A general route to 4-C-branched sugars. Synthesis of methyl alpha-caryophylloside.

The total synthesis of methyl 3,6-dideoxy-4-C-(D-altro-1,3,4,5 tetrahydroxyhexyl)-alpha-D-xylo-hexopyranoside, the methyl glycoside of the recently isolated 4-C-branched sugar caryophyllose, has been completed in a stereoselective and convergent manner. The synthesis of this dodecose relies on the diiodosamarium mediated coupling of two six-carbon fragments: a cyclic ketone and an acid chloride.

Synthesis of methyl beta-D-arabinofuranoside 5-[1D (and L)-myo-inositol 1-phosphate], the capping motif of the lipoarabinomannan of Mycobacterium smegmatis.

The total synthesis of methyl beta-D-arabinofuranoside 5-(myo-inositol 1-phosphate), the capping motif of the lipoarabinomannan (LAM) of Mycobacterium smegmatis, has been completed. The stereoselective synthesis of beta-D-arabinofuranosides has been achieved via an internal aglycon delivery approach using Ogawa and Ito's method. Coupling with enantiomeric myo-inositol derivatives gave the diastereoisomeric title compounds in good overall yield. Comparison with the natural product firmly established the proposed structure for the capping of the LAM but left the absolute configuration of the myo-inosityl moiety undetermined.

The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages.

The mannose receptor (MR) is involved in the phagocytosis of pathogenic microorganisms. Here we investigated its role in the bactericidal functions of human monocyte-derived macrophages (MDMs), using (i) trimannoside-bovine serum albumin (BSA)-coated latex beads and zymosan as particulate ligands of the MR, and (ii) mannan and mannose-BSA as soluble ligands. We show that phagocytosis of mannosylated latex beads did not elicit the production of O2-. Zymosan, which is composed of alpha-mannan and beta-glucan, was internalized by the MR and a beta-glucan receptor, but the production of O2- was triggered only by phagocytosis through the beta-glucan receptor. Activation and translocation of Hck, a Src family tyrosine kinase located on lysosomes, has previously been used as a marker of fusion between lysosomes and phagosomes in human neutrophils. In MDMs, Hck was activated and recruited to phagosomes containing zymosan later than LAMP-1 and CD63. Phagosomes containing mannosylated latex beads fused with LAMP-1 and CD63 vesicles but not with the Hck compartment, and the kinase was not activated. We also demonstrate that the MR was unable to distinguish between nonpathogenic and pathogenic mycobacteria, as they were internalized at similar rates by this receptor, indicating that this route of entry cannot be considered as a differential determinant of the intracellular fate of mycobacteria. In conclusion, MR-dependent phagocytosis is coupled neither to the activation of NADPH oxidase nor to the maturation of phagosomes until fusion with the Hck compartment and therefore constitutes a safe portal of entry for microorganisms.