Jumat, 30 November 2012

NICOTINE BIOSYNTHESIS


Nicotine biosynthesis
Nicotine biosynthesis pathway involves the reaction of cyclic coupling between the two structures that make up the nicotine. Metabolic studies indicate that the pyridine ring of nicotine from nicotinic acid while pyrrolidone is derived from the N-methyl-Δ1-pyrrollidium cations. Biosynthesis of two structural components results in two independent synthesis, NAD pathway for nicotinic acid and tropane pathway for N-methyl-Δ1-pyrrollidium cations.
NAD pathway in the genus nicotiana starting with aspartic acid oxidation to α-imino succinate by aspartate oxidase (AO). This is followed by condensation with glyceraldehyde-3-phosphate and cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with the acid-catalyzed pyrophosphate phosphoriboxyl quinolinic phosphoribosyl transferase (QPT). The reaction is now underway through the cycle to produce NAD rescue by converting nicotinamide nicotinic acid by the enzyme nicotinamidase.
Cation N-methyl-Δ1-pyrrollidium used in the synthesis of nicotine is an intermediate in the synthesis of tropane alkaloid derived. Biosynthesis begins with the decarboxylation of ornithine decarboxylase by ornithine (ODC) to produce putrescine. Then converted into putrescine N-methyl putrescine through methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination to 4-methylaminobutanal by N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize to N-methyl-Δ1-pyrrollidium cations.
The final step in the synthesis of nicotine is the coupling between the N-methyl-Δ1-pyrrollidium cation and nicotinic acid. Although studies suggest that some forms the link between the two components of the structure, processes and mechanisms that would still not been determined. The theory agreed today involving the conversion of nicotinic acid to 2,5-dihydropyridine with 3.6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate then reacts with the N-methyl-Δ1-pyrrollidium cations to form enantiomerically pure (-)-nicotine.

