Download Slid 7 Hops

Slid 7 Hops :
In chemical structure beta acidsarelike alpha acids but the difference is that we have an extra
isoprene unit (in alpha acids we have two isoprene units but here in beta we have three), Look
here:
Isoprene
units
Xanthohumol is not alpha or beta acid, it’s a flavonoid (we will study them later)flavonoid is
generally C6 C3 C6 (six carbon atoms then three then six).
C6
C6
C3
Also we have to know that we have two pathways in biosynthetic of flavonoid:
If we cut the compound from the middle [look at the pic.] we will have right side and left side one
is derived from acetate-malonate pathway (meta substitution, left side) and the other derived
from shikimic pathway (Para substitution, right side).
Cut
from
here
*Slide 8 Natural acetylenic Compounds :
- Dehydromatricaria ester (1A) : it has 3 triple bonds.
- Agrocybin contains three triple bonds, While steariolic acid, crepenynic acid , and tariric acid
contain only one triple bond.
1- Acetyl Co-A reacts with 8 malonyl Co-A in the presence of fatty acid synthase which lead to
the formation of our 18 Carbons saturated fatty acid (without = bond) "Stearic Acid" and this is
called the primary metabolite.
2- The saturated fatty acid "Stearic acid" is converted to the unsaturated fatty acid "Oleic acid"
under the effect of delta 9 desaturase enzyme.
(Oleic acid is an unsaturated fatty acid contains one double bond at carbon number 9)
3-Under the effect of delta 12 deasturase enzyme, our oleic acid is converted to linoleic acid.
(Linoleic acid is an unsaturated fatty acid contains two double bonds at carbon number 9 and
carbon number 12).
4- Delta 12 acetylenase enzyme (the enzyme which responsible for the formation of triple bond
by removing the two Hs) converts the double bond which is located at carbon number 12 to
triple bond; which mean we can't form triple bond directly from the saturated compound, we
have first to form double bond by desaturase enzyme then form triple bond by the action of
acetylenase enzyme and this lead to the formation of Crepenynic Acid.
5- Further desaturation of the crepenynic acid by using Delta 14 desaturase enzyme (form
double bond at position 14) leads to the formation of dehydrocrepenynic acid which has two
double bonds one at position 9 and the other at position 14, is only found in fungi.
6- Then delta 14 Acetylenase form triple point at position 14.
Acetyl co-A is formed in the mitochondria,
which under the effect of Polyketides
synthase result in the formation of
polyketides.
- In the cytosol, there's a pool of Acetyl co-A
which under certain processes lead to the
formation of VLCFA "very long chain fatty
acid"
- Fatty acid modification occurs in the
endoplasmic reticulum "ER".
*Slide 9 Anthraquinone :
It is a derivative of anthracene, here we have the numbering system which is
clock wise (1-10). We have different derivatives, one is Anthraquinone (which
has a keto groups at carbons no. 9,10), if the keto group at carbon number 10
was removed then its Anthrone, if carbon number 10 was oxidized we will have
Oxanthrone, and when carbon number 9 has a phenolic group (reduction of
anthrone) then its Anthranol.
Our compounds are synthesized from Acytel-CoA (which derives from the sugar glucose, not
from acetic acid. As we remember the glycolysis of glucose split it into pyruvic acid then we go
to the acetate malonate pathway). Here we can see that three malonyl-CoA cooperate with
other three acetyl –CoA in addition to three co2 to form the anthraquinone compounds.
1- ** Asphodelus spp. :
First portion
Third portion
second portion
If we see the first and second portions are oxanthrone , and the third portion is glucose sugar
(C-Sugar).
Slide 10 : Antibiotic
We can see that we have our phenol here
also we have nitrogen (amine).
the origin of nitrogen atom is the amino acid
Asparagine (Asparagine is the amino acid which
donate N atom)
When we talk about our compound mainly we talk about the one molecule of malonamyl CoA
with eight molecules of malonyl CoA [we have to know the basic; how molecules; 1 molecule
of malonamyl CoA react with 8 molecules of malonyl CoA], then we have
polyketide→cyclization → C-6 methylation in addition the other processes, this is biosynthetic
briefly that wecan see in our compound.
We will not talk about structure activity in details of our tetracycline but remember that all the
time we can divide into upper portion and lower portion; the upper portion is the position
available for modification.
**Fusidic acid :
we have the acidic group and we have a steroid (remember that steroid in the plant or
microorganism starting with isoprene unit) here we have our isoprene unit so fusidic acid is
derived from acetate malonate pathway.
** erythromycin A:
We can see the structure of erythromycin A we have sugar so it's glycoside.
*** Amphotericin:
Amphotericin is an example, we can see here a macrolide typical here we have large rings all
of them linked to each other via an oxygen bridge, so we don't have really cyclic like
tetracycline.Most of amphotericins are amino sugar.
**Nystatin :
Nystatin is one of the oldest macrolide
drugs, it's atypical macrolide (linked via
oxygen and we have amino glycoside).
**Grisofluvin :
Griseofulvin, it's not a tetracycline, it's contain ring A,B,C known as Xanthone nucleus similar
to anthraquinone but we have oxygen in ring "B" (in anthraquinone its Carbon), Griseofulvin
produced by different Penicillinspp. But it chemistry based on Xanthone, if we look at ring "A"
and "C "we have two oxygen meta to each other so it's derived from acetate malonate pathway.