Semi-synthesis of A23187 (calcimycin) analogs. III. Modification of benzoxazole ring substituents, ionophorous properties in an organic phase.

Prudhomme, Michelle; Dauphin, G.; Jeminet, Georges

doi:10.7164/antibiotics.39.922

Cited by 21 publications

(7 citation statements)

References 5 publications

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“…5-Hydroxy-4-benzoxazolecarboxylic acid ( 4 ) was generated from methyl 2-amino-3,6-dihydroxybenzoate ( 23 ) 17 as in Scheme 7. Methyl ester 23 was converted into oxazole 24 in 75% yield with triethyl orthoformate in refluxing EtOH.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of heterobactins A and B and Nocardia heterobactin

2011

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The synthesis of the Rhodococcus erythropolis siderophores heterobactins A and B, and the structurally related Nocardia heterobactin, is described. Two approaches for the assembly of these asymmetric ligand donor chelators are explored. In the first approach, a scheme predicated on the biosynthesis of the Paracoccus denitrificans siderophore, parabactin, is employed. In this approach, the central donor synthon is added last. In the second scheme, the central donor and the terminal 2,3-dihydroxybenzoyl fragment are first fixed to the ligand’s D-ornithine backbone. This is followed by condensation with the cyclic ornithine hydroxamate glycine segment. The schemes offer a flexible approach to other heterobactins. Job’s plots suggest that heterobactin A and Nocardia heterobactin form 1:1 ligand/metal complexes, while heterobactin B forms a 3:2 ligand/metal complex.

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Section: Resultsmentioning

confidence: 99%

Synthesis of heterobactins A and B and Nocardia heterobactin

2011

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“…Calcimycin and a number of similar molecules have been chemically synthesized (26)(27)(28). Calcimycin derivatives have also been generated by microbial transformation (1).…”

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confidence: 99%

Characterization of the Biosynthesis Gene Cluster for the Pyrrole Polyether Antibiotic Calcimycin (A23187) in Streptomyces chartreusis NRRL 3882

Lin

et al. 2011

Antimicrob Agents Chemother

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The pyrrole polyether antibiotic calcimycin (A23187) is a rare ionophore that is specific for divalent cations. It is widely used as a biochemical and pharmacological tool because of its multiple, unique biological effects. Here we report on the cloning, sequencing, and mutational analysis of the 64-kb biosynthetic gene cluster from Streptomyces chartreusis NRRL 3882. Gene replacements confirmed the identity of the gene cluster, and in silico analysis of the DNA sequence revealed 27 potential genes, including 3 genes for the biosynthesis of the ␣-ketopyrrole moiety, 5 genes that encode modular type I polyketide synthases for the biosynthesis of the spiroketal ring, 4 genes for the biosynthesis of 3-hydroxyanthranilic acid, an N-methyltransferase tailoring gene, a resistance gene, a type II thioesterase gene, 3 regulatory genes, 4 genes with other functions, and 5 genes of unknown function. We propose a pathway for the biosynthesis of calcimycin and assign the genes to the biosynthesis steps. Our findings set the stage for producing much desired calcimycin derivatives using genetic modification instead of chemical synthesis.

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“…Among semisynthetic compounds worth mentioning are Calcimycin derivatives. 14 The number of synthetic benzoxazole derivatives is enormous, and they exhibit various types of activity eg, antibacterial, antifungal, antiinflammatory, antiviral, anticancer, analgesic, anticonvulsant, antioxidant, antidepressant, anthelmintic, and herbicidal. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Furthermore, benzoxazole derivatives possess ability to inhibit the action of many enzymes such as DNA topoisomerase I and II, 32 cyclooxygenase II, 33 5-lipoxygenase, 34 microsomal prostaglandin E 2 synthase-1, 35,36 Aurora B kinase, 37 p90 ribosomal S6 kinase 2, 38 human fructose-1,6-bisphosphatase, 39 or protein tyrosine phosphatase 1B.…”

Section: Introductionmentioning

confidence: 99%

Lipase‐catalyzed kinetic resolution of novel antitubercular benzoxazole derivatives

2017

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Novel benzoxazole derivatives were synthesized, and their antitubercular activity against sensitive and drug-resistant Mycobacterium tuberculosis strains (M. tuberculosis H Rv, M. tuberculosis sp. 210, M. tuberculosis sp. 192, Mycobacterium scrofulaceum, Mycobacterium intracellulare, Mycobacterium fortuitum, Mycobacterium avium, and Mycobacterium kansasii) was evaluated. The chemical step included preparation of ketones, alcohols, and esters bearing benzoxazole moiety. All racemic mixtures of alcohols and esters were separated in Novozyme SP 435-catalyzed transesterification and hydrolysis, respectively. The transesterification reactions were carried out in various organic solvents (tert-butyl methyl ether, toluene, diethyl ether, and diisopropyl ether), and depending on the solvent, the enantioselectivity of the reactions ranged from 4 to >100. The enzymatic hydrolysis of esters was performed in 2 phase tert-butyl methyl ether/phosphate buffer (pH = 7.2) system and provided also enantiomerically enriched products (ee 88-99%). The antitubercular activity assay has shown that synthesized compounds exhibit an interesting antitubercular activity. Racemic mixtures of alcohols, (±)-4-(1,3-benzoxazol-2-ylsulfanyl)butan-2-ol ((±)-3a), (±)-4-[(5-bromo-1,3-benzoxazol-2-yl)sulfanyl]butan-2-ol ((±)-3b), and (±)-4-[(5,7-dibromo-1,3-benzoxazol-2-yl)sulfanyl]butan-2-ol ((±)-3c), displayed as high activity against M. scrofulaceum, M. intracellulare, M. fortuitum, and M. kansasii as commercially available antituberculosis drug-Isoniazid. Moreover, these compounds exhibited twice higher activity toward M. avium (MIC 12.5) compared with Isoniazid (MIC 50).

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Semi-synthesis of A23187 (calcimycin) analogs. III. Modification of benzoxazole ring substituents, ionophorous properties in an organic phase.

Cited by 21 publications

References 5 publications

Synthesis of heterobactins A and B and Nocardia heterobactin

Synthesis of heterobactins A and B and Nocardia heterobactin

Characterization of the Biosynthesis Gene Cluster for the Pyrrole Polyether Antibiotic Calcimycin (A23187) in Streptomyces chartreusis NRRL 3882

Lipase‐catalyzed kinetic resolution of novel antitubercular benzoxazole derivatives

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