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.
ABSTRACT
A methodology to build (E)-ß-alkoxy- and (E)-ß-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.
ABSTRACT
A review of our latest developments in the synthesis of sesquiterpenolides isolated from plants of the Umbelliferae family is presented.
Subject(s)
Apiaceae/metabolism , Sesquiterpenes/metabolism , Stereoisomerism , Thapsigargin/metabolismABSTRACT
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 Ca(2+)-dependent ATPases (SERCA) pump. Compounds 9, 10 and 11 increased significantly the cytoplasmic free calcium concentration ([Ca(2+)](c)) in human platelets in a concentration-dependent manner.
Subject(s)
Blood Platelets/metabolism , Calcium-Transporting ATPases/antagonists & inhibitors , Calcium/blood , Enzyme Inhibitors/pharmacology , Plant Extracts/pharmacology , Thapsia/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/isolation & purification , Heterocyclic Compounds, 3-Ring/isolation & purification , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Lactones/isolation & purification , Lactones/pharmacology , Molecular Structure , Plant Extracts/chemistry , Plant Roots , Propanols/chemistry , Propanols/isolation & purification , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Sesquiterpenes, Germacrane/chemistry , Sesquiterpenes, Germacrane/isolation & purification , Sesquiterpenes, Germacrane/pharmacology , Sesquiterpenes, Guaiane/isolation & purification , Sesquiterpenes, Guaiane/pharmacology , Sulfhydryl Compounds/isolation & purification , SulfurABSTRACT
Four meroterpenoids (3a, 3b, 4 and 5), a prenylated pyran-2-one (2) along with the known compounds 7-O-geranylscopoletin (1), and thapsitranstagin (6) have been isolated from the roots of Thapsia transtagana. The presence of 1 and 2 supports the biogenetic hypothesis that transtaganolides, a group of bioactive metabolites, are meroterpenoids which come from an O-prenylated coumarin via successive pericyclic reactions.
Subject(s)
Biological Products/biosynthesis , Pyrans/isolation & purification , Terpenes/isolation & purification , Thapsia/chemistry , Magnetic Resonance Spectroscopy , Pyrans/metabolism , Spectrometry, Mass, Electrospray Ionization , Terpenes/metabolismABSTRACT
Nine new eudesmanolides (1-9), two new guaianolides (12 and 13), and a new germacrane (10), along with a previously reported guaianolide (11), have been isolated from the roots of Thapsia nitida var. meridionalis. Thapsia nitida var. nitida also afforded compound 13 along with a new guaianolide (14). The structure of 13 was confirmed by X-ray crystallographic analysis. Compounds 1, 2, and 11-14 have been tested as potential inhibitors of the sarco- and endoplasmic Ca2+-dependent ATPases (SERCA) pump. None of them showed significant activities.
Subject(s)
Plants, Medicinal/chemistry , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Sesquiterpenes/isolation & purification , Thapsia/chemistry , Crystallography, X-Ray , Molecular Conformation , Molecular Structure , Plant Roots/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , SpainABSTRACT
[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.
Subject(s)
Sesquiterpenes, Guaiane/chemical synthesis , Thapsigargin/chemical synthesis , Catalysis , Molecular Structure , Sesquiterpenes, Guaiane/chemistry , Stereoisomerism , Thapsia/chemistryABSTRACT
Five phenylpropanoids have been isolated from the roots of Thapsia transtagana. Their structures have been elucidated by spectroscopic means.
Subject(s)
Apiaceae/chemistry , Propanols/chemistry , Propanols/isolation & purification , Molecular Structure , Morocco , Plant Roots/chemistryABSTRACT
Four novel and unusual C-19 compounds from Thapsia transtagana, named transtaganolides A-D, have been isolated. Their structures were established by physical methods, including X-ray analysis of transtaganolides A and B. This is the first time that a 7-methoxy-4,5-dihydro-3H-oxepin-2-one ring has been found in a natural product. [structure: see text]