**2.2 Coumarins**

Coumarin (benzopyrones) compound is one of the members of benzopyrone components. In the coumarin structure, there is a benzene ring which is tied with pyrone ring [23] as can be seen in **Figure 4**. They can be divided into four main types: simple coumarins, pyranocoumarins, furanocoumarins, and

**Figure 2.** *Possible position oxygenation xanthone compound.*

**31**

**Figure 4.**

**Figure 5.**

*Molecular structure of coumarins.*

*Molecular structure of isoprene.*

Calophyllum inophyllum*: Beneficial Phytochemicals, Their Uses, and Identification*

pyrone-substituted coumarins. All the reactions of coumarins focus on activation of C3,4—the double bond of the α,β-unsaturated lactone—and form a heterocyclic

Coumarins are commonly used in the agrochemical, perfume, and medical industries. They have high antitumor and antibacterial activities. Antitumor activity of 7-hydroxycoumarins against several tumor cell lines has been identified. Coumarins and their derivatives have activity as barrier against cellular proliferation in various carcinoma cell lines [25]. Besides that, they also have anticoagulant, antioxidant, antimicrobial, antiviral, anti-inflammatory, antimalarial, and analge-

The biosynthesis of coumarin compounds is derived from the shikimic acid pathway or still in line with the phenyl group propanoid. The skeleton benzopyran-2-on of coumarin is originating from the acid-cinnamic acid via ortho-hydrolysis. Ortho-coumaric acid produced after undergoing *cis-trans* isomerization undergoes condensation [27]. Characteristic of these compounds is their lactone group formed from the acid on the tip of propane with a hydroxy group on the phenyl group. Oxygenation coumarin compounds in the aromatic ring are also typical and are intermittent. The structure of the coumarin derivatives can be divided into four categories based on the group bound to the C4 : 4-metilcoumarin, 4-fenilcoumarin,

Benzodipyranones are derivative of chromone. These compounds have a skeleton similar to stilbene with two additional prenyl groups. Some benzodipyranone compounds have been isolated from the *C. inophyllum* leaves, such as (2S, 3R) and (2R, 3R)-2,3-dihydro-5-hydroxy-2,3,8,8-tetramethyl-6-(1 phenylethenyl)-4H, 8H-benzo [1,2-b: 3,4-b '] dipyran-4-one [14], inophynone,

Terpenes are naturally derived component in the biosynthesis of isoprene C5 with molecular formula C5H8 (CH2〓C (CH3)-CH〓CH2) (**Figure 5**). They commonly expressed in the formula (C5H8)n with n states the amount of isoprene which are there, so the amount of carbon is a multiple of 5. They are classified in hemiterpenes, monoterpenes (consisting of 2 units of C5 or 10 carbon atoms), sesquiterpenes (consisting of 3 units of C5 or 15 carbon atoms), diterpenes (consisting of

*DOI: http://dx.doi.org/10.5772/intechopen.86991*

system [24].

sic activities [26].

and 4-(n-propyl)coumarin.

and isoinophynone [20, 28].

**2.4 Terpenes and terpenoids**

**2.3 Benzodipyranones**

**Figure 3.** *Molecular structure of xanthones.*

Calophyllum inophyllum*: Beneficial Phytochemicals, Their Uses, and Identification DOI: http://dx.doi.org/10.5772/intechopen.86991*

pyrone-substituted coumarins. All the reactions of coumarins focus on activation of C3,4—the double bond of the α,β-unsaturated lactone—and form a heterocyclic system [24].

Coumarins are commonly used in the agrochemical, perfume, and medical industries. They have high antitumor and antibacterial activities. Antitumor activity of 7-hydroxycoumarins against several tumor cell lines has been identified. Coumarins and their derivatives have activity as barrier against cellular proliferation in various carcinoma cell lines [25]. Besides that, they also have anticoagulant, antioxidant, antimicrobial, antiviral, anti-inflammatory, antimalarial, and analgesic activities [26].