Minggu, 25 November 2012

MID SEMESTERS EXAM ANSWERS CHEMISTRY OF NATURAL PRODUCTS

NAME                   : YUNITA RUBI LESTARI
NIM                      : RSA1C110007

1). To find compound effective Dari Yang paled MATERIAL natural compounds, in addition to using Appropriate Toxicity Data can ALSO use analytical methods Isolation. Isolated compounds can be developed outreach process Illustrations That paled find effective compounds. Know the structure of the new compound CHEMICAL nil would be a "lead compound" In, formation so you can scale the Great Illustrations synthetic. Modify Structure O compounds, compounds Which Will Able to withstand levbih On. The pure compound was isolated ALSO be tested with different bioactivity, based not only related to the use of AT New Media bioactivity customary. In addition to using the method of extraction ALSO Insulation can be used to find active compounds. Illustration order to extract only contains active compounds contained in Yang, raw MATERIALS / Experience The penyari The optimal hedge Liquids Able to attract active compounds. Pure active compounds can be administered Illustration of looping, the dose given is more accurate. My husband, of course, can be achieved when kita managed to get pure compounds role Illustration biokativitasnya and share experimental dilakuakn selnajutnya to find the dose, the dose was prepared New Articles The RIGHT Way And The right way to give. The term is not Here Again gambling. There are several methods of extraction using Natural MATERIALS raw, such as maceration, infundasi, digestion, percolation and soxletasi.
2). Utilization of Plant Medicine
Since ancient times herbs have been utilized by humans to treat various types of diseases. How traditional medicine using the natural ingredients have been recorded in various documents stored neatly in China, India and North Africa. Even to this day still plant an exclusive source for producing chemical compounds that have a variety of pharmacological activities.
Data from a scientific journal reported, there were approximately 25% of all drugs prescribed to patients, a drug compounds derived from plants, 121 of which active substance is still in use today. Of 252 basic drugs and esential set by the WHO, 11% of whom are drug compounds that are exclusively derived from plants and in significant numbers also include synthetic compounds derived from natural precursor materials (1). Some examples of essential drugs isolated from plants antaralain digoxin from Digitalis spp plants, quinine and kinidin from Chinchona spp, morphine and codeine from Papaver somniferum and atropine from Atropa Belladona.
Prior to the 19th century in the form of extracts of plants used to treat various diseases. Around the beginning of the 19th century there was a change in the era of utilization of medicinal plants. At this time, scientists have managed to isolate pure compounds from plants such as strychnine, quinine, morphine, etc., which is still used as a drug. In this period of secondary metabolites from plants being the main target of research in order to find chemical compounds that have the potential as a medicine.
Plants selected as the source material providers are important in medicine caused by several things, among others:
• Plants can produce pure compounds that can be used directly as a drug. Examples are morphine quinine, vincristine and vinblastine.
• Plants can produce chemicals that can be used as model compounds in the synthesis of total or partial synthetic (modified structure) into compounds more effective or less toxic. Examples of drugs that are based on a model of natural compounds is metformin, verapamil, morphine, etc. taxolphodophyllotoxin.
• plant extracts can be used for treatment, without having to go through the insulating phase of pure compounds. Examples include gingko biloba and herbal medicines circulating in Indonesia.
Recent years these drug compounds produced from natural materials have become of particular concern to the pharmaceutical industry. As can be seen from the development representatifnya compound taxol, etoposide and artemisin who have managed through the clinical testing phase. Taxol is a chemical compound that was first isolated from the plant Taxus brevifolia. Isolation and structure determination of these compounds is based on the results of initial laboratory research showing that extracts of this plant showed activity against cancer cells. Although the bioactivity testing has been done in the early 1960s, the isolation and determination of new chemical structures completed in 1971. After going through the various stages of research, in 1980 the successful clinical testing in the 1990s dilakukan.Sekitar compound taxol and Taxotere derivatives turned out to have been clinically proven to be effective against breast cancer (breast cancer) and ovarian cancer (ovarian cancer) (2)
Podophyllin resin was first isolated from the plant Podophyllum peltatum, are compounds that are toxic. The main component of the resin is a memepunyai phodophyllotoxin lignans aktiviatas inhibit cell division. Due to the toxic nature of these compounds are less likely to be used as medicine. But look aktvitasnya can inhibit cell division, these compounds may be indicated compounds have potential cancer chemotherapy. A semisynthetic compound etoposide were made based on model compounds phodophyllotoxin apparently been tested clinically effective against lung cancer and testicular cancer (2)
Artemisinin is a chemical compound isolated from the plant Artemisia annua. Clinical testing has shown that this compound is used as an antimalarial effective and can be used for treatment of infections caused by Plasmodium falciparum (2)
The potential of plants as a source of drug discovery compounds to date have not fully utilized. Approximately 250000-500000 plant species existing in the world today, accounting for only about 6% of its bioactivity testing that has been done, and only about 15% that have examined levels of the chemical. Given the thousands of plants containing secondary metabolites are believed to play an important role as a producer of chemical compounds that have pharmacological activity. So a challenge for scientists to explore the chemical compounds found in plants that can be used for future drugs.
Synthesis and Structure Modification
To get a more effective compound or with the aim of reducing toxicity, can be modified structure. In addition to modification of the structure, which has been isolated compounds can serve as a model compound in the total synthetic process. Total synthetic compound performed usually for memepunyai simple structure, and does not cost more expensive. Adakalnya in the drug discovery process, it will require more time and cost expensive lenih if desired compounds were isolated from the repeated nature. It is therefore necessary that the total drug can be synthesized in the laboratory. But not all natural compounds can be synthesized, because the complexity of its structure, da vinblastine vincristine is still produced from the plant, and yet can be made synthetically.


3). Factors Influencing the Selection of Solvent

a. Selectivity
Solvents may only dissolve extract desired, not the other components of the material extraction.

b. Village
Solvents dissolve as much as possible have the ability to extract large.

c. Ability not intermingled
In liquid extraction, solvent should not dissolve in the extraction of materials.

d. Density
Especially in the extraction fluid, wherever there may be a large difference in density between the solvent and extraction materials. It is intended that both phases can be easily separated after mixing.

e. Reactivity
In general, the solvent should not cause chemical changes in the component material extraction komponent


f. Boiling point
The boiling point of the two materials should not be too close. In terms of economics, it is advantageous if the boiling point of the solvent extraction process is not too high.

g. Criteria

Solvents as much as possible should be:
*    Budget
*    Available in large quantities
*    Non-toxic
*    Not flammable
*    Not korotif
*    Do not cause the formation of emulsions
*    Having a low viscosity
*    Stable in chemical and thermal

Some of the most important solvent is water, organic acids and inorganic, saturated hydrocarbons, tolven, ether, acetone, isopropanol, ethanol, carbon disulfit (Bernasconi, et.all, 1995).

