Revision of the Structure and Total Synthesis of Altenuisol

Abstract

A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds – a structure originally proposed as the structure of altertenuol – matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23 % yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided.

Spotlight on the Underdogs—An Analysis of Underrepresented Alternaria Mycotoxins Formed Depending on Varying Substrate, Time and Temperature Conditions

“…ATX-I, ATX-II and STTX-III were provided by the group of Professor Metzler at the Institute of Applied Bioscience (Karlsruher Institut für Technologie (KIT), Karlsruhe, Germany) via preparative HPLC of Alternaria isolates [58]. Crystalline ALT, iso(ALT), AA-III, and ATL were synthesized and provided by the group of Professor Podlech at the Institute of Organic Chemistry (KIT) [11,12]. Analytical reagent quality ammonium acetate, ammonium hydroxide solution (25%), LiChrosolv LC-MS hypergrade quality methanol and acetonitrile were purchased from Merck, Darmstadt, Germany.…”

“…However, the chemical structures of only a few of them have been elucidated. Alternaria toxins (ATs) differ widely in their chemical structures and therefore can be divided into five groups [9]: Dibenzo-α-pyrone derivatives: e.g., alternariol (AOH), alternariol mono methylether (AME), altenuene (ALT), isoaltenuene (isoALT) and altenuisol (ATL) whose originally proposed structure [10] has been recently revised [11];Tetramic acid derivatives: e.g., tenuazonic acid (TeA);Perylene quinone derivatives: e.g., altertoxin I, II (ATX-I, -II) and stemphyltoxin III (STTX-III);Aminopentol esters: host-specific ATs that are produced by the fungus Alternaria alternata f. sp. lycopersici and collectively known as the AAL toxins, e.g., AAL TB1 and TB2;…”

“…Dibenzo-α-pyrone derivatives: e.g., alternariol (AOH), alternariol mono methylether (AME), altenuene (ALT), isoaltenuene (isoALT) and altenuisol (ATL) whose originally proposed structure [10] has been recently revised [11];…”

Natural Dibenzo-α-Pyrones and Their Bioactivities

“…Chemical syntheses have been achieved for a few bioactive dibenzo-α-pyrones such as altenuene (1) [94], isoaltenuene (2) [94], neoaltenuene (5) [95], alternariol (10) [96], alternariol 9-methyl ether (11) [96], altertenuol (15) [97], dehydroaltenusin (17) [98], graphislactones A (18), C (20), D (21) and H (25) [99], TMC-264 (28) [90], lysilactone A (34) [5], urolithins A-C (40, 42 and 43) [100], and urolithin M-7 (48) [101]. In addition, some dibenzo-α-pyrones are the important precursors of many synthetic drugs [14][15][16][17][18].…”

Rh(iii)-catalyzed oxidative C–H bond arylation with hydroquinones: sustainable synthesis of dibenzo[b,d]pyran-6-ones and benzo[d]naphtho[1,2-b]pyran-6-ones

“…The dibenzo [b,d]pyran-6-one (benzo[c]chromen-6-one) and benzo [d]naphtho [1,2-b]pyran-6-one structural motifs consist of the core of many natural products with pharmacological 15 relevance, 1 such as fasciculiferol, 2 alternariol, 3 autumnariol, 4 autumnariniol, 4 altenuisol, 5 gilvocarcins M, E and V, 6 ravidomycin, 7 chrysomycins A, B and C, 8 and arnottin I 9 (Fig. 1).…”