Mycobacterium tuberculosis synthesis

Babaogln K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE. Novel inhibitors of an emerging target in Mycobacterium tuberculosis, snbsti-tnted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett 2003 13 3227-30. 

Zhang W (2006) Microwave-Enhanced High-Speed Fluorous Synthesis. 266 145-166 Zhang X-E, Deng J-Y (2005) Detection of Mutations in Rifampin-Resistant Mycobacterium Tuberculosis by Short Oligonucleotide Ligation Assay on DNA Chips (SOLAC). 261 169-190... 

Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycoUc acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drag with respect to these microorganisms. 

Dapsone, which was first proposed in 1941, possesses both bactericidal as weU as bacteriostatic activity with respect to Mycobacterium leprae and Mycobacterium tuberculosis. It is used to treat patients with herpetiform dermatitis. It is believed that the mechanism of its action consists of competitive inhibition of the enzyme dihydroprotease synthetase, which blocks synthesis of folic acid in microorganisms, allowing it to also be viewed as an analog of p-aminobenzoic acid. Synonyms of this drug are avosulfon, croysulfon and others. 

Pharmacology Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels, isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

It is a peptide protein synthesis inhibitor antibiotic isolated from Streptomyces capreolus. It is second line antimycobacterial drug which exhibits activity against human strains of Mycobacterium tuberculosis. 

An illustration of the use of -methyl-substituted thioesters in the synthesis of natural products is present in the total synthesis of a /3-D-mannosyl phosphomycoketide from Mycobacterium tuberculosis (Figure 5). Addition of MeMgBr to ethyl 6-benzyloxy-2-hexene thioate catalyzed by Cu/Josiphos (92% yield, 93% ee) furnished one of the building blocks. The other four methyl groups were introduced using copper/phosphoramidite-catalyzed dimethylzinc addition. 

As is pointed out in Chapter 16, the acquisition of iron and control of its concentration is of crucial importance to bacteria. In E. coli the Fe2+-binding protein Fur (ferric uptake regulator) represses promoters controlling siderophore biosynthesis as well as other responses. It is a global regulator that controls 40 transcriptional units.124 Similar proteins repress synthesis of the diphtheria toxin by Corynebac-terium diphtheriae,125 126 uptake of iron in these bacteria and in Mycobacterium tuberculosis,127 and uptake of molybdate.1273... 

The Mexican sponge Aplysina gerardogreeni contains calafianin (2106) (1880) (structure revised and confirmed by total synthesis, (1881-1883)), the known aerothionin, and the new phenylacetic acid 2107 (1880). These studies confirm that calafianin (2106) and aerothionin have the same absolute configuration (1883). Whereas aerothionin displays antibacterial activity against Mycobacterium tuberculosis, calafianin does not (1884). The Brazilian sponge Aplysina caissara contains the new caissarines A (2108) and B (2109) (1885). 

Mannosides of phosphatidylinositol are important serologically active components of Mycobacterium tuberculosis. For the synthesis of the 2-O-mannosyl derivative (421), Stepanov et al. [291] treated the chiral prop-l-enyl ether (414) [and the corresponding racemic prop-l-enyl ether and racemic benzoate (415)] with the orthoesters (416) or (417) to give the disaccharide (418) [from chiral (414) and acetate (416)] in moderate yield. The disaccharide obtained from racemic (414) contained a high proportion of (418) as a result of asymmetric synthesis. Acidic hydrolysis of (418) gave in low yield (30%) the alcohol (419). 

Metaferia BB, Fetterolf B J, Shazad - U1 - Hussan S et al (2007) Synthesis of natural product-inspired inhibitors of Mycobacterium tuberculosis mycothiol-associated enzymes the first inhibitors of GlcNAc-Ins deacetylase. J Med Chem 50 6326-6336... 

Norman, R.A., McAlister, M.S., Murray-Rust, J., Movahedzadeh, E, Stoker, N.G., and McDonald, N.Q., 2002, Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in phosphatidylinositol synthesis. Structure 10 393 102. 

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