ABSTRACT
Biotin, hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid (Fig. 1), has been isolated from egg yolk. The structure of that vitamin, also called bios II, factor X, coenzyme R, anti-egg white injury, vitamin B8, 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 N1-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 HoffmannLa Roche process (5).
