FINAL EXAMINATION NATURAL PRODUCT CHEMISTRY

1. Fats generally are solidwhile the oil is liquid phase, however both are equally triglyceride. Explain why the from of two . Different triglyceride, and point out important factors that determine the from of fat.

Answer : fat is saturated and oil is unsaturated and then fat have high van derwalls and oil have low van derwalls so that fat are solid phase in room temperature and oil are liquid phase in temperature. 

A fat's constituent fatty acids may also differ in the C/H ratio. When all three fatty acids have the formula C_nH_(2n+1)CO₂H, the resulting fat is called "saturated". Values of n usually range from 13 to 17. Each carbon atom in the chain is saturated with hydrogen, meaning they are bonded to as many hydrogens as possible. Unsaturated fats are derived from fatty acids with the formula C_nH_(2n-1)CO₂H. These fatty acids contain double bonds within carbon chain. This results in an "unsaturated" fatty acid. More specifically, it would be a monounsaturated fatty acid. Polyunsaturated fatty acids would be fatty acids with more than one double bond; they have the formula, C_nH_(2n-3)CO₂H and C_nH_(2n-5)CO₂H. Unsaturated fats can be converted to saturated ones by the process of hydrogenation. This technology underpinned the development of margerine.

Saturated and unsaturated fats differ in their energy content and melting point. Since unsaturated fats contain fewer carbon-hydrogen bonds than saturated fats with the same number of carbon atoms, unsaturated fats will yield slightly less energy during metabolism than saturated fats with the same number of carbon atoms. Saturated fats can stack themselves in a closely packed arrangement, so they can freeze easily and are typically solid at room temperature. For example, animal fats tallow and lard are high in saturated fatty acid content and are solids. Olive and linseed oils on the other hand are highly unsaturated and are oily.

2. How primary metabolite can be converted into secondary metabolisme. what is the basic idea and how the mechanism could be desribed.

Answer: basic ideas to convered primary metabolite into secondary metabolite is from the reaction the fundamental processes of photosynthesis, glycolysis, and the Krebs cycle are tapped off from energy-generating processes to provide biosynthetic intermediates.To make biosynthesis intermediets needs the buillding blocks. By far the most important building blocks employed in the biosynthesis of secondary metabolites are derived from the intermediates acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid, and methylerythritol phosphate. These are utilized respectively in the acetate, shikimate, mevalonate, and methylerythritol phosphate pathways, Acetyl-CoA is formed by oxidative decarboxylation of the glycolytic pathway product pyruvic acid. It is also produced by the β-oxidation of fatty acids, effectively reversing the process by which fatty acids are themselves synthesized from acetyl-CoA. Important secondary metabolites formed from the acetate pathway include phenols, prostaglandins, and macrolide antibiotics, together with various fatty acids and derivatives at the primary–secondary metabolism interface. Shikimic acid is produced from a combination of phosphoenolpyruvate, a glycolytic pathway intermediate, and erythrose 4-phosphate from the pentose phosphate pathway. The reactions of the pentose phosphate cycle may be employed for the degradation of glucose, but they also feature in the synthesis of sugars by photosynthesis. The shikimate pathway leads to a variety of phenols, cinnamic acid derivatives, lignans, and alkaloids. Mevalonic acid is itself formed from three molecules of acetyl-CoA, but the mevalonate pathway channels acetate into a different series of compounds than does the acetate pathway. Methylerythritol phosphate arises from a combination of two glycolytic pathway intermediates, namely pyruvic acid and glyceraldehyde 3-phosphate by way of deoxyxylulose phosphate. The mevalonate and methylerythritol phosphate pathways are together responsible for the biosynthesis of a vast array of terpenoid and steroid metabolites.

