glucopyranoside decanoyl (2) 63 pyranoside: DBDM:
lauoryl (3) 72 fatty acid chloride =
Reaction conditions
myristoyl (4) 81
palmitoyl (5) 75
1:1.1:1.1
Solvent: dioxane
Temp.: 5 °C
stearoyl (6)
Methyl 2-acyl-a-D- octanoyl (7) 33
mannopyranoside decanoyl (8) 30
lauoryl (9) 31
78
myristoyl (10) 31
palmitoyl (11) 29
stearoyl (12) 28
Methyl a-D-manno
pyranoside: DBDM:
fatty acid chloride =
1:1.1:1.1
Methyl 3-acyl-a-D- octanoyl (13) 32
mannopyranoside decanoyl (14) 27
lauoryl (15) 30
Fig. 1. Structures of carbohydrate fatty acid ester de-
Solvent: dioxane
Temp.: 5 °C
rivatives synthesized with tin-mediated me-
thod.
myristoyl (16) 32
palmitoyl (17) 28
stearoyl (18) 28
cept for methyl a-D-mannopyranoside, in which an isomer
mixture of 2-O-acyl-a-D-mannopyranoside and methyl
3-O-acyl-a-D-mannopyranoside with ratio of 1:1 was ob-
served. The results showed that regioselective acylation
with long-chained fatty acid are nearly the same as those of
benzoylations; the long chained fatty acids seem not hinder
the selectivity of dibutylstannylene acetals formed in the
reaction system.
Methyl b-D-galacto
pyranoside: DBDM:
fatty acid chloride =
1:1.1:1.1
Methyl 3-acyl-b-D- octanoyl (19) 75
galactopyranoside decanoyl (20) 67
lauoryl (21) 74
myristoyl (22) 70
palmitoyl (23) 74
stearoyl (24) 70
Solvent: dioxane
Temp.: 25 °C
Methyl 2-acyl-a-D- lauoryl (25)
95
glucuronic acid
palmitoyl (26) 95
stearoyl (27) 96
The same with above
The origin of regioselectivity for tin-mediated acy-
lation has been attributed to the inherent structure of the
pyranoside, the selectivity rules governing benzoylation of
glycoside seem still be applied into the acylation of fatty
acid. For cis-ol system glycosides (CSG, at least one pair of
cis-diol on carbohydrate moiety), the hydroxyl group at
equatorial position has advantage of being acylated. For
example, methyl b-D-galactopyranoside acylation hap-
pened exclusively on 3-OH position. For trans-ol system
glycosides (TSG, all hydroxyl groups in trans-position),
regioselectivity was observed with the hydroxyl group ad-
jacent to the axial substituent if one adjacent substituent is
equatorial and one is axial. Herein acylation exclusively
happened at 2-OH position of methyl a-D-glucopyrano-
side, methyl a-D-glucopyranosiduronic acid and azido
a-D-glucopyranosiduronic acid. The results suggest that
the stannylene complex dimer of b-D-galactopyranoside,
a-D-glucopyranoside, and a-D-glucuronic acid is 1,1 or
2,2-dimer during the dimerization of 2,2-dibutyl-1,3,2-
dioxastannolanes formed from vicinal-diols of pyranoside
rings,25 which account for excellent selectivity; while for
Azido 2-acyl-a-D-
octanoyl (28) 85
glucuronic acid
lauoryl (29)
82 The same with above
palmitoyl (30) 87
methyl a-D-mannopyranoside a 1,2-dimer is formed, the
result of 1,2-dimerization is to activate both 2-OH and
3-OH of methyl a-D-manopyranoside, substitution occurs
equally on the 2 and 3 position, which account for the for-
mation of mixture of 2,3 isomers at a ration of 1:1 (Fig. 2).
Antibacterial structure-activity relationship of sugar
fatty acid ester
These regioselectively synthesized fatty acid esters
were screened as antibacterial agents against a gram-posi-
tive organism Staphylococcus aureus and a gram-negative
organism Salmonella agona of interest to the food industry.
The bacteria were grown as described in the experimental
section and were added to the sugar esters solution to a final
concentration of 100 ppm. The effect of configuration of
glycoside fatty acid esters on the antibacterial activity was
investigated; the esters investigated were classified into
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Tin-mediated Regioselective Synthesis of Carbohydrate Fatty Acid Esters as Antibacterial Agents
Fig. 2. The structure of dimers of the dialkylstanny-
lene acetal of 1,2-diol system.
two classes: cis-ol system and trans-ol system glycosides
fatty acid esters. Initially how the chain length of esters in-
fluence their antimicrobial activity was studied.
Influence of chain length of fatty acid moiety of two
types of glycoside esters on antibacterial activity
Figure 3 showed the results of screening of fatty acid
esters of trans-ol glycosides (methyl a-D-glucopyranoside
and methyl a-D-glucuronic acid as examples) against
Staphylococcus Aureus and Salmonella Agona.
