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

 

Synthesis of Vitamin D in the Skin by Sunlight

Rajah Serfoji Govt. College (Autonomous)

 Thanjavur – 613 005

M.Sc., Chemistry  SEMESTER – III

 Code: R3PCH6  Organic  Chemistry - III

When sunshine in the UV-B spectrum strikes the skin, it converts a substance in the skin called 7-dehydrocholesterol into vitamin D₃.²

7-dehydrocholesterol is a very close precursor to cholesterol. If you look at our flow chart showing the synthesis of cholesterol, you will see that it shows lanosterol being converted directly to cholesterol. This conversion is actually believed to take more than 18 different steps and hasn't been completely figured out, so it is usually simplified as one step.³ 7-dehydrocholesterol occurs very close to the end of this conversion, so is often referred to as "cholesterol" or "a form of cholesterol."

Figure 1: The Chemical Structure of 7-Dehydrocholesterol

Figure 2: The Chemical Structure of Vitamin D

When atmospheric conditions are ideal and skies are clear, 30 minutes of whole-body exposure of pale skin to sunlight without clothing or sunscreen can result in the synthesis of between 10,000 and 20,000 IU of vitamin D. These quantities of vitamin D are large, and therefore capable of supplying the body's full needs.²

At the same time, the body has two mechanisms to prevent an excess of vitamin D from developing: first, further irradiation converts excess vitamin D in the skin to a variety of inactive metabolites; second, the pigment melanin begins to accumulate in skin tissues after the first exposure of the season, which decreases the production of vitamin D.²

The availability of UV-B rays, however, depends on the angle at which sunshine strikes the earth, making vitamin D synthesis impossible for most people at most latitudes during parts of the year called the "vitamin D winter."⁴

Outside the vitamin D winter, sufficient UV-B rays for full vitamin D synthesis do not suddenly become available: the window of time during each day in which vitamin D synthesis can occur gradually expands as the season progresses, as does the amount of UV-B radiation available within that window.⁴

Many different factors can make the availability of UV-B widely variable during any given time of the year. Clouds alone, for example, can eliminate up to 99 percent of UV-B radiation.⁵

Natural variations in the density of the ozone layer can cause the length of the vitamin D winter to increase or decrease by up to two months. Aerosols and buildings block UV-B radiation, while increased altitude or reflective surfaces such as snow increase exposure to UV-B radiation.⁵

In the past, researchers suggested that any place outside of 34 degrees latitude experiences some degree of vitamin D winter, that the vitamin D winter in Boston extended for four months from November through February, and that the vitamin D winter in Edmonton extended for six months from October through March.⁵

More recently, researchers found that so many factors influence the availability of UV-B light that vitamin D winters under some conditions in Boston and Edmonton could be much shorter, whereas under other conditions, vitamin D winters can even occur at the equator.⁵

Since most of us live at latitudes that are covered by a vitamin D winter for at least part of the year, and since most of us work indoors and wear clothing and sunblock when outdoors in the summer sun, it is necessary for most of us to consume vitamin D in food for at least part of the year, or to supplement with vitamin D.

In order to consume vitamin D as food, we must eat the cholesterol-rich animal foods we are so often told to avoid.

Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism.

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Structure and Synthesis

The term vitamin D is, unfortunately, an imprecise term referring to one or more members of a group of steroid molecules. Vitamin D₃, also known as cholecalciferol is generated in the skin of animals when light energy is absorbed by a precursor molecule 7-dehydrocholesterol. Vitamin D is thus not a true vitamin, because individuals with adequate exposure to sunlight do not require dietary supplementation. There are also dietary sources of vitamin D, including egg yolk, fish oil and a number of plants. The plant form of vitamin D is called vitamin D₂ or ergosterol. However, natural diets typically do not contain adequate quantities of vitamin D, and exposure to sunlight or consumption of foodstuffs purposefully supplemented with vitamin D are necessary to prevent deficiencies.

Vitamin D, as either D₃ or D₂, does not have significant biological activity. Rather, it must be metabolized within the body to the hormonally-active form known as 1,25-dihydroxycholecalciferol. This transformation occurs in two steps, as depicted in the diagram to the right:

1. Within the liver, cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase.
2. Within the kidney, 25-hydroxycholecalciferol serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form.

Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours.

Control of Vitamin D Synthesis

Hepatic synthesis of 25-hydroxycholecalciferol is only loosely regulated, and blood levels of this molecule largely reflect the amount of amount of vitamin D produced in the skin or ingested. In contrast, the activity of 1-alpha-hydroxylase in the kidney is tightly regulated and serves as the major control point in production of the active hormone. The major inducer of 1-alpha-hydroxylase is parathyroid hormone; it is also induced by low blood levels of phosphate.

