Chapter Notes: Hydrocarbons and derivatives
Hydrocarbons contain only carbon and hydrogen. By addition or modification of functional groups (for example, carboxyl, hydroxyl, carbonyl or phenolic groups) most other natural organic compounds can be derived from hydrocarbon precursors. Closely related biosynthetic families often coexist in a single natural product (for example, menthol and menthone in peppermint oil) but differ in their functional groups and thus in their chemical reactivity and biological properties. Common functional groups in natural products include carboxylic acids, alcohols, ketones, aldehydes and phenols; biochemical transformations also produce esters, lactones and many other derivatives. This chapter concentrates on hydrocarbons and simple derivatives-simple acids, alcohols and esters-and on related natural materials such as fixed oils, fats and waxes. Where medicinal plants are better discussed under their biogenetic groups they are treated there; here emphasis is on general chemical features and representative drugs in which simple acids, alcohols or esters are principal constituents.
Hydrocarbons
Hydrocarbons appear in nature most commonly as components of cuticular and epicuticular waxes, and as volatile terpenoid hydrocarbons in essential oils. Long-chain alkanes found on plant surfaces are generally odd-numbered (approx. C25-C35) and are derived biosynthetically by decarboxylation of the next higher even-numbered fatty acid. Terpenoid hydrocarbons are constructed from the isoprene unit (C5H8) and include monocyclic and bicyclic compounds such as limonene, pinene, phellandrene and cadinene, which contribute significantly to essential-oil composition. Polyunsaturated terpenoids give rise to materials such as rubber, gutta and the carotenes.
Monobasic (Monocarboxylic) Acids
Organic monobasic acids contain a single carboxyl group and are represented generally as RCOOH. The carboxyl group is ubiquitous in biochemistry: acids appear as metabolic intermediates, as esterified components of volatile oils, resins and lipids, and as free acids in some plant exudates. Amino acids and larger carboxyl-containing biomolecules are discussed elsewhere.
C1-C6 Monocarboxylic Acids
Lower monocarboxylic acids and their hydroxy- and keto-derivatives participate as biosynthetic intermediates in the formation of fatty acids, isoprenoids and some amino acids. In plants they are more commonly found in esterified form (volatile esters, resins, coumarins, alkaloids) than as free acids.
| Name | Formula / structure | Comments |
|---|---|---|
| Formic acid | HCOOH | Named from ants (Formica). Occurs as a decomposition product of vegetable materials; found free in stinging nettle hairs. |
| Acetic acid | CH3COOH | Central metabolite as acetyl-CoA; common in esterified forms in many natural products. |
| Propionic acid | CH3CH2COOH | Occurs in traces in fats and as a metabolic intermediate. |
| n-Butyric acid | CH3CH2CH2COOH | Occurs in many fats in trace amounts. |
| iso-Butyric acid | (CH3)2CHCOOH | Found free in carob beans and as esters in some oils and resins. |
| n-Valeric acid | CH3(CH2)3COOH | Not common; component of some convolvulaceous resins. |
| iso-Valeric acid | (CH3)2CHCH2COOH | Free and esterified in Valeriana spp.; related to tropane alkaloid esters. |
| 2-Methylbutyric acid | CH3CH2CH(CH3)COOH | Found in some tropane and veratrum alkaloids and certain glycosides. |
| Caproic (hexanoic) acid | CH3(CH2)4COOH | Occurs in traces in many fats. |
| Crotonic acid (trans-butenoic) | CH3CH=CHCOOH (trans) | Constituent of croton oil. |
| Tiglic acid | CH3CH=CHCH(COOH)CH3 (structure as 2-methyl-2-butenoic) | Occurs in Croton tiglium; ester-acid in many tropane alkaloids. |
| Angelic acid | CH3CH=CHCH(COOH)H (isomeric with tiglic) | Found in Angelica rhizomes and as esterifying acids in some alkaloids. |
| Senecioic acid | CH3CH=CHCH(COOH)CH3 (isomeric) | Originally isolated from Senecio; occurs as ester in some alkaloids and coumarins. |
Fatty Acids
Plant fixed oils (acyl lipids) are predominantly triacylglycerols in which fatty acids are esterified to glycerol. Natural fatty acids commonly range from C10 to C20 (longer chains occur) and may be saturated (e.g., palmitic C16:0, stearic C18:0) or unsaturated (e.g., oleic C18:1). Most double bonds in plant fatty acids are cis. Some fatty acids are cyclic (e.g., hydnocarpic) or carry functional groups such as hydroxyl (ricinoleic acid in castor oil). Polyunsaturated fatty acids (PUFAs) are important nutritionally and pharmacologically (e.g., linoleic, α-linolenic, γ-linolenic, arachidonic acids).
