Synthesis of an ether-linked alkyl 5a-carba-β-d-glucoside, a 5a-carba-β-d-galactoside, a 2-acetamido-2-deoxy-5a-carba-β-d-glucoside, and an alkyl 5a′-carba-β-lactoside Original Research Article

For the purpose of providing biologically stable building blocks for the biocombinatorial synthesis using a living cell, some ether-linked alkyl 5a-carba-β-d-glycoside primers were prepared. The key step of the synthesis was coupling of 1-bromo-n-alkanes with the 1-OH unprotected derivatives of 5a-carba-sugar analogues of d-glucose, d-galactose, and 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine), in DMF in the presence of sodium hydride. Alternatively, alkyl carba-lactoside was synthesized by incorporation of a 5a-carba-β-d-galactose residue into the 4-position of dodecyl β-d-glucopyranoside. A strong and specific inhibition of β-galactosidase (Ki 0.67 μM, bovine liver) was found for dodecyl 5a-carba-β-d-galactopyranoside.