A stereospecific synthesis of biotin from an aromatic precursor.

The total synthesis of the important natural product biotin 1 from the readily available keto diester 3 is described. This approach features the stereospecific hydrogenation of the thiophene intermediate 19 as the key synthetic step. The required differentiation of the diacid functionality of compound 7 is achieved by selective lactam formation with the terminal acid to yield the 8-membered lactam 8. A modified Curtius reaction then affords the rearranged diurethane 18 through a series of acyl transfers. Finally, a novel conversion of the 3, 4-diurethane moiety to the imidazolidone portion of biotin is utilized to complete the synthesis.

[1]  M. Uskoković,et al.  Stereospecific total synthesis of d-biotin from L(+)-cysteine. , 1975, Journal of the American Chemical Society.

[2]  M. Uskoković,et al.  Letter: A'stereospecific total synthesis of d-biotin from L-(+)-cysteine. , 1975, Journal of the American Chemical Society.

[3]  B. Zwanenburg,et al.  Chemistry of strained polycyclic compounds—III: Synthesis of cubane and homocubane alcohols , 1972 .

[4]  G. M. Badger,et al.  The chemistry of heterocyclic compounds , 1961 .

[5]  Y. Subbarow,et al.  BIOTIN. VI. SYNTHESIS OF BIOTIN AND epiALLOBIOTIN , 1947 .

[6]  Y. Subbarow,et al.  BIOTIN. IV. A SECOND SYNTHESIS OF 2-(δ-CARBOXYBUTYL)-THIOPHANE-3,4-DICARBOXYLIC ACID , 1947 .

[7]  A. Moyer,et al.  BIOTIN. III. 2-(δ-CARBOXYBUTYL) THIOPHANE-3,4-DICARBOXYLIC ACID1 , 1947 .

[8]  D. Wolf,et al.  Biotin; synthesis of dl-biotin, dl-allobiotin and dl-epi-allobiotin. , 1945, Journal of the American Chemical Society.

[9]  S. A. Harris,et al.  Hydrogenation of compounds containing divalent sulfur. , 1945, Journal of the American Chemical Society.

[10]  D. Wolf,et al.  Biotin; resolution of dl-biotin. , 1945, Journal of the American Chemical Society.

[11]  J. Piening,et al.  The Synthesis of 3-Aminothiophenes by Aromatization of β-Keto Ester Oximes1 , 1945 .

[12]  O. Schnider,et al.  Versuche zur Synthese des β‐Biotins. (Vitamin H.). 1. Mitteilung. Synthese des 2‐Methyl‐3,4‐(2′‐oxo‐tetrahydro‐imidazol)‐thiophans , 1945 .

[13]  K. Folkers,et al.  Biotin. II. Synthesis of Biotin , 1944 .

[14]  C. C. Hall,et al.  The hydrogenation of some sulphur compounds , 1943 .