The biosynthesis of coumarin compounds is derived from the shikimic acid pathway or still in line with the phenyl group propanoid. The skeleton benzopyran-2-on of coumarin is originating from the acid-cinnamic acid via ortho-hydrolysis. Ortho-coumaric acid produced after undergoing *cis-trans* isomerization undergoes condensation [27]. Characteristic of these compounds is their lactone group formed from the acid on the tip of propane with a hydroxy group on the phenyl group. Oxygenation coumarin compounds in the aromatic ring are also typical and are intermittent. The structure of the coumarin derivatives can be divided into four categories based on the group bound to the C4 : 4-metilcoumarin, 4-fenilcoumarin, and 4-(n-propyl)coumarin.

### **2.3 Benzodipyranones**

*Phytochemicals in Human Health*

**2.2 Coumarins**

possible oxygenation position is shown in **Figure 2**.

hydroxy-2-methoxyxanthone, and xanthones [21, 22].

(VRE) and methicillin-resistant *Staphylococcus aureus* (MRSA) [18].

Xanthones compound that was isolated from *C. inophyllum* plants, there are prenylated and some are not prenylated. Most xanthone compounds isolated from these plants showed a characteristic, one of which is a hydroxy group at C1. The

Xanthones are known to have a variety of bioactive properties, notably the ability of antioxidants as can be seen in **Figure 3**. Mangosteen xanthones were isolated from *Garcinia mangostana* found against free radicals and prevent oxidative damage of low-density lipoprotein [16]. Moreover, isolated xanthones from mangosteen also can inhibit HL60 leukemia cells [17]. Also, α-mangosteen extracted from *G. mangostana* L. has antibacterial activity against vancomycin-resistant enterococci

Various xanthone compounds can be isolated from *C. inophyllum* leaves, such as caloxanthone A, caloxanthone B, caloxanthone C, maclura xanthones, inoxanthone, calophynic acid, 3,4-dihydroxy xanthones [4, 12, 19], brasilixanthone B, buchanaxanthone [20], inophyxanthone A, pancixanthone A, gerontoxanthone B, jacareubin, pyranojacaereubin, 2-hydroxy xanthone, 4-hydroxyxanthone, 1,3,5-tri-

Coumarin (benzopyrones) compound is one of the members of benzopyrone components. In the coumarin structure, there is a benzene ring which is tied with pyrone ring [23] as can be seen in **Figure 4**. They can be divided into four main types: simple coumarins, pyranocoumarins, furanocoumarins, and

**30**

**Figure 3.**

*Molecular structure of xanthones.*

**Figure 2.**

*Possible position oxygenation xanthone compound.*

Benzodipyranones are derivative of chromone. These compounds have a skeleton similar to stilbene with two additional prenyl groups. Some benzodipyranone compounds have been isolated from the *C. inophyllum* leaves, such as (2S, 3R) and (2R, 3R)-2,3-dihydro-5-hydroxy-2,3,8,8-tetramethyl-6-(1 phenylethenyl)-4H, 8H-benzo [1,2-b: 3,4-b '] dipyran-4-one [14], inophynone, and isoinophynone [20, 28].

## **2.4 Terpenes and terpenoids**

Terpenes are naturally derived component in the biosynthesis of isoprene C5 with molecular formula C5H8 (CH2〓C (CH3)-CH〓CH2) (**Figure 5**). They commonly expressed in the formula (C5H8)n with n states the amount of isoprene which are there, so the amount of carbon is a multiple of 5. They are classified in hemiterpenes, monoterpenes (consisting of 2 units of C5 or 10 carbon atoms), sesquiterpenes (consisting of 3 units of C5 or 15 carbon atoms), diterpenes (consisting of

**Figure 4.** *Molecular structure of coumarins.*

**Figure 5.** *Molecular structure of isoprene.*

#### *Phytochemicals in Human Health*

4 units of C5 or 20 carbon atoms), sesterterpenes, triterpenes (consisting of 6 units of C5 or 30 carbon atoms), tetraterpenes (consisting of 8 units of C5 or 40 carbon atoms), and polyterpenes.

