*2.3.1 Alkaloids*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

that control the synthesis of flavonoids have similar phenotypes [57].

**2.3 Nitrogen-containing compounds**

is the precursor for the cinnamic acid derivatives and flavonoids, and it is converted by an enzyme, phenylalanine ammonia-lyase (PAL) to cinnamic acid. Rosmarinic acid has high antioxidative potential and also good aromatic qualities. The cinnamic acid derivatives serve as precursors for polymers (lignin), which is synthesized via cinnamaldehydes and monolignols. Much information is also available from maize and a legume, the latter also contains isoflavonoids (**Figure 11**). Other mutants in the pathway of, for example, the next enzyme encoding chalcone isomerase (which is responsible for the synthesis of naringenin), also show this phenotype, and consequently, the mutations were numbered consecutively, starting with "1." Mutations in the transcription factors

Alkaloids are heterocyclic nitrogen compounds biosynthesized from amino acids. Alkaloids represent one of the biggest groups of natural products, with currently more than 12,000 known structures. In addition to alkaloids, benzoxazinoids, glucosinolates, and cyanogenic glucosides will be represented. Like alkaloids, these

*The main pathways for flavonoid synthesis derived from different plant species. CHS: chalcone synthase; CHI: chalcone isomerase; IFS: isoflavonoid synthase; FNS: flavone synthase; F3H: flavanone-3- hydroxylase; FLS: flavonol synthase; DFR: dihdroflavonol reductase; ANS: anthocyanidin synthase; UGT: glycosyltransferase;* 

**60**

**Figure 11.**

*ANR: anthocyanidin reductase [57].*

Alkaloid was introduced by a German Chemist, Carl F.W Meissnerin in 1815. Alkaloids are Alkali-like and derived from the word Alkali. They are a group of naturally occurring organic compounds which are basic, contain one or more nitrogen atoms normally of Heterocyclic nature. They also possess specific physiological actions on the human and animal bodies and are abundant in higher plants (Angiosperm). Major types of alkaloids and their examples are represented in **Table 1**. Families rich in alkaloids are- Apocynaceae, Rubiaceae, Solanaceae, Papaveraceae, Berberidaceae, etc. Alkaloids are present in many parts of the plant- Aerial part (Ephedra – Ephedrine), Entire plant (Vinca- Vincristine, Vinblastine), Leaves (Tea- Caffeine), Root (Rauwolfia- Reserpine), Bark (Cinchona- Quinine), Seed (Nuxvomica), Fruit (Black pepper- Piperine), Latex (Opium- Morphine, Codeine). Pharmacological uses include; Anagelsic, Antimalarial, Antispasmodic, Hypertension, Mental disorder, Anticancer etc. Alkaloids occur mainly in plants as Salts of organic acid (oxalic acid, citric acid, acetic acid, maleic acid, tartaric acid, fumaric, benzoic, etc). Functions in plants include; protective against insects and herbivores (bitterness and toxicity), a product of detoxification (a waste product) in a certain case, a reservoir for protein synthesis, and a source of nitrogen in case of deficiency. Many precursors are involved in various pathways, such as aromatic amino acids (tryptophan, tyrosine and phenylalanine), and also aspartate, glutamine, lysine, glycine and valine (**Figure 12**). Besides, the nonproteinogenic amino acid ornithine is an important precursor for various alkaloids.


#### **Table 1.** *Major types of alkaloids [53].*

#### **Figure 12.**

*Overview of the biosynthesis of selected alkaloids. Phenylalanine together with ornithine is needed for the synthesis of the second group of tropane alkaloids (violet). Caffeine and related substances are derived from purine (brown). The class of compounds is given in brackets [57].*

For several alkaloids, two different precursors are needed for the biosynthetic pathways. In the case of terpene indole alkaloids (**Figure 12**), it is not only tryptophan that is involved as a precursor for the indole moiety, but also monoterpenes for the synthesis of side chains. Another example is the biosynthesis of the tropane alkaloids hyoscyamine and scopolamine, where ornithine and phenylalanine are required for the different parts of the molecule (**Figure 12**) [57].