Interesting species differences exist in the ability to synthesize vitamin D through the sunlight-mediated pathway described above. The skin of humans, horses, pigs, rats, cattle and sheep contain adequate quantities of 7-dehydrocholesterol which can effectively be converted to cholecalciferol. In contrast, the skin of dogs and cats constains significantly lower quantities of 7-dehydrocholesterol than other species, and its photochemical conversion to cholecalciferol is quite inefficient; dogs and cats thus appear to rely on dietary intake of vitamin D more than do other animals.

The Structure of Cholesterol

Cholesterol has a molecular formula of C₂₇H₄₅OH. This molecule is composed of three regions (shown in the picture above): a hydrocarbon tail (shown in blue), a ring structure region with 4 hydrocarbon rings (shown in green), and a hydroxyl group (shown in red.).

The hydroxyl (OH) group is polar, which makes it soluble in water. This small 2-atom structure makes cholesterol an alcohol. The alcohol that we drink, ethanol, is a much smaller alcohol that also has a hydroxyl group (C₂H₅OH).

The 4-ring region of cholesterol is the signature of all steroid hormones (such as testosterone and estrogen). All steroids are made from cholesterol. The rings are called "hydrocarbon" rings because each corner of the ring is composed of a carbon atom, with two hydrogen atoms extending off the ring.

The combination of the steroid ring structure and the hydroxyl (alcohol) group classifies cholesterol as a "sterol." Cholesterol is the animal sterol. Plants only make trace amounts of cholesterol, but make other sterols in larger amounts.

The last region is the hydrocarbon tail. Like the steroid ring region, this region is composed of carbon and hydrogen atoms. Both the ring region and tail region are non-polar, which means they dissolve in fatty and oily substances but will not mix with water.

Because cholesterol contains both a water-soluble region and a fat-soluble region, it is called amphipathic.

Cholesterol, however, is not water-soluble enough to dissolve in the blood. Along with fats and fat-soluble nutrients, therefore, it travels in the blood through lipoproteins such as LDL and HDL.

CURRICULAM VITAE

NAME                     : RAJARAJAN.K

FATHER”S NAME    : KARUPPAIAH.N

DATE OF BIRTH       : 21.07.1966

EDUCATIONAL

QUALIFICATION      :

                                B.Sc CHEMISTRY BHARATHIDASAN UNIVERSITY 1987

                    M.Sc   APPLIED CHEMISTRTY ANNA UNIVERSITY 1992

                    M.Phil CHEMISTRY ANNA UNIVERSITY 1994

DESIGNATION         : ASSISTANT PROFESSOR OF CHEMISTRY         

                                   RAJAH SERFOJI GOVERNMENT COLLEGE.

                                   THANJAVUR.

TEACHING

EXPERIENCE            U.G: 16 YEARS

                                   P.G:   6 YEARS

DETAILS                :

·         LECTURER IN CHEMISTRY, T.B.M.L. COLLEGE PORAYAR (1995  TO 2005)

·          TEACHER IN A GRADE LEVEL CHEMISTRY GRAMMAR INTERNATIONAL   SCHOOL DUBAI.         UNITED ARAB EMIRATES (2005 to 2006)                  

·                     LECTURER IN CHEMISTRY & SENIOR INCHARGE FOR  S.F  SECTION.T.B.M.L.COLLEGE                    

                               PORAYAR. (2006 to 2008)

·         ASSISTANT PROFESSOR OF CHMISTRY, RAJAH SERFOJI GOVT COLLEGE.

                              THANJAVUR (FROM SEP 2008 TO TILL DATE)

CONFERENCES PARTICIPATED:

Ø    STAE LEVEL SEMINAR ON SPECTROSCOPY 12^TH MARCH 2007

                CONDUCTED BY DEPARTMENT OF CHEMISTRY, GOVTARTSCOLLEGE.CHIDAMBARAM

                              

Ø  NATIONAL CONFERENCE ON IMPENDING APPROACHES TO ENVIRONMENTAL

                                MENACE 25TH&26^TH SEP 2008 CONDUCTED BY DEPT OF CHEMISTRY,  

                                T.B.M.L.COLLEGE .PORAYAR

Ø  U.G.C SPONSORED  STATE LEVEL SEMINAR ON NMR APPLICATIONS AND ENERGY MATERIALS  21^ST FEB 2011 CONDUCTED BY  P.G AND RESEARCH

DEPARTMENT OF CHEMISTRY RAJAH SERFOJI GOVT COLLEGE THANJAVUR.

Ø  WORK SHOP ON MICROSCALE EXPERIMENTS IN CHEMISTRY 14 TH DEC 2011 CONDUCTED BY DEPARTMENT OF CHEMISTRY A. VEERAIYA VANDAYAR MEMORIAL SRI PUSHPAM COLLEGE.

LIST OF PAPERS PRESENTED IN THE NATIONAL SEMINARS.

Ø  “Growth and characterisation studies of succinic tartrate doped with ferrous sulphate.” *K.Rajarajan ¹ G.Madhurambal² J.Samusolomon³ USSE-2013 UGC sponsored National seminar organized by the Department of chemistry, T.B.M.L. College Porayar.

