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1.1.
Natural
products
chemistry,
natural
products,
classes,
and
primary
or
secondary
metabolism
Natural
products
chemistry
is
a
chemistry
branch
that
examines
chemical
compounds
produced
by
living
organisms.
Natural
products
lire
the
chemical
compounds
found
in
nature
that
usually
has
a
pharmacological
or
biological
activity
for
use
in
pharmaceutical
drug
discovery
and
drug
design.
Natural
Products
Chemistry
&
Research
emphasizes
the
study
of
chemistry
and
biochemistry
of
naturally
occurring
compounds
or
the
biology
of
living
systems
from
which
they
arc
obtained.
Л
natural
product
is
a
chemical
compound
or
substance
produced
by
a
living
organism
-
found
in
nature.
In
the
broadest
sense,
natural
products
include
any
substance
produced
by
life.
The
lerin
natural
product
has
also
been
extended
for
commercial
purposes
Io
refer
to
cosmetics,
dietary
supplements,
and
foods
produced
from
natural
sources
without
added
artificial
ingredients.
Within
the
field
of
organic
chemistry,
the
definition
of
natural
products
is
usually
restricted
to
mean
purified
organic
compounds
isolated
from
natural
sources
that
are
produced
by
the
pathways
of
primary
or
secondary
metabolism.
Within
the
field
of
medicinal
chemistry,
the
definition
is
often
further
restricted
to
secondary
metabolites.
Secondary
metabolites
are
not
essential
for
survival,
but
nevertheless
provide
organisms
that
produce
them
an
evolutionary
advantage.Many
secondary
metabolites
are
cytotoxic
and
have
been
selected
and
optimized
through
evolution
for
use
as
«chemical
warfare»
agents
against
prey,
predators,
and
competing
organ
isms
[4].
Natural
products
sometimes
have
pharmacological
or
biological
activity
that
can
be
of
therapeutic
benefit
in
treating
diseases.
As
such,
natural
products
are
the
active
components
of
many
traditional
medicines.
Furthermore
synthetic
analogs
of
natural
products
with
improved
potency
and
safety
can
be
prepared
and
therefore
natural
products
are
often
used
as
starting
points
for
drug
discovery.
In
fact,
natural
products
are
the
inspiration
for
approximately
one
half
of
U.S.
Food
and
Drug
Administration-approved
drugs.
The
broadest
definition
of
natural
product
is
anything
that
is
produced
by
life.
https://t.me/med1917
A
more
restrictive
definition
of
a
natural
product
is
an
organic
compound
that
is
synthesized
by
a
living
organism.
The
remainder
of
this
article
restricts
itself
to
this
more
narrow
definition.
Natural
products
may
be
classified
according
to
their
biological
function
or
the
chemical
structure/biosynthetic
pathway
as
described
below.
Following
Albrecht
Kossel's
original
proposal
in
1891,
natural
products
are
often
divided
into
two
major
classes,
the
primary
and
secondary
metabolites.
Primary
metabolites
have
an
intrinsic
function
that
is
essential
to
the
survival
of
the
organism
that
produces
them.
Secondary
metabolites
in
contrast
have
an
extrinsic
function
that
mainly
affects
other
organisms.
Secondary
metabolites
are
not
essential
to
survival
but
do
increase
the
competitiveness
of
the
organism
within
its
environment.
A
more
restrictive
definition
limiting
natural
products
to
secondary
metabolites
is
commonly
used
within
the
fields
of
medicinal
chemistry
and
pharmacognosy
[5].
Medicinal
chemistry
is
the
chemistry
discipline
concerned
with
the
design,
development
and
synthesis
of
pharmaceutical
drugs.
The
discipline
combines
expertise
from
chemistry
and
pharmacology
to
identify,
develop
and
synthesize
chemical
agents
that
have
a
therapeutic
use
and
to
evaluate
the
properties
of
existing
drugs.
Pharmacognosy
is
the
study
of
medicines
derived
from
natural
sources.
