Generation of Broad-Spectrum Antifungal Drug Candidates from the Natural Product Compound Aureobasidin A

Autor:	Ake P. Elhammer, Peter Wuts, Lloyd J Simons, Brian P. Metzger, Rachel C Sterling, Jerry L. Slightom
Rok vydání:	2015
Předmět:	Natural product biology Pinacol Stereochemistry Organic Chemistry Antifungal drug Phenylalanine biology.organism_classification Biochemistry Borylation Aspergillus fumigatus chemistry.chemical_compound chemistry Bromide Drug Discovery Moiety
Zdroj:	ACS Medicinal Chemistry Letters. 6:645-649
ISSN:	1948-5875
Popis:	The natural product aureobasidin A (AbA) is a potent, well-tolerated antifungal agent with robust efficacy in animals. Although native AbA is active against a number of fungi, it has little activity against Aspergillus fumigatus, an important human pathogen, and attempts to improve the activity against this organism by structural modifications have to date involved chemistries too complex for continued development. This report describes novel chemistry for the modification of AbA. The key step involves functionalization of the phenylalanine residues in the compound by iridium-catalyzed borylation. This is followed by displacement of the pinacol boron moiety to form the corresponding bromide or iodide and substitution by Suzuki biaryl coupling. The approach allows for synthesis of a truly wide range of derivatives and has produced compounds with A. fumigatus minimal inhibitory concentrations (MIC) of
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::109c99d7dc3dd0adb0c1509736e1d9f4 https://doi.org/10.1021/acsmedchemlett.5b00029 Zobrazit plný text záznamu