Mid Semesters Exam Answers Chemistry Of Natural Products

1. Express their own ideas on how to convert a mixture of natural ingredients that have the potential (inactive) can be transformed into higher compounds that have a high potential for biological activity.

        My idea is generally to obtain a compound of natural ingredients that do not have the potential (not active) that can be converted into an active compound that has a high potential for biological activity, can be done in stages as follows:

a. preparation phase of the plant material
b. Phase extraction
c. Phase fractionation and purification
d. Elucidation structure of the isolated compounds
e. Testing activity of the active compounds


Example

Xanthone compounds found in the bark mangosteen wildly

Uncultivated mangosteen (Garcinia sp) is a species of the family guttiferae, Garcinia species. This plant has a botanical classifications as follows:
   Division       : Spermatophyta
   Sub Division: Angiospermae
   Class            : Dicotyledonae
   Family          : guttiferae
  Genre            : Garcinia
  Species          : Garcinia sp
         

      

Figure 1 wild bark and sawdust wild mangosteen Mangosteen (Garcinia sp)
                 

             Santon is a compound made tricyclic aromatic ring substituted with groups other than phenolic, methoxy and isoprene (Walker, 2007). The compounds xanthones such as 9-hydroxycalabaxanthone, 3-isomangostin, gartanin, 8-desoxygartanin (Walker, 2007), α-mangostin, γ-mangostin, β-mangostin, and methoxy-β-mangostin (Akao et al., 2008). Santon are scattered in various organs of plants classified for subsituen linked nucleus (Bennett and Lee,1989).

            Xanthones present in the mangosteen fruit, among others, 9 - hidroksikalabaxanton, 3 isomangostin, gartanin, 8-deoksigartanin, α-mangostin and β-mangostin (Zarena, et al, 2009.). The majority of natural xanthones were found primarily in higher plants that can be isolated from the four tribes, namely guttiferae, Moraceae, and Polygalaceae Gentianaceae (Sluis, 1985). Family of four is rich in xanthones, as guttiferae: alpha and gamma mangostin mangosteen (Jung et al, 2006; Harrison, 2002; Suksamrarn et al, 2002 ..). Santon is reported to have pharmacological activity can stimulate the central nervous system and has an activity antituberculosis vitro on Mycobacterium tuberculosis (Bruneton, 1999; Sluis, 1985). Santon type gentisin Mangiferin and has an antitumor activity as an inhibitor of monoamine oxidase and (Robinson, 1995). Xanthones found in the rind of Garcinia mangostana and has the IUPAC name of (1,3,6-trihydroxy-7-methoxy-2 ,8-bis (3-methyl-2-butenyl)-9Hxanten-9-yl). (Chitra, MV2010) Structure of Xanton dapa you see in the image below:
 
 Chemical constituents of Garcinia xanthones which it is derived

 

              

           α-mangostin                             β-mangostin

       

    

      9- hydroxycalabaxantone                   3-isomangostin

                      

               Gartanin                                             8-desoxygartanin

           Santon derived structures (Walker, 2007)

            More than 60 compounds were isolated from xanthones mangosteen different sections, for example α-mangostin, 1-isomangostin, 3-isomangostin, 9-hidroksikalabaxanton, 8-deoksigartanin, dimetilkalbaxanton, garcinon B, gargarcinon D, E garcinon, gartanin, mangostanol, mangostanin and mangostinon (Ji et al, 2007;. Walker, 2007). Xanthone compounds can inhibit the growth of colon cancer cells DLD-1 with IC50 values ​​methoxy-β-mangostin <β-mangostin <α-mangostin <γ-mangostin (Akao et al., 2008). Search Matsumoto et al. (2003) stated that α-mangostin antiploriferatif have activity against leukemia HL60 by inducing apoptosis. In addition, α-mangostin has antibacterial activity against Mycobacterium tuberculosis and has antioxidant activity (Jung et al., 2006). The phenolic compounds of coumarin derivatives, xanthones, a prenylated benzophenone and biflavon. Of a series of compounds that have been found in species in these taxa, shows the properties of bioactivity are very interesting and varied, such as anti-HIV, antileukimia, anticancer, antitumor, anti-inflammatory, anti-hypertensive, hepatitis drugs and inflammatory bowel disease (Dharmaratne and Wanigasekera 1996, Huang, 2001; Peres and Nagem 1997) Ersam 2006.


There are some steps undertaken to obtain the active compounds are:

a. Preparation of plant materials
At this stage the plants are prepared sample that will be used. The samples were taken from the bark of the wild mangosteen (Garcinia sp).

b. Phase extraction
At this stage the dried sample, then diracang well after finely ground. Then maceration with alcohol and distilled water 1:3 solvent for 72 hours and repeat three times, filtered, evaporated results maceration.

c. Phase fractionation and purification
The result of the process of maceration executed fractionation with n-hexane. Formed by two layers, namely the n-hexane layer and lower layer. The top layer is translucent while the lower layer is added klorometana to the nodes of color. After all, the new transparent color coating rejected. The rest is added with ethyl acetate.

d. Phase chromatography
In this phase, chromatography, chromatography in each fraction of compounds to know compounds of natural ingredients contained in each fraction.
 

e.Elucidation structure of the isolated compounds

f. Check activity of compounds active against larvae of shrimp isolated

2. Explain how the idea of a compound of natural ingredients that have a high biological potency and prospective for the benefit of sentient beings can be synthesized in the laboratory

1. Supply of plant samples x containing compounds of natural ingredients that would be synthesized in the laboratory. samples may be leaves, stems, roots and flowers, and the sample can be dried in puree.