In addition to acetyl-CoA, shikimic acid, mevalonic acid, and methylerythritol phosphate, other building blocks based on amino acids are frequently employed in natural product synthesis. Peptides, proteins, alkaloids, and many antibiotics are derived from amino acids, and the origins of some of the more important amino acid components of these are briefly indicated in Figure 2.1. Intermediates from the glycolytic pathway and the Krebs cycle are used in constructing many of them, but the aromatic amino acids phenylalanine, tyrosine, and tryptophan are themselves products from the shikimate pathway. Ornithine, an amino acid not found in proteins, and its homologue lysine, are important alkaloid precursors and have their origins in Krebs cycle intermediates. Of special significance is the appreciation that secondary metabolites can be synthesized by combining several building blocks of the same type, or by using a mixture of different building blocks. This expands structural diversity and, consequently, makes subdivisions based entirely on biosynthetic pathways rather more difficult. A typical natural product might be produced by combining elements from the acetate, shikimate, and methylerythritol phosphate pathways.

3. Hormone progesterone is essensial for the survival of the pregnancy. these hormones are derived from a steroid biogenetically. explain the logic of chemical reactions which may occour in the formation progesterone.

answer : 

Biosynthesis

in mammals progesterone, like all other steroid hormones, is synthesized frompregnenolone, which in turn is derived from cholesterol.

Cholesterol 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 . This reaction is catalyzed bycytochrome P450scc. The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-hydroxyl group is oxidized to a keto group and second, the double bond is moved to C-4, from C-5 through a keto/enol tautomerizationreaction. This reaction is catalyzed by 3beta-hydroxysteroid dehydrogenase/delta -delta isomerase.

Progesterone in trun 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.

Top: Conversion of cholesterol (1) into pregnenolone (3) to progesterone (6).

Bottom: Progesterone is important for aldosterone (mineralocorticoid) synthesis, as 17-hydroxyprogesterone is for cortisol (glucocorticoid), and androstenedione for sex steroids.

In laboratory

An economical semisynthesis of progesterone from the plant steroid diosgenin isolated from yams was developed by Russell Marker in 1940 for the Parke-Davis pharmaceutical company (This synthesis is known as the Marker degradation. Additional semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane inchloroform to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone. Pregenolone and progesterone can also be synthesized by yeast.

The Marker semisynthesis of progesterone fromdiosgenin

A total synthesis of progesterone was reported in 1971 by W.S. Johnson. The synthesis begins with reacting the phosphonium salt 7 with phenyl lithium to produce the phosphonium ylide 8 . The ylide is reacted with analdehyde to produce the alkene 9. The ketal protecting groups of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as biomimetic. In the next step the enolorthoester is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce16. Finally, the diketone 17 undergoes an intramolecular aldol condensation by treating with aqueous potassium hydroxide to produce progesterone.

The Johnson total synthesis of progesterone

4. Many alkaloid are toxic to other organisms. They often have pharmacological effects and are used as medications, as recreational drugs, or in entheo genic rituals. Desribe in outline the process of biosynthesus of an alkaloid compound and desribe the function groups which play an important role in the biological activities.

