Amino acids imines

Peptide synthesis via a three or tour component condensation (amino acid, imine and bocyanide)... 

The mechanism of the first part of transamination is shown in Figure 29.14. The process begins with reaction between the a-amino acid and pyridoxal phosphate, which is covalently bonded to the aminotransferase by an iminc linkage between the side-chain -NTI2 group of a lysine residue and the PLP aldehyde group. Deprotonation/reprotonation of the PLP-amino acid imine in steps 2 and 3 effects tautomerization of the imine C=N bond, and hydrolysis of the tautomerized imine in step 4 gives an -keto acid plus pyridoxamine... 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

Q An amino acid reacts with the enzyme-bound PLP inline by nucleophilic addition of its -NH2 group to the C=N bond of the imine, giving a PLP-amino acid imine and releasing the enzyme amino group. 

Figure 29.15 Mechanism of steps 2-4 of amino acid transamination, the conversion of a PLP-amino acid imine to PMP and an a-keto acid.

Coordinated a-amino amides can be formed by the nucleophilic addition of amines to coordinated a-amino esters (see Chapter 7.4). This reaction forms the basis of attempts to use suitable metal coordination to promote peptide synthesis. Again, studies have been carried out using coordination of several metals and an interesting early example is amide formation on an amino acid imine complex of magnesium (equation 75).355 However, cobalt(III) complexes, because of their high kinetic stability, have received most serious investigation. These studies have been closely associated with those previously described for the hydrolysis of esters, amides and peptides. Whereas hydrolysis is observed when reactions are carried out in water, reactions in dimethyl-formamide or dimethyl sulfoxide result in peptide bond formation. These comparative results are illustrated in Scheme 91.356-358 The key intermediate (126) has also been reacted with dipeptide... 

The advent during the early 1990s of the O DonneU-Corey-Lygo protocol for the highly enantioselective alkylation of amino acids imines under PTC conditions, catalyzed by quaternized cinchona alkaloids, led to a series of investigations on the use of supported catalysts in these reactions [15]. 

Scheme 10.17 Insoluble supports for chiral PTC and their use in the alkylation of amino acids imines.

Epimerization. The ether 1 forms imines with a-amino acids. Imines of L-amino acids suffer from A -strain when maintaining a hydrogen-bonded conformation with the urea unit, therefore they are prone to undergo epimerization. ... 

Figure 4.24. (a) Addition to 1-naphthyloxazolines [142] (b) Addition to 2-naphthyloxazolines [142] (c) addition to 1-naphthyloxazolines lacking a chelating group [144] (d) addition to 1-naphthaldehyde imines [145] (e) addition to crotyl amino acid imines [146,147] (f) addition to cyclohexene and cyclopentene aldehyde amino acids imines [148]. 

A variety of heterocyclic compounds have been derived from the condensation of aldehydes with a-amino acids. Imines 1 (Fig. 3) are often used as intermediates in organic synthesis and are the starting point for chemical reactions such as cycloadditions, condensation reactions, and nucleophilic additions. The formation of imines via condensation of amines with aldehydes was first adopted for the reductive alkylation of resin-bound amino acids [29-31]. Imines have now been used as synthetic intermediates in the generation of a range of heterocyclic combinatorial libraries. 

Isoquinoline derivatives are an important family of natural products. They have diverse biological activities and are used, for example, as bronchodi-lators, skeletal muscle relaxants, and antiseptics. The solid-phase synthesis of a 43,000-compound tetrahydroisoquinoline 2 combinatorial library has been reported by Griffith et al. [32]. The library was synthesized by a three-step procedure. An imine was formed by reacting a substituted benzaldehyde with a methylbenzhydrylamine (MB HA) resin-bound amino acid. Imine formation was driven to completion using trimethylorthoformate as a dehydrating reagent. Treatment of the imine with homophthalic anhydride provided the desired tetrahydroisoquinoline (Fig. 3a). 

Pyridoxal 5 -phosphate is also a coenzyme for the enzyme-catalyzed racemization of amino acids. The key reaction is proton abstraction from the a carbon of the amino acid imine of PLP. This step converts the a carbon, which is a chirality center, from sp to sp. ... 

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