Ring Contraction of Furans to Oxetanes

FIGURE 4.8 Examples of bioactive natural products with an oxetane ring in their structure. 

Oxetanes have been used in medicinal chemistry to improve physicochemical properties and as stmcturally restricted mimetics to study different biological processes [27], Furthermore, oxetane amino acids are commonly used as monomers in peptide synthesis to investigate how their rigid structure affects the biological role of proteins. Their low flexibility affords a well-defined spatial distribution of its substituents leading to a more efficient binding to the target receptor. 

This reaction has been applied to the synthesis of oxetane p-amino acids mainly by the Fleet s group and oxetane 5-amino acids by Ranter s group, in collaboration with Wessel s group, in order to smdy the potential of oxetane amino acids as monomers for p-/5-peptide foldamers, a class of unnatural oligomers with propensities to adopt specific and compact conformations for potential clinical applications. 

SCHEME 4.12 Oxetane formation by ring contraction of aldonolactones. 

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