Guillermo Martínez Massanet

The synthetic feasibility of the oxidative cleavage: epoxidation of 7‐O‐geranylscopoletin followed by electrocyclic ring‐opening, proposed in the biogenesis of transtaganolides/basiliolides is studied. Unlike the proposed pericyclic reactions, this pathway has not yet been addressed. Three synthetic strategies have been tested consisting of: i) Baeyer–Villiger oxidation of p‐quinoids, ii) hydrolysis of quinone monoketals, or iii) direct fragmentation by using oxygen donors. Oxidation of the benzene ring of hydroxylated coumarins has been achieved using peroxyacids, but cleavage took place between undesired positions. The aromaticity conservation of the pyran‐2‐one cycle during oxidation is the controlling factor of these observed regioselectivities. The use of a 4,5‐dihydroxy‐2‐methoxycinnamate model, in which the pyran‐2‐one ring does not exert influence on oxidation, has allowed the design of a synthetic sequence toward an analogue of the natural pyran‐2‐one isolated from Thapsia transtagana, key in the biogenesis. Mechanistic proposals for the obtained results as well as their biogenetic implications are raised.

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 as a biomimetic route to this type of sesquiterpene lactones. The use of acetone as 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.

A methodology to build (E)-β-alkoxy- and (E)-β-aryloxyacrylate moieties from acetate and formate esters promoted by the TiCl₄/Et₃N system is presented. The reaction is compatible with a broad range of structural skeletons and elapses through an unusual condensation pathway. Taking into account the obtained results, we propose a plausible mechanism involving a bimetallic titanium intermediate for this type of transformation.

The regio‐ and stereoselective hydroxylation of α,β‐ or α,β,γ,δ‐ unsaturated ketones with air in the presence of KOtBu is investigated.

A strategy for the allylic oxidation of cyclic alkenes with a copper–aluminum mixed oxide as catalyst is presented. The reaction involves the treatment of an alkene with a carboxylic acid employing tert-butyl hydroperoxide as the oxidant. In all cases, the corresponding allylic esters are obtained. When l-proline is employed, the allylic alcohol or ketone is obtained. The oxidation of cyclohexene and valencene has been optimized by design of experiments (DoE) statistical methodology.

A review of our latest developments in the synthesis of sesquiterpenolides isolated from plants of the Umbelliferae family is presented.

A phenylpropanoid 1, a slovenolide 2, and two germacranes bearing a methylthiopropenoate moiety, 3 and 4, along with twenty known metabolites have been isolated from the roots of Thapsia villosa var. villosa L. The structures of two known phenylpropanoids 5 and 6 have been corrected. Compounds 7 and 8 showed activity as potential inhibitors of the sarco- and endoplasmic Ca²⁺-dependent ATPases (SERCA) pump. Compounds 9, 10 and 11 increased significantly the cytoplasmic free calcium concentration ([Ca²⁺]_c) in human platelets in a concentration-dependent manner.