Biologically important amines

It was only around 1850 that the first amines were discovered by Wurtz [2], who considered them as alkylated (or arylated) derivatives of NH3. Nowadays, it is well known that the amine function is widespread among biologically important compounds, but mostly it is present in polyfunctional molecules such as amino acids, alkaloids, etc. Simple amines are very rare in nature, with the exception of tri-ethylamine and the trimethylammonium ion which come from the putrefaction of proteins. 

Haley, F., and H. A. Lardy Phosphoric Esters of Biological Importance. VI. The Synthesis of D-Glucosamine 6-Phosphate and N-Acetyl-D-glucos-amine 6-Phosphate. J. Amer. chem. Soc. 78, 1393 (1956). 

The Schiff bases being derivatives of aldehydes or ketones and various amines have received considerable attention because of their interesting physical and chemical properties, involvement in biologically important reactions and widespread application of their metal complexes. Increasing interest in optically active Schiff bases is connected with the discovery at the beginning of the 1990s of the so-called Jacobsen catalysts used in several asymmetric reactions showing excellent enantioselectivity. 

In recent years, the formation of rhena-/3-ketoimine complexes has been extended to more complex amines that have biological importance. These... 

Incomplete conversion was observed at lower temperatures and significant amounts of undesired decomposition products were obtained at temperatures in excess of 150 °C. These processes were applied to the synthesis of biologically important amine-containing compounds such as the seratonin 5-HT4 agonist SC-53116. 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

Our discussions of the basicity of organic nitrogen compounds have concentrated predominantly on simple amines in which the nitrogen atom under consideration is part of an acyclic molecule. Many biologically important compounds, and especially drug molecules, are based upon systems in which nitrogen is part of a heterocycle. We shall consider the... 

The transition metal-catalyzed allylic amination is particularly pertinent, because of the synthetic utihty of aUyhc amines in the construction of biologically important natural and urmatural products [34]. The allylic amination of cyclic and acycHc substrates. 

The aldehyde can be replaced by an imine and the reaction is then called the aza-Baylis-Hillman reaction [87, 88]. (3-Amino-a-methylene structures obtained in this way could further be converted to a range of biologically important molecules, such as p-amino acids [89]. First reaction of this kind was published in 1984 [90]. Tosylimines and ethylacrylate reacted in the presence of DABCO as catalyst to give p-aminoesters. First three-component aza-Baylis-Hillman reaction was published in 1989 by Bertenshaw and Kahn [91], with imine formation in situ from an aldehyde and an amine. In the presence of triphenylphosphine as catalyst, the reaction with methylacrylate led to the formation of the p-amino-ot-methylene esters and ketones in good yields (Scheme 38). 

Due to the synthetic and biological importance of amines and a-aminoketones, acids and esters, the introduction of amino functionality into carbon nucleophiles provides a convenient and practical route for their synthesis "In addition, a number of electrophilic amination methodologies have been developed for the asymmetric synthesis of amines and a-aminocarbonyl compounds " ". 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

Macrocyclic ligands of biological importance as thiophenolate-containing Schiff-base macrocycles and their amine analogs (see review [138]) and new helical complexes with bis(bidentate) SchifF-base ligand [139] were also described. 

Stillwell, W.G, Biyant, M.S. Wishnok, J.S. (1987) GC/MS analysis of biologically important aromatic amines. Apphcation to human dosimetry. Biomed. environ. Mass Spectrom., 14, 221-227... 

Lasalocid is the more disruptive polyether antibiotic to biological systems. This is due to its high tendency to dimerize and form complexes with biologically important divalent ions such as ("a and Mg ". Lasalocid exhibits a wide range of complexation affinities and transport capabilities, encompassing not only inorganic polyvalent ions but also primary amines and catecholamines (22). 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

The portion of the molecule derived from the amine is shown in blue, and the portion of the molecule derived from the carboxylic acid is shown in black. The R groups on the nitrogen can either be alkyl groups or hydrogens. Proteins are the most biologically important example of amides, and we will discuss proteins in greater detail in the next chapter. 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

Many drugs and other biologically important amines are commonly stored and used as their salts. Amine salts are less prone to decomposition by oxidation and other reactions, and they have virtually no fishy odor. The salts are soluble in water, and they are easily converted to solutions for syrups and injectables. 

Allied with the chromatography of imidazoles have been methods of estimation of the compounds, particularly those of biological importance, either on the chromatograms or after elution. Most workers have used diazotized aromatic amines as colorimetric reagents,53,277-285 particularly nonsulfonated diazotized aniline derivatives.281-285 Mosebach et aZ.286 initially hydrolyzed. -substituted imidazoles with 10 A hydrochloric acid before separating the compounds by ion-exchange and paper chromatographic techniques prior to estimation. A number of other methods exist for the colori-... 

Shu-Jiang and co-workers [76] have developed a green approach for the synthesis of biologically important indeno[2,l-c]pyrazolo[5,4-/7]pyridines 36 via a MCR of a suitable aldehyde, 3-methyl-l-phenyl-l//-pyrazol-5-amine and 1,3-indane-dione in water under microwave irradiation without the aid of any catalyst. This protocol has the prominent advantages of being environmentally benign and having... 

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