An enantiospecific synthesis of solenopsin A

Article abstract of DOI:10.1016/S0040-4039(00)60479-3

Enantiomerically pure solenopsin A and B (1 and 2) are constituents of the venom of fire ant, Solenopsis invicta (= S. saevissima), the habitat of which is the south-east part of the United States of America (Scheme 1). Both molecules are biologically active in having hemolytic, insecticidal and antibiotic properties. Desite the apparent simplicity of their structure, the synthesis of the enantiomerically pure isomers is not trivial. The essential problem lies in the creation of the trans configuration for the 2,6-dialkyl substituents. So far four solutions have been reported. The first entails the transfer of chirality on successive alkylations of 2-cyano-6-oxazolopiperidine. The second involves the diastereoselective reduction of a bornyl β-keto ester to a chiral secondary alcohol which by conversion to its azide and subsequent internal dipolar addition controls the construction of the 2-methylpiperidine ring. The third depends essentially on the cyclization of 6R-aminoheptadecan-2-one to the related 1,2-dehydropiperidine which is then selectively reduced. The fourth solution exploits the innate chirality of 5-methyl L-glutamate which on elaboration provides an analogous amino-ketone which undergoes stereocontrolled cyclization. We now describe a practical enantiospecific synthesis of 1 that embodies the chief features of the last two approaches, but which takes advantage of our procedure for preparing enantiomerically pure β-amino acids from aspartic acid.