Geraniol

Geraniol is a, highly valuable aroma chemical and having extensive use in perfumery and flavour compounds. There are three sources to isolate this aroma chemical. Palmarosa oil Cymbopogon martini commonly known 'Rosha' or russa is the main source of geraniol (80-95%) and Jamrosa oil contains 80-89%. Another source of geraniol is Cymbopogon winterianus (Java citronella oil), which contains 40-45% including citronellol. This paper reports the processing of these essential oils to the recovery of geraniol content and find out the comparative study in respect of yield and cost economics.

Geraniol is a monoterpenoid C-10 (branched) alcohol found widely as a chief constituent in essential oils including ilang-ilang oil, palmarosa oil, geranium oil, orange flower oil, lemongrass oil, hops oil, and lavender oil. It is a clear to pale-yellow liquid; boiling point 230 C; insoluble in water; soluble in alcohol, ether and most common organic solvents. It is the major constituent of rose-like odor. It is used in perfumery and flavoring. Nerol is the cis-isomer of geraniol. Geranial and neral are the corresponding aldehydes. Citronellol is the dihydrogeraniol and citronellal is the corresponding aldehyde. Citral is the mixture of geranial (trans-citral, called citral A) and neral (cis--citral, called citral A). Citral is the major constituent of emongrass oil, verbena oil, lemon oil, nikkel oil, lime oil, ginger oil, and other plant essential oils. It is the main source of lemon odor. Neral has a less intense, but sweeter. Citral is also used as a flavor. Citral is used as a raw material in the synthesis ionone which is a perfumery and flavoring component itself and used in the production of retinol. Geraniol is a pheromone of certain species of bees, being secreted by the scent glands of worker bees to signal the location of nectar-bearing flowers and the entrances to their hives. Geraniol also find an application as an insect repellants or deterrants.

Isomeric with linalool is geraniol C₁₀H₁₈O which is distinguished from the former by its optical inactivity, higher boiling point and higher specific gravity. It is the "lemonol" of Barbier and Bouveault, the "rhodinol" of Erdmann and Huth and of Poleck. Both as such and as ester it is found rather frequently in volatile oils. It constitutes the bulk of palmarosa oil, of German and Turkish rose oils, and is found in appreciable quantities in the oils of geranium, citronella and lemongrass. It has further been found in the oils of gingergrass, Canada snakeroot, ylang-ylang, champaca flowers, nutmeg, sassafras leaves, laurel leaves, kuro-moji, tetranthera (?), cassie flowers (from Acacia Cavenia and A. Fames/ana), neroli, petitgrain, coriander, Mexican and Cayenne lignaloe, of Darwinia fascicularis (?), Eucalyptus Macarthuri, E. Staigeriana, Leptospermum Liversidgei, verbena, spike (?) and lavender. As acetate it occurs in the needle oil of Callitris glauca, the oils of palmarosa, lemongrass, sassafras leaves, kuro-moji, lemon, petitgrain, Eucalyptus Macarthuri, E. Staigeriana, Leptospermum Liversidgei, Darwinia fascicularis and lavender; as Isovalerianate in sassafras leaf oil; as /7-capronate in pal-marosa and lavender oils; and as tiglinate in geranium oil.

As a primary alcohol, geraniol forms a crystalline addition product with calcium chloride,1) which is insoluble in ether, ligroin, benzene and chloroform, and which is resolved into its components by water. By this extremely simple method, geraniol can be obtained chemically pure (see below). With magnesium chloride, calcium nitrate and magnesium nitrate, crystalline derivatives are likewise formed.

For the isolation of geraniol from mixtures with hydrocarbons and other substances a number of other methods have been suggested. All of them have this in common that they aim at the preparation of an acid phthalate of geraniol. This ester can be prepared either by the action of phthalic acid anhydride on the sodium compound of crude geraniol,3) or by heating geraniol with phthalic acid anhydride without solvent in the water bath4) or in benzene solution.5) The ester can be purified through the crystalline silver salt. The geraniol is regenerated by saponifying either the acid ester, or its sodium salt, the latter being prepared from the silver salt. These methods, however, do not possess any advantages over the calcium chloride method. Indeed, they are more complicated and yield no purer product.

