STEROIDS

Dr. Sukhbir Kaur

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Occurrence nomenclature basic skeleton.

Diel’s hydrocarbon and Stereochemistry Isolation structure determination and synthesis of

• cholesterol
• Bile acids
• Testosterone
• Estrone
• Progesterone
• Aldosterone

Biosynthesis of Steroids

Stereochemistry

Fusion of Ring A and B – Is it cis or trans ?

Ring B and C are trans

Ring C and D - trans

Configuration of hydroxy group at C-3

Cholesterol Synthesis ( Woodward and co workers )

Bile acid

• Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates.
• Diverse bile acids are synthesized in the liver. 
• Bile acids are conjugated with taurine or glycine residues to give anions called bile salts
• Primary bile acids are those synthesized by the liver. 
• Secondary bile acids result from bacterial actions in the colon
• Bile acids facilitate digestion of dietary fats and oils.
• Bile acids also have hormonal actions throughout the body

Bile salts constitute a large family of molecules, composed of a steroid structure with four rings, a five- or eight-carbon side-chain terminating in a carboxylic acid, and several hydroxyl groups, the number and orientation of which is different among the specific bile salts

• Bile acids are hydroxy derivatives of cholanic or allocholanic acid
• All the bile acids can be converted into either of these acids

• All the bile acids can be converted into either of these acids. Eg Lithocholic acid into cholinic acid

Position of Hydroxy group – It is determined by oxidative degradation

1. Coprostanol
2. Dicarboxylic acid
3. Lithobilianic acid
4. Lithocholic acid
5. Dehydrolithocholic acid

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Testosterone

• Testosterone is the primary sex hormone and anabolic steroid in males.
• In male humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair.
• Also, testosterone in both sexes is involved in health and well-being and in the prevention of osteoporosis.

Ruzicka (1935)

Estrone

• Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. 
• It is one of three major endogenous estrogens, the others being estradiol and estriol.
• Estrone, as well as the other estrogens, are synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue.
• Relative to estradiol, both estrone and estriol have far weaker activity as estrogens.
• Estrone can be converted into estradiol, and serves mainly as a precursor or metabolic intermediate of estradiol.
• It is both a precursor and metabolite of estradiol

The chemical formula of estrone is C₁₈H₂₂O₂ and its molecular weight is 270.366 g/mol. It is a white, odorless, solid crystalline powder, with a melting point of 254.5 °C (490 °F)

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1. Forms Oxime = Ketone
2. Forms monoacetate / monomethyl ether = -OH group which forms diazonium salt = phenolic
3. X ray analysis = steroidal nucleus
4. On Zn distillation = chrysene
5. Upon catalytic hydrogenation = octahydro-oestrone

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Monomethyl ether upon Wolff Kishner reduction followed by Se distillation gave 7-methoxy-1,2-cyclopentenophenantherene

Position of –OH group

Johnson et al. (1958,62)

Progesterone

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1. C21H30O2, m.p. 128
2. 2 Ketone groups
3. Upon catalytic hydrogenation adds one H2 = one C=C
4. Tetracyclic
5. X ray analysis = steroidal nucleus
6. UV spectra shows it to be conjugated ketone

Aldosterone

• Aldosterone is a mineralocorticoid hormone, a type of hormone that is essential to life because it regulates the amounts of electrolytes in the body.
• Aldosterone is secreted by the adrenal cortex and responsible for the reabsorption of sodium into the bloodstream.
• Aldosterone also stimulates the excretion of potassium.
• Aldosterone is the chief regulator of sodium, potassium, and chloride metabolism, thus controlling the body's water and electrolyte balances.