Pergamon Tetrahedron Letters 39 (1998) 1233-1236 TETRAHEDRON LETTERS Enantioselective Synthesis of N-Boc-2,2-Dimethyloxazolidine-5- Carbaldehydes, Versatile Precursors of Dipeptide Isosteres Mireia Past6, Albert Moyano, Miquel A. Perichs*, Antoni Riera* Unitat de Recercaen Slntesi Asim~trica. Departament de QutmicaOrg~nica,Facultatde Quimica,Universitatde Barcelona. Marti i Franqu~s,1-11, Barcelona E-08028, Spain. Received 14 November 1997; accepted 28 November 1997 Abstract. Highly enantioenriched cis and trans N-Boc-2,2-dimethyl-oxazolidine-5-carbaldehydes have been efficiently prepared from N-Boc-3-amino-l,2-alkanediols, readily available in enantiopure or enantioenriched form by Sharpless epoxidation methodology.These compounds have been converted into N-Boc-(S)-7-[(S)-l-aminoaikyl]-~'-lactones which are key intermediates of hydroxyethylene dipeptideisosteres. © 1998 ElsevierScienceLtd. All rights reserved. The successful development of aspartic protease inhibitors acting on renin or on the HIV protease has stimulated the research in the use of enzyme inhibitors as therapeutic agents. 1 The most usual strategy so far employed has been the replacement of the scissile amide bond in a peptidic substrate by hydrolytically stable functionality with isosteric character. 2 From the perspective of starting materials, most of the approaches to dipeptide mimics in enantiomerically pure form are based on natural sugars or amino acids. Taking into account that the stereochemistry of the peptidomimetic fragment is key to inhibitory action, stereoselective methodologies devoted to the synthesis of those fragments are of fundamental importance for the development of new drugs belonging to this class. Oxazolidine-5-carbaldehydes trans-la-e, which have been prepared from co-amino acids, 3-5 are precursors to several types of important dipeptide isosteres.3-6 It is evident that the development of stereoselective methodology of wide applicability for the synthesis of these and related compounds would overcome the limitations inherent to the use of natural products as starting materials and would allow the control of the configuration of the stereogenic centres. ..~ la: R = CH2CH(CH3) 2 0 lb: R = CH2Ph B°cN~ 0 ~ le: R = CH2CsH11 R1 H ld: R = OH3 le: R = Ph trans-1 During the last years we have shown how anti-N-Boc-3-amino-l,2-alkanediols 2, available in high enantiomeric purity through the use of a catalytic asymmetric Sharpless epoxidation of (E)-allyl alcohols followed by nucleophilic ring opening, can be efficiently converted into enantiomerically pure t~-amino acids7, [~-amino acids 8, t~-hydroxy-~-amino acids 9 and [~-hydroxy-7-amino acids, 10 which are important components of peptides and other biologically active compounds. We describe in the present paper an efficient stereoselective synthesis of N-Boc-2,2-dimethyloxazolidine-5-carbaldehydesle-e of any relative configuration from N-Boc-3-amino-l,2-alkanediols 2c-e. Moreover, as an illustration of the synthetic potential of these 0040-4039/98/$19,00 © 1998 Elsevier Science Ltd. All rights reserved. PIL" S0040-4039(97) 10738-9