Geraniol, or rather its acetate, results together with terpineol and nerol, when linalool is heated for a long time with acetic acid anhydride.1) The reverse reaction takes place when geraniol is heated with water to 200° in an autoclave. At higher temperatures hydrocarbons and their polymerization products are formed.2) When hydrogen chloride is allowed to act on a mixture of geraniol and toluene, linalyl chloride results which, with silver nitrate, yields linalool.3) Hence it can be explained how Tiemann3) could obtain linalool when treating geraniol with hydrogen chloride and saponifying the reaction product with alcoholic potassa.

In general, geraniol is not as readily acted upon by acids as is linalool. However, the action of acid reagents may cause ring formation, cyclogeraniol being produced. When boiled with acetic acid anhydride it is quantitatively converted into the acetate, but not isomerized. When shaken with dilute sulphuric acid it is converted into terpinhydrate, as is linalool, but not as readily.4) Concentrated formic acid, like potassium acid sulphate or phosphoric acid, acts as dehydrating agent. Whereas the action of potassium acid sulphate is said to produce an open chain hydrocarbon,5) the other reagents produce terpenes. Thus formic acid produces a-terpineol, dipentene and terpinene.6). Upon reduction of geraniol with platinum sponge and hydrogen, Willstatter and Mayer7) obtained a mixture of 2,6-dimethyl octane and 2,6-di-methyloctanol-8. The same products were obtained by Enklaar8) with Sabatier's method. In addition, however, there resulted a cyclic alcohol C₁₀H₂₀O not further characterized.

MID SEMESTER EXAM of Natural Product Chemistry

Name                  : Ekki Widya Lestary

Student Number  : RSA1C110001

1.   In order to find new biological active compound  in plants, it is necessary to screen extracts for the presence of novel compounds and to investigate their biological activities. Chemical screening of crude plant extracts therefore constitutes an efficient complementary approach, allowing localization and targeted isolation of new types of constituents with potential activities. Once novel compounds are suspected, they are generally isolated in order to have material available for further biological testing.The path which leads from the intact plant to its pure constituents is long. It involves work which might last anything from weeks to years. Once a target compound has been decided upon, the pure active substance has to be separated from the hundreds of other components of the plant extract matrix.

For example : A naphthylisoquinoline dimeric alkaloid, michellamine B (5), has recently been isolated from the leaves of the liana A. korupensis, found in the Korup National Park in Cameroun. Bioactivity guided isolation of this compound was performed after it was discovered that an extract of the plant was active in the National Cancer Institute (NCI, USA) anti-HIV screening programme. Michellamine B shows in vitro activity against a broad range of strains of both HIV-1 and HIV-2, including several resistant strains of HIV-1 [16]. Preclinical development is underway, despite the narrow therapeutic index of the drug. And in order to assure sufficient quantities of material, attempts are being made at the synthesis and semi-synthesis of the compound.

michellamine

 To find the biological active compound in A. korupensis and the other plants includes the following         steps:

•   correct identification of the plant with the aid of specialists (botanists)
• collection and drying of the vegetable material; precautions need to be taken to avoid the formation of artefacts
•  preparation of extracts using different solvents; analysis of these extracts by different chromatographic methods 
• fractionation of the extracts by different preparative chromatographic techniques (column chromatography, centrifugal partition chromatography etc 
• purity control of the isolated products.
• structure elucidation of the constituents by combinations of diverse spectroscopic techniques (UV/VIS, IR spectrophotometry, carbon and proton nuclear magnetic resonance, mass spectrometry, X-ray diffraction) and chemical techniques (hydrolyses, formation of derivatives, degradation reactions etc.) 
• synthesis or semi-synthesis of the natural product 
• modification of structure with a view to establishing structure-activity relationships 
• pharmacological and toxicological testing.

2. Many elements in nature with various modifications to the nature and usefulness to human life.  Reliable     method of approach to designing a synthesis known as "retrosynthesis", in which we start from the target molecule and then we try to cut it into small parts that are easily recognized as starting materials are either commercially available or available in nature in abundance. Each  rewind step is recognized as a process of transformation which is then reversed later became a real step synthesis. There are two approaches to this retrosynthesis, the convergent and linear. In the convergent approach is possible there could be more than one alternative starting material, while the linear approach there is only one starting material. Consider the following scheme for more details.

