Squaric Acid Bioisostere

In the previous section, the utility of squaric acid is described from the viewpoint of developing biologically active substances, especially focusing on synthetic strategies for ring transformation to various heterocycles. The structure of cyclobutenedione itself is also intriguing and occasionally exploited for studies on biologically interesting molecular design. One reason is the peculiar acidic functionality of squaric acid. Therefore, "bioisostere" with this ring investigates how the acid derivatives show their activity relative to naturally occurring products or pharmacologically interesting products. These compounds are mainly attained by functional interconversion of acid ester to acid amide (i.e., squarate to squaramide). This section deals with chemistry of biologically active cyclobutenediones bearing heterocycles at the C-2 and/or C-3 position.

Amino squaric acids 186 and 188, the relatives of natural amino acids, represent an intuitive example of bioisostere, although the heterocycle is absent in these molecules. These were obtained by radical reaction of 2-stannylcyclobutenedione [133] and carbanion addition to squarate ester [134,135] (Scheme 33).

R Of-Bu BocLiN OLi

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