The
American
Society
of
Pharmacognosy
defines
pharma
cognosy
as
«the
study
of
the
physical,
chemical,
biochemical
and
biological
properties
of
drugs,
drug
substances
or
potential
drugs
or
drug
substances
of
natural
origin
as
well
as
t
he
search
for
new
drugs
from
natural
sources».
It
is
also
defined
as
the
study
of
crude
drugs.
Chemistry
of
Natural
Products
deals
with
the
chemistry
of
metabolites.
Metabolites
arenaturally-occurring
organic
compounds
synthesised
by
plants,
through
metabolic
actitivities
inplants,
aided
by
enzymes.There
are
two
types
of
metabolites,
viz:
(a)
Primary
metabolites
such
as
c
arbohydrates,
proteins,
fatty
acids
and
glycerol,mevalonicacids,
etc.
(b)
Secondary
metabolites
such
as
steroids,
alkaloids,
triterpenes,
tannins,
saponnins,flavonoids,
etc.
Chemistry
of
Natural
Products
is
dated
far
back
to
early
century.
An
aspect
of
Natural
Products
that
deals
with
plants
is
known
as
https://t.me/med1917
Г
liyt«chemistry
.
Natural
Products
is
define
as
organic
compounds
uid
oilier
chemicals
synthesised
by
plants
through
metabolic
pioccsscs
aided
by
sunlight,
involving
CO
2
,
H
2
O
vapour
and
<
hlorophyll.
Generally,
natural
products
are
characterised
by
specific
liiiH
iions
they
form
in
plants
and
animals.
Categories
of
natural
I'lodticts
are
called
metabolites.
Primary
metabolites
are
usually
found
in
all
living
organisms
m
il
as
plants
and
animals.
They
form
the
fundamental
building
block
of
living
material
e.g.
mevalonic
acids
and
nucleotides.
Primary
metabolites
have
wide
distribution
in
living
systems
and
are
usually
involved
in
essential
life
processes.
However,
secondary
metabolites
are
chemicals
synthesized
by
plants
but
are
not
directly
used
by
them,
but
are
used
indirectly
by
man
as
a
s
ource
of
pharmaceutical
preparations.
Secondary
metabolites
are
generally
built
from
primary
metabolites.
Secondary
metabolites
have
restricted
distribution
and
are
characteristics
of
individual
genera
or
species.
Secondary
metabolites
are
essential
to
the
existence
of
the
organism
but
play
an
important
role
to
the
survival
of
the
plant.
Reports
have
shown
presence
of
secondary
metabolites
in
yeast
and
microbes.
All
living
organisms
from
the
simplest
protozoan
to
the
most
developed
animals
contain
a
wide
range
of
organic
compounds.
Millions
of
secondary
metabolites
have
been
isolated
from
plants
and
animals,
some
of
which
are
known
to
have
medicinal
features.
Examples
are:
the
popular
Quinine-an
antimalarial
drug
and
Chloroquuine
isolated
from
medicinal
plants.
It
is
good
to
note
that
Natural
Products
is
restricted
specifically
to
major
organic
compounds
obtained
from
natural
origin,
especially
from
marine
plants
and
plants
growing
on
land.
Plants
are
generally
classified
on
the
basis
of
the
family
they
belong.
Each
family
of
plant
contains
a
GENUS
and
SPECIES.
Leguminoseae
is
a
family
of
a
pant
of
the
genus
Berlinia
and
several
species
of
Berlinia
exists;
such
as
B.
confusa,
B.
grandiflora,
B.
auriculata,ete.
In
the
present
days,
millions
of
secondary
metabolites
are
in
existence;
and
majorities
are
isolated
from
natural
sources
such
as
plants.
Examples
are
steroids,
terpenoids,
alkaloids,
glycosides,
flavonoids,
etc.
However,
some
secondary
metabolites
have
varying
structures
within
a
group
or
a
specific
specie
e.g.
monoterpenoids,
diterpenoids,
triterpenoids,
sesquiterpenoids,
etc.