Ø  “Growth and characterization studies on diphenyl amine-picrate -A nonlinear optical crystal.” *K.Rajarajan¹ A.Anandhi ² K.R.Dhanalakshmi alias reka³J.Samusolomon⁴ G.Madhurambal⁵ GCGP-2013 UGC sponsored National seminar organized by the Department of chemistry, ADM College for Women Nagapattinam.

Ø  “Growth and characterization studies on acetamide-picrate doped with copper sulphate-A nonlinear optical crystal.” *K.Rajarajan¹ K.R.Dhanalakshmi alias reka² A.anandhi ³J.Samusolomon⁴ G.Madhurambal⁵ GCGP-2013 UGC sponsored National seminar organized by the Department of chemistry, ADM College for Women Nagapattinam.

Ø  “Spectral Diffraction and Optical Properties of Succinic-Picrate doped with Copper sulphate- A nonlinear optical crystal” *K.Rajarajan¹ G.Madhurambal² GCGP-2013 UGC sponsored National seminar organized by the Department of chemistry, ADM College for Women Nagapattinam.

Ø  “Growth and characterization of nonlinear optical crystal of picric acid and acetamide” *K.Rajarajan ¹ G.Madhurambal² S.Kalyanasundaram³ J.Samusolomon⁴ GCGP-2013 UGC sponsored National seminar organized by the Department of chemistry, ADM College for Women Nagapattinam.

Ø  “X-ray Diffraction and Spectroscopic studies on Acetamide –Tartrate-A Non linear optical crystal.”* K.Rajarajan¹ S.Kalyanasundaram² G.Madhurambal³ J.Samusolomon⁴ GCGP-2013 UGC sponsored National seminar organized by the Department of chemistry, ADM College for Women Nagapattinam.

Ø   “Synthesis growth and characterization of thio-urea picrates-  A nonlinear optical crystal”.*K.Rajarajan G.Madhurambal² J.Samusolomon³ USSE-2013 UGC sponsored National seminar organized by the Department of chemistry, T.B.M.L. College Porayar.

LIST OF PUBLISHED PAPERS IN THE INTERNATIONAL JOURNAL

1.      “XRD and FTIR studies on ferrous sulphate and copper chloride doped Glycine picrate crystal- A non linear optical material”. K.Rajarajan,J.Samusolomon,G.Madhurambal RJPBCS ISSN:0975-8585 vol-3 issue-1 2012

2.      “XRD and FTIR studies on Lead (ii) nitrate doped Histidine picrate crystal-A non linear material”. K.Rajarajan et al. J. chem.,pharm,Res, 2012,4(8)

3.      “Structural characterization studies on copper chloride doped Glycine picrate crystal- A non linear optical material”. . K.Rajarajan et al. J. chem.,pharm,Res, 2012,4(1)

4.      “Spectral diffraction and optical properties of Succinic picrate doped with copper sulphate- A non linear optical crystal”. K.Rajarajan. G.Madhurambal ISSN : 2249-9504  IJPCBS 2013, 3 (3), 461-469.

5.      “Synthesis and characterization studies of diphenyl amine picrate crystal- A non linear optical crystal”. K.Rajarajan et al., ISSN: 2249-9504 IJPCBS 2013, 3 (3), 480-487

6.      “Growth and characterization studies of Acetamide-picrate crystal doped with copper sulphate- A non linear optical crystal”. K.Rajarajan et al., ISSN : 0975-8585 RJPBCS VOL 4, Issue 2

ORIENTATION COURSE ATTENDED:

      ORIENTAION PROGRAMME (INTENSIVE PROGRAMME)  13TH  OCTOBER TO 08TH NOVEMBER  CONDUCTED  BY  TAMIL NADU STATE COUNCIL FOR HIGHER EDUCATION ANDUNIVERSITY  GRANTS COMMISION-ACADEMIC  STAFF COLLEGE  UNIVERSITY OF MADRAS

      REFRESHER COURSE ATTENDED

^{U.G.C Sponsored Refresher Course in research Methodology From 16.05.2012 TO 05.06.2012 Conducted BY Academic Staff College, Pondicherry University and obtained grade A.}

 ^{A three day lecture workshop on “Emerging trends in Chemical sciences from 21.09.2012 to 23.09.2012 conducted by the Central University, Thiruvarur.}

^{Awarded with Ph.D. Degree in Chemistry on November 2015 by the Syndicate of Bharathidasan University, Trichirappalli.}

FIELDS OF TEACHING INTEREST                      

v  ORGANIC CHEMISTRY

v  QUANTUM CHEMISTRY

v  COORDINATION CHEMISTRY

v  CRYSTAL GROWTH

v  POLYMER CHEMISTRY

v  ENVIRONMENTAL CHEMISTRY

ADDRESS FOR COMMUNICATION:

Prof.DR.K.RAJARAJAN
No. B-38, NEW HOUSING UNIT
THANJAVUR

TAMILNADU- 613005

       INDIA

       MOBILE NO: 9994853691

       E-MAIL :  rajakrrsg@gmail.com