A Totally Synthetic Route to Enantiomerically Pure D and L-Aminooctoses: Stereocontrolled Synthesis of Methyl α-D-Lincosaminide

Abstract

Abstract A general method for the stereoselective synthesis of monosaccharides from furan compounds has provided a route to higher-carbon sugars with defined relative configuration of the side chain and the pyranose ring.2 For the synthesis of enantiomeritally pure 6-amino-6, 8-dideoxy-octoses, of which an antibiotic sugar lincosamine3 (1) is a notable representative, substituted furans of the type 2 with defined absolute configuration are required. Compounds 2 could be obtained by the addition of furan to the appropriate four-carbon chiral synthons,4 e.g., α-aminoaldehydes. Various N-protected α-aminoaldehydes prepared5 from natural amino acids are extensively used6 as chiral building blocks for the asymmetric synthesis of complex molecules. Recently, high diastereoselectivities have been reported for the reactions of N- or N,O-protected alaninals and serinals with different reagents,7 including 2-trimethylsilyloxyfuran8 and furyllithium.9 From these studies it appeared that the diastereoselectivity of the addition depended mostly on the protecting groups of the α-aminoaldehyde. Now we report on the addition of furyllithium to N-benzenesulfonyl-N,O-isopro-pylidene derivatives of D-threoninal 4 and D-allothreoninal 5 which provides an access to enantiomerically pure 2-amino-l-(2-furyl)butan-1,3-diols 7 – 10 (Scheme 2). Availability of these compounds opens a route to the synthesis of aminooctoses of the D or L series in optically pure form.2 The method is demonstrated by the total synthesis of methyl α-D-lincosaminide, the sugar moiety of the commercial antibiotic lincomycin.3