Some
are
acyclic
https://t.me/med1917
while
others
are
cyclic
in
their
structures.
Some
secondary
metabolites
are
synthesised
via
biosynthesis
and
or
biogenesis.
Higher
plants
synthesised
chemical
compounds
in
vivo
and
degrade
them
by
means
of
series
of
chemical
reactions,
each
aided
by
enzymes,
by
a
process
known
as
metabolism.
The
products
of
metabolic
pathways
are
called
metabolites.
1.2.
Isolation
and
purification
and
structure
elucidation
of
natural
products
<>-OH
Penicillin
G,
the
first
of
its
class
fungal
antibiotic,
first
studied
by
Scottish
microbiologist
Alexander
Fleming
in
the
late
1920s,
and
made
practical
as
a
therapeutic
via
natural
product
isolation
in
the
late
1930s
by
Ernst
Boris
Chain,
Howard
Florey,
and
others,
these
three
named
sharing
the
1945
Nobel
Prize
in
Medicine
for
the
work.
Fleming
recognized
the
antibiotic
properties
and
remarkable
lack
of
toxicity
of
«pen
G»
in
humans,
but
was
unable
to
capture
its
clinical
utility
because
he
could
only
prepare
aqueous
extracts;
his
removal
of
water
led
to
decomposition
of
the
drug.
Developments
in
chromatographic
separations
and
freeze
drying
helped
move
progress
forward
in
the
production
of
commercial
quantities
of
penicillin
and
other
natural
products
[6-7].
All
natural
products
of
interest
begin
as
mixtures
with
other
compounds
from
the
natural
source,
often
very
complex
mixtures,
from
which
the
particular
product
of
interest
must
be
isolated
and
purified.
The
isolation
of
a
natural
product
refers,
depending
on
context,
either
to
the
isolation
of
the
considerable
quantities
of
pure
chemical
matter
required
for
chemical
structure
elucidation,
derivitzation/degradation
chemistry,
biological
testing,
and
other
research
needs
(generally
milligrams
to
grams,
but
historically,
often
more),or
to
the
isolation
of
«analytical
quantities»
of
the
substance
of
interest,
where
the
focus
is
on
identification
and
quantitation
of
the
substance
(e.g.,
in
biological
tissue
or
fluid),
and
where
the
amount
isolated
depends
on
the
analytical
method
applied
(but
is
https://t.me/med1917
umierally
always
sub-microgram
in
scale).
The
ease
with
which
the
.u
live
agent
can
be
isolated
and
purified
depends
on
the
structure,
■dnbility,
and
quantity
of
the
natural
product.
The
methods
of
isolation
applied
toward
achieving
these
two
distinct
scales
of
product
are
likewise
distinct,
but
generally
involve
extraction,
precipitation,
adsorptions,
chromatography,
and
sometimes
crys
tallizations.
In
both
cases,
the
isolated
substance
is
purified
to
chemical
homogeneity,
i.e.,
specific
combined
separation
and
ana
lytical
methods
such
as
LC-MS
methods
are
chosen
to
be
«orthogonal»
-
achieving
their
separations
based
on
distinct
modes
ol
interaction
between
substance
and
isolating
matrix
-
with
the
goal
being
repeated
detection
of
only
a
single
species
present
in
the
putative
pure
sample.
Early
isolation
is
almost
inevitably
followed
by
structure
determination,
especially
if
an
important
pharmacologic
activity
is
associated
with
the
purified
activity.
Structure
determination
refers
to
methods
applied
to
determine
the
chemical
structure
of
an
isolated,
pure
natural
product,
a
process
that
involves
an
array
of
chemical
and
physical
methods
that
have
changed
markedly
over
the
history
of
natural
products
research;
in
earliest
days,
these
focused
on
chemical
transformation
of
unknown
substances
into
known
substances,
and
measurement
of
physical
properties
such
as
melting
point
and
boiling
point,
and
related
methods
for
determining
molecular
weight.In
the
modern
era,
methods
focus
on
mass
spectrometry
and
nuclear
magnetic
resonance
methods
(NMR),
often
multidimensional,
and
when
feasible,
small
molecule
crystallography.
