Biotin commercial synthesis

Togni and Spindler introduced non-C2-symmetric ferrocene-based Josiphos-type ligands [47], which are effective for rhodium-catalyzed hydrogenation of a-(acetami-do)cinnamate, dimethyl itaconate, and / -keto esters. The Josiphos-type hgands have been applied as the stereodefming step in a number of industrial processes, as exemplified the use of PPF- Bu2 for the commercial synthesis of (-i-)-biotin [48], and Xyli-Phos for the preparation of the herbicide (S)-metolachlor [49]. 

The commercial synthesis of biotin developed in the laboratories of Hoffmann-La Roche, Inc., is given in Fig. 4. It differs from the other syntheses in several respects. The imidazolidone ring is formed first with the... 

The importance of biotin in nutrition and increasing commercial needs combine to suggest the need for short and economical synthesis. Retrosynthetic analysis using cysteine as SM goal suggested a number of synthetic pathways for study, one of which has been demonstrated as shown below. 

Biotin can be produced commercially by using, for starting the synthesis, meso-diamino succinic acid derivative of fumaric acid. 

Allowing Nature to do part of the work is the central theme of Method 3. Numerous chiral molecules, isolated from natural sources and often available commercially, already contain much of the appropriate stereochemistry required in an enantioselective synthesis. These compounds are called the pool of chiral compounds. One reported synthesis of biotin (2), a molecule involved in enzymatic transfer of C02, used the methyl ester of the amino acid cysteine (1) as starting material.5 Note how 1 possesses a key stereocenter that later appears in biotin. 

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. 

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