*2.2.3 Quinolizidine alkaloids*

In the legume alkaloids, the largest single group is quinolizidine alkaloids. In distribution to species in the more primitive tribes of the Papilionoideae, they appear to be restricted. Because of their toxicity in humans and animals as

**Figure 1.** *Molecular structure of synephrine and ephedrine alkaloids (\*chiral center).*

**Figure 2.**

*Molecular structure of (S)-hyoscyamine, (S)-scopolamine, and anisodamine.*


**Figure 3.**

*Molecular structure of aconitine, mesaconitine and hypaconitine.*

components of poisonous plants, these compounds become important. In contrast, some of them are potentially useful in pharmacological activities [18]. Radix sophorae flavescentis (*Sophora flavescens*) is frequently used in Traditional Chinese medicine for treating acute hepatitis and jaundice; it was found that quinolizidine alkaloids were the main constituents of this herbal drug such as matrine, sophoridine, sophocarpine, lehmannine, sophoranol, oxy-matrine, oxysophocarpine which have some chiral center [10, 19]. In natural, they exist as an isomer, sophocarpine (**Figure 4**) is an example. The naturally (−)-sophocarpine isolated from the root of the Chinese medicinal herb *Sophora flavescens* Ait. (Fam. Leguminosae) [20]**.**

#### *2.2.4 Isoquinoline alkaloids*

Bis-benzylisoquinoline alkaloids have fascinated by the significant pharmacological impacts; especially, protoberberines are a structural class of organic cations (quaternary ammonium alkaloids) mostly distributed in Ranuncolaceae (e.g., Rhizoma coptidis), Berberidaceae (e.g. Cortex berberdis), Papaveraceae (e.g. Herba chelidoni) and Rutaceae (e.g. Cortex phellodendri) [10]. The most considered chiral isoquinoline alkaloids are tetrahydroprotoberberine backbone structure such as tetrahydropalmatine (THP), tetrahydroberberine (THB), and corydaline [21]. (DL)-THP and (DL)-THB are highly abundant in C. yanhusuo and a variety of Corydalis plants. (L)-THP can also be isolated from Stephania plants [22]. Tetrahydropalmatine is one of the active ingredients isolated from Rhizoma Corydalis (yanhusuo), a traditional Chinese medicine that has been used for the treatment of chest pain, epigastric pain, dysmenorrhea, traumatic swelling, and pain for thousands of years [23]. The analgesic activity of (−)-THP is much higher than that of (+)-THP. Clinically, THP is used as the racemic mixture (**Figure 5**) [22].

Amaryllidaceae alkaloids are an important class of iso-quinoline derivatives; among them galanthamine, that is found in Galanthus and Narcissus species, has been approved for the pharmacological treatment of Alzheimer's disease [24]. There are several chiral centers in this molecule, but only one S-enantiomer responsible for Alzheimer's disease, other stereoisomers considered as impurity (**Figure 6**) [25].

Morphinane alkaloids (opium alkaloids) such as morphine, codeine, thebaine, papaverine and narcotine belong to isoquinoline derivatives and show a broad

**43**

*Chiral Alkaloid Analysis*

**Figure 4.**

**Figure 5.**

**Figure 6.**

*DOI: http://dx.doi.org/10.5772/intechopen.96009*

*Molecular structures of four quinolizidine alkaloids.*

range of pharmacological activities; their major application is in analgesia, sedation and cough depression [26]. Although opiate alkaloids have an important place in medicine, the illegal trafficking and abuse of heroin (the diacetyl derivative of morphine) has become a widespread problem [27]. Opium, the exudates from *Papaver somniferum*, contains more than 30 alkaloids and is the raw material for extraction; also, the dried heads of *P. somniferum*, so-called poppy straw, is used as a source of morphine and thebaine. **Figure 7** show the molecular structure of

*Molecular structures of the enantiomers of tetrahydropalmatine (THP), and tetrahydro-berberine (THB).*

Although these alkaloids have at present no great medicinal significance, they are important in that they constitute the poisonous hepatotoxic constituents of plants of the genus Senecio (Compositae), well-known for their toxicity to livestock [28]. Pyrrolizidine alkaloids are found in a variety of plant species growing wide world such as Gynura segetum that belongs to the Compositae family and Senecio and Tussilago genera [10]. The majority of naturally occurring pyrrolizidine alkaloids (PA) are hepatotoxic causing liver damage and in some cases liver cancer. Toxic PAs are often responsible for serious health problems through direct consumption of PA-containing herbal teas, herbal medicines, and herbal dietary supplements [29].

opium alkaloids, most of them have multi chiral center.