For
instance,
the
chemical
structure
of
penicillin
was
determined
by
Dorothy
Crowfoot
Hodgkin
in
1945,
work
for
which
she
later
received
a
Nobel
Prize
in
Chemistry
(1964)
[8].
1.2.1.
Extraction
of
plant
material
Most
of
the
bulk
of
the
biomass,
irrespective
of
whether
it
is
plants
or
microbes,
exists
asfairly
inert,
insoluble,
and
often
polymeric
material,
such
as
cellulose
of
plants
or
fungi
and
the
microbial
cell
wall
[9].
The
first
step
of
the
extraction
is
therefore
to
release
and
solubilize
the
smaller
secondary
metabolites
in
the
matrix,
resulting
in
the
initial
extract.
https://t.me/med1917
In
liquid
extractions
the
choice
of
extraction
solvent
or
solvents
provides
the
first
and
most
obvious
means
of
sample
preparation
[10].
Initial
extraction
with
low-polarity
solvents
yields
the
more
lipophilic
components,
while
alcohols
isolate
a
broader
spectrum
of
apolar
and
polar
compounds
from
the
material.
In
addition
to
the
choice
of
extraction
solvent,
there
are
also
different
approaches
to
the
actual
extraction
procedure.
While
stirring
or
mechanical
agitation
are
the
most
common
methods,
percolation
or
even
pres
surized
solid-liquid
extraction
are
possible.
The
most
commonly
used
extraction
methods
are
reviewed
in
the
following
chapter.
Selection
of
extraction
method
The
most
widely
used
extraction
processes
have
traditionally
been
based
either
on
different
liquid
extraction
methods
or
on
vapor
phase
extraction
methods
[11].
A
more
recent
method
whose
application
has
steadily
increased
is
supercritical
fluidextraction
(SFE),
which
is
based
on
the
properties
of
gases
compressed
and
heated
to
a
st
ateabove
their
critical
pressure
and
temperature,
at
which
no
d
istinction
between
the
gas
andliquid
phases
can
be
discerned
[12].At
the
present
time,
there
are
also
a
number
of
non-
conventional
extraction
methods
in
usethat
are
all,
in
principle,
solid
liquid
extractions
(SLE)
but
which
introduce
some
form
of
additional
energy
to
the
process
in
order
to
facilitate
the
transfer
of
analytes
from
sample
to
solvent.
These
methods
include
ultrasonic
extraction,
microwave-assisted
extraction
and
pressurized
liquid
extraction
[13],
as
well
as
vertical
(turbo)
extraction.
Even
extraction
by
electrical
energy
has
been
studied
[14].
Forced-flow
solid-liquid
extraction
(FFSLE)
techniques,
such
as
medium-pressure
solid-liquid
extraction
(MPSLE)
and
rotation
planar
extraction
(RPE),
are
methods
in
which
the
extraction
solvent
is
forced
through
the
sample
bed
either
by
means
of
pressure
or
by
centrifugal
force,
respectively,
thus
increasing
the
efficiency
of
the
extraction
process
[15].
The
main
advantage
of
these
non-conventional
methods
compared
to
conventional
SLE
methods
is
the
increased
extraction
efficiency,
which
leads
to
increased
yields
and/or
shorter
extraction
times.
The
simplest
method
of
extraction,
however,
needs
no
extraction
medium.
Mechanical
pressing
has
been
traditionally
applied
to
the
extraction
of
oils
from
oilseeds
[16].
This
process
may
be
combined
https://t.me/med1917
iih
sonic
form
of
pretreatment
such
as
cleaning,
dehulling,
crushing
■
■I
linking
before
the
extraction
but,
in
general,
the
only
equipment
in
i
did
is
a
hydraulic
press.