Moreover, terpenoids are isoprenoid structural components which contain oxygen in its structure and can react with ketone, aldehyde, or alcohol. Chemically, they are generally soluble in fat and contained within the plant cell cytoplasm. Usually, they can be extracted with petroleum ether, ether, or chloroform and can be separated by chromatography on silica gel [29].

Terpenes are widely used as a medicine and flavor enhancers. They are commonly used in the rubber industry. They have a low molecular weight, such as essential oils that are used as natural food additives and fragrances in the perfume industry. They are also used in anticancer drug Taxol which is a diterpene. Taxol is used in the treatment of breast, ovarian, and lung cancer. One example is imberbic acid, a triterpenoid that has activity against *Mycobacterium fortuitum* and *S. aureus* [30].

Triterpenoids are a class of terpenoid compounds which consist of 30 carbon atoms or 6 units of isoprene. In plant tissue, they can be found in their native form but are also often found in the form glycoside. They are divided into cyclic and acyclic structures. The important acyclic triterpenoid is only the squalene that is considered only as an intermediate in the biosynthesis of steroids. The most widespread of triterpenoids are the pentacyclic triterpenoids. The frameworks most often found on a class of compound triterpenoids are ursam, lupan, oleanan, and friedelin [31].

Friedelin has the molecular formula C30H50O and a molecular weight of 426,7174 g/mol (**Figure 6**). Friedelin has a melting point of 259–260°C. The structure mass spectrometry of friedelin is 426 (M<sup>+</sup> ), 411, 302, 273, 246, 231, 218, 205, 191, 179, 163, 149, 137, 125, 123, 109, 95, 81, 69, and 55. The IR spectra of friedelin in KBr was obtained using vmax at 1720 cm−1. The form of friedelin is white crystallineamorphous solid. Friedelin has an anti-fungal activity and has antinociceptive effects in rodents [32]. Friedelin was developed on a TLC plate by using a solvent system of 10% ethyl acetate and 90% hexane. Friedelin gave a dark spot on a TLC when exposed under UV light and iodine vapor chamber. Friedelin gave an Rf value of 0.75 with the use of a relatively nonpolar solvent system [33].

Several studies have been conducted on the benefits of friedelin. Friedelin has hepatoprotective activity [34]. It has an activity against Bacillus Calmette-Guerin (BCG) that causes tuberculosis [35]. It and some types of friedelin compound are widely used for the treatment of cancer of the bladder [36], convulsion, inflammation [37], topical ulcers, rheumatic inflammation, fever, and dysentery [38]. It is also found to have antifeedant activity in some insects [39].

**33**

**Figure 7.**

*Molecular structure of cholesterol.*

clic ring [47].

Calophyllum inophyllum*: Beneficial Phytochemicals, Their Uses, and Identification*

Moreover, some compound triterpenoids have been isolated from the *C. inophyllum* leaves, such as 3β, 23-epoxy-friedelane-28-OIC acid, 3-oxofriedelin-28-OIC acid, epifriedelanol, oleanolic acid [40], 3,4-secofriedelane-3,28-dioic [41],

β-amyrin [20], friedelin, canophyllal, canophyllol, and canophyllic acid [4, 20, 41].

Sterols are steroids which have a hydroxy group at C3 position as can be seen in **Figure 7**. They are found in free form or in association with glucose to form glycosides (sterolin) or as fatty acid esters (FASE). They are the natural compound that is generally composed of 27 carbon atoms [31]. They are terpenoids in which their basic framework consists of the system perhydrophenanthrene cyclopentane ring. They are a class of secondary metabolic compounds which are widely used as a drug. Steroid hormones are generally derived from natural steroid compounds, especially in plants [42]. Some steroid compounds have been isolated from the *C. inophyllum* leaves such as campesterol [20]. Campesterol also has analgesic activity.

