Estrogens - Biosynthesis and chemical synthesis

Summary

This video provides an in-depth look at the biosynthesis and chemical synthesis of estrogens. The process begins with cholesterol and progresses through several intermediates like pregnenolone, dehydroepiandrosterone (DHEA), and androstenedione, eventually leading to the formation of estrogens. Key enzymes like aromatase and 17 beta-hydroxysteroid dehydrogenase play pivotal roles in these transformations. The video also covers the chemical synthesis of estrogens, using methods such as Marcus degradation and fermentation processes, along with the preparation of synthetic estrogens like ethinylestradiol and mestranol. It highlights both natural and synthetic pathways for estrogen production.

Takeaways

• 😀 Estrogens are synthesized from cholesterol, with pregnenolone being a key intermediate in the process.
• 😀 Pregnenolone acts as a precursor for both estrogens and androgens, with its conversion to estrogens requiring specific modifications.
• 😀 The first step in estrogen biosynthesis is the 17 alpha-hydroxylation of pregnenolone, which adds a hydroxyl group at the 17th position.
• 😀 After the 17 alpha-hydroxylation, the side chain at the 17th position is removed through oxidation, leading to the formation of dehydroepiandrosterone (DHEA).
• 😀 Aromatization of DHEA involves oxidation and tautomerization, converting it into androstenedione, a crucial step for estrogen formation.
• 😀 Aromatase enzyme plays a pivotal role in converting androstenedione into estrogens by introducing the aromatic ring and removing the methyl group at the 19th position.
• 😀 Estrone is the first estrogen produced in this biosynthetic pathway, which can be further converted into estradiol by the enzyme 17 beta-hydroxysteroid dehydrogenase.
• 😀 Estradiol can also be directly synthesized from testosterone by aromatase, bypassing estrone as an intermediate.
• 😀 Chemical synthesis of estrogens involves using the Marcus degradation pathway, where intermediates like androsta-diene-dione are used to generate estrogens.
• 😀 Synthetic estrogens such as ethinylestradiol and mestranol are derived by modifying estrone through nucleophilic addition and other chemical processes.

Q & A

What is the precursor for the biosynthesis of estrogens?

Estrogens are obtained from cholesterol, and an important intermediate in this process is pregnenolone.

How is pregnenolone converted into estrogens?

Pregnenolone is first hydroxylated at the 17th position to form 17 alpha-hydroxy pregnenolone. This modification removes the side chain, after which the structure is further converted into androgens before being aromatized into estrogens.

What is the first step in the biosynthesis of estrogens from pregnenolone?

The first step is the 17 alpha-hydroxylation of pregnenolone in the presence of auxin and NADPH.

What role does the enzyme aromatase play in the biosynthesis of estrogens?

Aromatase introduces an aromatic ring into the first steroid ring structure and removes the methyl group at the 19th position, converting androgens like androstenedione into estrogens.

How does the conversion of androstenedione into estrone occur?

In androstenedione, oxidation occurs, which introduces the aromatic nature to the first ring, while the methyl group is oxidized to an aldehyde, removed, and replaced with a double bond, forming estrone.

What is the next step after estrone formation in estrogen biosynthesis?

Estrone can be converted into estradiol through the action of the enzyme 17 beta-hydroxysteroid dehydrogenase, which reduces the ketone group at the 17th position to a hydroxyl group.

Can estradiol be synthesized from testosterone directly?

Yes, estradiol can be directly synthesized from testosterone via the aromatase enzyme, which catalyzes the conversion of testosterone into estradiol.

What is the role of the marcus degradation in chemical synthesis of estrogens?

Marcus degradation involves modifying intermediates like androstenedione to introduce the required modifications, including reducing double bonds and introducing aromaticity to form synthetic estrogens like estrone.

How is synthetic estrogen mestranol synthesized?

Mestranol is synthesized by modifying ethyl estradiol, which involves adding a methyl ether group at the third position using a methane sulfonate reagent.

How is the androstadiene dione used in the industrial synthesis of estrogens?

Androstadiene dione can be derived from cholesterol or cytosterol through fermentation processes using *Mycobacterium flae*. This intermediate can then be converted into synthetic estrogens like estrone and mestranol.