Despite
the
simple
operating
principle,
iln
и
arc
several
operating
parameters
that
need
to
be
controlled
in
oiili'i
lo
obtain
a
sufficient
extraction
rate
and
yield.
The
most
important
parameters
affecting
the
yield
of
the
extraction
procedure
пи
the
moisture
content
of
the
seeds
and
temperature
.
Traditional
extraction
processes
may
be
classified
as
follows:
■
-.ti
act
ion
with
organicsolvents:
percolation,
maceration,
and
ex
tinction
using
a
Soxhlet
apparatus;
and
extraction
with
water:
mliision,
decoction,
and
steam
distillation.
An
old
method
also
worth
пн
nlioning
is
extraction
with
cold
fat,
called
enfleurage,
used
mainly
Im
the
extraction
of
fragrances
from
flowers.
Percolation
is
one
of
tin-
most
widespread
methods
employed
in
plant
extraction
since
it
docs
not
require
much
sample
manipulation
or
long
pre-treatment
times.
The
only
equipment
required
is
a
conical
glass
container
with
.1
lap
at
the
base
used
to
set
the
rate
of
solvent
elution.
Percolation
is
и
continuous
process
in
which
the
saturated
solvent
is
constantly
displaced
by
fresh
solvent,
but
normally
the
sample
is
steeped
in
solvent
in
the
percolator
for
24
hours
for
up
to
three
times,
and
the
extracts
are
then
collected
and
pooled.
In
maceration
the
sample
is
placed
in
a
stoppered
container
and
is
in
contact
with
the
solvent.
This
allows
the
solvent
to
penetrate
into
the
cellular
structure
in
order
to
dissolve
the
soluble
compounds.
Ils
efficiency
may
be
increased
by
occasionally
shaking
the
container
or
by
using
a
mechanical
or
magnetic
stirrer
to
homogenize
the
final
solution
andsaturate
the
solvent.
As
maceration
is
a
discontinuous
method,
the
solvent
should
be
renewed
until
the
plant
material
is
exhausted;
this
requires
filtration
steps
that
may
result
in
the
loss
of
solvent,
analytes,
and/or
plant
material.
Soxhlet
extraction
is
a
very
old,
clean-up
method,
but
it
is
still
relatively
widely
used
in
plant
analysis.
It
is
used
mainly
with
one
solvent
at
a
time
due
to
the
fact
I
hat
individual
solvents
may
distill
off
at
different
temperatures,
with
I
lie
result
that
the
mixture
in
the
chamber
containing
the
drug
becomes
enriched
in
the
solvent
of
lower
boiling
point.
The
main
advantages
of
the
Soxhlet
technique
are
that
it
is
an
automatic
and
continuous
method
that
does
inut
require'm
u
ch
manipulation.
It
1'
also
been
shown
to
be
very
ef
A
rive
емкмнв^у^Ш
a
not
require'm
u
ch
manipula
t
ion.
It
1'
as
id
окулык
коры
-
17
;
3
3
5263
мул|к
....
https://t.me/med1917
therefore
often
used
as
areference
method
for
newer
extraction
methods.
One
disadvantage
is
that
the
extractives
are
heated
during
extraction
at
the
boiling
point
of
the
solvent
employed
and
thermally
labile
compounds
may
hydrolyze,
decompose,
or
produce
artifacts.
Infusion
and
decoction
are
simple
methods
for
extraction
with
water.
In
the
infusion
technique,
boiling
or
cold
water
is
added
to
the
milled
sample;
in
decoction
the
sample
is
boiled
for
about
15
minutes
in
water.
Extraction
with
pure
water,
however,
is
seldom
used
for
plant
material
as
hydrophilic
compounds
are
usually
extracted
with
methanol-water
or
ethanol-water
mixtures.
Steam
distillation
is
an
old
extraction
method
that
is
primarily
used
to
obtain
essential
oils
from
plant
material.
