Lipase-catalyzed regioselective preparation of fatty acid esters of hydrocortisone

• Main Authors: Quintana, P.G., Baldessari, A.
• Format: Journal/Newspaper
• Language: unknown
• Subjects: Hydrocortisone fatty acid esters; Lipase-catalyzed reactions; 21 9 octadecanoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 9,12 octadecadienoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 9,12,15 octadecatrienoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 acetoxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 decanoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 hexanoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 octadecanoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 21 octanoyloxy 11beta,17alpha dihydroxypregn 4 en 3,20 dione; 3,11beta,17alpha triacetoxy 21 hydroxypregna 3,5 dien 20 one; fatty acid ester; hydrocortisone derivative; hydrocortisone fatty acid ester derivative; solvent; triacylglycerol lipase; unclassified drug; alcoholysis; article; biocatalyst; Candida antarctica; catalysis; enzyme substrate; esterification; methodology; stereochemistry; temperature; transesterification; Candida; Fatty Acids; Hydrocortisone; Lipase; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/20.500.12110/paper_0039128X_v74_n13-14_p1007_Quintana

A series of fatty acid derivatives of hydrocortisone has been prepared by an enzymatic methodology. Nine 21-monoacyl products and one 3,11,17-triacetyl derivative, nine of them novel compounds, were obtained in a highly regioselective way through lipase-catalyzed esterification, transesterification and alcoholysis reactions. The influence of various reaction parameters such as acylating agent: substrate ratio, enzyme: substrate ratio, solvent, temperature and nature of acylating agent and alcohol was evaluated. Among the tested lipases, Candida antarctica lipase appeared to be the most appropriate and showed a high efficient behavior especially in a one-pot transesterification. The advantages presented by this methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to prepare acyl derivatives of hydrocortisone. These lipophilic compounds are potential products in the pharmaceutical industry. © 2009 Elsevier Inc. All rights reserved.