First Synthesis of (−)-Altenuene-D3 Suitable as Internal Standard for Isotope Dilution Mass Spectrometry

Abstract

Metabolites from Alternaria fungi exhibit a variety of biological properties such as phytotoxic, cytotoxic, or antimicrobial activity. Optimization of a literature procedure culminated in an efficient total synthesis of (−)-altenuene as well as a stable isotope-labeled derivative suitable for implementation in a LC-MS/MS method for mycotoxin analysis.

Concise Syntheses of Alternariol, Alternariol-9-monomethyl Ether and Their D3-Isotopologues

“…Regarding our experience during the synthesis of a deuterated (-)-altenuene (1) derivative, we decided to develop a new strategy avoiding the tedious synthesis and proteolytic instability of the boronic ester used previously. 23 A few decades ago, the functionalization of C-H bonds required an intermediary oxidation step until advances in transition-metal chemistry enabled the formation of C-C, C-N and C-O bonds from non-acidic hydrocarbons in a single step. 24 Previously developed C-H functionalization protocols relied on the inherent reactivity of the substrates, 25 possibly forming regioisomeric side products.…”

“…Regarding our experience during the synthesis of a deuterated (–)-altenuene ( 1 ) derivative, we decided to develop a new strategy avoiding the tedious synthesis and proteolytic instability of the boronic ester used previously. 23…”

Editorial to the Special Issue “Total Synthesis of Natural Products: A Themed Issue Dedicated to Professor Dr. Dieter Schinzer for His 65th Birthday”

“…Those produced by Alternaria fungi are frequently found in agricultural crops as well as soil, wallpapers, and textures, and have been implicated in several animal and human health ailments. The paper by Sebald et al [ 2 ] describes the synthesis of (−)-altenuene in trideuterated form to be used as an internal standard in stable isotope dilution analysis (SIDA) LC/MS-MS method for mycotoxins. The synthesis is based on an earlier reported synthesis of the natural product, and through successful optimization of the synthesis route the deuterium labeled natural product was obtained with an overall yield of 17% after nine steps from inexpensive commercially available d -(−)-quinic acid.…”