## *2.3.2 Benzoxazinones*

Benzoxazinones is a class of natural products known as cyclic hydroxamic acid, found in wheat, rye and maize in the family of Gramineae [61]. They act as plant resistance to insects and microbes. At present, it is still being investigated

**63**

**Figure 13.**

*Biosynthesis of Natural Products*

natural herbicides [67].

*2.3.3 Glucosinolates*

*DOI: http://dx.doi.org/10.5772/intechopen.97660*

whether the pathway developed only once or several times independently after the divergence of monocots and dicots [62, 63]. Besides, they serve as feeding deterrents and reduce the vitality of pests. In particular, these metabolites confer resistance to one of the major corn pests, the European corn borer (*Ostrinia nubialis*) [64]. The mode of action of benzoxazinones can be explained by the modification of amino and thiol groups of biomolecules. The aldehyde function of the tautomeric open-ring form can react as an electrophile with NH2 groups and form Schiff bases [65]. The structural prerequisite for this oxidation is an electron-donating substitution at C-7 of the benzoxazinone skeleton (**Figure 13**) [66]. Benzoxazinoids that have been bio-activated by N -acetylation may act as alkylating agents towards nucleic acids and proteins. Due to their toxicity, benzoxazinones can also function as allelochemicals and are therefore discussed as

Glucosinolates are b -thioglucosides of (Z) - N - hydroximinosulfate esters (**Figure 14**). They share the first steps of cyanogenic glucoside biosynthesis. About 120 different structures of glucosinolates are known [68]. The glucosinolates are hydrolyzed by myrosinase (if the plant tissue is damaged), a thioglucosidase is spatially separated in the undamaged tissue [69] (**Figure 14**). The main product of the "mustard bomb" consisting of glucosinolates and myrosinase is isothiocyanates. These compounds are also responsible for many of the biological effects of glucosinolates, e.g., antibacterial, antifungal, nematicidal, and feeding deterrent activities [68]. The formation of hydrolysis products distinct from thiocyanates depends on the structure of the glucosinolates, pH, and the presence or absence of Fe2+ ions or specifier proteins [70]. Hydrolysis of b -hydroxyalknyl glucosinolates yields oxazolidine-2-thiones that can cause goiter by inhibiting the incorporation of iodine into thyroid hormones. To make the protein-rich seed cake that remains after the extraction of the oil suitable as animal foodstuff, Grape plants with low levels of glucosinolates have been developed by breeding efforts [68]. Sulforaphane enhances the excretion of cancerogenic compounds by inducing glutathione-S-transferase, UDP-glucuronosyl transferase, and NADPH quinone oxidoreductase (phase II detoxification enzymes) [70, 71]. The glucosinolates act as feeding deterrents, and many insect herbivores feed on plants containing these natural products. The detoxification of glucosinolates is known from two insect species which has two very different mechanisms [72]. The cabbage white butterfly (*Pieris rapae*) contains a specified protein that transforms glucosinolates in the presence of myrosinase to nontoxic nitriles that are excreted with the feces [73]. This requires either an endogenous myrosinase that is spatially separated from the glucosinolates in the insects or

myrosinases from the gut microflora of their enemies [69].

*Enzymatic and chemical degradation of benzoxazines with hydroxamic acid function [61].*

#### *Biosynthesis of Natural Products DOI: http://dx.doi.org/10.5772/intechopen.97660*

whether the pathway developed only once or several times independently after the divergence of monocots and dicots [62, 63]. Besides, they serve as feeding deterrents and reduce the vitality of pests. In particular, these metabolites confer resistance to one of the major corn pests, the European corn borer (*Ostrinia nubialis*) [64]. The mode of action of benzoxazinones can be explained by the modification of amino and thiol groups of biomolecules. The aldehyde function of the tautomeric open-ring form can react as an electrophile with NH2 groups and form Schiff bases [65]. The structural prerequisite for this oxidation is an electron-donating substitution at C-7 of the benzoxazinone skeleton (**Figure 13**) [66]. Benzoxazinoids that have been bio-activated by N -acetylation may act as alkylating agents towards nucleic acids and proteins. Due to their toxicity, benzoxazinones can also function as allelochemicals and are therefore discussed as natural herbicides [67].

