Synthesis and Biological Evaluation of 7‐Deoxy Analogues of the Human Rhinovirus 3C Protease Inhibitor Thysanone

Abstract

The synthesis of (±)‐7‐deoxythysanone and three analogues has been developed. The key oxa‐Pictet–Spengler reaction enabled the synthesis of the naphthopyran precursor, which could be readily converted to 7‐deoxythysanone and three related analogues. The biological activity of these compounds was also evaluated against HRV 3C protease, the results of which suggest that inhibition of the enzyme requires the presence of the 7‐oxa functionality.

A continuous-flow resonator-type microwave reactor for high-efficiency organic synthesis and Claisen rearrangement as a model reaction

“…Next, we tested the Claisen rearrangement of allyl 1naphthyl ether 1 as a model reaction using this system (Scheme 1) [63,64]. The Claisen rearrangement of an allyl aryl ether generally requires an elevated temperature for an extended reaction time [57][58][59].…”

Pd-Catalyzed Dearomative Asymmetric Allylic Alkylation of Naphthols with Alkoxyallenes

“…The racemic products used to determine the ee values were synthesized by using Pd­(PPh 3 ) 4 as the catalyst. The starting materials 1 and 2 were prepared according to the literature reported …”

Iridium-Catalysed C–H Borylation Facilitates a Total Synthesis of the HRV 3C Protease Inhibitor (±)-Thysanone

“…We have recently shown that the oxa-Pictet-Spengler reaction between homobenzylic alcohol 5 with dimethoxymethane 4 gives the naphthopyran 3 (Scheme 1). 5 With a stock of 3 to hand, we considered a C-H activation reaction to install the phenol at C7, thus providing the full oxygenation pattern present in thysanone (1). Based on our own work regarding the C-H activation chemistry of related naphthalenes, 6 we were confident that the regiochemical outcome required to complete the total synthesis of (±)-1 would be observed.…”