Antibacterial screening studies showed that the length
of fatty acid chain played a vital role on the antibacterial ef-
fect for TSG esters, the chain length of 12 carbons being
optimal, it is observed from Fig. 3 that the lauroyl deriva-
tives of both methyl a-D-glucopyranoside and methyl
a-D-glucuronic acid, had a specific and potent antibacte-
rial effect against Staphylococcus aureus. The population
of S. aureus was reduced from 5.445 (water control) to
0.814 Log10 CFU/m for glucopyranoside laurate, and the
population of S. aureus was reduced from 5.263 (water
control) to 1.150 Log10 CFU/ml for methyl 2-lauroyl-
a-D-glucuronic acid. However, the two same esters didn’t
show any sign to inhibit the growth of gram-negative bac-
terial Salmonella Agona.
Figure 4 showed the results of screening of fatty acid
esters of cis-ol system glycosides (methyl a-D-manno-
pyranoside and methyl b-D-galactopyranoside as exam-
ples) against Staphylococcus Aureus and Salmonella
Agona.
For CSG esters antibacterial screening studies
showed that the length of fatty acid chain played a marked
Fig. 3. Influence of chain length of fatty acid esters of
methyl a-D-glucopyranoside and methyl a-D-
glucuronic acid on the growth of Staphylococ-
cus aureus (left) and Salmonella agona (right)
in culture.
role on the antibacterial effect as well. It appears that the
chain length of the fatty acid moiety is critical with a chain
length between 12-14 carbons being optimal. The laurate
and myristate for methyl a-D-mannopyranoside and me-
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thyl b-D-galactopyranoside are moderate inhibitors against
S. Aureus. The population of S. aureus was reduced from
5.348 (water control) to 3.319 (C14) and 2.924 Log10
CFU/ml (C12) for myristate and laurate of mannopy-
ranoside, and the population of S. aureus was reduced
from 5.322 (water control) to 3.441 (C14) and 3.563
Log10 CFU/ml (C12) for galactopyranoside myristate
and laurate. Interestingly it is the same two esters that are
moderate effective aginst S. Agona as well. The popula-
tion of S. agona was reduced from 5.964 (water control) to
4.113 (1c) and 3.911 Log10 CFU/ml for myristate and
laurate of mannopyranoside, the population of S. agona
was reduced from 6.094 (water control) to 3.813 and
3.830 Log10 CFU/ml for myristate and laurate of galac-
topyranoside.
Influence of carbohydrate moiety of sugar esters on
antibacterial activity
Antibacterial screening showed that some lauroyl
esters of sugar had a potent antibacterial effect against
Staphylococcus aureus, in order to investigate the rela-
tionship between the structure of carbohydrate moiety
and antimicrobial activity, the chain length of fatty acid
moiety is confined to 12 carbons, their corresponding
esters as antibacterial agents against Staphylococcus
aureus and Salmonella agona were screened as shown in
Fig. 5.
The results showed that the structure of the carbohy-
drate moiety is closely correlated with affected antimicro-
bial activity of carbohydrate esters, the laurates of CSG
(galactopyranoside and mannopyranoside) were less effec-
tive than that of TSG (glucopyranoside and glucuronic acid
derivative) as an inhibitor of the growth of S. aureus. The
population of S. aureus was reduced from 5.348 (water
control) to a level appropriately 3 Log10 CFU/ml for CSG
esters, while for TSG esters encouragingly reduced to a
level appropriately 1Log10 CFU/ml, that means that the
trans configuration of hydroxyl groups of carbohydrate
moiety is a key factor for the esters’ inhibition of micro-
biology, however all these laurates of glycosides were not
so effective to inhibit the growth of S. agon when com-
pared to S. Aureus. It is of interest that the alkyl group on
anomeric position of carbohydrate moiety also takes a role
in the inhibition of bacteria, when methyl group is replaced
with azido group for 2-O-acyl-a-D-glucuronic acids, the
azido derivative had an better antibacterial effect against
Salmonella agona than methyl derivative.
Fig. 4. Influence of chain length of fatty acid esters of
methyl a-D-mannopyranoside and methyl b-
D-galactopyranoside on the growth of Staphy-
lococcus aureus and Salmonella agona in cul-
ture.
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an equal volume of saturated NaHCO3. A white emulsion was
formed and the organic and aqueous layers were easily separated
after filtering through filter paper. Following removal of the or-
ganic solvent, a white powder was obtained (2.4 g, 7.19 mmol,
72%). Protected methyl a-D-glucuronic acid (2.4 g, 7.18 mmol)
was suspended in 0.1 N LiOH in MeOH/H2O/THF (2.5/1.0/0.5,
10 ml) at 0 °C (ice bath) and stirred for 2 h. The solution was di-
luted with water and acidified to pH 2 using Amberlite IR-120.
