New Quinazolinone Alkaloids within Rare Amino Acid Residue from Coral-Associated Fungus, Aspergillus versicolor LCJ-5-4

Abstract

Cottoquinazoline D (3), a new alkaloid with a 1-aminocyclopropane-1-carboxylic acid residue rarely discovered in nature, was isolated and identified together with two new quinazolinone alkaloids, cottoquinazolines B (1) and C (2), from coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures including absolute configurations were elucidated based on spectroscopic methods, X-ray single crystal diffraction analysis, and chemical methods. A possible biogenetic pathway for them was proposed.

Oximoaspergillimide, a Fungal Derivative from a Marine Isolate of Aspergillus sp.

“…Spectroscopic and biogenetic considerations suggested that an N-hydroxyleucine derivative could form part of the molecule. 1 H, 15 N HSQC spectroscopy established that the exchangeable proton at δ H = 9.24 ppm was linked to a nitrogen atom, whereas the exchangeable proton at δ H = 9.44 ppm was not directly linked to a nitrogen atom. Moreover, the 1 H, 15 N HMBC spectrum showed a correlation between the nonprotonated nitrogen N-7 and H 2 -3.…”

“…1 H, 15 N HSQC spectroscopy established that the exchangeable proton at δ H = 9.24 ppm was linked to a nitrogen atom, whereas the exchangeable proton at δ H = 9.44 ppm was not directly linked to a nitrogen atom. Moreover, the 1 H, 15 N HMBC spectrum showed a correlation between the nonprotonated nitrogen N-7 and H 2 -3. This information, taken together with the 1 H, 13 C HMBC correlations of H 2 -3/C-1, H 2 -3/C-2, and H-4/C-2, and the chemical shift of C-2 (δ C = 152.1 ppm), provided support for the placement of the oxime at C-2 embedded within the leucine framework.…”

Complexity Generation in Fungal Peptidyl Alkaloid Biosynthesis: Oxidation of Fumiquinazoline A to the Heptacyclic Hemiaminal Fumiquinazoline C by the Flavoenzyme Af12070 from Aspergillus fumigatus

“…This fascinating piece of biosynthetic origami, though unusual, is not unique to Af12070; instead it appears to form part of a small group of fungal biosynthetic enzymes that build-up complex multicyclic scaffolds. TqaG (which bears 72% amino acid sequence similarity to Af12070) from the recently characterized tryptoquialanine pathway in Pencillium aethiopicium (8), and as yet unassigned enzymes in Aspergillus versicolor (9, 10) and an Acremonium sp. (11), appear to catalyze potentially analogous and equally intriguing transformations en route to tryptoquialanine, cottoquinazolines, and fumiquinazoline H, respectively (Figure 2).…”

Domino Reaction of Arylglyoxals with Pyrazol-5-amines: Selective Access to Pyrazolo-Fused 1,7-Naphthyridines, 1,3-Diazocanes, and Pyrroles

“…16 Therefore, the derivatives of diazocines are a significant class of synthons for biomimetic molecular recognition and supramolecular compunds. 17 Furthermore, 1,3-diazocane units commonly exist in natural products, represented by N 3 ,5′-cycloxanthosine 18 and cottoquinazolines A and D. 19 In view of their importance, we then explored the feasibility of this p -TsOH-promoted reaction for the formation of fused 1,3-diazocanes. Various functional groups in arylglyoxals 1 did not hamper the reaction process.…”