Fatty acids are often referred to by their shorthand notation X:Y(n-Z), where X is the carbon count, Y is the number of double bonds and Z indicates the position (counted from the methyl end, ω or n end) of the first double bond. Example: α-linolenic acid = 18:3(n-3), equivalent chemically to all-cis Δ9,12,15-octadecatrienoic acid.
Biosynthesis of Fatty Acids and Unsaturation
Saturated fatty acids are synthesised by successive addition of two-carbon units derived from malonyl units onto an acyl carrier protein (ACP). Introduction of double bonds (desaturation) in aerobic organisms is carried out by specific desaturase enzymes using molecular oxygen and cofactors (NADH or NADPH). The position of the introduced double bond is enzyme-dependent so that, for example, a Δ9 desaturase converts stearoyl-S-ACP (C18:0) to oleoyl-S-ACP (C18:1 Δ9, cis). Further desaturation and elongation steps produce linoleic and linolenic acids and, in some pathways, the conversion of double bonds to triple bonds (acetylenic fatty acids) may occur via analogous enzyme systems.
Aromatic Carboxylic Acids
Common aromatic acids in plants include benzoic acid and cinnamic acid (phenylpropanoid side chain). Derivatives bearing additional phenolic or methoxy groups are frequent: salicylic acid (o-hydroxybenzoic), protocatechuic acid (3,4-dihydroxybenzoic), veratric acid (3,4-dimethoxybenzoic), gallic acid (3,4,5-trihydroxybenzoic). From cinnamic acid are derived p-coumaric, caffeic and ferulic acids. Quinic and shikimic acids are cyclic hydroxy acids that function as intermediates in the biosynthesis of aromatic compounds; shikimic acid is used industrially as a starting material for the semi-synthesis of antiviral agents.
Dibasic and Tribasic Acids
Dicarboxylic acids such as oxalic acid (COOH-COOH), malonic acid (CH2(COOH)2), succinic acid ((CH2)2(COOH)2), fumaric acid (COOH-CH=CH-COOH) and malic and tartaric acids (hydroxylated dicarboxylic acids) occur widely in fruits and other plant parts. Citric, isocitric and aconitic acids are tribasic acids central to metabolism (Krebs cycle). Tartaric acid is abundant in many fruits (grapes) and in tamarinds; malic acid is prominent in apples.
Alcohols
Alcohols contain hydroxyl groups (-OH) and occur free or esterified in plants. They are classified by the number of hydroxyl groups (mono-, di-, tri- and polyhydric) and by the position of the -OH (primary, secondary, tertiary). Examples range from simple aliphatic alcohols (ethanol, cetyl alcohol C16H33OH) and terpene alcohols (geraniol, linalool, menthol) to aromatic alcohols (benzyl alcohol, cinnamyl alcohol). Polyhydric alcohols include glycerol (propan-1,2,3-triol), essential for glycerides in fats, and sugar alcohols such as sorbitol and mannitol.
Monohydric Aliphatic and Terpene Alcohols
Lower aliphatic alcohols are often present as esters contributing to aroma (methyl salicylate). Long-chain monohydric alcohols (cetyl, ceryl, myricyl) are components of waxes. Terpene alcohols derive from isoprenoid biosynthesis and are widespread in essential oils: for example, geraniol and nerol (acyclic), terpineol (monocyclic), borneol and menthol (bicyclic).
Monohydric Aromatic Alcohols
Benzyl alcohol (C6H5CH2OH) and cinnamyl alcohol (C6H5CH=CHCH2OH) occur in balsams and other resins, free or as esters. Coniferyl alcohol is a phenylpropanoid alcohol that is a major unit in lignin biosynthesis.
