Lycoperdic acid (1), which incorporates a ring structure in the 4-position of Glutamic Acid, was isolated from the mushroom Lycoperdon perlatum in 1978. Due to the similarities in structure that are found between it and the amino acid (S)-glutamic acid, (S)-(+)-lycoperdic acid is expected to have either antagonistic or agonistic activity for the glutamate receptor within the central nervous system for mammals. (S)-(+)-lycoperdic acid is very important because it can either bind to the receptor and therefore activate it, hence producing a response in the central nervous system or it can help provide a way to block agonist related responses. Due to these possibilities happening within the central nervous system, not only will (S)-(+)-lycoperdic acid help provide help for memory but also play a vital role in disabling certain neurodegenerative disorders from occurring such as Alzheimer’s disease and stroke. The significant biological activity and the low abundance of lycoperdic acid 1, has sparked its total synthesis. Using chemistry that we have done in our group, we propose the synthesis of 1 and its analogs from the 1,3-dipolar cycloaddition of furfural oxime (2) and the alkene (3). These compounds are derived from inexpensive starting materials; furfanal and α-ketoglutaric acid respectively. The cycloaddition reaction will generate the (S) and (R)- cycloadducts 4a and 4b respectively. The desired compound 4a will be separated by flash column chromatography, and transformed to the desired product 1 after deprotection of the para-methoxy benzyl groups followed by reductive cleavage of the isoxazolidine ring and oxidation of the resulting primary alcohols to generate S-(+/-)-lycoperdic acid. (Scheme 1)

Synthesis of S -(+/-)-lycoperdic acid

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.