A new type of sugar-amino acid hybrid, which is comprised of a sugar unit (gluco-, galacto-, or mannopyranose) linked through a C-glycosidic linkage to the beta-position of an alpha-unsubstituted beta-amino acid unit, is presented. It is hypothesized that these new compounds, or the oligomeric peptides derived therefrom, might possess the structural features of beta-amino acid oligomers and the chemical and enzymatic resistance of C-glycosides to hydrolysis. The synthetic strategy is based on a new Mannich-type reaction between a chiral acetate enolate equivalent and alpha-amido sulfones derived from the corresponding sugar-C-glycoside aldehydes. While the sugar-C-glycoside aldehyde partner is prepared from well-established transformations on known sugar precursors, the lithium enolate derived from (1R)-endo-2-acetylisoborneol 3 is employed as the key element. This Mannich approach proceeds with essentially perfect diasteromeric control leading to the new beta-amino carbonyl adducts in good yields. Further, cleavage of the camphor auxiliary is smoothly performed by oxidative treatment with ammonium cerium nitrate (CAN). Complementarily, direct peptide-type coupling of the beta-amino carbonyl Mannich adducts with an alpha- or beta-amino acid residue and subsequent CAN-promoted detachment of the auxiliary yields dipeptide fragments bearing a sugar-containing aliphatic side chain and is a process that can be iterated. A preliminary conformational study based on the combination of experimental NMR data and molecular mechanics and molecular dynamics (MD) of one particular adduct is also provided.

The insufficient diastereoselectivity and generality, which are the main problems of the “acetate” aza – aldol reaction, can now be addressed through the reaction of the lithium enolate of endo‐O‐trimethylsilyl acetyl isoborneol with various N‐[(p‐tolylsulfonyl)alkyl]carbamates (see scheme). This development provides record levels of asymmetric induction in a new Mannich‐type synthesis of β‐amino acids which is general even for inherently enolizable imino compounds.

(1R)-2-endo-Bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (endo-2-bromoacetylisoborneol) 4 and its trimethylsilyl ether 3 are presented as efficient reagents for the asymmetric Darzens reaction. From the alpha,beta-epoxy ketone adducts the chiral inductor camphor is removed, by treatment with ceric(IV) ammonium nitrate, to yield the corresponding epoxy acids which are isolated as their dicyclohexylammonium salts.