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The biologically important amino acid statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, as well as optically active statine analogues, are readily accessible in the ester form by simple reduction of the corresponding N,N-dibenzyl P-keto esters using NaBH4 followed by deprotection.Chiral p-amino alcohols are biologically and pharmacologically interesting compounds.1 An example is statine (l), a constituent of the naturally occurring small peptide pepstatin which is a strong inhibitor of such aspartic proteinases as pepsin, renin, and cathepsin.2 Since renin inhibitors are currently of great interest in the treatment of hypertension and congestive heart failure, considerable efforts have gone into the synthesis of statine and statine analogues.3Since the (3S,4S)-configuration is an essential requirement for biological activity, stereoselective routes are required. The most efficient approach to date involves the conversion of t-butoxycarbonyl (Boc) protected L-amino acids into the corresponding P-keto esters (2) followed by reduction to (3). Unfortunately, common achiral reducing agents such as NaBH4 or NaCNBH3 lead to mixtures of diastereoisomers (3)/(4) or to the wrong (3R74S)-diastereoisomer (4) , and bulky reagents such as K(Bus)~BH afford <25% of (3).3-5 Therefore, chiral reducing agents had to be applied, e.g., enzymes5 or optically active Wilkinson catalysts.6

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291ChemInform Abstract The first systematic study is given of the non-racemizing synthesis of the chiral α-amino ketones (IV) from the α-amino acids (I) and the non-chelation controlled reduction of (IV) to the amino alcohols (V). For the ketones (IV) e.e. values in the range of 98.5-100% are found.