Esters
Esters form by condensation of an alcohol and an acid (R'OH + RCOOH → RCOOR' + H2O). In plants esterification is enzyme controlled (esterase reversibility). Acetylation (acetate esters) of alcohols is common in volatile metabolites (e.g., linalyl acetate in lavender). Many alkaloids (atropine, reserpine) are ester derivatives. Lipids are esters of fatty acids with glycerol (triacylglycerols) or with more complex backbones (phospholipids, glycolipids).
Lipids: Simple and Complex
Simple lipids (fixed oils, fats, waxes) are largely triacylglycerols. Complex lipids (phosphatides, lecithins) contain phosphorus and nitrogen and are key components of cellular membranes. The three fatty-acyl chains and the polar head group determine physical properties. The stereospecific numbering convention (sn-) is used for glycerides.
Fats and Fixed Oils
Fixed oils are predominantly seed or fruit storage lipids and are major agricultural commodities. Their physical state (liquid oil vs solid fat) depends on fatty acid composition: triglycerides rich in saturated fatty acids tend to be solid, while those rich in unsaturated acids are liquid. Commercial extraction methods include cold or hot expression and solvent extraction; refining removes impurities, free acids and pigments and may include deacidification, bleaching and deodorising. For pharmaceutical use special purity criteria apply (low acid value, low peroxide value, absence of solvents, specified sterol composition).
Important analytical values:
- Acid value: mg KOH required to neutralise free acids in 1 g of oil. High values indicate rancidity.
- Saponification value: mg KOH required to hydrolyse and neutralise esters in 1 g of oil; a measure of average molecular weight of fatty acids.
- Iodine value: grams of iodine absorbed by 100 g of substance; measures degree of unsaturation.
- Peroxide value and anisidine value: indicators of primary and secondary oxidative degradation.
- Unsaponifiable matter: sterols and hydrocarbons remaining after saponification.
| Oil | Melting point (°C) | Saponification value | Iodine value | Approx. fatty composition (saturated / unsaturated %) |
|---|---|---|---|---|
| Almond oil | -18 | 183-208 | 99-103 | 12% sat. / 88% unsat. (mainly oleic, linoleic) |
| Castor oil | -18 | 175-183 | 84 | High ricinoleic (≈88-92%) |
| Olive oil (typical) | varies (soft solidifies near 2°C) | 185-196 | 79-88 | High oleic (≈75-93% unsat. in some types) |
| Coconut oil | 23-26 | 250-264 | 7-11 | ≈92% saturated (medium chain acids) |
| Palm oil | ≈30 | ≈248 | 13.5 | ≈50% saturated / 50% unsaturated |
| Theobroma (cocoa butter) | 31-34 | 193-195 | 33-42 | ≈59% saturated / 41% unsaturated |
| Lard | 34-41 | 192-198 | 50-66 | ≈60% saturated / 40% unsaturated |
Biosynthesis and Hydrolysis
Acylglycerols are assembled enzymically from fatty acyl-CoA or fatty acyl-ACP and glycerophosphate derivatives. Hydrolysis (saponification) of triacylglycerols yields glycerol and the potassium or sodium salts of fatty acids (soaps). Selective hydrolysis and fractionation provide fractions (stearin, olein) with different melting behaviour.
Quantitative and Quality Tests for Oils
Standards include acid value, saponification value, iodine value, peroxide and anisidine values, unsaponifiable matter and specific sterol limits (for example brassicasterol limits in some oils). Gas chromatography of fatty-acid methyl esters produced by hydrolysis and methylation is an official method for determining the detailed fatty-acid composition and for detecting adulteration.
