Chlorinated Guaiane-Type Sesquiterpene Lactones of Natural Origin

Abstract

Organohalogen natural products play a crucial role in drug research, with halogenation generally enhancing the bioactivity of natural compounds. Chlorinated natural compounds, a major category of organohalogens, are found in both marine and terrestrial environments. Among these, terpenoids are abundant compounds with diverse structures. Guaiane-type sesquiterpene lactones, with a [5,7,5] tricyclic skeleton, are one such class. Since the first examples in 1968, 102 natural chlorinated guaiane-type sesquiterpene lactones has been isolated from Asteraceae family plants. These compounds exhibit significant structural diversity, with chlorine located at various positions, including C-1, C-2, C-3, C-4, C-5 in the cyclopentyl, and C-13, C-14, C-15, and C-18 at the C-8 substituent. Determining the structure of these compounds, especially regarding chlorine position and stereochemistry, is challenging, with some structures revised using chemical computational techniques. Although few studies have examined their bioactivity, these compounds exhibit various bioactivities, including cytotoxic, anti-inflammatory, melanogenesis and tyrosinase stimulation, antimicrobial, antiviral, neuroprotective, inhibition effects on butyrylcholinesterase and acetylcholinesterase, and hematopoietic stem cell expansion activities. This review summarizes the natural origin, structural and NMR characteristics, and bioactivities of these rare compounds, offering an overview of their current research status, future pharmaceutical potential, and highlighting existing gaps and further directions.