Design and use of an oxazolidine silyl enol ether as a new homoalanine carbanion equivalent for the synthesis of carbon-linked isosteres of O-glycosyl serine and N-glycosyl asparagine

A trimethylsilyl enol ether carrying the N-Boc 2,2-dimethyloxazolidine ring was designed to serve as a synthetic equivalent of the homoalanine carbanion for the introduction of the alpha-amino acid side chain at the anomeric carbon of sugars. This new functionalized silyl enol ether was prepared in multigram scale and high enantiomeric purity starting from methyl N-Boc-L-threoninate (six steps, 49% yield). This reagent was employed in two synthetic approaches to C-glycosyl amino acids. In one approach, the BF3. Et2O-promoted coupling with tetra-O-benzyl-D-galactopyranosyl trichloroacetimidate afforded the alpha-linked C-glycoside as main product (30% isolated yield), which upon treatment with tert-butyllithium was converted into the beta-linked isomer. Deoxygenation of these compounds by the Barton-McCombie method and unmasking of the glycyl moiety from the oxazolidine ring by oxidative cleavage with the Jones reagent gave the C-glycosyl serine isosteres alpha- and beta-Gal-CH2-Ser. In a similar way were prepared alpha- and beta-Glc-CH2-Ser starting from tetra-O-benzyl-D-glucopyranosyl trichloroacetimidate. In a second approach, the same oxazolidine silyl enol ether was condensed with formyl tetra-O-benzyi-beta-D-C-galactopyranoside in the presence of BF3. Et2O to give the beta-linked C-glycoside in 78% yield without any anomerization. The deoxygenation of this product and the cleavage of the oxazolidine ring as described above afforded the glycosyl asparagine isostere beta-Gal-(CH2)(2)-Asn. The same reaction sequence was applied to convert formyl tetra-O-benzyl-beta-D-C-glucopyranoside and mannopyranoside into the C-glycosyl amino acids P-Glc(CH2)(2)-Asn and beta-Man-(CH2)(2)-Asn, respectively.