15-Hydroxygermacranolides as Sources of Structural Diversity: Synthesis of Sesquiterpene Lactones by Cyclization and Rearrangement Reactions. Experimental and DFT Study

Abstract

A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G(d,p) level] were undertaken.

Spatial and developmental synthesis of endogenous sesquiterpene lactones supports function in growth regulation of sunflower

“…The decisive step for the skeletal type is the subsequent hydroxylation through additional P450 enzymes which stereospecifically either introduce an α-hydroxyl at position C-6 through the costunolide synthase HaCOS (Frey et al 2020) or a β-hydroxyl at C-8 of the germacrene ring through the germacrene A acid 8β-hydroxylase HaG8H (Ikezawa et al 2011), respectively. The subsequent spontaneous internal esterification with the C-12 carboxyl in the first case leads to the trans-7,6-lactone costunolide, from which the guaianolide skeleton of dehydrocostuslactone can derive in further steps (Álvarez-Calero et al 2018;Liu et al 2018). In the second case, the cis-7,8-lactone inunolide is formed, which is an intermediate in the biosynthesis to the two xanthanolides 8-epixanthatin and tomentosin.…”

Enhancing structural diversity through chemical engineering of Ambrosia tenuifolia extract for novel anti-glioblastoma compounds

“…From these, the ATD extract held the greater concentration of SLs, (PsiA 21.8%, PsiB 47.3% and PsiC 19.5%, evidenced by 1 H-NMR). Based on our previous experience with the chemical modification of this extract, the dichloromethane extract was treated with p -toluenesulfonic acid in toluene (reflux conditions for 1 h) 44 . This extract (ATM) was subjected to bioguided fractionation as depicted in Fig.…”

Study of the Oxidative Cleavage Proposed in the Biogenesis of Transtaganolides/Basiliolides: Pyran‐2‐one Aromaticity‐Mediated Regioselective Control and Biogenetic Implications

“…Taking into account the above considerations, we decided to test peracetic acid with the model oxygenated coumarins, and for that, this oxidant was generated in situ by using silica sulfuric acid (SSA) as catalyst (Figure ). SSA is a nontoxic heterogeneous solid acid catalyst very used in Organic Synthesis for its easy handling and high reactivity, recently used by our research group to promote transannular cyclizations of germacranolides …”