Synthesis and Cytotoxicity of Monomethylated Betulinic Acid 3-O-α-l-Rhamnopyranosides.

Three original derivatives of the cytotoxic betulinic acid 3-O-α-l-rhamnopyranoside featuring a monomethylated rhamnoside residue were synthesized. An improved catalytic procedure was involved to functionalize the O-3 position of the monosaccharide in a site-selective fashion. The cytotoxicity of the novel compounds was evaluated in vitro to highlight the moderate impact of carbohydrate monomethylation on the biological activity of betulinic acid 3-O-α-l-rhamnopyranoside.

Total Synthesis of 6-Amino-2,6-dideoxy-α-Kdo from d-Mannose.

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) biosynthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from d-mannose as a potential inhibitor of Kdo-processing enzymes. Key steps of the synthetic sequence involve a Horner-Wadsworth-Emmons reaction for the two-carbon chain homologation followed by either a 6-exo-trig Pd-catalyzed reductive cyclization or a tandem Staudinger/aza-Wittig reaction with concomitant α-iminoester reduction, enabling the α-stereoselective formation of the Kdo-like six-membered azacyclic ring.