Synthetic strategies for solid-phase synthesis: I. Design, synthesis, and applications of handles. II. Combinatorial synthesis of small molecules

The emergence of combinatorial methods has had significant impact on the field of solid-phase synthesis. Typically associated with the preparation of oligomeric biopolymers, solid-phase methodology is now well established in the fields of organic and medicinal chemistry.; Regardless of the application, the general principles of solid-phase synthesis remain unchanged. One such principle is the method used for anchoring substrates to the solid support. The Backbone Amide Linker “BAL” concept was established as a means to access cyclic and C-terminal modified peptides. Details regarding the application of this handle strategy for the preparation of C-terminal peptide aldehydes are presented. Also described are studies related to a methionine-based handle, cleavable upon treatment with cyanogen bromide, which was designed for the solid-phase synthesis of amines.; Lastly, a parallel strategy for preparing 1,3,4-thiadiazolium-2-aminides in library format has been achieved. The synthetic strategy permits incorporation of diversity via substituted aldehydes, hydrazines, and isothiocyanates.