The above synthesis method is very useful for the synthesis of compounds that are more complex, especially the results of screening new compounds of natural materials, such as curacin A obtained from sea cyanobactery showed antitumor activity. Synthesis of complex compounds requires good planning and deep knowledge of a wide variety of reactions. This is a challenge with the scientists to continue to develop intellectually. Things to keep in mind that not all natural materials can be synthesized in total. To compound that is very complex, are too long and too expensive to be synthesized.

 

3.  When deciding upon the best solvent for isolation and purification of a natural product compound, consideration must be given to the polarity of the compound of interest and the interaction of the compound to binding proteins.

Usually secondary metabolites have different degrees of polarity so the solvent(s) should be chosen for the extraction should be considered carefully to ensure dissolution of secondary metabolites under study.

Solvent should have following properties:

1. Easy to remove

2. Inert

3. Nontoxic

4. Not easily inflammable

5. No interaction or less chemical interaction

Solvent employed are:

1. Polar: Water

2. Non-polar: Petroleum ether, chloroform, Diethyl ether

3. Semipolar: Ethanol, Acetone

4. Azetropic mixtures

Several sample preparation, pre-purification and clean-up steps are used prior to isolation and/or analysis of natural products. Initial extraction with low-polarity solvents yields the more lipophilic components, while ethanolic solvents obtain a larger spectrum of non-polar and polar material. If a more polar solvent is used for the first extraction step subsequent solvent partition allows a finer division into different polarity fractions.

For examples :

Terpenoids are chemically lipid-soluble compounds and they can be extracted with petroleum ether generally. Sesquiterpene lactones, diterpenes, sterols and less polar triterpenoids extraction can be also performed by using benzene, ether and chloroform. Ethyl acetate and acetone extracts contain oxygenated diterpenoids, sterols and triterpenoids. Ethanol, methanol and water led to the extraction of highly oxygenated namely polar triterpenes as well as triterpenoid and sterol glycosides. Total extraction of the material carried out by any polar solvents such as acetone, aqueous methanol (%80) and aqueous ethanol and then re-extraction with hexane, chloroform and ethyl acetate is also leads to successive extraction of terpenoids and sterols.

Extraction of the flavonoids can be performed with solvents that are chosen according to their polarity. Less polar aglycones such as isoflavones, flavanones, dihydroflavonols, higly methylated flavones and flavonols can be extracted with CH₂Cl₂, CHCl₃, ether, EtOAC. However the more polar aglycones including hydroxylated flavones, flavonols, chalcones and flavonoid glycosides are generally extracted by polar solvents such as acetone, alcohol, water and their combinations.

In order to isolate the medicinally important alkaloids (reserpine and ajmaline) from the root of Rauvolfia serpentina, it usually has to be soaked with dilute ammonia before being extracted with an organic solvent (e.g. ether). The extracted alkaloids were then partitioned with an acid solution, converted back into the free bases, and taken into another water-insoluble organic solvent (e.g. benzene) to give, after evaporation, the crude alkaloid extract.

Procedures for isolation of steroids differ according to the chemical nature of the steroids and the scale and purpose of the isolation. Steroids are isolated from natural sources by extraction with organic solvents, in which they usually dissolve more readily than in the aqueous fluids of tissues. The source material often is treated initially with an alcoholic solvent, which dehydrates it, denatures (renders insoluble) proteins associated with the steroids, and dissolves many steroids. Saponification either of whole tissues or of substances extracted from them by alcohol splits the molecules of sterol esters, triglycerides.

4. Structural elucidation is the determination of the chemical structure of chemically uncharacterised substances such as natural products. It is preceded by the extraction and isolation steps. It makes use of various chromatography techniques (MPLC, HPLC) as well as spectrometric techniques (MS, 1D and 2D NMR UV/VIS, IR spectrophotometry, carbon and proton nuclear magnetic resonance, mass spectrometry, X-ray diffraction) and chemical techniques (hydrolyses, formation of derivatives, degradation reactions etc.). MS spectrometers like ions traps can use the fragmentation techniques to further investigate the structure of the molecule.

It is a technique used notably in phytochemistry, for instance to characterise polyphenol oxidation products. Phytochemical evaluation gives basic foundation on the  structure elucidation  of  compounds present in the plant extracts.

The following chromatogram show the caffeine structural elucidation by using NMR