Removal of the solvents gave methyl a-D-glucuroinc acid (1.3 g,
6.25 mmol, 87%). Azido a-D-glucuroinc acid was prepared with
the same method mentioned above and overall yield was 59.8
from lactone.
Selective Synthesis of Sugar Fatty Acid Esters: D-gly-
copyranoside or glucopyranosiduronide (5 mmol) was dissolved
in dioxane or other solvents (40 mL). DBDM (1.47 mL, 5.5
mmol) was added into the solution, causing effervescence. The
reaction mixture was kept at r.t. and a solution of fatty acid chlo-
ride in dioxane (5.5 mmol, 10 mL) was added dropwise over one
hour. The reaction was monitored using TLC and terminated
when all the starting material had been converted (24 h). The mix-
ture was evaporated under vacuum to give syrup. This was frac-
tionated by flash chromatography using a solvent mixture of chlo-
roform and methanol to give the desired monoester.
Fig. 5. Influence of glycoside configuration of lauroyl
esters on the growth of S. aureus (above) and S.
agona (below) in culture.
HPLC Method Development for Analysis and Separation
of Fatty Acid Ester Position Isomers: Thin-layer (TLC), gas-liq-
uid (GLC) and high performance liquid chromatographic (HPLC)
methods have been developed to identify and separate isomers of
sucrose fatty acid esters.26 However when these same methods are
applied to analysis of the positional isomers of fatty acid esters of
D-glycoside satisfactory separation of isomers couldn’t be
achieved. In order to examine the regioselectivity of
esterification and separate monoester isomers of D-glycoside a
variety of solvent combinations were probed to determine the
suitable system, and a three solvent system (methanol:aceto-
nitrile:water = 70:20:10) was eventually found to separate com-
pletely these isomers.
EXPERIMENTAL
Materials and Instrumentation: 1H chemical shifts in
CD3OD were referenced to CHD2OD (3.30 ppm); constants are
reported in hertz. FTIR spectra were recorded with a Nicolet
FTIR 3000 using KBr discs, as specified. Melting points were
measured on a STUART melting point apparatus. Low and high-
resolution mass spectra were measured on electrospray mass
spectrometry in ES negative mode unless otherwise indicated.
Flash column chromatography was carried out with silica gel 60
(0.040-0.630 mm, E. Merck) and using a solvent mixture system
correlated with TLC mobility. DBDM, DBO, glycopyranosides,
octanoyl chloride, decanoyl chloride, lauroyl chloride, myristoyl
chloride, palmitoyl chloride, stearoyl chloride, were purchased
from Sigma-Aldrich.
Bacterial growth on agar plates and inhibition assay
Preparation of Test Organisms: Staphylococcus aureus
stock cultures were maintained in 20% glycerol at -20 °C. 1 ml of
thawed culture was transferred to 30 ml of BHI and incubated at
37 °C for 24 hours. 1 ml of the 24 hour culture was transferred into
100 ml BHI and incubated at 37 °C for 14 hours. 50 ml of the 14
hour culture was centrifuged at 4800 rpm for 10 minutes. The
supernatant was discarded and the pellet washed and suspended
in 9 ml of Maximum Recovery Diluent (Oxoid, CM733, MRD).
The culture was centrifuged again at 4800 rpm for 5 minutes and
the pellet suspended in 9 ml BHI. This culture was diluted 1: 100
Stereoselective Synthesis of Methyl a-D-glucuronic Acid
and Azido a-D-glucuronic Acid: Lactone (3.02 g, 10 mmol),
TMSOMe (2.6 g, 25 mmol, 2.5 equiv.) and SnCl4 (4.68 mL, 40
mmol, 4 equiv.) were added into anhydrous dichloromethane (40
ml) under N2 and the reaction mixture was stirred overnight. The
mixture was diluted with dichloromethane and the solution was
vigorously stirred for a further 30-40 minutes in the presence of
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to yield a working culture. Salmonella agona was prepared using
the same method. All bacterial counts were expressed in log
Colony Forming Units per ml (log CFU/ml).
REFERENCES
1. Conlay, A. J.; Kabara, J. J. Antimicrob. Agents Chemother.
1973, 4, 501.
2. Kato, N.; Shibasaki, I. J. Antibacter. Antifug. Agents(Jpn.)
1975, 8, 355.
Addition of bacteria to Sugar Ester Solution: 1 ml
aliquots of each bacterial suspension were transferred into 10 ml
of sugar ester solution to yield a final concentration of 100 or 150
mg/ml (ppm). Each tube was incubated at 37 °C for 6 hours. Each
trial was carried out in duplicate.
