Synthetic and stereochemical studies directed towards anatoxin-a

Abstract

The synthesis and stereocontrolled Ag^I-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 8avia9a 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.