SYNTHETIC AND STEREOCHEMICAL STUDIES DIRECTED TOWARDS ANATOXIN-A

The synthesis and stereocontrolled Ag(l)-catalysed cyclisation of a series of allenic amino esters 8a-e is described. For compounds 8a-d the cis-2,5-disubstituted pyrrolidine 9 is formed exclusively but the primary amine 8e undergoes cyclisation nonselectively to give a mixture of cis- and trans-pyrrolidines 9e and 10e. The synthetic potential of this allene-based methodology has been illustrated by the conversion of compound 8a via 9a into (+/-)-anatoxin-a 1 and the methoxy phosphine oxides 18 and 19 have been studied as ketone homologating agents within this context. The enzymatic resolution of (+/-)-8a using chymotrypsin is also described.