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

Abstract

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.

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

“…This is another case of biomimetic synthesis being used as an effective tool for the study of biosynthesis. [29] Revision of the Structures of Trichoderone B, Flavichalasine C, Spicochalasin A, and Aspergilluchalasin Since the proposed structures of trichoderone B( 4)a nd flavichalasine C( 9)were not the real ones,wenext turned to seek the correct structures (Scheme 5). [30] Simple comparison of the chemical shifts between natural and synthetic samples was fruitless (Figures S5 and S6 in Supporting Information).…”

Synthetic Approaches to the New Drugs Approved During 2022

“…Although several routes to 14 are known, no kilo-scale synthesis has been reported to date. − The most likely process route was disclosed by Dermavant Sciences GMbH, in which 305 g of 14 were prepared utilizing a chromatography free synthesis (Scheme ). The synthesis of 14 began with the aldol condensation of cinnamaldehyde ( 14.1 ) and ketone 14.2 to produce the α,β,γ,δ-unsaturated ketone 14.3 , which was used without further purification.…”