Terpenoids

Terpenoids are derivatives dehydrogenation and oxygenation of terpene compounds. Terpenes are a class of hydrocarbons produced by many plants and some animal groups. Terpenes molecular formula is (C5H8) n.
Terpenoids also called isoprenoids. This is due to the same carbon skeleton as compound isoprene. Terenoid chemical structure is a combination of the isoprene unit, can be either open-chain or cyclic, may contain a double bond, hydroxyl, carbonyl or other functional groups. The solvent used to extract the methanol terpenoid compounds.
Flavonoids
Generally most of the extraction process materials containing flavonoids is done simply with the addition of direct solvent extraction.
Powdered plant material can also be extracted using a Soxhlet, initially with hexan, to remove lipids and then with ethyl acetate or ethanol to obtain phenolic compounds. This method is unsuitable for the content of compounds that are not heat resistant. The procedure is safe and commonly used sequential solvent extraction.
The first phase, with dichloromethane, to extract flavonoid aglycone and content of non-polar. The next stage of the alcohol will extract and flavonoid glycoside content of polar compounds.

Steroids
Broadly speaking, the isolation of the sea cucumber steroid compounds consisting of two phases in the extraction part of fat cucumbers, followed by extracting the steroid compounds. Here is one study conducted Sarifah Nurjanah, et al (2009) to identify steroid sand sea cucumber (Holothuria scabra) in Indonesia.
Extraction of steroid cucumbers done in two stages, namely fat extraction followed by extraction of steroids. Fat extraction performed with acetone solvent by maceration, saponification process is then performed using a solution of 1 M KOH and carried reflux at 70 C for 1 hour. Steroids extracted using diethyl ether solvent.

Alkaloids
Alkaloids are one type of secondary metabolites.
what is of secondary metabolites??
that the metabolism of which is used by plants as a defense, but specific and limited only owned by certain plants. Alkaloids are more soluble in organic solvents than water.

4). Infrared spectrophotometry is more widely used for identification of a compound through the group functions. For the purpose of structure elucidation, the wavenumber region 1400 - 4000 cm-1 which is at the left of the IR spectrum, an area that is particularly useful for the identification of functional groups, which is the absorption of the stretching vibration. Furthermore, the area just to the right of wave numbers 1400 cm-1 are often very complicated because in this region occurred absorption of stretching vibration and bending vibration, but any organic compound having a Characteristic absorption in this region. It is therefore part of the spectrum is called fingerprint region (fingerprint region). Currently there are two kinds of instruments, namely IR and FTIR spectroscopy (Furier Transformation Infra Red). FTIR is more sensitive and accurate example to distinguish cis and trans forms, conjugated and isolated double bonds and others are in indistinguishable IR spectrophotometer.

Furthermore, also known regions vibration of each bond held by the organic compounds can be seen in Fig. below.

 In interpreting the IR spectrum of the isolated compound / synthesis, the focus of attention focused on the major functional groups such as carbonyl (C = O), hydroxyl (OH), nitrile (CN) and others. Uptake single CC and CH sp3 should not be so confused because almost all organic compounds have absorptions in the region.
Here's a guide in analyzing the IR spectrum of an organic compound:
1. Consider whether there is a carbonyl group (C = O) in the region 1820-1600 cm-1 and a sharp peak is very characteristic.
2. If there is a carbonyl group, then consider the possibility of the following functional groups, if not then proceed to step 3.
a. Carboxylic acid will bring apda OH absorption region 3500-3300 cm-1
b. Amida will give a sharp NH absorption in the region around 3500 cm-1
c. Esther will bring a sharp and strong CO absorption at 1300-1000 cm-1
d. Anhirida will bring up the C = O absorption twins in 1810 and 1760 cm-1.
e. Aldehyde aldehyde CH will bring weak intensity sharply in 2850-2750 cm-1 both
symmetry and anti-symmetry
f. Ketones, if all the above does not arise.