## *2.3.3 Glucosinolates*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

For several alkaloids, two different precursors are needed for the biosynthetic pathways. In the case of terpene indole alkaloids (**Figure 12**), it is not only tryptophan that is involved as a precursor for the indole moiety, but also monoterpenes for the synthesis of side chains. Another example is the biosynthesis of the tropane alkaloids hyoscyamine and scopolamine, where ornithine and phenylalanine are required for the

*Overview of the biosynthesis of selected alkaloids. Phenylalanine together with ornithine is needed for the synthesis of the second group of tropane alkaloids (violet). Caffeine and related substances are derived from* 

Benzoxazinones is a class of natural products known as cyclic hydroxamic acid, found in wheat, rye and maize in the family of Gramineae [61]. They act as plant resistance to insects and microbes. At present, it is still being investigated

different parts of the molecule (**Figure 12**) [57].

*purine (brown). The class of compounds is given in brackets [57].*

**62**

*2.3.2 Benzoxazinones*

**Figure 12.**

Glucosinolates are b -thioglucosides of (Z) - N - hydroximinosulfate esters (**Figure 14**). They share the first steps of cyanogenic glucoside biosynthesis. About 120 different structures of glucosinolates are known [68]. The glucosinolates are hydrolyzed by myrosinase (if the plant tissue is damaged), a thioglucosidase is spatially separated in the undamaged tissue [69] (**Figure 14**). The main product of the "mustard bomb" consisting of glucosinolates and myrosinase is isothiocyanates. These compounds are also responsible for many of the biological effects of glucosinolates, e.g., antibacterial, antifungal, nematicidal, and feeding deterrent activities [68]. The formation of hydrolysis products distinct from thiocyanates depends on the structure of the glucosinolates, pH, and the presence or absence of Fe2+ ions or specifier proteins [70]. Hydrolysis of b -hydroxyalknyl glucosinolates yields oxazolidine-2-thiones that can cause goiter by inhibiting the incorporation of iodine into thyroid hormones. To make the protein-rich seed cake that remains after the extraction of the oil suitable as animal foodstuff, Grape plants with low levels of glucosinolates have been developed by breeding efforts [68]. Sulforaphane enhances the excretion of cancerogenic compounds by inducing glutathione-S-transferase, UDP-glucuronosyl transferase, and NADPH quinone oxidoreductase (phase II detoxification enzymes) [70, 71]. The glucosinolates act as feeding deterrents, and many insect herbivores feed on plants containing these natural products. The detoxification of glucosinolates is known from two insect species which has two very different mechanisms [72]. The cabbage white butterfly (*Pieris rapae*) contains a specified protein that transforms glucosinolates in the presence of myrosinase to nontoxic nitriles that are excreted with the feces [73]. This requires either an endogenous myrosinase that is spatially separated from the glucosinolates in the insects or myrosinases from the gut microflora of their enemies [69].

**Figure 13.** *Enzymatic and chemical degradation of benzoxazines with hydroxamic acid function [61].*

**Figure 14.**

*Exemplary structures of glucosinolates (a) and hydrolysis of glucosinolates by myrosinase and rearrangement to various products (b) Isothiocyanates are the predominant degradation products.*

#### *2.3.4 Cyanogenic glycosides*

Cyanogenic glucosides are b-glucosides of a–hydroxy nitriles (syn. cyanohydrins), which are derived from the five proteinogenic amino acids phenylalanine, tyrosine, valine, isoleucine, leucine, and the non-proteinogenic amino acid cyclopentenyl-glycine. About 2500 different plant species including ferns, gymnosperms, and angiosperms produce cyanogenic glycosides [74, 75]. Despite their widespread occurrence, these natural products are found predominantly in the families Araceae, Asteraceae, Euphorbiaceae, Fabaceae, Passifloraceae, Poaceae, and Rosaceae [9, 76]. Some of the most abundant molecules are amygdalin (Rosaceae), linamarin and lotaustralin (Fabaceae), and the epimers dhurrin and taxiphyllin in the genus Sorghum [75]. The b-glucosidic bond can also be hydrolyzed by intestinal bacteria in the gut of herbivores. The hydrogen cyanide toxicity can be explained by its affinity to metal ions. Cyanide ions complex iron (III) in the active site of cytochrome oxidase thus inhibits the respiratory chain [77, 78]. Cyanogenic glucosides act as feeding deterrents, by transferring all genes required for the formation of the cyanogenic glucoside dhurrin from *Sorghum bicolor* into Arabidopsis, proved that cyanogenic glucosides play a role in plant defense [79, 80]. Several herbivores, especially insects, can feed on plants containing these natural products, despite the toxicity of the cyanogenic glucosides, and the toxic compounds may act as phagostimulants. Cyanogenic glucosides act as defense compounds for some species of beetles, centipedes, and millipedes, but particularly many moths and butterflies (**Figure 15**). The compounds are either taken up by feeding on cyanogenic plants or synthesized by endogenous enzymes [77, 78]. It has been postulated that cyanogenic

