An Efficient Lipase‐Catalyzed Synthesis of Fatty Acid Derivatives of Vanillylamine with Antiherpetic Activity in Acyclovir‐Resistant Strains. Issue 4 (8th February 2017)

• Record Type: Journal Article
• Authors: Chanquia, Santiago N.; Boscaro, Nadia; Alché, Laura; Baldessari, Alicia; Liñares, Guadalupe García
• Is Part Of: ChemistrySelect. Volume 2:Issue 4(2017)
• Page Start: 1537
• Page End: 1543
• Publication Date: 2017-02-08
• Subjects: Antivirals -- Enzymatic synthesis -- Molecular modeling -- N-vanillylamides -- Thermomyces lanuginosus; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201700060
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A series of eleven N ‐fatty acid derivatives of vanillylamine was synthesized following an enzymatic approach, in excellent yield and a chemoselective way. The excellent results obtained by catalysis of Thermomyces lanuginosus lipase made the procedure very efficient, considering the low amount of enzyme required and its lower price in comparison with other commercial lipases. The influence of various reaction parameters in the lipase‐catalyzed reactions, such as enzyme source, nucleophile/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. In order to evaluate the influence of the fatty acid chain length and configuration on the reaction rate and yield, HPLC analysis and molecular modeling experiments were performed. The results showed that a chain length between 12–14 carbon atoms favors the activity of the enzyme, while insaturation had no effect on the reaction rate. These facts confirm the experimental results. In addition, some of the evaluated compounds exhibited antiviral activity against Herpes simplex virus type 1 (HSV‐1) KOS strain (TK+) and Field and B2006 strains (TK‐) in Vero cells. Abstract : N ‐vanillylamides derivated from fatty acids was synthesized in excellent yield and chemoselective form. The best results were obtained using a Thermomyces lanuginosus lipase in very low quantity at room temperature. The reaction was studied by HPLC and molecular modeling; both analyses showed that a chain length between 12–14 carbon atoms favors the enzymatic activity. Some of the evaluated compounds showed antiviral activity against Herpes simplex virus type 1 (HSV‐1) KOS strain and acyclovir‐resistant strains Field and B2006 multiplication in Vero cells.