Answer :   biosynthesis of alkaloid compound example from purine alkaloid. The purine derivatives caffeine, theobromine, and theophylline are usually referred to as purine alkaloids. They have a rather limited distribution, and their origins are very closely linked with those of the purine bases adenine and guanine, fundamental components of nucleosides, nucleotides, and the nucleic acids. Caffeine, in the form of beverages such as tea, coffee, and cola, is one of the most widely consumed and socially accepted natural stimulants. It is also used medicinally, but theophylline is more important as a drug compound because of its muscle relaxant properties, utilized in the relief of bronchial asthma. Theobromine is a major constituent of cocoa and related chocolate products . The purine ring is gradually elaborated by piecing together small components from primary metabolism. The largest component incorporated is glycine, which provides a C2N unit, whilst the remaining carbon atoms come from formate and bicarbonate. Two of  the four nitrogen atoms are supplied by glutamine and a third by aspartic acid. Synthesis of the nucleotides adenosine 5_-monophosphate (AMP) and guanosine 5_-monophosphate (GMP) is by way of inosine 5_-monophosphate (IMP) and xanthosine 5_-monophosphate (XMP) (Figure 6.141), and the purine alkaloids then branch away through XMP. AMP, if available, can also serve as a source of IMP. Methylation and then loss of phosphate generates the nucleoside 7-methylxanthosine, which is then released from the sugar. Successive methylations on the nitrogen atoms give caffeine by way of theobromine, whilst a different methylation sequence can account for the formation of theophylline. Theophylline can also be produced by demethylation of caffeine as part of a degradative pathway. Some of the N-methyltransferases display rather broad substrate specificity, and this allows minor pathways to operate in certain plants, e.g. the alternative sequence to 7-methylxanthosine via 7-methyl XMP shown in Figure 6.141. In addition, the enzyme caffeine synthase in coffee (Coffea arabica; Rubiaceae) has dual functionality, and methylates both theobromine and 7-methylxanthine; a tea (Camellia sinensis; Theaceae) enzyme is specific for theobromine.

This is purine synthesis

This is biosynthesis purine alakaloid to produced caffeine, theobromine, and theophylline

HOMO AND LUMO

HOMO-LUMO ("filled-empty") Orbital Interactions

A fundamental principle: all steps of all heterolytic reaction mechanisms are either Bronsted or Lewis acid-base reactions

• They involve either proton transfer (Bronsted), or unshared pair/empty orbital interactions (Lewis).
• When the interacting atomic orbitals are considered, the Bronsted reactions can be seen as simply a special case of the Lewis, in which the empty orbital is the antibonding orbital of the H-X bond.

In short, all heterolytic reactions are just examples of interactions between filled atomic or molecular orbitals and empty atomic or molecular orbitals - that is, Lewis acid-base reactions. Here is a diagram to explain this point:

The interaction of any two atomic or molecular orbitals, as you learned in general chemistry, produces two new orbitals.

• One of the new orbitals is higher in energy than the original ones (the antibonding orbital), and one is lower (the bonding orbital).
• When one of the initial orbitals is filled with a pair of electrons (a Lewis base), and the other is empty (a Lewis acid), we can place the two electrons into the lower energy of the two new orbitals.
• The "filled-empty" interaction therefore is stabilizing.

When we are dealing with interacting molecular orbitals, the two that interact are generally

• The highest energy occupied molecular orbital (HOMO) of one molecule,
• The lowest energy unoccupied molecular orbital (LUMO) of the other molecule.
• These orbitals are the pair that lie closest in energy of any pair of orbitals in the two molecules, which allows them to interact most strongly.
• These orbitals are sometimes called the frontier orbitals, because they lie at the outermost boundaries of the electrons of the molecules.

Here is the filled-empty interaction redrawn as a HOMO-LUMO interaction.

Let's look at some examples. First, a reaction that you would have categorized as a Lewis acid-base reaction when you were studying general chemistry:

NH₃ has an unshared pair on nitrogen, occupying the HOMO (it is generally true that unshared pairs occupy HOMOs). BH₃ has an empty valence orbital on B, since B is a Group II element. This is the LUMO.

Here are pictures of the two orbitals from AM1 semi-empirical molecular orbital calculations:

NH3 HOMO	BH3 LUMO

The HOMO-LUMO energy diagram above describes the formation of a bond between N and B.

Now let's try a slightly more complex case. Here's a typical Bronsted acid-base reaction:

The curly arrows track which bonds are made, and which are broken, but they do not indicate what orbitals are involved.

• Water is both a Bronsted base (capable of accepting a proton) and a Lewis base, with one of its unshared pairs (the HOMO).
• H-Cl is a Bronsted acid, capable of donating a proton, but it also is a Lewis acid, using the s* orbital of the H-Cl bond (the LUMO).
• Here are pictures of the relevant HOMO and LUMO, again from AM1 semi-empirical molecular orbital calculations:

H2O HOMO	HCl LUMO

• The interaction stabilizes the unshared pair of the oxygen, while simultaneously breaking the H-Cl bond because the interaction is with the antibonding orbital.