3. Kato, N.; Shibasaki, I. J. Ferment. Technol. 1975, 53, 793.
4. Beuchat, L. R. Appl. Environ. Microbiol. 1980, 39, 1178.
5. Hill, K.; Rhode, O. Fett/Lipid. 1999, 101, 25.
6. Therisod, M.; Klibanov, A. M. J. Am. Chem. Soc. 1986, 108,
5638.
Microbiological Analysis: Each bacterial suspension and
sugar ester solution mixture was serially diluted and enumerated
in duplicate on Plate Count Agar (Oxoid, CM325, PCA). Plates
were incubated at 37 °C for 24 hours and plates with appropriate
levels of bacteria were selected for counting.
7. Riva, S.; Chopineau, J.; Klibanov, A. M. J.Am. Chem. Soc.
1988, 110, 584.
8. Kennedy, J. F.; Kumar, H.; Panesar, P. S. J. Chem. Technol.
Biotechnol. 2006, 81, 866.
9. Ganske, F.; Bornscheuer, U. T. Org. Lett. 2005, 7, 3097.
10. Kumari, S.; Devulapalle, D. Carbohydr. Res. 2004, 339,
1029.
CONCLUSIONS
11. Ferrer, M.; Soliveri, J.; Plou, J. F. Enzyme Microb. Technol.
2005, 36, 391.
Stannylene acetal method can be used to synthesize
fatty acid esters of glycoside with high regioselectivity, the
sugar substrate can be extended into those containing ac-
tive group as COOH, the general selective rule of stan-
nylene acetal method still govern the acylation of fatty acid
on glycosides. For the antibacterial activity of glycoside
fatty acid esters, the essential structural features as antibac-
terial agents can be partly defined from this study. It ap-
pears that the chain length of the fatty acid moiety is critical
with a chain length between 12-14 carbons being optimal.
Fatty acid esters of TSG are more dependent on combining
a suitable length of fatty acid to produce desired antibacte-
rial effect than esters of CSG. For sugar moiety, the con-
figuration of hydroxyl group in the carbohydrate moiety
markedly affects their antibacterial activity, sugar esters of
trans configuration are more effective to inhibit the growth
of bacteria than that of cis configuration, subsequently fur-
ther work is needed to define the precise structural features
of carbohydrate fatty acid esters crucial to the antibacterial
activities observed in this work.
12. David, S.; Hanessian, S. Tetrahedron 1985, 41, 643.
13. Blunden, S. J.; Cusack, P. A.; Smith, P. J. J. Organomet.
Chem. 1987, 325, 141.
14. Hannesian, S. Preparative Carbohydrate Chemistry; Marcel
Dekker Inc.: New York, 1997; Chapter 4.
15. Grindley, T. B. Carbohydr. Chem. Biochem. 1998, 53, 17.
16. Goncalves, A. G.; Noseda, M. D.; Grindly, T. B. J. Org.
Chem. 2007, 72, 9896.
17. Kabara, J. J. Medium-chain Fatty Acids and Esters. In
Antimicrobial in Food, 2nd ed.; Davidson, P. M.; Branen, A.
L., Eds.; Marcel Dekker Inc.: New York, 1993, 307.
18. Ruzin, A.; Novick, R. P. J. Bacteriol. 2000, 182, 2668.
19. Tosin, M.; Murphy, P. V. Org. Lett. 2002, 4, 3675.
20. Brien, C. O.; Poláková, M.; Pitt, N.; Tosin, M.; Murphy, P. V.
Chem. Eur. J. 2007, 13, 902.
21. Poláková, M.; Pitt, N.; Tosin, M.; Murphy, P. V. Angew.
Chem. Int. Ed. 2004, 43, 2518.
22. Boons, G. J.; Castle, G. H.; Clase, J. A.; Grice, P.; Ley, S. V.;
Pinel, C. Synlett 1993, 12, 913.
23. Barrow, R. A.; Hemscheidt, T.; Liang, J.; Paik, S.; Moore, R.
E.; Tius, M. A. J. Am. Chem. Soc. 1995, 117, 2479.
24. Kornilov, A. V.; Sukhova, E. V.; Nifantiev, N. E. Carbohydr.
Res. 2001, 336, 309.
ACKNOWLEDGEMENTS
25. Grindley, T. B. Adv. Carbohydr. Chem. Biochem. 1998, 53,
17.
This work was supported and funded by DIT Re-
search Foundation and Anhui Provincial-level University
Research Projects Funding KJ2014 A181, State Key Labo-
ratory of Fine Chemicals Funding KF1211, We thank Pro-
fessor Gary Henehan and Dr. Julie Dunne at DIT for their
help for this work.
26. Torres, M. C.; Dean, M. A.; Wagner, F. W. J. Chromatogr.
1990, 522, 245.
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