Alternariol: evidence for biosynthesis via norlichexanthone

Abstract

. Can. J. Chem. 64, 1590 (1986). Alternaria molds produce numerous mycotoxins including many a-dibenzopyrones such as alternariol (AOH) and related polyketides. AOH, presumed to be the initial a-dibenzopyrone produced, has for 20 years been considered to be biosynthesized from a single polyketide chain in a single step reaction. The present study presents evidence that the reaction may proceed through an intermediate, norlichexanthone (NLX). Bond cleavage and rearrangement of NLX to form AOH may be similar to aflatoxin B1 formation from sterigmatocystin. The 2-D INADEQUATE experiment was used to assign the I3c spectrum of AOH and to distinguish between possible mechanisms by which AOH may be synthesized from 1-13C and 2-I3C acetates via NLX.E. E. STINSON, W. B. WISE, R. A. MOREAU, A. J. JUREWCZ et P. E. PFEFFER. Can. J. Chem. 64, 1590 (1986). Les moisissures Alternaria produisent diverses mycotoxines, y compris plusieurs a-dibenzopyrones, comme l'alternariol (AOH) et des polycktides apparent&. I1 est supposC que le AOH est l'a-dibanzopyrone qui est produite initialement et, depuis plus de 20 ans, on a considkrk que ce composC est produit par une biosynthkse impliquant une seule chaine polycCtide rtagissant au cours d'une seule rkaction. Dans le present travail, on prksente des donnkes suggCrant que le rkaction procMe peut-Stre par le biais d'un intermkdiaire, la norlichexanthone (NLX). I1 est possible que le bris de la liaison et la transposition de la NLX pour former le AOH se produisent d'une faqon semblable h ce qui se produit lors de la formation de l'aflotoxine B1 B partir de la stkrigmatocystine. On a fait appel B des expkriences de 2-D INADEQUATE pour attribuer le spectre rmn du 13C du AOH et pour distinguer entre les mkcanismes possibles pour la synthkse du AOH B partir d'acktates marquCs au 13c dans les positions 1 et 2 et par le biais de la NLX.[Traduit par la revue]The Alternaria, a group of molds frequently involved in food

Natural Dibenzo-α-Pyrones and Their Bioactivities

“…We know very little about the biosynthesis of dibenzo-α-pyrones in living organisms, including their genetics, biochemistry and biosynthetic pathways [2,25,65,66]. In plants, gallic acid (54), which is biosynthesized via the shikimate pathway [67], was considered as the precursor of ellagitannins [68].…”

“…Alternariol (10) was first thought to be biosynthesized via norlichexanthone [65], which was ruled out later, and it was proven that alternariol (10) could be biosynthesized by simple cyclization and aromatization of a polyketide precursor [69]. After administration of [1][2][3][4][5][6][7][8][9][10][11][12][13] C]acetate and [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]acetate to cultured lichen mycobionts of Graphis spp., acetate units were incorporated into the 6H-dibenzo[b,d]pyran-6-one derivatives including alternariol (10), AME (11) and graphislactones A-F (18-23) [3].…”

Classic fungal natural products in the genomic age: the molecular legacy of Harold Raistrick

“…The origin of the aromatic methyl and the methoxy group was conrmed by feeding [ 14 C]-methionine. 130 Further labelling studies with [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]-acetate conrmed equal integration of acetate into the aromatic nucleus and side chain, which was consistent with polyketide biosynthesis, but also a possible terpene origin. Feeding of [2][3][4][5][6][7][8][9][10][11][12][13][14] C]-mevalonic acid resulted in labelled 10, and label was located in the side-chain by degradation to levulinic acid 116.…”

Induced biosyntheses of a novel butyrophenone and two aromatic polyketides in the plant pathogen Stagonospora nodorum

“…As a result, the production of two new products (1 and 3) was induced, and the intensity of one peak for compound 2 was enhanced ( Figure 1 (1H, m)). Analyses of its 13 C NMR, HSQC and 1 H-1 H COSY data further revealed the presence of a 1,4-disubstituted aromatic ring (δ C 128.0 (s, C-1'), 132.7 (d, C-2', and 6'), 114.9 (d, C-3', and 5'), 163.3 (s, C-4')), one methoxy carbon (δ C 52.9 (q, C-7')), and a 2-methylbutan-1-one moiety (δ C 191.5 (s, C-1), 36.5 (d, C-2), 27.8 (t, C-3) 11.0 (q, C-4), 17.4 (q, C-5)). Further detailed interpretation of the HMBC correlations from H-2' and H-6' to C-1, and from H-7' to C-4', allowed us to assign the methoxy group and the 2-methylbutan-1-one moiety to C-4' and C-1', respectively.…”

“…Thus, its NMR data were identical to those of alternariol, a known mycotoxin metabolite from the mold Alternaria tenuis. 13 Compound 3 was obtained as a white solid. Its molecular formula was established as C 11 3.77 (3H, s, H-10)).…”