MCRs, cyclization precursor

Generally, MCRs based on aminoazoles and synthetic precursors of a,p-unsaturated carbonyl compounds proceed via a sequence of Knoevenagel-type condensation, which was already mentioned (see Scheme 3), Michael-like addition, cyclization, and water elimination. For example, the authors of [47] considered the following mechanism (Scheme 9). 

There are only a few records of macrocycle synthesis where the linear precursor was cyclized by a MCR. The first one to observe an MCR-macrocyclization by coincidence were Failli et al. who tried to couple oligoglycines [92]. 

As a route to more highly functionalized molecules, MCR of a sugar amino acid or alcohol, an aldehyde, and an isocj oacetamide was used to prepare the acyclic precursor (240) for an acid-promoted cyclization that produced interesting macrodepsipeptides 241 (Scheme 11.31). In this approach, the 5-aminooxazole in 240 acts as an internal activator of the terminal carbo)q lic acid to facilitate the macrolactonization. Subsequent saponification followed by treatment with excess trifluoroacetic acid led to the cyclic target molecules. 

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