Stereoselective synthesis of analogues of deoxyfebrifugine

The preparation of six new optically active analogues of the natural product febrifugine (1) is reported. These analogues, lacking the hydroxy group from the natural product, were prepared from optically active N-protected S-pelletierine (7) and differ in terms of the specific quinazolinone portion included. The required S-7 (80% enantiomeric excess) was prepared from an asymmetric Mannich reaction between piperideine (8) and acetone in the presence of l-proline. The differently substituted quinazolinone used in this study (10a-10g) was either commercially available or was prepared from the corresponding substituted anthranilic acid and were installed via a bromination-alkylation sequence. N-Deprotection of the subsequent adducts (12a-12g) gave target compounds 13a-13f and completed the synthetic sequence.