Alternaric acid

Expedient asymmetric total syntheses of both (R)-podoblastin-S and (R)-lachnelluloic acid, representative of natural 3-acyl-5,6-dihydro-2H-pyran-2-ones, were performed. Compared with the reported total synthesis of (R)-podoblastin-S (14 steps, overall 5% yield), the present study was achieved in only five steps in an overall 40% yield and with 98% ee (HPLC analysis). In a similar strategy, the first asymmetric total synthesis of the relevant (R)-lachnelluloic acid was achieved in an overall 40% yield with 98% ee (HPLC analysis). The crucial step utilized readily accessible and reliable Soriente and Scettri's Ti(OiPr)₄/(S)-BINOL‒catalyzed asymmetric Mukaiyama aldol addition of 1,3-bis(trimethylsiloxy)diene, derived from ethyl acetoacetate with n-butanal for (R)- podoblastin-S and n-pentanal for (R)-lachnelluloic acid. With the comparison of the specific rotation values between the natural product and the synthetic specimen, the hitherto unknown absolute configuration at the C(6) position of (-)-lachnelluloic acid was unambiguously elucidated as 6R.

Alternaria causes pathogenic disease on various economically important crops having saprophytic to endophytic lifecycle. Pathogenic fungi of Alternaria species produce many primary and secondary metabolites (SMs). Alternaria species produce more than 70 mycotoxins. Several species of Alternaria produce various phytotoxins that are host-specific (HSTs) and non-host-specific (nHSTs). These toxins have various negative impacts on cell organelles including chloroplast, mitochondria, plasma membrane, nucleus, Golgi bodies, etc. Non-host-specific toxins such as tentoxin (TEN), Alternaric acid, alternariol (AOH), alternariol 9-monomethyl ether (AME), brefeldin A (dehydro-), Alternuene (ALT), Altertoxin-I, Altertoxin-II, Altertoxin-III, zinniol, tenuazonic acid (TeA), curvularin and alterotoxin (ATX) I, II, III are known toxins produced by Alternaria species. In other hand, Alternaria species produce numerous HSTs such as AK-, AF-, ACT-, AM-, AAL- and ACR-toxin, maculosin, destruxin A, B, etc. are host-specific and classified into different family groups. These mycotoxins are low molecular weight secondary metabolites with various chemical structures. All the HSTs have different mode of actions, biochemical reactions, and signaling mechanisms to causes diseases in the host plants. These HSTs have devastating effects on host plant tissues by affecting biochemical and genetic modifications. Host-specific mycotoxins such as AK-toxin, AF-toxin, and AC-toxin have the devastating effect on plants which causes DNA breakage, cytotoxic, apoptotic cell death, interrupting plant physiology by mitochondrial oxidative phosphorylation and affect membrane permeability. This article will elucidate an understanding of the disease mechanism caused by several Alternaria HSTs on host plants and also the pathways of the toxins and how they caused disease in plants.

Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein-protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp. NH-F6, a fungus isolated from deep-sea sediment samples, were analyzed systematically. Five new compounds including two new perylenequinones (1-2), one new alternaric acid (3), 2-(N-vinylacetamide)-4-hydroxymethyl-3-ene-butyrolactone (4), one new cerebroside (5), together with 19 known compounds (6-24) were isolated from the ethyl acetate extracts of this strain. Their structures were elucidated using nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses. Finally, all these compounds were evaluated for their inhibitory activity against BRD4 protein, and compound 2 exhibited a potent inhibition rate of 88.1% at a concentration of 10 µM. This research provides a new BRD4 inhibitor which may possess potential antitumoral, antiviral, or anti-inflammatory pharmaceutical values.