Biotin structure determination

The structure of biotin was determined in the early 1940s by Kogl in Europe and by dn Vigneand and coworkers in the United States. Interestingly, the biotin molecule contains three asymmetric carbon atoms, and biotin could thus exist as eight different stereoisomers. Only one of these shows biological activity. 

The structure determination by Du Vigneaud and co-workers AO was completed in 1942 and it was established that biotin (vitamin H) was i -2 -keto-... 

The interesting structure determination of biotin by Du Vigneaud, Hofmann, Melville, and co-workers which involved some very fine and complicated chemical work can be discussed here only very briefly. ... 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Biotin was first isolated in pure form in 1936 by two Dutch chemists, Koegel and Tonnis, who obtained 1.1 milligrams from 250 kilograms of dned egg yolk. They showed that the compound was necessary for the growth of yeast and gave it the name, biotin. Five years later, in America, Gyorgy and co-workers found that the same compound prevented the toxicity of raw egg white in animals and, in 1942, du Vigneaud and collaborators determined the structure of the compound. 

Mozingo, Folkers, and co-workers (143) used the desulfuration reaction in the determination of the structures of biotin and its derivatives. 

Many compounds of biomedical interest, both of endogenous and exogenous origin, are heterocyclic in structure. Many of these compounds are electroactive at potentials useful for LCEC analysis. Methods for the determination of both ascorbic acid ° and uric acidt l were developed in the early days of LCEC. The important enzyme cofactors, the folates,the pterW biotin,f and NADH, " are all electroactive heterocycles that have been determined by LCEC. 

D-(+)-Biotin (1), a biocatalyst of reversible metabolic reactions of carbon dioxide transport in organisms, is one of the water-solnble B-complex gronp of vitamins and has immense commercial importance in ponltry feeds and animal nntrition. Componnd 1 was isolated from egg yolk, liver and milk concentrates. " It is an important vitamin for human nutrition and animal health. " Its structure was determined and confirmed by the first total synthesis. Its absolute configuration by X-ray crystallographic analysis was established. Syntheses of biotin from noncarbohydrate and its analogues from carbohydrate and noncarbohydrate have been reported. " Syntheses from carbohydrate precursors are discussed in this part. 

Each ACC half-reaction is catalyzed by a different protein sub-complex. The vitamin biotin is covalently coupled through an amide bond to a lysine residue on biotin carboxyl carrier protein (BCCP, a homodimer of 16.7-kDa monomers encoded by accB) by a specific enzyme, biotin-apoprotein ligase (encoded by birA), and is essential to activity. The crystal and solution structures of the biotinyl domain of BCCP have been determined, and reveal a unique thumb required for activity (J. Cronan, 2001). Carboxylation of biotin is catalyzed by biotin carboxylase (encoded by accC), a homodimeric enzyme composed of 55-kDa subunits that is copurified complexed with BCCP. The accB and accC genes form an operon. The three-dimensional structure of the biotin carboxylase subunit has been solved by X-ray diffraction revealing an ATP-grasp motif for nucleotide binding. The mechanism of biotin carboxylation involves the reaction of ATP and CO2 to form the shortlived carboxyphosphate, which then interacts with biotin on BCCP for CO2 transfer to the I -nitrogen. 

Figure 4.13 Competitive fluorescence assay performed on arrays of 40-pun sized squares of PGMA structures grafted from ETFE. The samples were post-modified with biotin and incubated with fluorescently labeled strepta-vidin and biotin of increasing concentrations (0, 0.005. 0.05, 0.5, 5, and 50 pglmL). Relative fbtorescaux mtensi-ties were determined from fluorescence images shown as insets.

Szent-Gyorgyi and US biochemist Vincent Du Vigneaud (1901-78) discover vitamin H (the B vitamin biotin). Roger Williams determines the structure of pantothenic acid. US biochemist Edward Doisey synthesizes vitamin K. 

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