140715-85-1

Basic information

• Product Name: fumiquinazoline A
• Synonyms: fumiquinazoline A
• CAS NO: 140715-85-1
• Molecular Formula: C24H23N5O4
• Mol File: 140715-85-1.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: fumiquinazoline A(CAS DataBase Reference)
• NIST Chemistry Reference: fumiquinazoline A(140715-85-1)
• EPA Substance Registry System: fumiquinazoline A(140715-85-1)

Safety Data

• Hazardous Substances Data: 140715-85-1(Hazardous Substances Data)

Upstream product

• 56-41-7 L-alanin 
• 169626-35-1 (1S,4R)-4-[(1H-indol-3-yl)methyl]-1-methyl-1,2-dihydro-4H-pyrazino[2,1-b]quinazoline-3,6-dione 
• 118-92-3 anthranilic acid 
• 496961-79-6 C₂₆H₂₄Cl₃N₃O₈ 
• 496961-80-9 C₂₆H₂₄Cl₃N₃O₈ 
• 422319-37-7 methyl (2S,9S,9aR,αR)-9-hydroxy-α-[[(2,2,2-trichloroethoxy)carbonyl]amino]-2-methyl-3-oxo-1-[(phenylmethoxy)carbonyl]-2,3,9,9a-tetrahydro-1H-imidazo(1,2-a)indole-9-propanoate 
• 316828-49-6 C₄₇H₄₁N₅O₉ 
• 316828-51-0 C₄₇H₃₉N₅O₈ 
• 316828-44-1 methyl (αR,2S,9S)-2,3,9,9a-tetrahydro-9-hydroxy-9a-methoxy-2-methyl-3-oxo-1-[(phenylmethoxy)carbonyl]-α-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1H-imidazo(1,2-a)indole-9-propanoate 
• 316828-35-0 N_in-L-benzyloxycarbonylalanyl-N_a-2,2,2-trichloroethoxycarbonyl-2-iodo-D-tryptophan methyl ester 
• 316828-48-5 C₂₉H₂₆N₄O₆ 
• 316828-46-3 C₂₅H₂₂Cl₃N₃O₇ 
• 316828-33-8 methyl (αR,2S)-2,3-dihydro-2-methyl-3-oxo-1-[(phenylmethoxy)carbonyl]-α-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1H-imidazo(1,2-a)indole-9-propanoate 
• 316828-31-6 N_in-L-benzyloxycarbonylalanyl-N_a-2,2,2-trichloroethoxycarbonyl-D-tryptophan methyl ester 

Relevant articles and documents

Fumiquinazolines, novel metabolites of a fungus isolated from a saltfish

Fumiquinazolines A, B and C, exhibiting moderate cytotoxicity, were isolated from the mycelium of a strain of Aspergillus fumigatus which existed in the gastrointestinal tract of the saltwater fish Pseudolabrus japonicus. Their structures were elucidated by spectroscopic and X-ray diffraction analyses and chemical evidence.

Enzymatic processing of fumiquinazoline F: A tandem oxidative-acylation strategy for the generation of multicyclic scaffolds in fungal indole alkaloid biosynthesis

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.

Complexity generation in fungal peptidyl alkaloid biosynthesis: Oxidation of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the flavoenzyme Af12070 from aspergillus fumigatus

The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ) peptidyl alkaloids of increasing scaffold complexity using l-Trp, 2 equiv of l-Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ gene cluster encodes two non-ribosomal peptide synthetases (NRPS) and two flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an oxidative annulation sequence to couple alanine to the indole side chain of FQF to yield the imidazolindolone-containing FQA. In this study we show that the fourth enzyme, the monocovalent flavoprotein Af12070, introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring (and therefore acting in an unprecedented manner as an FAD-dependent amide oxidase). FQC subsequently converts nonenzymatically to the known cyclic aminal FQD. We also investigated the effect of substrate structure on Af12070 activity and subsequent cyclization with a variety of FQA analogues, including an FQA diastereomer (2′-epi-FQA), which is an intermediate in the fungal biosynthesis of the tremorgenic tryptoquialanine. 2′-epi-FQA is processed by Af12070 to epi-FQD, not epi-FQC, illustrating that the delicate balance in product cyclization regiochemistry can be perturbed by a remote stereochemical center.

Total synthesis of (-)-fumiquinazolines A, B, C, E, H, and I. Approaches to the synthesis of fiscalin A

The first syntheses of (-)-fumiquinazolines A, B, and I, which proceed in 14 steps from protected tryptophan, anthranilic acid, leucine, and alanine in 7% overall yield, are described. Tricycle 30 was formed by a palladium-catalyzed cyclization. Oxidation of 30a with saccharine-derived oxaziridine 21 for fumiquinazolines A and B and oxidation of 30b with dimethyldioxirane for fumiquinazoline I selectively formed the appropriate imidazoindolone stereoisomers. Application of the Ganesan-Mazurkiewicz cyclization completed the syntheses. Efficient 14-step syntheses of (-)-fumiquinazolines C (7) and E (3) and a 15-step synthesis of (-)-fumiquinazoline H (8) using FmocNHCH(CH2SePh)CO2H as a dehydroalanine precursor that spontaneously eliminated benzeneselenol without oxidation under the cyclization conditions are also reported. Model 86 for fiscalins A with the H and OH anti to each other has been prepared, but the procedure that worked for the model failed with the fully functionalized side chain.

Total syntheses of (-)-fumiquinazolines A, B, and I.

[structure] The first total syntheses of (-)-fumiquinazolines A, B, and I have been accomplished efficiently using the Pd-catalyzed cyclization of an iodoindole carbamate to construct the imidazoindolone moiety and the dehydrative cyclization of a diamide

Fumiquinazolines A-G, novel metabolites of a fungus separated from a Pseudolabrus marine fish

Seven new fumiquinazolines (FQs) A-G have been isolated from a strain of Aspergillus fumigatus originally separated from the marine fish Pseudolabrus japonicus, and their stereostructures and conformations have been established on the basis of spectral and X-ray analyses and some chemical transformations.All the compounds exhibited moderate cytotoxicity against cultured P388 cells.