Biotin absolute configuration

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. 

II, factor X, coenzyme R, anti-egg white injury, vitamin Bg, or vitamin H, was established in 1942 and its synthesis was achieved a year later (1). The absolute configuration of biotin was elucidated by x-ray crystallographic analysis on biotin and on a TVi-carboxy derivative (reviewed in 2). NMR studies (3,4) demonstrated that the conformation of the thiophene ring is the same in the solid state and in solution the sulfur atom lies above the thiophene ring and the valeric chain adopts a quasi-equatorial position (Fig. 1). The same conformation is encountered in the biotin sulfoxides (Fig. 2) (3,4). Numerous total syntheses of biotin have been published and this topic has been thoroughly reviewed recently (5), but the bulk of biotin is still produced according to the original Hoffmann-La Roche process (5). 

The stereospecific total synthesis of (+)-biotin (470) has been achieved from D-mannose by the route shown in Scheme 151. Canadian and Japanese groups have independently established the absolute configuration of the naturally occurring antifungal compound avenaciolide (471) isolated from Asperigillus avenaceus. The route used by Anderson and Fraser-Reid is illustrated in Scheme 152, and that used by the Japanese workers follows closely similar lines. 

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