Waxes
Natural waxes are complex mixtures dominated by esters of long-chain monohydric alcohols with long-chain fatty acids, together with free alcohols, free acids, hydrocarbons and sterols. Unlike triacylglycerol fats, waxes are saponified only by alcoholic alkali (a distinguishing test for adulteration). Common natural waxes include beeswax, spermaceti, carnauba wax and wool fat (lanolin).
| Wax | Acid value | Saponification value | Iodine value | Important constituents |
|---|---|---|---|---|
| Spermaceti | below 1 | 120-136 | below 5 | Cetyl palmitate and related esters |
| Beeswax (yellow / white) | 18-24 | 70-80 (ester value) | 8-11 | Mainly myricyl palmitate (myricin); free cerotic acid; steryl esters |
| Carnauba wax | 4-7 | 79-95 | 10-14 | Myricyl cerotate and related esters |
| Wool-fat (lanolin) | below 1 | 90-106 | 18-32 | Steryl esters, sterols, free alcohols and hydrocarbons |
Representative Drugs Containing Acids, Alcohols and Esters
The following are illustrative pharmacognostic and chemical summaries of selected natural drugs in which simple acids, alcohols or esters are important constituents.
Roselle (Hibiscus sabdariffa)
Source: dried calyces and epicalyces. The material is crimson to violet and, microscopically, contains mucilage cells, calcium oxalate crystals and glandular trichomes. Major constituents include free organic acids (citric, tartaric, malic, and the lactone hydroxycitric acid) and anthocyanin pigments (glycosides of delphinidin and cyanidin). The pharmacopoeial requirement is a minimum acid content expressed as citric acid (example: BP/EP requires ≥13.5% expressed as citric acid) and specified absorbance values for anthocyanins at 520 nm. Traditional uses include use as a cooling astringent, mild diuretic and as a colourant and flavouring; antioxidant and hypocholesterolaemic activities have been investigated.
Tamarind Pulp (Tamarindus indica)
The pulp is a sticky, acid-sweet preserved product used as a mild laxative and dietary ingredient. It typically contains ≈10% free organic acids (tartaric, citric and malic), salts (potassium hydrogen tartrate), sugars and polysaccharides. Seeds contain fixed oil (glycerides) and high polysaccharide content; leaves contain C-glycosyl flavones (vitexin, isovitexin, orientin).
Manna (Fraxinus ornus exudate)
A sugary exudate containing ≈55% mannitol and other oligosaccharides (mannotriose, mannotetrose). It has a mild laxative (osmotic) action.
Sumatra and Siam Benzoin (Styrax spp.)
Benzoin is a balsamic resin rich in esters and free aromatic acids (benzoic and cinnamic acids). Sumatra benzoin typically contains significant cinnamic and benzoic acids and esters such as benzyl cinnamate and benzyl benzoate. Siam benzoin is richer in benzoic derivatives (for Siam benzoin the combined acid fraction has a higher benzoic ester content). Both are used in perfumery, as components of friar's balsam and as antiseptic expectorants. Pharmacopoeial assays quantify total balsamic acids and use chromatographic tests for identity and to detect adulteration.
Peru Balsam and Tolu Balsam (Myroxylon spp.)
Resinous balsams containing esters of cinnamic and benzoic acids (e.g., benzyl cinnamate, benzyl benzoate) and resinous triterpenoid fractions. They have historically been used as expectorants, antiseptics and flavouring agents. Their collection involves tapping of the trunk; the material is rich in esters and free aromatic acids and must meet pharmacopoeial standards for ester content.
Storax (Liquidambar orientalis; Levant storax)
Storax is a balsam rich in cinnamic acid esters and volatiles including styrene (phenyl-ethylene), vanillin and cinnamic esters. Steam distillation yields an aromatic volatile fraction. Storax is used in formulations such as inhalations and as a component of traditional balsams.
Ash Leaf (Fraxinus spp.)
Leaves contain hydroxycinnamic derivatives (chlorogenic acid and related compounds), the coumarin glycoside fraxin, tannins and mannitol. Ash leaf preparations are used traditionally as mild diuretics and laxatives. Pharmacopoeial assays commonly measure hydroxycinnamic acid derivatives (expressed as chlorogenic acid).
Artichoke Leaf (Cynara scolymus)
Leaves are rich in phenolic acids (chlorogenic acid, cynarin), flavonoids (luteolin glycosides) and bitter sesquiterpene lactones (cynaropicrin). Standardised extracts are used for dyspepsia and hepatoprotective indications.