Another example is the S_N2 reaction, which involves the HOMO of the nucleophile and the s* orbital of the R-X bond:

Here are the relevant orbitals:

OH- HOMO	CH3-Cl LUMO

The interaction stabilizes the unshared pair of the oxygen, while simultaneously breaking the CH₃-Cl bond because the interaction is with the antibonding orbital.

Other examples include the reaction of alkenes with H-X, where the HOMO is the p MO of the alkene and the LUMO is the H-X s* orbital:

and the capture of the carobcation in an SN1 reaction by nucleophile:

You should need no reminder that the carbocation is stabilized by a filled-empty interaction between the empty p orbital of the positive carbon and the s orbital of an adjacent C-H or C-C bond

In short, all heterolytic reactions proceed because the energy of a pair of electrons is lowered by the interaction of a filled atomic or molecular orbital with an empty one.

The same reasoning can be appllied to bimolecular pericyclic reactions like the Diels-Alder cycloaddition.

Diastereomers

Diastereomers (sometimes called diastereoisomers) are stereoisomers that are not enantiomers. Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other. When two diastereoisomers differ from each other at only one stereocenter they are epimers. Each stereocenter gives rise to two different configurations and thus to two different stereoisomers.

Diastereomers differ from enantiomers in that the latter are pairs of stereoisomers which differ in all stereocenters and are therefore mirror images of one another. Enantiomers of a compound with more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image. Diastereomers have different physical properties and different reactivity, unlike enantiomers.

Cis-trans isomerism and conformational isomerism are also forms of diastereomerism.

Diastereoselectivity is the preference for the formation of one or more than one diastereomer over the other in an organic reaction.

L-Threonine (2S,3R) and D-Threonine (2R,3S)

Enantiomers

Enantiopure compounds refer to samples having, within the limits of detection, molecules of only one chirality.
Enantiomers have, when present in a symmetric environment, identical chemical and physical properties except for their ability to rotate plane-polarized light (+/−) by equal amounts but in opposite directions (although the polarized light can be considered an asymmetric medium). A mixture of equal parts of an optically active isomer and its enantiomer is termed racemic and has zero net rotation of plane-polarized light.
Enantiomers of each other often show different chemical reactions with other substances that are also enantiomers. Since many molecules in the body of living beings are enantiomers themselves, there is often a marked difference in the effects of two enantiomers on living beings. In drugs, for example, the working substance is often one of two enantiomers, while the other one is responsible for adverse effects.
Enantioselective preparations
There are two main strategies for the preparation of enantiopure compounds. The first is known as chiral resolution. This method involves preparing the compound in racemic form, and separating it into its isomers. In his pioneering work, Louis Pasteur was able to isolate the isomers of tartaric acid because they crystallize from solution as crystals each with a different symmetry. A less common method is by enantiomer self-disproportionation.
The second strategy is asymmetric synthesis: the use of various techniques to prepare the desired compound in high enantiomeric excess. Techniques encompassed include the use of chiral starting materials (chiral pool synthesis), the use of chiral auxiliaries and chiral catalysts, and the application of asymmetric induction. The use of enzymes (biocatalysis) may also produce the desired compound.
Enantioconvergent synthesis is the synthesis of one enantiomer from a racemic precursor molecule utilizing both enantiomers. Thus, the two enantiomers of the reactant produce a single enantiomer of product.

Enantiopure medications
Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers. In some cases, the enantiomers have genuinely different effects. In other cases, there may be no clinical benefit to the patient. In some jurisdictions, single-enantiomer drugs are separately patentable from the racemic mixture. It is possible that both enantiomers are active. Or, it may be that only one is active, in which case separating the mixture has no objective benefits, but extends the drug’s patentability.