AN EXPEDITIOUS ASYMMETRIC-SYNTHESIS OF ALLOPHENYLNORSTATINE

Allophenylnorstatine [APNS; (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid], a novel amino acid found in the kynostatin class of HIV-1 protease inhibitors, has been prepared in 39% overall yield via a tandem conjugate addition-electrophilic hydroxylation protocol using lithium (S)-(alpha-methylbenzyl)benzylamide and (+)-(camphorsulfonyl)oxaziridine. An unprecedented level of molecular recognition between a homochiral beta-amino enolate and a homochiral oxaziridine is identified and the importance of enolate geometry upon hydroxylation stereoselectivity is also addressed.