UNIT - V Steroids

                              Rajah Serfoji Govt. College (Autonomous), Thanjavur – 613 005

          M.Sc., Chemistry

                                      Code: R3PCH6  Organic  Chemistry - III

                                 UNIT - V          Steroids


Estrone (E1, and also oestrone) is an estrogenic hormone secreted by the ovary as well as adipose tissue with the chemical name of 3-hydroxyestra-1,3,5(10)-triene-17-one and the chemical formula C₁₈H₂₂O₂. Estrone is an odorless, solid crystalline powder, white in color with a melting point of 254.5 °C and a specific gravity of 1.23. Estrone is one of several natural estrogens, which also include estriol andestradiol. Estrone is the least abundant of the three hormones; estradiol is present almost always in the reproductive female body, and estriol is abundant primarily duringpregnancy. Estrone is known to be a carcinogen for human females as well as cause breast tenderness or pain, nausea, headache, hypertension, and leg cramps.^[1][4] In men, estrone has been known to cause anorexia, nausea, vomiting, and erectile disfunction. Estrone is relevant to health and disease states because of its conversion to estrone sulfate, a long-lived derivative. Estrone sulfate acts as a reservoir that can be converted as needed to the more active estradiol. It is the predominant estrogen in postmenopausal women.

Estrone is synthesized via aromatase from androstenedione, a derivative of progesterone. The conversion consists of the de-methylation of C-19 and the aromaticity of the 'A' ring. This reaction is similar to the conversion of testosterone to estradiol.

Estrone is a white, solid crystalline powder that is odorless. It has a melting point of 254.5 °C (490 °F) and has a specific gravity of 1.23. At high temperatures estrone is combustible and the products of combusting estrone are carbon monoxide (CO) and carbon dioxide (CO₂)

Estrone has been proven to be a known carcinogen for human females. The Occupational Safety and Health Administration (OSHA) classifies estrone as an OSHA Select carcinogen. Exposure to estrone can cause breast tenderness or pain, cervical hyper secretion, menstrual disorders including menorrhagia and metrorrhagia, nausea, headache, hypertension, leg cramps, vision disturbances, and endometriosis pain in women. Mothers lactating can also experience a decrease in the production of breast milk.

Progesterone (pregn-4-ene-3,20-dione; abbreviated as P4) is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called theprogestogens,^[1] and is the major progestogen in the body. Progesterone is also a crucial metabolic intermediate in the production other endogenous steroids, including the sex hormones and the corticosteroids, and plays an important role in brain function as a neurosteroid.

Progesterone was independently discovered by four research groups.^[3][4][5][6]

Willard Myron Allen co-discovered progesterone with his anatomy professor George Washington Corner at the University of Rochester Medical School in 1933. Allen first determined its melting point, molecular weight, and partial molecular structure. He also gave it the name Progesterone derived fromProgestational Steroidal ketone

Like other steroids, progesterone consists of four interconnected cyclic hydrocarbons. Progesterone contains ketone and oxygenated functional groups, as well as two methyl branches. Like all steroid hormones, it is hydrophobic.

Biosynthesis

In mammals, progesterone (6), like all other steroid hormones, is synthesized frompregnenolone (3), which in turn is derived from cholesterol (1) (see the upper half of the figure to the right).

Cholesterol (1) undergoes double oxidation to produce 20,22-dihydroxycholesterol .This vicinal diol is then further oxidized with loss of the side chain starting at position C-22 to produce pregnenolone (3). This reaction is catalyzed by cytochrome P450scc. The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-hydroxyl group is oxidized to a keto group (4) and second, the double bond is moved to C-4, from C-5 through a keto/enol tautomerization reaction This reaction is catalyzed by 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase.

Progesterone in turn (see lower half of figure to the right) is the precursor of the mineralocorticoid aldosterone, and after conversion to 17-hydroxyprogesterone(another natural progestogen) of cortisol and androstenedione. Androstenedione can be converted to testosterone, estrone and estradiol.

Pregnenolone and progesterone can also be synthesized by yeast