A combinatorial biocatalysis approach to an array of cholic acid derivatives.
A 39-member library of bile acid derivatives was prepared starting from 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic acid methyl ester using a combinatorial biocatalytic approach. A regioselective oxidation step, catalyzed by hydroxysteroid dehydrogenases, followed by an acylation step with a series of different acyl donors catalyzed by Candida antarctica lipase B, led to the modification of the bile acid scaffold. Each member of the library was obtained in high purity and good yield.
Secundo
Francesco
F
Istituto di Chimica del Riconoscimento Molecolare del CNR, via Mario Bianco 9, 20131 Milano, Italy. secundo@ico.mi.cnr.it
Carrea
Giacomo
G
De Amici
Marco
M
Joppolo Di Ventimiglia
Samuele
S
Dordick
Jonathan S
JS
D000215:Acylation; D001647:Bile Acids and Salts / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D019826:Cholic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004951:Esterification; D005656:Fungal Proteins; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry*; D007536:Isomerism; D008049:Lipase / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000737:chemistry; D010084:Oxidation-Reduction; D010865:Pilot Projects; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D006913:Hydroxysteroid Dehydrogenases; D008049:Lipase; C431349:lipase B, Candida antarctica; D019826:Cholic Acid