Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements

Abstract

Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A.

The biosynthesis of the anti‐microbial diterpenoid leubethanol in Leucophyllum frutescens proceeds via an all‐cis prenyl intermediate

“…While relatively few have been identified in other genera, the Eremophila genus is especially rich in these anti‐microbial compounds (Ndi et al ., 2007b; Anakok et al ., 2012; Barnes et al ., 2013; Mon et al ., 2015; Algreiby et al ., 2018; Hossain et al ., 2019) and at least three are found in the Myoporum genus (Aminimoghadamfarouj and Nematollahi, 2017). Given their promise in therapeutic applications, there has been a substantial effort to devise total chemical syntheses (Best and Wege, 1986; Lu et al ., 2013; Yu et al ., 2016; R. Kumar et al ., 2017; Tenneti et al ., 2018; Penjarla et al ., 2019) as an alternative to extraction and purification from natural sources (Figure 2).…”

Enantioselective Total Synthesis of Pseudopteroxazole and Ileabethoxazole

“…Harmata and co‐workers reported a synthetic route to 1 through benzothiazine chemistry . Based on asymmetrically conjugated addition of cyclohexeone and stereoselective Cope rearrangement, Luo and co‐workers developed a divergent and enantioselective approach to 1 and other natural products . The Williams group achieved the first total synthesis of 2 through an iron‐mediated [2+2+1] carbocyclization .…”

Recent Advancement of the Cope Rearrangement in Organic Synthesis

“…As aplicações recentes que ilustram rearranjos de Cope também foram descritos por outros pesquisadores. [93][94][95][96][97][98][99][100] Esquema 30. Proposta mecanistica para obtenção de de hapalindole e fischerindole Esquema 31.…”