Nettle Leaf (Urtica dioica, U. urens)
Leaves contain chlorogenic and caffeoylmalic acids, flavonoids (quercetin glycosides), scopoletin and minerals (high ash due to silicic acid and salts). Stinging hairs contain 5-hydroxytryptamine (serotonin). Pharmacopoeial assays measure combined caffeoylmalic and chlorogenic acid content and use TLC for identity.
Echinacea spp.
Roots and aerial parts of Echinacea species contain caffeic acid derivatives (echinacoside, cichoric acid), high-molecular-weight polysaccharides and alkylamides. Standardised extracts (assayed for echinacoside or related markers) are used for immunostimulant claims and for prevention/treatment of common colds; clinical evidence is mixed but meta-analyses suggest some reduction in incidence and duration of colds.
Pygeum Bark (Prunus africana)
Bark contains aliphatic alcohol esters, phytosterols, pentacyclic triterpenoid acids and a lipid fraction; extracts are used in benign prostatic hyperplasia symptom relief. Pharmacopoeial tests include extractive value and TLC markers (β-sitosterol, ursolic acid).
Saw Palmetto Fruit (Serenoa repens)
Fruit contains free fatty acids (oleic, lauric, myristic, palmitic) in the mesocarp and triacylglycerols in the seed. Sterols (β-sitosterol), flavonoids and polysaccharides are also present. Hexane, CO2 supercritical and ethanolic extracts have been studied for inhibition of 5α-reductase and for symptomatic treatment of benign prostatic hyperplasia.
Hydnocarpus / Chaulmoogra Oils
Seeds yield cyclopentenyl fatty acids (hydnocarpic, chaulmoogric acids) with historical antibacterial activity against Mycobacterium species; ethyl esters or salts of these acids were used in the past for leprosy treatment.
Pharmaceutical Fixed Oils and Fats - Selected Monographs
The following summaries give the botanical source, key constituents and principal pharmaceutical uses of several pharmaceutically important oils and fats. Pharmacopoeial specifications include compositional limits (fatty-acid profiles via GC), values for acid, peroxide and iodine values, and sterol composition.
Almond Oil (Prunus dulcis)
Obtained from sweet and/or bitter almonds by expression. Contains ≈40-55% oil; refined oil is high in oleic and linoleic acids (BP/EP typically specify oleic 62-86%, linoleic 20-30%, palmitic 4-9%). Used as an emollient and vehicle for injections; bitter almond volatile oil contains benzaldehyde and hydrocyanic acid (if seeds are bitter) and requires processing to remove hydrocyanic acid for medicinal use.
Arachis (Peanut) Oil
Expression or extraction of Arachis hypogaea seeds gives an oil rich in oleic and linoleic acids. Commercial processing can produce an edible oil and hydrogenated fractions; the press cake is a valuable animal feed. Arachis oil is a common adulterant of other oils.
Coconut Oil and Fractionated (Medium-Chain Triglycerides)
Coconut oil is solid at room temperature (m.p. ≈24°C) and rich in medium-chain saturated acids (caprylic, capric, lauric). Fractionated coconut oil and medium-chain triglycerides (MCT) maintain low viscosity near 0°C and are useful as non-aqueous vehicles and in nutritional support for patients with fat-absorption problems.
Cottonseed Oil
Expressed from Gossypium seeds; semi-drying oil with relatively high iodine value. Quality control includes specific refining procedures and tests for winterization and absence of contaminants.
Linseed (Flaxseed) Oil
Drying oil with high iodine value (≥175) due to α-linolenic and linoleic acids. Linseed oil oxidises to form drying films and is used industrially in paints and varnishes. Medicinally, crushed linseed and whole seeds are used as demulcents and poultices.
Olive Oil (Olea europaea)
Virgin and refined olive oils are important edible and pharmaceutical oils. Olive oil is rich in oleic acid; olive oils are characterised by GC fatty-acid profiles and sterol composition. High-grade oils are used as vehicles for parenteral preparations when suitably refined and low in peroxides and free acids.
