Previous Article in event Previous Article in session
Next Article in event Next Article in session
Semi-Synthetic Analogs of 17-Hydroxycativic Acid and their Biological Evaluation
Published: 31 October 2013 by MDPI in The 17th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural Products
Abstract: In the course of our ongoing studies of natural products from our regional flora with acetylcholinesterase (AChE) inhibitory activity, a bioassay-guided fractionation of the ethanolic extract of Grindelia ventanesis Bartola & Tortosa (Asteraceae) resulted in the isolation of a labdane diterpene of the normal series identified as 17-hydroxycativic acid. Taking into account that this compound showed a significant inhibition of AChE (IC50 = 21.1 μM) and that it was easily isolated from the plant extract in a very good yield (150 mg/ 100 g of aerial parts), we decided to obtain semisynthetic analogs of this natural diterpene through simple structural modifications of the three hot spots of this molecule: the carboxylic group (C15), the double bond (C7-C8) and the primary allylic alcohol (C17). Until now the following transformations have been achieved: reduction of the carboxylic acid to alcohol using LiAlH4, synthesis of the methyl ester with K2CO3 and CH3I, sulfation with trimethylamine-sulfur trioxide complex and acetylation with Ac2O/pyridine of the hydroxyl group. These four derivatives are new diterpenes and have been fully characterized by mono- and bidimensional NMR spectroscopy. The results obtained in the in vitro evaluation of their AChE and butyrylcholinesterase inhibitory activity and structure-activity relationship will be discussed.
Keywords: Grindelia ventanensis, acetilcholinesterase inhibition, 17-hydroxycativic acid, semisynthesis