How estrogens are synthesized in the body? Even they can be prepared by chemical process and what is the intermediate in this pathway that yields synthetic estrogens? Here we will discuss biosynthesis and chemical synthesis of estrogens.
Hi everyone today in this video let us discuss about the biosynthesis and chemical since of estrogens estrogens are obtained from the cholesterol biosynthesis and one of the important intermediate is the pregnant loan and this intimate again acts as a precursor for the biosense of the androgens like the testosterone but here we will see how this pregnant loan can
Be converted into estrogens in our previous video we have already discussed about the estrogens estrogens are having an eastern nucleus which is having the 18 carbon nucleus and they are not having any side chain at the 17th position so one other thing we have to remove the side chain and second thing estrogens are having the aromatic ring so we have to introduce
An aromatic nature to the first string and finally they are not having a methyl group at the 19th position which should be removed so all this modification can be done by which this pregnant loan can be converted into estrogens so the first step is to remove this side chain but in order to remove the side chain initially we have to introduce a hydroxyl group at
The 17th position so here the first step is the 17 alpha hydroxylation in presence of auxin and nadph then this pregnant loan can be common to another intermediate now here you can observe the hydroxyl group is attached by alpha configuration so this is nothing but the 17 alpha hydroxy pregnant alone now in prince of hydroxyl group at the 17th position this carbon
Chain can be easily removed now the next step is the 17 alpha hydroxy pregnant which is having a side chain this side chain is going to be removed again by oxidation now this 17 alpha hydroxy pregnant is going to be converted into another intermediate and here you can see the side chain is going to be removed along with the ketone group at the 17th position so
This is nothing but the dehydro ap androsterone which is having a ketone group at the 17th portion so we have removed the side chain at the 17th position and another important thing is we have to introduce the aromatic nature to the first string so how can we do this so in this dehydrator ap endosterone we can observe third position hydroxyl group is there and
Fifth and six position a double bond is there so this can undergo the oxidation followed by tautomerization so by oxidation the oh group is coming to ketone and by tautomerization the double bond is going to be shifted to the accent position so by this this dehydrator ap endosterone is going to come to another intermediate this is nothing but the androstenedione
Now in the androsyne dion you can observe that a ketone group is present at the third position and fourth and fifth position a double bond is present we have already seen these steps in the biosensor of the androgens but here after the androstenedione this ring is going to be aromatized such that they are going to produce the estrogens so this is androstenedione
Which is having only one double bond now it should be aromatized so we have to introduce the extra double bonds and another important thing is the removal of the methyl group at the 19th position now this is going to be reacted by one of the enzyme aromatase this enzyme can introduce the aromatic nature to the first string first step in the serum days action
Is the oxidation on oxidation the methyl group is going to be oxidized such that this androstenedione is going to form a structure like this now you can observe here an aldehyde group is going to be produced so methyl group is common to aldehyde functionality by oxidation and this undergoes further oxidation and cleavage of this aldehyde group says that the
Formaldehyde group is going to be removed and again this reaction is going to be mediated by aromatase enzyme such that it is going to form a and the double bond simultaneously the ketone is converted to a enol so that one more double bond is going to produce and it is going to produce the estrone you can observe that by removal of this formaldehyde one double
Bond is going to be produced by conversion of the ketone to the enol and the double bond is going to produce in this way two new double bonds are going to be reduced which makes the ring aromatic in nature in this pathway eastern is the first estrogen that is going to be biosynthesized now this is stone can be converted into easter dial so here it requires the oh
Group at the 17th position so 17 beta hydroxy steroidal dehydrogenase enzyme which is going to produce the reduction of this ketone group into the alcohol this enzyme converts the eastern to the estradiol now in the easter dial you can observe a 17 beta hydroxyl group and this easter dial can also be obtained from the testosterone by the same enzyme aromatase
Enzyme this aerobic enzyme can convert the testosterone directly into the estradiol so estradiol can be obtained through the histone otherwise directly from the testosterone now let us see the chemical sensor of the estrogens again we can use the marcus degradation just like we have seen the androgens the dioxin is one of the precursor that can act as a source