In
this
method,
a
packed
bed
of
plant
material
is
continuously
flushedwith
steam
and
the
volatile
organic
compounds
present
in
the
material
are
taken
up
by
the
vapor
phase
due
to
their
low
partial
vapor
pressure.
Compounds
carried
by
the
vapor
stream
are
then
separated
after
decreasing
the
temperature
of
the
vapor
by
forced
condensation.
Ultrasonic
extraction
takes
advantage
of
the
very
high
effective
temperatures
(which
increase
solubility
and
diffusivity)
and
pressures
(which
favor
penetration
and
transport)
at
the
interphase
between
the
solvent
solution
subjected
to
ultrasonic
energy
and
a
solid
matrix,
combined
with
the
oxidative
energy
of
radicals
crea
ted
during
sonolysis,
resulting
in
high
extractive
power
[17].
Ultrasonically
assisted
extraction
methods
have
been
employed
for
a
great
number
of
different
plant
materials,
e.g.
Salvia
officinalis
L.,
Valeriana
officinalis
L.,
Calendula
officinalis
L.,
Gentiana
lutea
L.,
Hibiscus
tiliaeus
L.,
and
chrysanthemum
flowers
to
name
a
few
[17-24].
Compound
groups
that
have
been
obtained
by
ultrasonic
extraction
include
polysaccharides,
volatile
oils,
fatty
acids
and
their
esters,
stigmasterol
derivatives,
and
pyrethrins.
Another
way
of
increasing
the
efficiency
of
conventional
extraction
methods
is
to
usemicrowave
irradiation.
Microwave-
assisted
extraction
consists
of
heating
the
solvent
in
contact
with
the
sample
by
means
of
microwave
energy.
The
process
involves
disruption
of
hydrogen
bonds,
as
a
result
of
microwave-induced
dipole
rotation
of
molecules,
and
migration
of
the
ions,
which
enhance
penetration
of
the
solvent
into
the
matrix,
allowing
dissolution
of
the
components
to
be
extracted
[23].
The
main
https://t.me/med1917
advantages
of
microwave
assisted
extraction
over
the
conventional
extraction
techniques
are
reduced
solventconsumption,
shorter
operational
times,
moderately
high
recoveries,
good
reproducibility
niidminimal
sample
manipulation
for
extraction
process
[24-29].
Mn
rowave-assisted
extraction
methods
have
been
applied
to
the
■
xl
ruction
of
oil
from
olive
seeds,
pigments
from
paprika
powders,
glycy
rrhizic
acid
from
liquorice
root,
lipids
from
several
oleaginous
seeds,
cocaine
and
benzoylecgonine
from
coca
leaves,
and
alkamides
Iron)
lichinaceapurpurea
L.
roots
[30].
Pressurized
liquid
extraction
(PLE,
also
commonly
known
as
accelerated
solvent
extraction;
ASE)
works
according
to
the
principle
ol
static
extraction
with
superheated
liquids.
The
method
uses
an
organic
solvent
at
high
pressures
and
temperature
above
the
boiling
point.
The
main
reasons
for
the
enhanced
performance
of
PLE
are
(lie
higher
solubility
of
analytes
in
solvent
at
higher
temperatures,
higher
diffusion
rate
as
a
result
of
higher
temperatures,
and
disruption
of
the
strong
solute
matrix
interaction
caused
by
van
der
Waals
forces,
hydrogen
bonding
and
dipole-dipole
attractions
between
solute
molecules
and
active
sites
on
the
matrix.
The
PLE
technique
is
well
suited
for
the
extraction
of
various
types
of
compound
from
different
plant
materials
because
parameters
other
than
temperature
can
be
varied
and
the
polarity
of
the
extraction
solvent
can
be
chosen
from
a
wide
range
and
adapted
to
the
respective
matrix.
