Research progress on the structure and structure-activity relationship of cyclohexene ether terpenes
Cycloterpenoids are active ingredients in many traditional Chinese medicines. They are found in various dicotyledonous plants such as Scrophularia and Rehmannia, Gentiana in Gentianaceae, Gardenia and Scutellaria in Rubiaceae, and Lonicera japonica in Lonicera japonica. According to incomplete statistics, over 800 types of iridoid compounds have been isolated and structurally identified from plants, most of which are glycoside components. There are only over 60 non glycoside iridoid compounds and more than 30 split ring iridoid compounds. Cycloterpenes have dual biological activities. Firstly, they have a defensive effect on certain plant species, such as the defense response of iridoid glycosides in Rehmannia plants against Fusarium oxysporum; Secondly, it has various pharmacological effects on animals, such as neuroprotective effects, anti hepatotoxicity, hypoglycemic effects, anti-inflammatory effects, antispasmodic effects, anti-tumor effects, antiviral effects, immune regulation, and laxative effects.

Cycloterpenes are monoterpenoids in terpenoid compounds, which are aldehyde derivatives of ant odor. They have typical binary rings, ene bonds, and ether bonds. Naturally occurring cyclic terpenes are often linked to sugars to form cyclic terpenoid glycoside structures. The skeleton of cyclic terpenoid compounds can be divided into three main types: cyclic terpenoid glycosides, split cyclic terpenoid glycosides, and cyclic terpenoid ethyl esters (cyclic terpenoid esters). The diversity of cyclohexene ether terpenes is due to the basic skeleton undergoing epoxidation, hydroxylation, and esterification of aromatic acids obtained through the shikimic acid pathway. The diversity of structures leads to different biological activities of iridoid compounds in plants, and the study of the structure-activity relationship of active ingredients in traditional Chinese medicine is an important way to develop innovative drugs with independent intellectual property rights. There have been no reports on the research progress of structural modification and biological activity of derivatives of cyclohexene ether terpenes at home and abroad. This article reviews the structural modification, biological activity, structure-activity relationship, and mechanism of action of cyclohexene ether terpenes in the past thirty years by reviewing a large number of domestic and foreign literature. The aim is to predict the activity of other cyclohexene ether terpenes with unknown activity, and provide theoretical basis for the development of new cyclohexene ether terpene drugs with higher activity.

As monoterpenes, cyclohexene ether terpenes have various important pharmacological activities, complex structure-activity relationships, abundant reserves in nature, and simple extraction processes. They can be obtained through chemical synthesis. However, current research on most iridoid compounds is still limited to determining their structures and analyzing certain activities. Their low lipid solubility and short plasma half-life greatly restrict their clinical applications. By analyzing and summarizing the structure and structure-activity relationship of cyclohexene ether terpenes, we can fully explore their multi-target regulatory mechanisms, improve their bioavailability, enhance drug activity, and provide important avenues for the future development of related new drugs.