Biomimetic Approaches to the Synthesis of Natural Disesquiterpenoids: An Update

Abstract

Natural disesquiterpenoids represent a small group of secondary metabolites characterized by complex molecular scaffolds and interesting pharmacological profiles. In the last decade, more than 400 new disesquiterpenoids have been discovered and fully characterized, pointing out once more the “magic touch” of nature in the design of new compounds. The perfect blend of complex and unique architectures and biological activity has made sesquiterpene dimers an attractive and challenging synthetic target, inspiring organic chemists to find new and biomimetic approaches to replicate the efficiency and the selectivity of natural processes under laboratory conditions. In this work, we present a review covering the literature from 2010 to 2020 reporting all the efforts made in the total synthesis of complex natural disesquiterpenoids.

Chemistry and bioactivity of lindenane sesquiterpenoids and their oligomers

“…To date, some mini reviews on LSs and their oligomers, [6][7][8]51,53,[55][56][57][58] as well as secondary metabolites from plants from the Chloranthaceae family 10,[14][15][16][17][59][60][61] and Lindera genus 5,12,13,62 have been published, but a complete and in-depth review is lacking. Therefore, in this review, we provide an overview of the research on 354 naturally occurring LSs since 1925, including their structure determination, distribution, biosynthetic origins, synthesis, and biological activities.…”

Design and synthesis of guaianolide‐germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma

“…Disesquiterpenoids, biogenetically assembled by two monomeric sesquiterpenoid units via different pathways, are a unique class of sesquiterpenoids with different bioactivities (Caprioglio et al, 2021).…”

“…Recently, numerous studies had focused on the development of sesquiterpene lactone natural products such as arglabin (Lone et al, 2015), thapsigargin (Isaacs et al, 2021), micheliolide (Dong et al, 2022), parthenolide (Sztiller‐Sikorska & Czyz, 2020), and artemisinin (Bhaw‐Luximon & Jhurry, 2017) and their analogs as anticancer agents. Disesquiterpenoids, biogenetically assembled by two monomeric sesquiterpenoid units via different pathways, are a unique class of sesquiterpenoids with different bioactivities (Caprioglio et al, 2021). Disesquiterpenoids usually exhibited more potent bioactivities than their parent monomers due to a great number of functional proteins act as heterodimers or homodimers and disesquiterpenoids had the potential to bind both monomeric parts of a dimeric protein (Ma et al, 2020).…”

Macrocephatriolides A and B: Two Guaianolide Trimers from Ainsliaea macrocephala as PTP1B Inhibitors and Insulin Sensitizers

“…Sesquiterpene and its oligomers are an important group of secondary metabolites, which have attracted considerable attention of both natural products and organic chemists for their fascinating structures and profound pharmacological potency. − The Ainsliaea genus of the family Compositae, distributed mainly in the Southeast Asia, is approximately composed of 70 species, of which more than 20 are used as folk medicines . From this genus, sesquiterpenes, especially guaiane-type sesquiterpene lactones, have been reported the most characteristic constitutes.…”