3. If no carbonyl absorption then:
1. Test alcohol (-OH), taking into account the wider uptake (typically once) at 3500-3300 cm-1 (confirmed with a carboxylic acid) and reinforced with CO absorption at around 1300-1000 cm-1
2. Test amine (NH), with respect to the uptake medium at about 3500 cm-1 (confirmed by amide)
3. Test ether (CO), taking into account the absorption at 1300-1000 cm-1 (confirmed with alcohols and esters)
4. C = C bond of alkenes and aromatics. For alkene absorption appears at 1650 cm-1, whereas for the aromatic around 1650-1450 cm-1. Uptake CH aliphatic alkenes will appear below 3000 cm-1, whereas CH vinilik benzene will appear above 3000 cm-1
5. Alkyne C C bond will appear sharply weaker 2150 cm-1, whereas the C N nitrile medium and sharp will appear at 2250 cm-1
6. NO2 nitro group, giving a strong absorption around 1600-1500 cm-1 of the anti-symmetric and also at 1390-1300 cm-1 for symmetric
7. When you get 1 to 6 above does not exist then the IR spectrum is strong suspicion of hydrocarbons.

Jumat, 02 November 2012

STEROID


STEROIDS HORMONES
After a steroid hormone secretion by the endocrine glands, 95-98% will be in circulation or bound to a specific transport protein. 2-5% is freely diffuses into all cells. Once in the cell, can only produce steroid response in cells that have receptors for the hormone specific intracellular concerned. The bond between the hormone with specific receptors is key to the hormones in target tissues.
Thus:
• estrogen receptors found in the brain and reproductive cells specific targets for women such as uterus and breast.
• Hair follicles on the face, erectile tissue of the penis contains the androgen receptor
• glucocorticoid receptors are found in all cells because glucocorticoids needed to set the common functions such as metabolism and stress
All the faculties of the main group of sex steroids (androgens, progestins and estrogens) work through a series of similar work to produce a cellular response in the form of:
1. Transfer of steroid into the nucleus
2. Binding of intra-nuclear
3. Activates the receptor from an inactive form to an active
4. Binding of steroid-receptor complex to the DNA regulatory elements (desoksiribunukleic acid)
5. Transcription and synthesis of messenger ribonucleic acid (mRNA) in the new
6. MRNA translation by synthesizing new proteins in the cell
 Agonists and antagonists
The potential steroid hormone depends on:
1. The combination of hormone-receptor affinity or certain medications
2. Affinity hormone-receptor complex to the SRE-steroid receptor element
3. The efficiency of hormone-receptor complexes that are active in regulating gene transcription. Molecules with high affinity to the receptor and the hormone-receptor complex has a high affinity for the SRE will work as agonists of the parent compound.
Other molecules with high affinity to the receptor, but the bond between the hormone-receptor complex with the SRE less efficient antagonists will work with the parent compound. Tamoxifen is a compound with mixed agonist and antagonist properties.
Tamoxifen is an antiestrogen that works strongly to the estrogen receptor antagonist in breast and agonist on bone and uterus.
Clomiphene citrate can be used to ovulation induction. Clomiphene citrate interaction with estrogen receptors and the hypothalamic pituitary receptor binding will result in no further stimulation is accompanied by an efficient transcription of genes related to estrogen. The hypothalamus recognize this situation as a state hipoestrogen that GnRH pulse frequency increases. Production will pituitary FSH in stimulation and lead to increased levels of ovarian estrogen. Estrogen will work locally for recruitment of ovarian follicles in order to air ovulation. When clomiphene discontinued, the estrogen receptor in the hypothalamus is ready to bind again with SRE estrogen and respond accordingly. The hypothalamus can respond normally to high estrogen levels in the circulation and causing ovulation LH surge.
STEROIDS HORMONES IN CIRCULATION
Steroid hormone in the circulation is in the form of a bond with a specific protein. Hormones are bound by proteins do not penetrate the cell plasma membrane. Nearly 70% of testosterone and estradiol in the circulation bound to a β globulin known as SHBG-sex hormone - binding globulin. 30% are in a loose bond with albumin and a small portion (1-2%) in the free state and can enter into the cell. Synthesis of SHBG will increase in pregnancy, hiperestrogenemia and hyperthyroidism. Androgens, progestins, growth hormone and corticoids will lower SHBG synthesis. Changes in SHBG concentration will affect the amount of steroid in the circulation of free and not bound thereby affecting biological steroids work by changing the number of steroid-free entry into the cell.
METABOLISM STEROIDS
