264602-12-2Relevant academic research and scientific papers
Three-component one-pot total syntheses of glyantrypine, fumiquinazoline F, and fiscalin B promoted by microwave irradiation
Liu, Ji-Feng,Ye, Ping,Zhang, Bailin,Bi, Grace,Sargent, Katie,Yu, Libing,Yohannes, Daniel,Baldino, Carmen M.
, p. 6339 - 6345 (2005)
A microwave-promoted three-component one-pot reaction has been developed to provide access to the core pyrazino[2,1-b]quinazoline-3,6-dione (1) scaffold, which is common to several families of alkaloids with significant biological activities. By adapting this synthetic strategy through the use of selected Boc-amino acids and amino acid esters, we have accomplished highly efficient and concise total syntheses of glyantrypine (2), fumiquinazoline F (3), and fiscalin B (5), achieving overall yields of 55, 39, and 20%, respectively.
Enzymatic processing of fumiquinazoline F: A tandem oxidative-acylation strategy for the generation of multicyclic scaffolds in fungal indole alkaloid biosynthesis
Ames, Brian D.,Liu, Xinyu,Walsh, Christopher T.
experimental part, p. 8564 - 8576 (2011/11/07)
Aspergillus fumigatus Af293 is a known producer of quinazoline natural products, including the antitumor fumiquinazolines, of which the simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid, tryptophan, and alanine. FQF is the proposed biological precursor to fumiquinazoline A (FQA) in which the pendant indole side chain has been modified via oxidative coupling of an additional molecule of alanine, yielding a fused 6-5-5 imidazoindolone. We recently identified fungal anthranilate-activating nonribosomal peptide synthetase (NRPS) domains through bioinformatics approaches. One domain previously identified is part of the trimodular NRPS Af12080, which we predict is responsible for FQF formation. We now show that two adjacent A. fumigatus ORFs, a monomodular NRPS Af12050 and a flavoprotein Af12060, are necessary and sufficient to convert FQF to FQA. Af12060 oxidizes the 2′,3′-double bond of the indole side chain of FQF, and the three-domain NRPS Af12050 activates l-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier protein domain, and acylates the oxidized indole for subsequent intramolecular cyclization to create the 6-5-5 imidazolindolone of FQA. This work provides experimental validation of the fumiquinazoline biosynthetic cluster of A. fumigatus Af293 and describes an oxidative annulation biosynthetic strategy likely shared among several classes of polycyclic fungal alkaloids.
