Bioinspired Synthesis of Spirochensilide A from Lanosterol.

A bioinspired synthesis of spirochensilide A from commercially available lanosterol is reported. The synthesis features a directed C-H oxidation, a Wagner-Meerwein-type double methyl migration, a Meinwald rearrangement, and a double-bond isomerization/spiroketal formation cascade. The proposed biosynthetic speculation was modified by this synthetic sequence, which also served as a platform for the synthesis of other lanostanes with migrating methyl groups.

Total Synthesis of (±)-Spiroaxillarone A via a Reversible Sulfa-Michael Addition.

A bioinspired strategy is described for the total synthesis of spiroaxillarone A, which exhibited significant antimalarial activity against resistant (IC = 2.32 μM). The key steps include an intermolecular ethanethiol Michael addition, -quinone Michael addition, and subsequent β-ethanethiol elimination.

Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans.

We accomplished the divergent total syntheses of ten pentacyclic cytochalasans (aspergillin PZ, trichodermone, trichoderones, flavipesines, and flavichalasines) from a common precursor aspochalasin D and revised the structures of trichoderone B, spicochalasin A, flavichalasine C, aspergilluchalasin based on structure network analysis of the cytochalasans biosynthetic pathways and DFT calculations. The key steps of the syntheses include transannular alkene/epoxyalkene and carbonyl-ene cyclizations to establish the C/D ring of pentacyclic aspochalasans. Our bioinspired approach to these pentacyclic cytochalasans validate the proposed biosynthetic speculation from a chemical view and provide a platform for the synthesis of more than 400 valuable cytochalasans bearing different macrocycles and amino-acid residues.

Biomimetic Total Synthesis of (±)-Carbocyclinone-534 Reveals Its Biosynthetic Pathway.

Carbocyclinone-534 is a new antibiotic produced after the metabolism of tapinarof. We identify a biomimetic total synthesis of carbocyclinone-534 in eight steps by taking advantage of an intermolecular Diels-Alder homodimerization/dehydrogenation/intramolecular Diels-Alder cycloaddition cascade. This synthetic sequence provides direct experimental evidence for revealing the biosynthetic pathway of carbocyclinone-534.

Total Synthesis of (-)-Perezoperezone through an Intermolecular [5+2] Homodimerization of Hydroxy p-Quinone.

The first copper-catalyzed intermolecular [5+2] homodimerization of hydroxy p-quinone is presented, furnishing bicyclo[3.2.1]octadienone core structures in typically good yields and excellent diastereoselectivities.

Total Synthesis of Asperchalasines A, D, E, and H.

The first total syntheses of the cytochalasan dimers asperchalasines A, D, E, and H have been accomplished. The key steps of the synthesis include a highly stereoselective intermolecular Diels-Alder reaction and a Horner-Wadsworth-Emmons macrocyclization to establish the key monomer aspochalasin B, and an intermolecular Diels-Alder reaction followed by a biomimetic oxidative heterodimerization by 5+2 cycloaddition to furnish asperchalasine A. The synthetic efforts provide insight into the biosynthetic pathway of cytochalasan dimers and enables the further study of their biological properties.