Unusually cyclized triterpenoids: Bioactive compounds with potential.
In an international team, IPB chemists recently completed a review of 180 new unusually cyclized triterpenoids. The review was published as the second of its kind in Natural Product Reports and covers all unusually cyclized triterpenoids described from 2009 to 2021. The article focuses on the discovery of new compounds in this substance class, as well as their synthesis and biosynthesis. The authors categorized all listed unusual cyclized triterpenoids and discussed their biological activity.
Triterpenes are natural products that are generally composed of three terpene units, i.e., a total of six isoprene units with a 30 carbon atoms in total. The major part of triterpenes is composed of tetra- or pentacyclic ring systems. Their biosynthesis consist of cascade cyclizations from linear squalene compounds. In addition to the compounds with the usual tetra- and pentacyclic skeletons, a number of triterpenoids with ring systems deviating from these have been found in recent years, which are formed by unusual cyclization reactions. With the discovery of these new compounds, scientists identified not only various triterpene synthases that function as key enzymes in biosyntheses, but also numerous new enzymes that form the precursors of the cyclic backbones.
To date, more than 30,000 triterpenes originating from various organisms are known. Triterpenes occur naturally in fruits, vegetables and medicinal plants and are therefore a regular part of the daily human diet. However, the driving force behind triterpene research is their broad spectrum of biological and pharmacological activities. Numerous triterpenes have cytotoxic, anti-epileptic, anti-diabetic, neuroprotective, antimicrobial and anti-inflammatory effects. In addition to plants and fungi, marine organisms, most notably sponges, also produce a remarkable chemical diversity of unusual cyclized triterpenoids with diverse biological activities. The intensive study of the corresponding cyclizing enzymes will be an important area of future natural products research, the authors conclude, and many fundamental questions on enzyme mechanisms remain to be addressed. In the future, these unusual triterpenoid molecules could be harnessed as new lead structures for potential biomedical applications through enzyme engineering and synthetic biology.
