Synthetic studies toward penitrem E: enantiocontrolled construction of B–E rings

Abstract

Enantiocontrolled construction of B-E rings of penitrem E was accomplished from 4-iodoindole in 13 steps with an overall yield of 1.7%. Diastereoselective Tf2NH-catalyzed (2+2)-cycloaddition between silyl enol ether and methyl acrylate furnished a tetracyclic product possessing the characteristic cyclobutane ring bearing a hydroxyl group.

Recent advances in the total synthesis of cyclobutane-containing natural products

“…56 This effective method has been successfully applied to the synthetic studies toward penitrems, a family of indole diterpene alkaloids isolated from Penicillium cyclopium and Penicillium crustosum with strong neurotoxicity. 57 Most recently, the same group reported the first total synthesis of cytotoxic paesslerin A (146) through a Tf 2 NH-catalyzed multicomponent reaction between cyclopentenone 140, 2-siloxy-butadiene 141 and methyl acrylate 144 (Scheme 21). 58 This catalytic three-component reaction consists of a [4 + 2] cycloaddition, an alkene isomerization and an ionic stepwise [2 + 2] cycloaddition.…”

Triflimide (HNTf2) in Organic Synthesis

“…In 2015, the Tokuyama group employed this highly useful reaction as a key step in the construction of the B−E ring core of the natural product penitrem E (Scheme 4). 42 While the above cycloaddition reaction proceeds efficiently under cryogenic conditions, it was found that the same reaction could not give the desired product at room temperature due to significant decomposition of substrates and products via side reactions, including substrate oligomerization and retro-aldoltype ring-opening of the cycloadduct. Nevertheless, the same group introduced a flow microreactor system and successfully rendered this process to proceed with significantly enhanced efficiency at room temperature, thereby allowing potential applications in a more sustainable manner.…”

Triflimide

“…28 They also utilized one of these reactions in natural product synthesis. 29 Furthermore, the same group demonstrated that flow microreactor system could be used to enhance the efficiency of these reactions. 30 In 2008, Hsung and coworkers reported that triflimide is an excellent promoter of the intramolecular Gassman [2+2] cycloaddition.…”