Amines from transamination

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Soloshonok and co-workers have developed a method for the synthesis of a-(perfluoro-alkyl)amines from perfluoroalkyl carbonyl compounds by a transamination involving an azomethine a/omethine (Schiffbase) isomerization. They call this method a biomimetic, base-catalyzed 1,3-proton shift reaction, and have applied it to perfluoroaldehydes,12-15 perfluoroalkyl ketones,12 18 / -(perfluoroalkyl)-/l-oxo esters,15 16 19 24 and - -( perfluoroalkyl)-a-oxo es-ters2 " -26 to synthesize the corresponding a-(perfluoroalkyl)amincs, / -(perfluoroalkyl )-/i-amino acids, and 3 -(perfluoroalkyl)- x-amino acids. 

Decarboxylation of an amino acid is an important reaction, catalyzed by a pyridoxal-dependent decarboxylase, that affords an amine as product (Scheme 2.6). It is very attractive to learn how to mimic this process to generate various amines from a-amino acids. Unfortunately, our previous studies established that treatment of a-alkyl amino acids with pyridoxal afforded only ketone and pyridoxamine as products, by a transamination-dependent oxidative decarboxylation process (pathway b in Scheme 2.5) [41]. Consequently, non-oxidative decarboxylation, using pyridoxals to generate amines, remains elusive. 

In spite of its limited applicability the Bucherer reaction1057 is the most important method of preparing aromatic amines from phenols. This consists of the conversion of phenols into amines, and the reverse conversion of amines into pnenols, as well as transamination of aromatic amines (cf. page 538), each in the presence of hydrogen sulfite ions. 

Pseudoalkaloids are compounds, the basic carbon skeletons of which are not derived from amino acids.In reality, pseudoalkaloids are connected with amino acid pathways. They are derived from the precursors or postcursors (derivatives of the indegradation process) of amino acids. They can also result from the amination and transamination reactions of the different pathways coimected with precursors or postcursors of amino acids. 

Although methylamine is widespread in plants, it is probably produced as an artifact of isolation in many cases. Other simple amines arise from transamination. An enz)mie system from Mercurialis perennis (Euphorbiaceae) was capable of producing a series of amines from ethylamine to undecylam-ine in the presence of the corresponding aldehydes and alanine (Fig. 28.2) (Smith, 1980). 

In view to access both stereoisomers of a chiral amine via transamination by choice of an appropriate (R)- or (S)-selective co-TA, screening studies were undertaken which revealed an impressive number of (S)-co-TAs and some more rarely occurring (/ )-selective enzymes [1719-1722]. The most widely used enzymes are obtained from Vibrio fluvialis [1723], Chromobacterium violaceum [1724, 1725], Pseudomonas aeruginosa [1726], Bacillus megaterium [1727], and Alcaligenes denitrificans [1728]. Thermostable mutants were derived from an co-TA from Arthrobacter citreus [1729]. 

The amines taking part in the formation of the azomethines usually derive from amino acids (D 9.2). They are frequently methylated. The carbonyl compounds may be formed from amines by transamination (C 5), but may originate also from acetate/malonate (D 3.3.1, formation of coniine). 

Mannich bases and reactions have found new applications. Preparation of Mannich bases from ar. amines by transamination, transquaternization of quaternized Mannich bases reactions... 

Cyclic tert. amines from cyclimmonium salts by transamination -... 

In transamination an amine group is transferred from L glutamic acid to pyruvic acid An outline of the mechanism of transamination is presented m Figure 27 4... 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

Alternatively, l//-3-benzazepin-2-amines can be obtained from the 2-ethoxy compounds,61 or by transamination, e.g. 23-+24, of li/-3-benzazepin-2-amine (23) in refluxing alkylamine or cycloalkylamine solution.41... 

The deamination of primary amines such as phenylethylamine by Escherichia coli (Cooper et al. 1992) and Klebsiella oxytoca (Flacisalihoglu et al. 1997) is carried out by an oxidase. This contains copper and topaquinone (TPQ), which is produced from tyrosine by dioxygenation. TPQ is reduced to an aminoquinol that in the form of a Cu(l) radical reacts with O2 to form H2O2, Cu(ll), and the imine. The mechanism has been elucidated (Wihnot et al. 1999), and involves formation of a Schiff base followed by hydrolysis in reactions that are formally analogous to those involved in pyridoxal-mediated transamination. 

Transamination The reaction in which an amine group is transferred from an amino acid to a carboxylic acid, thereby creating a new amino acid. 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

This has obvious advantages over the process seen for glutamate synthesis via the reductive amination of 2-oxoglutarate, in that it no longer requires the intervention of free ammonia. We thus have the situation that some organisms are able to carry out the fixation of ammonia via reductive amination, whereas others manipulate via transamination the amino acid structures obtained from protein in the diet. 

From a practical viewpoint they suffer from serious product inhibition and/or equilibrium constraints. One way of avoiding the latter issue is to couple the transamination step to a second enzymatic step which removes the coproduct In the example shown in Scheme 6.16 acetophenone undergoes TA-catalyzed transamination using L-alanine as the amine donor. The unfavorable equilibrium and... 

Other papers of interest in this section report transamination of camphor-3-carbothioamides with secondary cyclic amines, reaction of camphorquinone with dimethyl /S-ketoglutarate, the use of fenchone (212 X=0) in alkene formation from Grignard reagents, bromination of 2-e/itfo-6-endo-dibromobornane to yield 2,3,6-endo-tribromoborn-2-ene, and camphor-enol trimethylsilyl ether formation by quenching the reaction mixture of butyl-lithium and camphor tosyl-hydrazone with trimethylsilyl chloride. ... 

In this transamination, the effect of para substitient groups has been studied using fluorinated phenylpyruvic acids and L-aspartic acid. From these results, the migratory preference is H > F > Cl > Br > CF3. This order has been attributed to the bulkiness of the substituted group [57]. Direct amination of p-substituted succinic acid with phenylalanine ammonialyase (EC 4.3.1.5) has suggested very high substrate specificity that the order of reaction rate is m-F o-F P-p-F >CF3. 

From alcohols or ethers 0-47 Transamination 0-48 Alkylation of amines with diazo compounds... 

The As—N bond is labile and this has been widely exploited in synthetic arsenic chemistry. Some idea of the versatility168 can be seen from Schemes 1 and 2. Refluxing secondary amines with tris(dimethylamino)arsine effects transamination (equation 6). These tris(dialkyl-amino)arsines undergo the general reactions in Scheme 1, enabling ready access to a wide variety of compounds, many of them finding use as ligands in transition metal complexes (see Chapter 14 of this work). 

The phosphate ester of the aldehyde form of vitamin B6, pyridoxal phosphate (pyridoxal-P or PLP), is required by many enzymes catalyzing reactions of amino acids and amines. The reactions are numerous, and pyridoxal phosphate is surely one of nature s most versatile catalysts. The story begins with biochemical transamination, a process of central importance in nitrogen metabolism. In 1937, Alexander Braunstein and Maria Kritzmann, in Moscow, described the transamination reaction by which amino groups can be transferred from one carbon skeleton to another.139 140 For example, the amino group of glutamate can be transferred to the carbon skeleton of oxaloacetate to form aspartate and 2-oxoglutarate (Eq. 14-24). 

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