**65**

**Author details**

Stella O. Bruce1

Nigeria

\* and Felix A. Onyegbule2

glucosides in roots are currently underway [76, 80, 83, 84].

\*Address all correspondence to: stellaobruce@yahoo.com

provided the original work is properly cited.

Azikiwe University, Awka, Anambra State, Nigeria

1 Pharmacognosy and Traditional Medicine, Pharmaceutical Sciences, Nnamdi

glucosides also serve as storage compounds for reduced nitrogen and sugar [81, 82]. These treatments often results in loss of protein, minerals, and vitamins. Various approaches to produce transgenic cassava with reduced content of cyanogenic

*Representative structures of cyanogenic glucosides (a) and degradation of cyanogenic glucosides with* 

Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Anambra State,

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Department of Pharmaceutical & Medicinal Chemistry, Faculty of

*Biosynthesis of Natural Products*

**Figure 15.**

*DOI: http://dx.doi.org/10.5772/intechopen.97660*

*concomitant release of toxic hydrogen cyanide (b).*

*Biosynthesis of Natural Products DOI: http://dx.doi.org/10.5772/intechopen.97660*

#### **Figure 15.**

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

**64**

*2.3.4 Cyanogenic glycosides*

**Figure 14.**

Cyanogenic glucosides are b-glucosides of a–hydroxy nitriles (syn. cyanohydrins), which are derived from the five proteinogenic amino acids phenylalanine, tyrosine, valine, isoleucine, leucine, and the non-proteinogenic amino acid cyclopentenyl-glycine. About 2500 different plant species including ferns, gymnosperms, and angiosperms produce cyanogenic glycosides [74, 75]. Despite their widespread occurrence, these natural products are found predominantly in the families Araceae, Asteraceae, Euphorbiaceae, Fabaceae, Passifloraceae, Poaceae, and Rosaceae [9, 76]. Some of the most abundant molecules are amygdalin (Rosaceae), linamarin and lotaustralin (Fabaceae), and the epimers dhurrin and taxiphyllin in the genus Sorghum [75]. The b-glucosidic bond can also be hydrolyzed by intestinal bacteria in the gut of herbivores. The hydrogen cyanide toxicity can be explained by its affinity to metal ions. Cyanide ions complex iron (III) in the active site of cytochrome oxidase thus inhibits the respiratory chain [77, 78]. Cyanogenic glucosides act as feeding deterrents, by transferring all genes required for the formation of the cyanogenic glucoside dhurrin from *Sorghum bicolor* into Arabidopsis, proved that cyanogenic glucosides play a role in plant defense [79, 80]. Several herbivores, especially insects, can feed on plants containing these natural products, despite the toxicity of the cyanogenic glucosides, and the toxic compounds may act as phagostimulants. Cyanogenic glucosides act as defense compounds for some species of beetles, centipedes, and millipedes, but particularly many moths and butterflies (**Figure 15**). The compounds are either taken up by feeding on cyanogenic plants or synthesized by endogenous enzymes [77, 78]. It has been postulated that cyanogenic

*Exemplary structures of glucosinolates (a) and hydrolysis of glucosinolates by myrosinase and rearrangement to* 

*various products (b) Isothiocyanates are the predominant degradation products.*

*Representative structures of cyanogenic glucosides (a) and degradation of cyanogenic glucosides with concomitant release of toxic hydrogen cyanide (b).*

glucosides also serve as storage compounds for reduced nitrogen and sugar [81, 82]. These treatments often results in loss of protein, minerals, and vitamins. Various approaches to produce transgenic cassava with reduced content of cyanogenic glucosides in roots are currently underway [76, 80, 83, 84].
