Guanidine 2-amino-4 -oxazolones

The first derivatives of the 4(5/f)-oxazolone ring system 1 were prepared almost 90 years ago when Traube and Ascher described the synthesis of 2-amino-4(5H)-oxazolones (pseudohydantoins) 2 via condensation of guanidine with a-hydroxy esters (Scheme 6.1). This is quite remarkable in that it was 36 years later before Sheehan and Izzo prepared the hrst example of a simple 2-aryl analogue via... 

Other examples of spirocyclic 2-amino-4(5//)-oxazolones have been prepared and evaluated for their CNS activity and as potential antiviral agents. " In these reports, cyclization of the appropriate ot-hydroxy ester with guanidine afforded the novel analogues 93, albeit in low-to-modest yields. Representative examples are shown in Table 6.4 (Fig. 6.10). 

TABLE 6.4. SPIROCYCLIC 2-AMINO-4(5/7)-OXAZOLONES EROM a-HYDROXY ESTERS AND GUANIDINE... 

En route to a total synthesis of an antibacterial natural product indolmycin which contains an amino-substituted oxazolone, a-hydroxy acid 254 was treated with guanidine and KOr-Bu in /-BuOH in the presence of 4 A molecular sieves to produce oxazolone 255 with minimal epimerization of the acidic stereogenic center (Scheme 75) <2001CPB1604>. 

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