*2.2.5 Pyrrolizidine alkaloids*

*Molecular structures of galanthamine.*

## *Chiral Alkaloid Analysis DOI: http://dx.doi.org/10.5772/intechopen.96009*

**Figure 5.**

*Current Topics in Chirality - From Chemistry to Biology*

*Molecular structure of aconitine, mesaconitine and hypaconitine.*

*Molecular structure of (S)-hyoscyamine, (S)-scopolamine, and anisodamine.*

components of poisonous plants, these compounds become important. In contrast, some of them are potentially useful in pharmacological activities [18]. Radix sophorae flavescentis (*Sophora flavescens*) is frequently used in Traditional Chinese medicine for treating acute hepatitis and jaundice; it was found that quinolizidine alkaloids were the main constituents of this herbal drug such as matrine, sophoridine, sophocarpine, lehmannine, sophoranol, oxy-matrine, oxysophocarpine which have some chiral center [10, 19]. In natural, they exist as an isomer, sophocarpine (**Figure 4**) is an example. The naturally (−)-sophocarpine isolated from the root of the Chinese medicinal herb *Sophora flavescens* Ait. (Fam. Leguminosae) [20]**.**

Bis-benzylisoquinoline alkaloids have fascinated by the significant pharmacological impacts; especially, protoberberines are a structural class of organic cations (quaternary ammonium alkaloids) mostly distributed in Ranuncolaceae (e.g., Rhizoma coptidis), Berberidaceae (e.g. Cortex berberdis), Papaveraceae (e.g. Herba chelidoni) and Rutaceae (e.g. Cortex phellodendri) [10]. The most considered chiral isoquinoline alkaloids are tetrahydroprotoberberine backbone structure such as tetrahydropalmatine (THP), tetrahydroberberine (THB), and corydaline [21]. (DL)-THP and (DL)-THB are highly abundant in C. yanhusuo and a variety of Corydalis plants. (L)-THP can also be isolated from Stephania plants [22]. Tetrahydropalmatine is one of the active ingredients isolated from Rhizoma Corydalis (yanhusuo), a traditional Chinese medicine that has been used for the treatment of chest pain, epigastric pain, dysmenorrhea, traumatic swelling, and pain for thousands of years [23]. The analgesic activity of (−)-THP is much higher than that of (+)-THP. Clinically, THP is used as the racemic mixture (**Figure 5**) [22]. Amaryllidaceae alkaloids are an important class of iso-quinoline derivatives; among them galanthamine, that is found in Galanthus and Narcissus species, has been approved for the pharmacological treatment of Alzheimer's disease [24]. There are several chiral centers in this molecule, but only one S-enantiomer responsible for Alzheimer's disease, other stereoisomers considered as impurity (**Figure 6**) [25]. Morphinane alkaloids (opium alkaloids) such as morphine, codeine, thebaine, papaverine and narcotine belong to isoquinoline derivatives and show a broad

**42**

*2.2.4 Isoquinoline alkaloids*

**Figure 3.**

**Figure 2.**

*Molecular structures of the enantiomers of tetrahydropalmatine (THP), and tetrahydro-berberine (THB).*

range of pharmacological activities; their major application is in analgesia, sedation and cough depression [26]. Although opiate alkaloids have an important place in medicine, the illegal trafficking and abuse of heroin (the diacetyl derivative of morphine) has become a widespread problem [27]. Opium, the exudates from *Papaver somniferum*, contains more than 30 alkaloids and is the raw material for extraction; also, the dried heads of *P. somniferum*, so-called poppy straw, is used as a source of morphine and thebaine. **Figure 7** show the molecular structure of opium alkaloids, most of them have multi chiral center.