Palm Oil and Palm Kernel Oil
Palm oil (mesocarp) is rich in palmitic and oleic acids and is a major global oil crop; palm kernel oil (from seed kernel) is lauric-acid rich and similar to coconut oil. Fractionated and hydrogenated derivatives are used in pharmaceutical formulations such as suppository bases.
Rapeseed, Safflower, Sesame, Soyabean and Sunflower Oils
Each oil has characteristic fatty-acid composition (e.g., rapeseed/rapeseed oil: oleic, linoleic; safflower: high linoleic or high oleic types; sesame: oleic/linoleic and characteristic phenolic markers; soya: linoleic/oleic proportions; sunflower: linoleic or high-oleic cultivars). Pharmacopoeial monographs set limits for undesired acids (erucic, eicosenoic) and sterol content.
Theobroma Oil (Cocoa Butter)
Cocoa butter consists of mixed triglycerides of stearic, palmitic, arachidic and oleic acids; melting point ≈31-34°C makes it suitable for suppositories and other dosage forms. It is expensive and subject to adulteration; GC characterisation and melting behaviour are used in quality control.
Wheat-Germ Oils
Wheat-germ oil is rich in linoleic acid and contains useful vitamin components; refined grades have strict limits for acid and peroxide values for pharmaceutical use.
Castor Oil (Ricinus communis)
Castor oil is rich in ricinoleic acid (≈88-92%) and is a potent laxative; medicinal (virgin) castor oil is obtained by cold expression and refined by steaming/filtration. Castor seeds contain highly toxic glycoproteins (ricins) and must not be used as a substitute for the oil. Castor oil derivatives (hydrogenated castor oil, polyoxyl castor oil, hydrogenated polyoxyl castor oil) are official and used as excipients (e.g., non-ionic surfactants for parenteral formulations).
Evening Primrose, Borage and Other GLA-Containing Oils
Evening primrose (Oenothera spp.) and borage (Borago officinalis) seed oils are significant sources of γ-linolenic acid (GLA, 18:3(n-6)), a precursor of prostaglandins. These oils are used as dietary supplements and have been investigated for atopic eczema, premenstrual syndrome and other indications. Clinical results are variable and depend on formulation and patient biochemistry.
Saw Palmetto, Hydnocarpus and Other Specialty Oils
Saw palmetto fruit extracts (lipid extracts) are used in benign prostatic hyperplasia; hydnocarpus oils contain cyclopentenyl fatty acids with historical use against leprosy; other speciality oils are used in niche medicinal applications or as sources of chemical markers.
Animal Fats and Lanolin
Wool fat (lanolin) is a complex mixture of sterol esters, free alcohols and fatty esters obtained from sheep wool and is widely used as an emollient base. Lard and suet are animal depot fats used historically as ointment bases; their composition (saturated vs unsatuated glycerides) determines melting point and stability.
Waxes: Beeswax and Carnauba
Beeswax: a natural wax largely composed of myricyl palmitate and related esters with free cerotic acid and steryl esters. White beeswax is bleached. Uses include ointment bases, plasters and polishes.
Carnauba wax: obtained from Copernicia cerifera leaves; principal ester myricyl cerotate; used in tablet coatings and cosmetic preparations.
Practical Notes and Quality Control
Quality control of natural acids, alcohols, esters, oils and waxes relies on a combination of physical constants (melting point, refractive index, specific gravity), chemical assays (acid, saponification, iodine, peroxide and anisidine values), chromatographic fingerprints (TLC, GC of fatty-acid methyl esters, HPLC for phenolic markers) and selected pharmacopoeial identity and purity tests. Adulteration detection often employs GC profiling of fatty acids, sterol composition analysis, specific colour tests (for example for sesame oil phenolics), and chromatographic assays for marker compounds.
Summary
Hydrocarbons and their simple derivatives-carboxylic acids, alcohols and esters-form a foundational chemical vocabulary of natural products chemistry. Fatty acids and their esters dominate plant and animal storage lipids; aromatic acids and phenolic derivatives underpin many plant resins and balsams; alcohols and their esters contribute to essential oils, resins and waxes. Understanding their structures, biosynthetic origins and analytical characteristics is essential for the identification, quality control and pharmaceutical use of natural drugs and excipients.
