Reflections on the intriguing occurrence of some recently isolated natural products as racemates and scalemic mixtures

Abstract

This review continues our interest in the intriguing reports of a variety of new racemic natural products (at least 11 in the past 4 years). These include the polyphenolic racemate galewone, the polycyclic prenylated acylphloroglucinol garcinielliptone; variecolortide, a combination of an anthraquinone and a isochinulin‐type alkaloid; the isoindoline alkaloid irpexine, the new hybrid phenylproanoid asarone; colletopyandione an indolydenepyradione; the enantiomerically enriched (scalemic) neolignans, gardenifolins; and meroterpenoid pabmaragramin in addition to some marine lipids. We also present a recent biomimetic synthesis of the polyketide preuisolactone A; synthesis of the polyketide spiromamakone A, which also corrected the proposed structure of another metabolite as identical to spiromamakone A; and the melicolones A and B. The continuing reports of natural racemates provoke speculation as to their role in the producing organism.

Truncatenolide, a Bioactive Disubstituted Nonenolide Produced by Colletotrichum truncatum, the Causal Agent of Anthracnose of Soybean in Argentina: Fungal Antagonism and SAR Studies

“…Thus, it was apparently isolated as a racemic mixture. We 64,65 and others 66,67 have previously isolated several racemic natural Truncatenone, to the best of our knowledge, is the first naturally occurring oct-2-en-4-one. Some cyclic compounds containing a similar moiety were found as synthetic and natural compounds.…”

“…Thus, it was apparently isolated as a racemic mixture. We , and others , have previously isolated several racemic natural products, possibly originating from nonenzymatic pathways. Therefore, the final structure of truncatenone has to be indicated as rel -(5 S ,6 S )-6-hydroxy-3,5-dimetyloct-2-en-4-one ( 2 ).…”

Scalemic natural products

“…The occurrence of racemic natural products has been the subject of several recent reviews, [10][11][12][13][14][15] one comprehensively covering the years 2012-2019. 15 Conversely, the grey area of natural products' optical "impurity" (scalemicity) has so far been largely overlooked, and the inventory of scalemic natural products is probably underestimated for various reasons.…”

Chiral NMR analysis reveals the environmental dependence of areolal scalemization in Piptothrix areolare

“…Such a variation can be related with DNA, as well as the volatility of compounds 6 . Recently, several interesting cases of new natural products that have been found as racemic or scalemic mixtures have been examined 7 and selected studies on biomimetic syntheses of racemic metabolites have been reviewed, 8 providing support for their proposed nonenzymatic spontaneous biosynthesis. In addition, scalemization has been associated to degradation phenomena by the microbiome, 9,10 while environmental factors have not been taken into consideration to explain scalemization in wild plant metabolites.…”