2. The extraction with an appropriate solvent with a compound of natural ingredients contained in the plant that will be synthesized.

3. Subsequently in the fractionation, with the aim of mermisahkan by nature - the nature of the compounds contained, for example, polar compounds and non-polar.

4. In doing chromatography separates the components of a mixture for the purpose perfectly.

5. Purification or purification, the method gets the compounds of the pure components natural ingredients free of chemical components which are not needed.

6. The pure compound was obtained by the structure can be determined by spectroscopy, such as IR, NMR, UV.

3. Explain the basic rules in choosing a solvent for the isolation and purification of a compound of natural ingredients. Set an example for 4 classes of compounds of natural products: terpenoids, alkaloids, flavonoids and steroids.

Some of the selection criteria for the isolation and purification of solvents:
1. Selectivity: choice of solvent can affect the purity of the extracts

2. Chemical and thermal stability: solvent chosen must be stable under the conditions of the extraction process and the downstream

3. Compatibility with the solute: solvent is selected that does not react with the solute

4. Viscosity: low diffusion coefficient of viscosity of the solvent which would increase the extraction rate is also increased

5. Solvent recovery: to improve the economic process, the solvent must direkoveri so that it can be reused. Solvent with low boiling point cheaper direkoveri and reused.

6. Non-combustible for safety reasons should be selected solvents are not flammable.

7. Non-toxic: no sailor toxic safer for the production and workers.

8. Cheap and easily available: the choice of solvent must be solvent cheap and easy to obtain.


example:
1. flavonoids with a semi-polar acetone solvent
2. alkaloid with a non-polar solvent ethanol
3. trepenoid with a solvent methanol semipolar
4. steroids with the solvent n-hexane polar

4. Explain the basic starting point for the determination of the structure of an organic compound. When the compounds of natural ingredients such as caffeine is tersebuat. Express their ideas matter - whatever the subject is necessary to determine the general structure.

To identify the structure of a compound of natural ingredients can use spektoskopis IR, ¹³C NMR, UV, ¹ H NMR.
For example, using ¹³C NMR

Carbon-13 NMR (¹³C NMR or sometimes simply referred to as carbon NMR) is the application of nuclear magnetic resonance (NMR) spectroscopy to carbon. It is analogous to proton NMR (1H NMR) and allows the identification of carbon atoms in an organic molecule just as proton NMR identifies hydrogen atoms. As such ¹³C NMR is an important tool in chemical structure elucidation in organic chemistry. ¹³C NMR detects only the 13C isotope of carbon, whose natural abundance is only 1.1%, because the main carbon isotope, 12C, is not detectable by NMR since it has zero net spin.

Implementation

¹³C NMR has a number of complications that are not encountered in proton NMR. ¹³C NMR is much less sensitive to carbon than ¹H NMR is to hydrogen since the major isotope of carbon, the ¹²C isotope, has a spin quantum number of zero and so is not magnetically active and therefore not detectable by NMR. Only the much less common ¹³C isotope, present naturally at 1.1% natural abundance, is magnetically active with a spin quantum number of 1/2 (like ¹H) and therefore detectable by NMR. Therefore, only the few ¹³C nuclei present resonate in the magnetic field, although this can be overcome by isotopic enrichment of e.g. protein samples. In addition, the gyromagnetic ratio (6.728284 10⁷ rad T⁻¹ s⁻¹) is only 1/4 that of ¹H, further reducing the sensitivity. The overall receptivity of ¹³C is about 4 orders of magnitude lower than ¹H.^[1]

Another potential complication results from the presence of large one bond J-coupling constants between carbon and hydrogen (typically from 100 to 250 Hz). In order to suppress these couplings, which would otherwise complicate the spectra and further reduce sensitivity, carbon NMR spectra are proton decoupled to remove the signal splitting. Couplings between carbons can be ignored due to the low natural abundance of ¹³C. Hence in contrast to typical proton NMR spectra which show multiplets for each proton position, carbon NMR spectra show a single peak for each chemically non-equivalent carbon atom.

In further contrast to ¹H NMR, the intensities of the signals are not normally proportional to the number of equivalent ¹³C atoms and are instead strongly dependent on the number of surrounding spins (typically ¹H). Spectra can be made more quantitative if necessary by allowing sufficient time for the nuclei to relax between repeat scans.

High field magnets with internal bores capable of accepting larger sample tubes (typically 10 mm in diameter for ¹³C NMR versus 5 mm for ¹H NMR), the use of relaxation reagents,^[2] for example Cr(acac)₃ (chromium (III) acetylacetonate, CAS number 21679-31-2), and appropriate pulse sequences have reduced the time needed to acquire quantitative spectra and have made quantitative carbon-13 NMR a commonly used technique in many industrial labs. Applications range from quantification of drug purity to determination of the composition of high molecular weight synthetic polymers.

¹³C chemical shifts follow the same principles as those of ¹H, although the typical range of chemical shifts is much larger than for ¹H (by a factor of about 20). The chemical shift reference standard for ¹³C is the carbons in tetramethylsilane (TMS), whose chemical shift is considered to be 0.0 ppm.

Typical chemical shifts in ¹³C-NMR

Here the example of the determination of the structure of nicotine by 13C NMR