Synthesis and Determination of Absolute Configuration of α-Pyrones Isolated from Penicillium corylophilum

Abstract

The first total synthesis of (S)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one, 4-hydroxy-3-methyl-6-((2S,4R)-2,4,11-trihydroxyundecyl)-2H-pyran-2-one, and its unnatural 2R,4R-isomer starting from commercially available 1,8-octanediol is described. The synthesis led to the revision of the proposed structural assignment of the natural product as (R)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one. The key steps include chiral auxiliary mediated asymmetric acetate aldol reaction, dianion addition, and base mediated cyclization to form an α-pyrone ring.

Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species

“…1991 (reported under the synonym P . citreovirens ), Malmstrom et al., 2000 , McMullin et al., 2014a , McMullin et al., 2014b , Yadav et al., 2014 ). Production of decarestrictins and epoxyagroclavine-I has also been reported from P .…”

Synthesis and Absolute Configuration of Natural 2‐Pyrones

“…[23] The tricarbonyl compound can be traced back to an aldehyde and an ethyl acetoacetate derivative. The core structure of the 4hydroxy-2-pyrones is accessible from a tricarbonyl precursor in a biomimetic and DBU-catalyzed cyclization reaction reported by Yadav and co-workers.…”

“…Oxidation with Dess-Martin periodinane [25] produced 11, mainly in the enol form, which underwent base-induced cyclization to 4hydroxygibepyrone A (12) upon treatment with DBU. [23] Com-pound 12 is a natural product from Aspergillus unguis. [26] Its Omethylation employing dimethyl sulfate produced nectriapyrone (2).…”

“…Although the base treatment for the ring closure diminished the ee, the absolute configurations of the natural products were unambiguously assigned as (S)-(+)-germicidin C, (R)-(-)-phomapyrone C, (R)-(-)-desoxyphomapyrone C, and (R)-(-)-prolipyrone A. [41] While the efficiency of this method in terms of the yield in the cyclization reaction is better than for Yadav's approach, [23] Fürstner's method cannot be used for the synthesis of 5-alkyl-2-pyrones as represented by gulypyrone A. Also in this case both enantiomers are available from the corresponding enantiomers of the starting material 2-methylbutanal.…”

“…Germicidin C, desoxyphomapyrone C and prolipyrone A were synthesized for the first time. [39] Yadav's method [23] used in this work has the advantage that it gives access to 4-hydroxy-2-pyrones and its 3-, 5-and 6-alkyl derivatives. Although the base treatment for the ring closure diminished the ee, the absolute configurations of the natural products were unambiguously assigned as (S)-(+)-germicidin C, (R)-(-)-phomapyrone C, (R)-(-)-desoxyphomapyrone C, and (R)-(-)-prolipyrone A.…”