Flavonoids are the largest group of phenolic compounds found in nature, especially in tissues of higher crops. They are the product of secondary metabolites that occur from the cells and accumulate on the body crop as a toxic substance [43]. They are commonly known as flavonoids, which are water-soluble polyphenol component. They have a basic framework consisting of 15 carbon atoms where a chain of benzene (C6) is bound to a chain of propane (C3), thus forming a bond arrangement C6-C3-C6 which is particularly called phenylbenzopyran (**Figure 8**). This arrangement can produce three structures, namely, 1,3-diarilpropana (flavonoids), 1,2-diarilpropana (isoflavonoids), and 2,2-diarilpropana (neoflavonoid) [44]. Moreover, flavonoids are classified into various categories based on differences in molecular structure, such as chalcones, flavanols, catechins, flavonoes, isoflavone,

According to Markham [47], flavonoids are polar compounds because they have a hydroxyl group which does not bind to sugar, so the flavonoid is quite soluble in polar solvents such as ethanol, methanol, butanol, or water. Because of the presence of sugar bound, flavonoids become more soluble in water. Conversely, the less polar aglycone, such as isoflavones, flavanones, flavones, and flavonols, which is methox-

The largest group of flavonoids is flavones. Flavonoids have a 2-phenyl Croman order in which the ortho-position of the A ring and the carbon atom attached to the ring B of 1.3 diarilpropana is connected by bridging oxygen to form a new heterocy-

ylated tends to be more soluble in solvents, such as ether and chloroform.

*DOI: http://dx.doi.org/10.5772/intechopen.86991*

dihydroflavonol, and anthocyanidins [45, 46].

**2.5 Steroid**

**2.6 Flavonoids**

**Figure 6.** *Molecular structure of friedelin.*

Calophyllum inophyllum*: Beneficial Phytochemicals, Their Uses, and Identification DOI: http://dx.doi.org/10.5772/intechopen.86991*

Moreover, some compound triterpenoids have been isolated from the *C. inophyllum* leaves, such as 3β, 23-epoxy-friedelane-28-OIC acid, 3-oxofriedelin-28-OIC acid, epifriedelanol, oleanolic acid [40], 3,4-secofriedelane-3,28-dioic [41], β-amyrin [20], friedelin, canophyllal, canophyllol, and canophyllic acid [4, 20, 41].

#### **2.5 Steroid**

*Phytochemicals in Human Health*

atoms), and polyterpenes.

be separated by chromatography on silica gel [29].

ture mass spectrometry of friedelin is 426 (M<sup>+</sup>

of 0.75 with the use of a relatively nonpolar solvent system [33].

also found to have antifeedant activity in some insects [39].

4 units of C5 or 20 carbon atoms), sesterterpenes, triterpenes (consisting of 6 units of C5 or 30 carbon atoms), tetraterpenes (consisting of 8 units of C5 or 40 carbon

Moreover, terpenoids are isoprenoid structural components which contain oxygen in its structure and can react with ketone, aldehyde, or alcohol. Chemically, they are generally soluble in fat and contained within the plant cell cytoplasm. Usually, they can be extracted with petroleum ether, ether, or chloroform and can

used in the rubber industry. They have a low molecular weight, such as essential oils that are used as natural food additives and fragrances in the perfume industry. They are also used in anticancer drug Taxol which is a diterpene. Taxol is used in the treatment of breast, ovarian, and lung cancer. One example is imberbic acid, a triterpenoid that has activity against *Mycobacterium fortuitum* and *S. aureus* [30]. Triterpenoids are a class of terpenoid compounds which consist of 30 carbon atoms or 6 units of isoprene. In plant tissue, they can be found in their native form but are also often found in the form glycoside. They are divided into cyclic and acyclic structures. The important acyclic triterpenoid is only the squalene that is considered only as an intermediate in the biosynthesis of steroids. The most widespread of triterpenoids are the pentacyclic triterpenoids. The frameworks most often found on a class of compound triterpenoids are ursam, lupan, oleanan, and friedelin [31]. Friedelin has the molecular formula C30H50O and a molecular weight of 426,7174 g/mol (**Figure 6**). Friedelin has a melting point of 259–260°C. The struc-

