Aldehyde amine capture

Reductive amination of an aldehyde with excess primary amine, using a support-bound borohy-dride, provides the desired secondary amine contaminated with the primary amine precursor. Covalent capture of the primary amine with a support-bound aldehyde provides the pure secondary amine. Treatment with excess isocyanate yields the final urea product, which is purified by reaction with a support-bound amine to remove unreacted isocyanate. For the full potential of this method to be realized, further development of support-bound reagents and scavengers for most of the important chemical transformations will be necessary. Al-... 

To capture electrophilic substrates such as acid halides, aldehydes, alkyl halides, isocyanates, and isothiocyanates, a variety of nucleophilic resins are commonly used. Some commercially available and representative examples are tris-(2-aminoethyl)amine (9), thiophenol (10), sulfonylhydrazide (11), triphenylphosphine (12), and methylthiourea (13) polymer resins (Fig. 6). 

D. Chambers, Extractive derivatization of primary amines and beta-aminoalcohols with aromatic aldehydes to form Schiff base or oxa-zolidine products for analysis by electron capture gas chromatography, Diss. Abstr. Int. b. 44(7) 2148, (1984). 

The first consideration when setting up an AlphaScreen assay is the choice of an assay format In most cases, the decision will depend on the interaction partners under investigation and on the biological tools available for their detection. The interaction partners can be coupled to the beads directly via reductive amination of reactive aldehyde groups, similar to the immobilization on a Biacore sensor chip (see above). The usefulness of this approach is limited by the reaction conditions, which may not be appropriate for maintaining the biologically active conformation of the biomolecule. Therefore the biomolecule of interest is usually not coupled to the beads directly, but instead captured via an antibody, also preventing steric hindrance. While not strictly necessary, it is often convenient to use a biotinylated molecule which can be captured by streptavidin-coated donor beads. 

Structure (Scheme 3.9). A mechanism that has been proposed is shown in Scheme 3.10. Intermediate 60 was formed upon activation of phytal 56 by dien-amine catalysis. Subsequently, an intermolecular aldol reaction between phytal 56 and aldehyde 55 occurred in the presence of catalyst 57. Finally, the tricyclic core structure 58 was built after the adjacent phenol group captured the newly formed iminium ion 61 via an oxa-Michael reaction. The cascade product desired was obtained in 58% yield with 97% diastereomeric excess. The total synthesis of natural product a-tocopherol was achieved through a four-step chemical synthesis. 

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