IN300551: A facile enantioselective synthesis of (s)-n-(5-chlorothiophene-2-sulfonyl)-ãŸ-ãŸ-diethylalaninol via proline catalyzed asymmetric î± aminooxylation and î± -amination of aldehyde

A high-yielding enantioselective synthesis of the bioactive (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β -diethylalaniol (7.b.2), a Notch-1-sparing y-secretase inhibitor metabolite (with EC5o = 28 nM) effective in reduction of A β production in vivo, has been realized starting from readily available 3-pentanone. The key steps of the synthesis are proline-catalyzed α-aminooxylation and α -amination of aldehyde; the latter contributing an overall yield of 50-75% and 90-99% ee.