Synthesis and Structural Revision of the Fungal Tetramic Acid Metabolite Spiroscytalin

Abstract

Spiroscytalin, a natural 3-spirotetramic acid of hitherto uncertain absolute configuration, was synthesized for the first time by a one-pot Knoevenagel-IMDA reaction of an l-phenylalanine-derived tetramic acid and (R)-2-methyl-deca-6E,8E-dienal. Its absolute configuration was assigned by the known configurations of the starting compounds and by NOESY correlations. Its identity with the natural isolate was proved by the comparison of the NMR and circular dichroism spectra and of the specific optical rotations. Its absolute configuration (3R,5S,6S,7R,11S,14R) is enantiomeric to that originally proposed by the isolating group. This natural isomer of spiroscytalin showed moderate activity against Candida albicans and good activity against an export-deficient mutant of Escherichia coli.

Spirocyclic Tetramates by Sequential Knoevenagel and [1,5]-Prototropic Shift

“…While the barbiturate nucleus is well suited to this process, − given our interest in related tetramates both for antibacterial drug discovery and for the generation of novel three-dimensional drug templates, we examined them for their suitability in the T-reaction. Access to spirocyclic tetramates has been rarely reported. − In our case, an additional level complexity is added by the chiral nature of the tetramate, as opposed to the nonchiral barbiturate, which converts the spirocenter into yet another quaternary carbon.…”

“…Access to spirocyclic tetramates has been rarely reported. [36][37][38][39] In our case, an additional level complexity is added by the chiral nature of the tetramate, as opposed to the non-chiral barbiturate, which converts the spirocentre into yet another quaternary carbon.…”

General [4 + 1] Cyclization Approach To Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides

“…Moreover, this asymmetric cyclization strategy was also applicable to other chiral substrates. For example, chiral compound 15 showed excellent asymmetric induction for the reaction and delivered the product 16 as a single diastereomer (dr >20:1), although a significant amount of O-alkylation side product 17 was concomitantly formed during the reaction.…”

Silver Nanoparticles Architectured HMP as a Recyclable Catalyst for Tetramic Acid and Propiolic Acid Synthesis through CO2 Capture at Atmospheric Pressure

“…Decalin comprises of tetramic acid frameworks and 4‐hydroxy‐2‐pyridones having good cytotoxic and antimicrobial activity were isolated from the fungus Coniochaeta cephalothecoides collected in Tibetan Plateau (Medog) . Spiroscytalin was separated from the solid‐phase cultures of the bioactive fungus Scytalidium cuboideum . For instance, discodermide retards the development of Candida fungi, and reutericyclin retards the development of Gram‐positive bacteria .…”

“…[4] Spiroscytalin was separated from the solidphase cultures of the bioactive fungus Scytalidium cuboideum. [5] For instance, discodermide retards the development of Candida fungi, [6] and reutericyclin retards the development of Grampositive bacteria. [7] Additionally, spirotetramat was employed as an agricultural agent.…”