Amine bonds

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

Norwalk, CT) Waters pBondapak -NH2 Amine-bonded silica 10 p, 125 A 3.5% C not endcapped... 

Figure 1.8 Derivatives of amines can be prepared from acylating or alkylating agents to give amide, secondary amine, or tertiary amine bonds.

Schiff base interactions between aldehydes and amines typically are not stable enough to form irreversible linkages. These bonds may be reduced with sodium cyanoborohydride or a number of other suitable reductants (Chapter 2, Section 5) to form permanent secondary amine bonds. However, proteins crosslinked by glutaraldehyde without reduction nevertheless show stabilities unexplainable by simple Schiff base formation. The stability of such unreduced glutaraldehyde conjugates has been postulated to be due to the vinyl addition mechanism, which doesn t depend on the creation of Schiff bases. 

Fluorobenzene-type compounds have been used as functional groups in homobifunctional crosslinking agents (Chapter 4, Section 4). Their reaction with amines involves nucleophilic displacement of the fluorine atom with the amine derivative, creating a substituted aryl amine bond (Reaction 9). Detection reagents incorporating reactive aryl chemistry include 2,4-dinitrofluorobenzene and trinitrobenzenesulfonate (Eisen et al., 1953). These compounds form... 

Katti, 1996 Katti et al., 1999). Nucleophiles react with the hydroxymethyl arms by attack on the electron-deficient carbon atom with loss of water to form secondary or tertiary amine bonds (Reaction 16). 

Figure 3.14 Carbonyl groups can react with amine nucleophiles to form reversible Schiff base intermediates. In the presence of a suitable reductant, such as sodium cyanoborohydride, the Schiff base is stabilized to a secondary amine bond.

Figure 4.24 Two amine-containing molecules can be crosslinked by formaldehyde through formation of a quaternary ammonium salt with subsequent dehydration to an immonium cation intermediate. This active species then can react with a second amine compound to form stable secondary amine bonds.

Figure 6.4 THPP reacts with amine-containing molecules to form secondary or tertiary amine bonds.

Figure 7.11 Oxidation of glycoproteins with periodate, such as glycosylated antibodies, results in the formation of aldehyde groups that can be used for conjugation to dendrimers containing amine groups. Reductive amination with sodium cyanoborohydride results in coupling via secondary (or tertiary) amine bonds.

The reaction of the epoxide with a thiol group yields a thioether linkage, whereas reaction with a hydroxyl gives an ether and reaction with an amine results in a secondary amine bond. The relative reactivity of an epoxy group is thiol > amine > hydroxyl, and this is reflected by... 

Hapten molecules containing aldehyde residues may be crosslinked to carrier molecules by use of reductive animation (Chapter 3, Section 4). At alkaline pH values, the aldehyde groups form intermediate Schiff bases with available amine groups on the carrier. Reduction of the resultant Schiff bases with sodium cyanoborohydride or sodium borohydride creates a stable conjugate held together by secondary amine bonds. 

Figure 25.9 Epichlorohydrin can be used to activate the hydroxyl group of mPEG, creating an epoxy derivative. Reaction with amine-containing molecules yields secondary amine bonds.

Figure 28.4 Formaldehyde can be used to capture protein interactions if it is used at low concentrations. The reaction proceeds through modification of a protein to create an intermediate immonium cation, which then goes on to react with a neighboring protein to form the crosslinked product via secondary amine bonds.

Bromocriptine is rapidly and completely metabolised in animals and man. The major components of the urinary metabolites have been identified as 2-bromo-lysergic acid and 2-bro-mo-isolysergic acid. Apart from the hydrolytic cleavage of the amine bond and the isomerization at position 8 of the lysergic acid moiety, a third principal biotransformation pathway consists in the oxidative attack of the molecule at the proline fragment of the peptide part, predominantly at position 8, giving rise to the formation of a number of hydroxylated and further oxidized derivatives of bromocriptine, and in addition of conjugated derivatives thereof. 

Figure 14.13 Preferred addition sites (a) in an azahomofullerene and Mulliken charges at the vinyl amine bond.

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