Alkaloids, naturally occurring amines

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

Some Naturally Occurring Amines. Alkaloids and Related Compounds... 

SOME NATURALLY OCCURRING AMINES. ALKALOIDS AND RELATED COMPOUNDS... 

Because of their basicity ( alkalinity ), naturally occurring amines are often called alkaloids. Simple amines are named by naming the alkyl groups bonded to nitrogen and adding the word amine. The structures of some simple amines are shown below, together with the structure of nicotine, a toxic alkaloid found in tobacco leaves. 

Caffeine is a bitter-tasting compound found in coffee, tea, cola beverages, and chocolate. Caffeine is a mild stimulant, usually imparting a feeling of alertness after consumption. It also increases heart rate, dilates airways, and stimulates the secretion of stomach acid. Caffeine is an alkaloid, a naturally occurring amine derived from a plant source. In Chapter 25 we learn about the properties and reactions of amines. 

Naturally occurring amines derived from plant sources are called alkaloids. Alkaloids previously encountered in the text include quinine (Problem 17.14), morphine (Section 22.9), and cocaine (Problem 3.35). Three other common alkaloids are atropine, nicotine, and coniine, illustrated in Figure 25.5. 

Amines and amides, like ammonia, tend to be weak bases (see Chapter 12). Amines are used in the synthesis of disinfectants, insecticides, and dyes. They re in many drugs, both naturally occurring and synthetic. Alkaloids are naturally occurring amines found in plants. Most amphetamines are amines. 

Amines are abundant in nature. Naturally occurring amines isolated from plants are called alkaloids. Below are examples of several alkaloids that have garnered public awareness as a result of their physiological activity ... 

Naturally occurring amines isolated from plants are called alkaloids. 

Alkaloids are naturally occurring amines that are powerfully active biologically. They are among the most useful medicinal agents known. The painkiller morphine and the antimalarial agent quinine are typical examples. At the same time, some of the... 

Alkaloid (Section 4.9) A nitrogen-containing compound, often polycyclic and generally of plant origin. The term is more loosely applied to other naturally occurring amines. 

Alkaloids such as caffeine, nicotine, cocaine, and digitalis, which have powerful physiological activity, are naturally occurring amines obtained from plants. In an amide, the functional group consists of a carbonyl group attached to an amine. Amides, which are derived from carboxylic acids, are important in biology in proteins. In biochemistry, the amide bond that links amino acids in a protein is called a peptide bond. Some medically important amides include acetaminophen (Tylenol) used to reduce fever phenobarbital, a sedative and anticonvulsant medication and penicillin, an antibiotic. 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

For the purposes of this book, an alkaloid is regarded as a relatively complex, organic base, occurring naturally in a plant and usually possessing marked pharmacological activity. This excludes simple, naturally Occurring bases and the biological amines, which are adequately dealt with... 

The dimeric carbazole alkaloids often occur along with the corresponding monomeric carbazoles in terrestrial plants [7,62] (Scheme 7). Clausenamine-A was obtained by Wu from the stem bark of Clausena excavata [63]. Clausen-amine-A and its synthetic analogs, like bis(O-demethylmurrayafoline-A), show cytotoxic activities against diverse human cancer cell lines [64] and exhibit moderate antimalarial activity [65,66]. Furukawa isolated l,r-bis(2-hy-droxy-3-methylcarbazole) and bismurrayaquinone-A, the first dimeric car-bazolequinone alkaloid found in nature, from Murraya koenigii [67]. 

As indicated in the introdnction, Wegler and coworkers were the first to report suc-cessfnl asymmetric acylation nsing naturally occurring fert-amine-based alkaloids (e.g. brucine) in their KR studies on 1-phenylethanol [23], While the selectivities achieved were rather modest, proof-of-concept was thereby established. 

Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stim-ulating effect in addition to its peripheral actions. The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with aU indirectly acting adrenomimetic amines,... 

Pilocarpine is a naturally occurring cholinomimetic alkaloid that is structurally distinct from the choline esters. It is a tertiary amine that crosses membranes relatively easily. Therefore, it is rapidly absorbed by the cornea of the eye, and it can cross the blood-brain barrier. Pilocarpine is a pure muscarinic receptor agonist, and it is unaffected by cholinesterases. Muscarine is an alkaloid with no therapeutic use, but it can produce dangerous cholinomimetic stimulation following ingestion of some types of mushrooms (e.g., Inocybes). 

Atropine and its naturally occurring congeners are tertiary amine alkaloid esters of tropic acid (Figure 8-1). Atropine (hyoscyamine) is found in the plant Atropa belladonna, or deadly nightshade, and in Datura stramonium, also known as jimsonweed (Jamestown weed), sacred Datura, or thorn apple. Scopolamine (hyoscine) occurs in Hyoscyamus niger, or henbane, as the /(-) stereoisomer. Naturally occurring atropine is /(-)-hyoscyamine, but the compound readily racemizes, so the commercial material is racemic d,/-hyoscyamine. The /(-) isomers of both alkaloids are at least 100 times more potent than the d(+) isomers. 

AicohoJ oxidation can aJso be enantioselective. The best systems reported to date for the selective oxidation of one enantiomer of 7 to 9 depend on the naturally-occurring alkaloid sparteine as a source of chirality. Unfortunately, only one enantiomer of sparteine is available. Peter O Brien of the University of York has developed (J. Org. Chem. 2004,69, 5789) an alternative tricyclic amine 8 that is complementary to sparteine, directing oxidation toward R-7. 

The chemical behavior and reactions of pyrrolizidine derivatives were investigated for the most part during structural analysis of naturally occurring pyrrolizidine alkaloids and in the course of the syntheses of their degradation fragments there are several publications concerned specially with this subject. Pyrrolizidine derivatives are typical tertiary amines, and consequently their chemical behavior is a combination of the properties of tertiary amines and of those of the substituent functions. However, some peculiarities of the class can be explained only in terms of the configuration of the bicyclic system. 

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