Of steroidal hormones so diazonin can be common to one of the important intermediate that is the androstene alone now this androstenone is coming to estrogen nucleus but again you can see what are the modifications we have to produce here it is having a double bond at the fifth and sixth position which should be removed and the first ring should be aromatized
So here this double bond is not required so first step is the reduction where this double bond is going to be reduced followed by oxidation with the chromium trioxide such that it is going to be converted into structure like this where you can observe that double bond is going to be saturated and oh group is going to be a ketone group so reduction as well as
Oxidation results in the formation of this intermediate now already we got one ketone here and then we have to introduce the double bonds now this intermediate is reacted with the bromine and acetic acid such that it is undergoing the alpha bromination on both side of the ketone you can observe a bromine group is attached on both sides of this ketone now
This bromine group can be easily removed such that it is going to form a double bond so here in the next step the two hydrogen bromide molecules are going to be removed such that it is going to introduce the two double bonds now what is the name of this intermediate this is the androstar diene diode we should not confuse this with the androstenedione this is a
Different intermediate androstar dienedione so it is having a two double bonds and two ketone groups with an androstene nucleus so androstar diendion now this androstar diendion is undergoing the thermolysis so here you can observe the methyl group is present at the 19th position which is not required so it undergoes that thermal ic says that this methyl group is
Going to be removed and simultaneously it is going to form an aromatic ring to produce the eastern in this way by marcus degradation histone can be synthesized but nowadays we can directly derive the androstardiene dion from cholesterol cholesterol can be counted to androsta diendion otherwise cytosterol can also be converted into this intermediate and this can
Be carried by fermentation process with the mycobacterium flea which releases the androstadia in dion from which we can prepare the synthetic estrogens now let’s see the synthetic estrogens how they can be prepared syndromic estrogens can be prepared from the east rome so histone can be modified to produce the synthetic estrogens and we know one of the synthetic
Histogen is the ethereal easter dial which is having a ethereal group at the 17th position now since this eastern is having a ketone group at the 17th portion it can undergo the nucleophilic addition so when it is going to be reacted with the sodium acetylide along with the liquid ammonia it can produce a drug like this this is nothing but the ethyl easter dial
Now you can observe at the 17th position ethereal group is going to be attached at the same time the ketone group is common to oh group so now this stone becomes estradiol with an extra ethereal group so that is nothing but the ethernyl easter dial and already we have seen in the previous video ethereal easter dial is having the less inactivation compared with the
Ester dial so it is 12 times more effective compared with the easter dial similarly from the ethereal easter dial we can prepare the enderdrag mestranol mestranol is having a methyl ether at the third position so whatever the oh group at the third position should be modified so this can be mediated by one of the rays and methane sulfonate the methane sulfonate
Acts as a donor for the methyl group so now in prince of this reagent this ethereal easter dial is going to be converted into mestanol now the mestranol is having a methoxy group at the third portion which acts as a protract when this ether bridge is going to be cleared it produces the ethernet easter dial as the active drag in this way from the histone we can
Prepare the ethereal star dial and from the ethereal easter dial we can prepare the mestanol so that’s about the biosenses and chemical sense of the estrogens so biosense of the estrogens is obtained from the pregnant loan just like the androgens but here the aromatize is one of the enzyme which specifically prepare the estrogens by introducing the more double
Bond to the first ring making it aromatic in nature similarly the chemical senses we can use the marcus degradation and one of the important intermediate is the androstar diendion which can be converted into histone but nowadays by fermentation process by using the mycobacterium flea we can directly get this androstadian dion from the cholesterol or cytosterol
Then this androstadian dion can be converted into histone ethereal star dial and mestanol in this way the estrogens can be synthesized within the body as well as chemically so that’s for today if you like this video please subscribe to our channel share this video with your friends post your comments in the comment box thank you for watching this video
Transcribed from video
Estrogens – Biosynthesis and chemical synthesis By egpat
