Troponoid Compounds as Therapeutic Agents and as Targets and Templates for Chemical Synthesis

Abstract

The renewed interest in troponoid compounds as potential therapeutic agents and the ongoing discovery of new, naturally-occurring and biologically active members of the class has resulted in an attendant focus on developing and deploying methods for their synthesis. This review highlights some of the significant recent developments in the area of troponoid chemistry that serve to contextualize our group’s longstanding and ongoing interest in the synthesis of such compounds through the cyclopropane-mediated ring-expansion of cyclohexanoid and benzenoid compounds. The various means by which such conversions can be accomplished and their application to the synthesis of both natural and non-natural troponoids are detailed.

Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues

“…Tropones and tropolones have a rich history as nonbenzenoid aromatic compounds and are also found in a large number of biologically active natural products. There are various synthetic methods for the construction of their seven-membered ring motifs . General preparatory approaches to troponoids are briefly outlined to place total syntheses of 1 in the proper context (Scheme ).…”

“…Another impetus for launching a synthesis campaign was its scarcity from natural sources. It thus represented an attractive target for total synthesis and a useful lead for discovery of an antitumor compound, as bolstered by increasing interest in the development of troponoids as therapeutic agents . We report herein a concise synthesis of pareitropone ( 1 ) and congeners to probe the effects of oxygenation on biological activity …”

Lactam-fused tropolones: a new tunable, environmentally sensitive fluorophore class

“…14,15 However, these examples have very narrow structural diversity on the tropone core, reflecting the challenges to tropolone synthesis. 16 New strategies that provide rapid access towards more structurally diverse and tuneable fluorescent tropolones would be valuable in harnessing the dynamic environmental responsiveness of the chemotype.…”

Synthesis of dihydrotropone derivatives using an anionic 8π-electrocyclic reaction

“…4 Synthetic approaches to these compounds generally involve ring expansion of benzenes or [4+3] cycloaddition/oxidation strategies via dihydrotropones. 5,6 In this study, we investigated the utility of our 8π-electrocyclic reaction for the synthesis of dihydrotropones. As 2-oxycyclohepta-1,4-dienes 4a/b are obtained from the triene substrates 1a/b , the reaction of further unsaturated dienynes 6 would give 3-oxycyclohepta-1,3,5-trienes, namely dihydrotropones 7 (Scheme 1c).…”