*2.2.1 Tropane alkaloids*

*Current Topics in Chirality - From Chemistry to Biology*

**2. Background on chiral alkaloid**

**2.1 Non-heterocyclic alkaloids**

can be different [4].

compounds in nature. It is important to emphasize that some phytochemicals exist in only one enantiomeric form, while others the optical rotation of the metabolite

Alkaloids are cyclic organic compounds that contain nitrogen in a negative oxidation state. They are generally distributed in flora and are an essential role in plant protection, sprouting and stimulating plant growth. Alkaloids-containing plants are often used as traditional medicines and these compounds usually have marked pharmacological activity [5]. Over 21,000 alkaloids have been identified, which thus constitute the largest group among the nitrogen-containing secondary metabolites [6]. Alkaloids are significantly pharmaceutical, e.g. morphine as pain relief medicines, codeine as an antitussive in cough medicines, colchicine in the treatment of gout and familial Mediterranean fever (FMF), Quinine as an anti-malarial and a muscle relaxant, Quinidine, as an antiarrhythmic agent to prevent ventricular arrhythmias and L-hyoscyamine (in the form of its racemic mixture known as atropine) as antimusca-

The first isolations of alkaloids in the nineteenth-century new investigation into medicine of several alkaloid-containing drugs and were accidental with the advent of the separation process for the extraction of drugs. In 1803, the French apothecary Derosne probably isolated narcotine. Several years later, the Hanoverian apothecary Sertürner further investigated opium (1806) and isolated morphine (1816) [7]. Based on their structures, alkaloids are divided into several subgroups: nonheterocyclic alkaloids and heterocyclic alkaloids, which are again divided into 7 major groups according to their basic ring structure [8]. Families reported to be rich in alkaloids are: Liliaceae, Amaryllidaceae, Apocynaceae, Berberidaceae, Leguminosae, Papaveraceae, Ranunculaceae, Rubiaceae and Solanaceae [9]. Most of alkaloids are chiral compounds and are clinically administered as the racemic mixture, although its

rinic; i.e., as an antagonist of muscarinic acetylcholine receptors [7].

enantiomers have been shown to exert different pharmacological activity.

Phenylethylamine alkaloids in medicinal herbs (i.e. Citrus species and *Ephedra sinica*) are used ubiquitously for their effects on the metabolic process of humans by stimulating lipolysis and thus supporting to reduce the fat mass in obese people. Particularly, Ephedra Herba (Ma Huang) contain several alkaloids such as (1R, 2S)- (−)-ephedrine, (1S, 2S)-(+)-pseudoephedrine, (1R, 2S)-(−)-norephedrine, (1S, 2S)-(+)-norpseudoephedrine, (1R,2S)-(−)-N-methylephedrine, and (1S, 2S)-(+)-Nmethylpseudoephedrine [10]. Each of these six compounds also has an enantiomer that does not occur naturally in the plant [11, 12]. Separation and quantification of optical isomers of ephedrine-type alkaloids are important since ephedrine-type alkaloids in natural have been found to be strengthened with inexpensive (racemic) synthetic similarity, and these enantiomers could exhibit important differences in pharmacological activities. To diminish essential public health risk, adulteration of Ephedra products could be discovered by the presence of both enantiomers, such as naturally occurring (−)-ephedrine and synthetic (+)-ephedrine in the samples [13]. In the case of C. urantium alkaloids, synephrine has also effect on human metabolism that could help to reduce fat mass in obese people, since it stimulates lipolysis, raises the metabolic rate and promotes the oxidation of fat through increased thermogenesis [14]. Synephrine is a chiral compound and is clinically administered as the racemic mixture, although its enantiomers have been

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Solanaceae contain mainly tropane alkaloids such as atropine, anisodamine and scopolamine; these plants are extensively used both in traditional medicine and as sources for the extraction of the pharmacologically important (parasympatolytic and anti-cholinergic) alkaloids [10]. Atropine is existed in racemic mixture of (S)-hyoscyamine and (R)-hyoscyamine. (S)-hyoscyamine is original in plants and (R)-hyoscyamine forms under alkaline conditions. (S)-hyoscyamine functions competitive antagonist of muscarinic receptors, thereby inhibiting the parasympathetic activities of acetylcholine on the salivary and sweat glands, as well as gastrointestinal tract, while the (R)-hyoscyamine is mostly inactive. Atropine, which is more often applied than (S)-hyoscyamine, exhibits approximately half of the pharmacological activity of (S)-hyoscyamine. In reverse, Scopolamine is mostly applied as pure enantiomer, e.g. (S)-scopolamine bromide [16].

Anisodamine, a tropane alkaloid isolated from Solanaceae family (Scopolia tangutica Maxim.). In China for decades, Anisodamine is an effective cholinoceptor antagonist and has been used as a spasmolytic drug to effect on smooth muscle by feature of its weaker side effect on the central nervous system than atropine. This kind of alkaloids have biological characteristic including cholinoceptor agonists and antagonists, like most chiral drugs, depend strongly on their stereochemistry. The effectiveness differences among four isomers of anisodamine racemic on muscarinic receptors have been perceived (**Figure 2**) [17].