PLE
has
been
reported
to
have
been
applied
Io
e.g.
the
extraction
of
dianthrons
from
Hypericum
perforatum
I
.deacylsaponins
from
Aesculus
hippocastanum
L.,
silybin
from
SHybum
marianum
L.,
curcumin
from
Curcuma
xanthorrhiza,
thy
mol
from
Thymus
vulgaris
L.,
flavanones
andxanthones
from
Maclura
pomifera,
aristolochic
acids
from
Radix
aristolochiae,
berberinefrom
Coptidis
rhizoma
and
oxysterols
from
whole
egg
powder
and
egg-containing
foods.
Subcritical
water
extraction
(SWE,
also
called
pressurized
hot
water
extraction,
PHWE,
orsuperheated
water
extraction)
is
based
on
the
unique
solvent
properties
of
water,
namely
^disproportionately
high
boiling
point
for
its
mass,
a
high
dielectric
constant
and
high
polarity.
The
method
involves
heating
water
above
its
boiling
point
but
below
itscritical
point
(i.e.
374°C)
under
elevated
pressure
so
that
the
water
remains
in
a
liquid
state.
As
the
temperature
rises
there
is
a
https://t.me/med1917
marked
and
systematic
decrease
in
permittivity,
an
increasein
the
diffusion
rate
and
a
decrease
in
the
viscosity
and
surface
tension.
SWE
has
been
foundto
be
an
efficient
extraction
method
and
a
potential
alternative
to
steam
distillation
andsolvent
extraction
in
the
extraction
of
essential
oils
from
plant
material.
Satisfactory
resultshave
been
reported
for
SWE
of
essential
oils
from
marjoram
(Thymus
mastichina),
c\o\'e(Syzygium
aromaticum),
fennel
(Foeniculum
vulgare)
and
sage
(Salvia
officinalis).
Besides
essential
oils,
the
method
has
also
beenapplied
to
the
extraction
of
lactones
from
kava
root
(Piper
methysticum)
and
iridoidglycosides
from
Veronica
longifolia
leaves.
In
recent
years,
the
extraction
method
that
has
received
increasing
attention
and
manyindustrial
applications
in
the
isolation
of
natural
products
is
supercritical
fluid
extraction(SFE).
SFE
has
several
advantages
over
the
conventional
liquid-liquid
and
solid
liquidextraction
techniques,
e.g.
the
elimination
of
most
of
the
organic
solvents
that
may
pose
asafety
risk
during
extraction,
elimination
of
carry-over
of
the
more
or
less
toxic
solvents
in
thefmal
extracts,
and
the
possibility
of
avoiding
the
detrimental
effects
of
these
solvents
on
theenvironment
[31].
The
disadvantages
of
SFE
includethe
low
polarity
of
the
most
commonly
used
fluid,
i.e.
carbon
dioxide,
possible
problems
caused
by
the
presence
of
water,
unpredictability
of
the
matrix
effect
and
the
need
forspecialized/
expensive
equipment.
A
number
of
compounds
have
been
tested
as
supercritical
fluids,
including
pentane,
nitrousoxide,
ammonia
and
Freon
fluorocarbons
but,
on
the
grounds
of
cost
and
safety,
carbondioxide
either
alone
or
modified
with
methanol
or
some
other
polar
solvent
is
by
far
the
most
widely
used
supercritical
extraction
solvent.
It
has
also
the
advantage
of
alow
critical
temperature
and
pressure,
which
enable
pressurization
of
the
gas
into
a
supercritical
fluid.
Thepractical
aspects
of
SFE
and
its
applications
have
been
recently
reviewed
[32].
Due
to
the
low
polarity
of
carbon
dioxide
it
is
best
suited
for
the
extraction
of
nonpolarcompounds.
SFE
has
been
successfully
applied
to
e.g.
the
extraction
of
essential
oilfrom
Angelica
archangelica
L.
roots,
as
well
as
from
Matricaria
chamomilla
flowerheads,and
the
extraction
of
lycopene
from
tomato
skins
[33-34].
However,
by
varying
the
pressure
and
temperature
of
thesupercritical
carbon
dioxide
and
the
amount
of
polar
modifiers,
https://t.me/med1917
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