Unless progestins, androgens are obligatory precursors of the androgen steroid hormone that is made in all steroid-producing tissues, including the testes, ovaries and adrenal glands. The main androgen in the circulation in men is testosterone produced testes. Work androgen hormone produced directly by binding to androgen receptors or indirectly after conversion to DHT-dihydrotestosterone in the target tissue. Testosterone berkeja internal genital tract and the male fetus to stimulate muscle growth. In adult men, DHT acts locally to maintain the masculinization of the external genitalia and secondary sexual CIC as facial and pubic hair. Other types of androgens in men are: androstenedione, androstenediol, dehidroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S).  
All types of androgens found in the circulation of women, except for androstenedione, the concentration of androgen in women less than men. Androstenedione in women acts as a prohormone and is converted in the target tissue to testosterone, estrone and estradiol. Estradiol (E2) is the major estrogen secreted by the ovaries. Estrone (E1) is also in the secretion by the ovaries in large quantities. Estriol (E3) is produced by the ovaries, but is produced from estradiol and estrone in peripheral tissues, the placenta of androgens; estimated is estriol less active metabolite of estrogen. The adrenal glands are the main source of sex steroids in men and women. Adrenal androgens play an important role in post-menopausal women. Progestin in circulation is at most progesterone. Progesterone is produced by the ovary, testis, placenta and adrenal glands. 17-hydroxyprogesterone from adrenal and ovarian cancers are the type most often found in the circulation
Excretion STEROIDS
Steroid excretion occurs via the urine and bile. Prior to elimination, occurs as sulfate conjugates or glukoronida. Several types of conjugates in forms such as DHEA-S in the active secretion. The hormones in these conjugated metabolites serve as precursors to active hormones in target tissues that have enzymes to perform hydrolysis of ester bonds involved in conjugation
Steroid hormones are divided into two groups, namely adrenokortikoid hormones and sex hormones.
A. Hormones Adrenokortikoid
Adenokortikoid hormone is a steroid hormone synthesized from cholesterol and is produced by glands adrenalis part of the cortex. Expenditure is influenced by hormones adrenokortiko tropin hormone (ACTH) from the anterior pituitary. This hormone is also called by the name adrenokortikosteroid, adrenocortical, corticosteroids or corticoids. Some relate to the physiological function of the cardiovascular system and blood, central nervous system, smooth muscle and stress.
Adrenokortikoid hormones are divided into two groups: mineralocorticoid and glucocorticoid hormones.
a. Hormones mineralkortikoid
This hormone is primarily used for the treatment of chronic Addison's disease, a disease caused by a malfunctioning gland adrenalis for any reason, eg gland tumors, resulting in the production of hormones decreases. Since Addison's disease is difficult to cure, then treatment can last a lifetime. This hormone can increase the intake of sodium ions and potassium spending ditubulus kidney.
Mechanism of action of mineralocorticoid hormones related to metabolism of electrolytes and water. This hormone is to maintain normal kidney function, namely by adjusting income and expenses natrim ion potassium ion. At the molecular level, these hormones interact to form complexes recovered resptor degan typical core embedded on the kidneys. Complex formation stimulates the synthesis of RNA and enzymes necessary for the active transport of Na ions, mineralocorticoid effect. Examples of mineralocorticoid hormones are: Aldosterone, Deoksikortikosteron and fludrocortisone.
b. Glucocorticoids Hormones
Glucocorticoid hormones have anti-inflammatory effects and is used to treat disorders of the collagen network, hematologic disorders (leukemia) and respiratory (asthma), for the treatment of rheumatism, arthritis pengobatn because of allergies, such as severe dermatological, gastrointestinal diseases and liver diseases. Effective for the treatment of glucocorticoid hormones schock Addison's disease, swollen brain, hypercalcemia, and myasthenia gravis. Glucocorticoid hormones can be dangerous if used improperly. Long-term use causes pretty severe side effects, such as hypokalemia, peptic ulcers, growth suppression, osteoporosis, round face, suppression of corticotropin secretion, atrophic skin, aggravate diabetes mellitus, mudsh infection, glaucoma, hypertension, menstrual disorders, and mental changes and behavior. Discontinuation of treatment suddenly cause acute adrenal insufficiency, and cause withdrawal symptoms, such as muscle becomes weak, muscle pain, fever, mental changes, muia, hypoglycemia, hypotension, dehydration and sometimes even cause death. Therefore, long-term treatment with glucocorticoids, drug discontinuation should be done gradually by reducing the dose.
Examples of drugs that belong to the hormones kortikosteroida is as follows:
 - Cortisone acetate
-Hydrocortisone
-Prednisone
-Prednisolone
-Methyl prednisolone
-Parametason
-Triamniolon
-Fluokortolon
-Betamethasone
-Dexamethasone