Biological significance and development of practical synthesis of biotin.
Biotin (1), a water-soluble B series vitamin, distributes widely in microorganisms, plants, and animals. Biosynthesis of 1 involves five steps sequence starting from pimelic acid. The last step, a transformation from dethiobiotin (DTB) to 1, includes an iron clusters-mediated radical process. The compound 1 is a cofactor of carboxylation enzymes and plays crucial roles in the metabolism of fatty acids, sugars, and alpha-amino acids. In addition to the increasing application to feed additives, recent reports have revealed that 1 enhances insulin secretion in animals, suggesting it for a promising therapeutic candidate for an anti-diabetes drug. The remarkably strong affinity of 1 with avidin and streptavidin has been extensively applied for such technologies as photoaffinity labeling. Among the number of approaches to 1 so far developed in 50 years, a synthesis using L-cysteine and thiolactone as a starting material and a key intermediate, respectively, represents one of the best routes leading to 1, because of short steps, high yield, use of inexpensive reagents, and ease of operation.
Seki
Masahiko
M
Tanabe Seiyaku Co., Ltd., 3-2-10, Dosho-Machi, Osaka 541-8505, Japan. m-seki@tanabe.co.jp