191, 179, 163, 149, 137, 125, 123, 109, 95, 81, 69, and 55. The IR spectra of friedelin in KBr was obtained using vmax at 1720 cm−1. The form of friedelin is white crystallineamorphous solid. Friedelin has an anti-fungal activity and has antinociceptive effects in rodents [32]. Friedelin was developed on a TLC plate by using a solvent system of 10% ethyl acetate and 90% hexane. Friedelin gave a dark spot on a TLC when exposed under UV light and iodine vapor chamber. Friedelin gave an Rf value

Several studies have been conducted on the benefits of friedelin. Friedelin has hepatoprotective activity [34]. It has an activity against Bacillus Calmette-Guerin (BCG) that causes tuberculosis [35]. It and some types of friedelin compound are widely used for the treatment of cancer of the bladder [36], convulsion, inflammation [37], topical ulcers, rheumatic inflammation, fever, and dysentery [38]. It is

Terpenes are widely used as a medicine and flavor enhancers. They are commonly

), 411, 302, 273, 246, 231, 218, 205,

**32**

**Figure 6.**

*Molecular structure of friedelin.*

Sterols are steroids which have a hydroxy group at C3 position as can be seen in **Figure 7**. They are found in free form or in association with glucose to form glycosides (sterolin) or as fatty acid esters (FASE). They are the natural compound that is generally composed of 27 carbon atoms [31]. They are terpenoids in which their basic framework consists of the system perhydrophenanthrene cyclopentane ring. They are a class of secondary metabolic compounds which are widely used as a drug. Steroid hormones are generally derived from natural steroid compounds, especially in plants [42]. Some steroid compounds have been isolated from the *C. inophyllum* leaves such as campesterol [20]. Campesterol also has analgesic activity.

#### **2.6 Flavonoids**

Flavonoids are the largest group of phenolic compounds found in nature, especially in tissues of higher crops. They are the product of secondary metabolites that occur from the cells and accumulate on the body crop as a toxic substance [43]. They are commonly known as flavonoids, which are water-soluble polyphenol component. They have a basic framework consisting of 15 carbon atoms where a chain of benzene (C6) is bound to a chain of propane (C3), thus forming a bond arrangement C6-C3-C6 which is particularly called phenylbenzopyran (**Figure 8**). This arrangement can produce three structures, namely, 1,3-diarilpropana (flavonoids), 1,2-diarilpropana (isoflavonoids), and 2,2-diarilpropana (neoflavonoid) [44]. Moreover, flavonoids are classified into various categories based on differences in molecular structure, such as chalcones, flavanols, catechins, flavonoes, isoflavone, dihydroflavonol, and anthocyanidins [45, 46].

According to Markham [47], flavonoids are polar compounds because they have a hydroxyl group which does not bind to sugar, so the flavonoid is quite soluble in polar solvents such as ethanol, methanol, butanol, or water. Because of the presence of sugar bound, flavonoids become more soluble in water. Conversely, the less polar aglycone, such as isoflavones, flavanones, flavones, and flavonols, which is methoxylated tends to be more soluble in solvents, such as ether and chloroform.

The largest group of flavonoids is flavones. Flavonoids have a 2-phenyl Croman order in which the ortho-position of the A ring and the carbon atom attached to the ring B of 1.3 diarilpropana is connected by bridging oxygen to form a new heterocyclic ring [47].

**Figure 7.** *Molecular structure of cholesterol.*

Flavonoids have a variety of biological functions including pharmaceutical use and their function in plants. Examples of pigments in flowers, they provide color and attract insects for pollination. Flavonoids which are contained in the leaves have to prevent fungal infections and protect leaves from UV radiation [45]. In the aspect of pharmacology, flavonoids interact with cytochrome P450 and are used to treat heart disease. They are also known to have antioxidant activity and antifree radicals that are useful in anticancer and antiaging. Furthermore, they also have antileukemic activity, vitamin C, 5-lipoxygenase, cyclooxygenase inhibitors, protein kinase C, tyrosine kinase, and genetic toxicity [27].

Several flavonoid compounds that have been isolated from the *C. inophyllum* leaves are bioflavonoids, neoflavonoid [48], amentoflavone [20, 40], and quercetin-3-O-α-L-rhamnoside [8, 48].
