ABSTRACT
Compared with flat aromatic scaffolds, three-dimensional aliphatic ring systems feature high structural complexity and topological diversity and, thus, have received increasing attention in drug discovery. Herein, we describe a mild and general electrochemical method for the modular synthesis of structurally distinct cyclic compounds, including monocyclic alkanes, benzo-fused ring systems, and spirocycles, from readily available alkenes and alkyl halides via a radical-polar crossover mechanism.
ABSTRACT
Wickerols A and B are diterpene natural products that have a novel fused 6-5-6-6 ring framework and exhibit potent antiviral activity against the H1N1 type A influenza virus. Herein, we report a divergent synthesis of wickerols A and B in 16 and 15 steps, respectively, from commercial sitolactone. The key reactions of the synthesis are a SmI2-mediated intramolecular ketone-allylic acetate reductive cyclization, a Claisen rearrangement, and an intramolecular alkylation/aldol reaction that rapidly assembled the compact tetracyclic core framework in a stereocontrolled manner. The work described herein allowed us to confirm the absolute configurations of wickerols A and B.
Subject(s)
Antiviral Agents/chemical synthesis , Diterpenes/chemical synthesis , Cyclization , Oxidation-Reduction , StereoisomerismABSTRACT
Furans are versatile synthons in organic chemistry. Described is a general method for transforming furans into alkynes by dual C-C double-bond cleavage. The reaction is proposed to proceed by sequential [4+2] cycloaddition between furan and singlet oxygen and a formal retro-(3+2) fragmentation of the endoperoxide intermediate. A wide array of furans, including those derived from sapogenins, are amenable to this reaction, thus providing the corresponding alkynoic acids in up to 88 % yields. The synthetic utility was demonstrated by a seven-step synthesis of the proposed structure of a pregnane natural product, aglatominâ B, from a known intermediate.
