A method for the parallel synthesis of multiply substituted oxazolidinones.
There are many examples of both naturally occurring and synthetic molecules containing a 2-oxazolidinone ring that have significant biological activity. The oxazolidinone ring potentially has three sites for attachment of diversity elements. A synthesis that can provide for inclusion of diversity elements at all three positions should be a powerful method for the preparation of oxazolidinone libraries. In this paper we present the preparation of a 3 x 3 x 3 array yielding 27 different products with minimal workup, high yields, and, most importantly, high purity. Using an intramolecular acylnitrene-mediated aziridination reaction, we have prepared (triphenylmethoxymethyl)-3-oxa-1-azabicyclo[3.1.0]hexan-2-one as a starting material for library generation. The first substitution involves opening the aziridine ring of the azabicyclo[3.1.0]hexane ring system using a Grignard reagent. The nitrogen of the oxazolidinone is now ready for substitution via alkylation or arylation. Removing the trityl protecting group via esterification under mildly acidic conditions accomplishes the final substitution.
Bergmeier
Stephen C
SC
Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701, USA.
Katz
Steven J
SJ
D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D001388:Aziridines / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D023303:Oxazolidinones / Q000138:chemical synthesis*
D000890:Anti-Infective Agents; D001388:Aziridines; D023303:Oxazolidinones; C033132:aziridine