#### *2.2.5 Pyrrolizidine alkaloids*

Although these alkaloids have at present no great medicinal significance, they are important in that they constitute the poisonous hepatotoxic constituents of plants of the genus Senecio (Compositae), well-known for their toxicity to livestock [28]. Pyrrolizidine alkaloids are found in a variety of plant species growing wide world such as Gynura segetum that belongs to the Compositae family and Senecio and Tussilago genera [10]. The majority of naturally occurring pyrrolizidine alkaloids (PA) are hepatotoxic causing liver damage and in some cases liver cancer. Toxic PAs are often responsible for serious health problems through direct consumption of PA-containing herbal teas, herbal medicines, and herbal dietary supplements [29].

The most important pyrrolizidine alkaloids senecionine, seneciphylline, retrorsine and senkirkine, contain the 4-azabicyclo [3.3.0] octane system with senecionine and seneciphylline differing only for the presence in the latter of the C13-C23 double bond (**Figure 8**) [30].

## *2.2.6 Indole alkaloids*

Indole alkaloids constitute a wide class of natural products most of them pharmacologically important and characterized by very different activities [31]. In the recent years, attention has been focused on the biological activity of yohimbine which is a monoterpenoid indole alkaloid (**Figure 9**). It displayed the treatment of erectile functional disturbance and anxiogenic [32]. Hydroindole alkaloids such as mesembrine and congeners (mesembrenone, Δ7 mesembrenone, mesembranol and its stereoisomer epimesembranol) have been isolated from Sceletium species used for the psychoactive effects [33].

The vinca alkaloids were isolated from the Madagascar periwinkle, Catharantus roseus G. Don., which included a class of about 130 terpenoid indole alkaloids [32]. In early 1965, people obviously know their clinical quality. And this group of compounds has been taken advantage of as an anticancer servant for more than 40 years and is a symbol of the compound that gives the trend to drug development [34, 35]. Among these base (+)-vincamine exhibits a valuable therapeutic activity in cerebral insufficiencies. Due to the presence of three stereogenic centers eight stereoisomers (four enantiomeric pairs) are in fact possible (**Figure 10**) [36].

#### **Figure 7.**

*Molecular structures of: (1) morphine; (2) codeine; (3) oripavine; (4) thebaine; (5) pseudomorphine.*

#### **Figure 8.**

*Molecular structures of four toxic PAs. (1) senkirkine; (2) senecionine; (3) retrorsine; (4) seneciphylline.*

**45**

**Figure 12.**

*Chiral Alkaloid Analysis*

(**Figure 12**).

**Figure 10.**

**Figure 11.**

*Molecular structures of verticine and verticinone.*

*Molecular structure of stemonamine and parvistemoline.*

*(*−*)-Vindoline (B).*

*2.2.7 Miscellaneous alkaloids*

*DOI: http://dx.doi.org/10.5772/intechopen.96009*

Steroidal alkaloids including verticine and verticinone are distinguished by cholestane carbon skeleton (isosteroid alkaloids) with a hexacyclic benzo [7, 8] fluoreno [2,1-b] quinolizine nucleus (**Figure 11**). These compounds have been isolated from plants from Liliaceae family typically Bulbus fritillariae used as a traditional medicine in Japanese, Turkish, Pakistani, and south-east Asian folk medicines [10]. Pharmacological studies demonstrate that verticine and verticinone in Bulbus Fritillariaeare the primary active ingredients responsible for the antitussive activity [37]. Stemona, belonging to Stemonaceae family, is known in the folk medicine of Southeast Asia, China, and Japan since its Phyto-preparations (primary the roots) are used to treat diseases about bronchitis, pertussis and tuberculosis. Interestingly many alkaloids, structurally defined as pyrido[1,2-α]azepines, have been recognized in this plant species and are considered the important pharmacological activity. All the Stemona alkaloids are polycyclic and contain multiple stereocenters [38]. Up to now, there are about 139 Stemona alkaloids which the scientist isolated

*Molecular structure of major vinca alkaloids isolated from* Catharanthus roseus*: (+)-Catharanthine (A) and* 
