Cord factor synthesis

Asselineau, J., H, Bloch and E. Lederer Synthesis of Cord-Factor active... 

The chemical synthesis of derivatives and emalogs has long coimnanded much interest, as such compounds are required for the study of structure—activity relationships in the action of trehalases (23,28), may serve as substitutes for 51 in the synthesis of cord-factor analogs to be used as probes in the field of mycobacterial biochemistry (29, 30), and could possibly prove to possess interesting properties as enzyme inhibitors or antibiotic agents. 

S. Bottle and I. A. Jenkins, Improved synthesis of cord factor analogues, J. Chem. Soc., Chem. Commun. (1984) 385. 

I. D. Jenkins and M. B. Goren, Improved synthesis of cord factor analogues via the Mitsunobu reaction, Chem. Phys. Lipids, 41 (1986) 225-235. 

Four methods of synthesis of cord factor and its analogs have been developed. 

The method of synthesis of these compounds was suggested by the synthesis of two stearic acid esters of a,a-trehalose by Willstaedt and Borg ,rd in 1946, and, in 1956, Lederer and coworkers synthesized cord factor. Mycolic acid was acetylated with acetic anhydride in the presence of pyridine and the product was converted into the acid chloride, which was reacted with anhydrous a,a-trehalose in pyridine for two to... 

The purification procedure of 6,6 -esters of OMf-trehalose from Coryne-bacterium diphtheria has been modified and the products were analysed by m.s. of the permethylated derivative.The constituent fatty acids have been extensively examined and the detailed structure of the major acids have been confirmed by a variety of techniques. Novel glycolipids in the cord factor fraction from C. diphtheria were a 6,6 -bis(3-oxo-acyl)-o a -D-trehalose and a 6, 6 -mixed ester of aa-trehalose with the 3-oxo-acyl group and a corynomycolic acid. The metabolic implications of these structural studies suggest that condensation of the common fatty acids by a Claisen-like process via the oxo-ester pathway may not be the only pathway for the synthesis of the cord factors. 

Glycolipids and Gangliosides.—Approaches to the synthesis of D-galactosyl-glycerol, D-galactosyldiglycerides, and plant galactolipids have been reviewed. A new approach to the synthesis of cord factor (the toxic glycolipid of Mycobacterium tuberculosis) is based on the use of ester derivatives of aa-trehalose... 

An improved synthesis of cord factor analogues via the i-iitsunobu... 

The solvent also plays an important role in the success of the reaction. In general, reaction in benzene or toluene gives higher yields of inverted products. - Although pyridine is not suitable in the preparation of nucleotides, pyridine can be used for the synthesis of sucrose epoxide, and a mixture of dioxane-pyridine (9 1) can be utilized in the preparation of sugar carboxylates. Mixed solvent systems may be necessary when the acid and alcohol components have widely differing solubilities. Thus a mixture of HMPA and dichloromethane works well in the synthesis of lipophilic carbohydrate esters such as cord factor. ... 

Vitamin B12 deficiency is associated with increased synthesis of tumor necrosis factor-a and decreased synthesis of epidermal growth factor in the spinal cord in experimental animals, injection of tumor necrosis factor-a... 

What is the mechanism controlling the rate of synthesis of each of these hemoglobin chains during development It has been suggested that the site of red cell production is a major factor however, (and 8) and 7 chains can be synthesized by red cell precursors in the bone marrow as well as in the liver (Fll, T4) whereas the presence of small amounts of Hb-Gower 2 (or 2 2) and of Hb-Portland-1 (or 72 2) in (some) cord blood samples (C2, H22) show that red cell precursors in sites other than in the metamorphosing embryo are able to synthesize these polypeptide chains. 

Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells ( cytokines") stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/ inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. 

At least two rare alleles, Fj and Sj, have been found. Significant differences between Bf types of maternal and cord blood suggest fetal synthesis of the protein. No deficiency of Factor B has as yet been found. 

Ballow and coworkers [21, 22] studied the differentiation of B cells from adult PBMC and cord blood mononuclear cells (CBMC) in response to stimulation with Cowan I strain Staphylococcus aureus (SAC), a TD factor that induces immunoglobulin synthesis. RA increased the synthesis of IgM by CBMC and the synthesis of IgG by adult PBMC. RA-incubated T cells from either CBMC or PBMC provided comparable help for the differentiation of B cells. These results [21] and others from Epstein-Barr virus-transformed B cells [23] suggested an increase in the production of IL-6 in the mechanism of RA-enhanced immunoglobulin synthesis. 

---