ABSTRACT
The first synthesis of antifungal sesquiterpene quinol dasyscyphin E was achieved starting from trans-communic acid. The process described involves the first diastereoselective synthesis of this type of compound by cyclization of an aryl bicyclosesquiterpene. The acid was efficiently transformed into a sesquiterpene synthon, which was converted into the corresponding bromoaryl sesquiterpene. The key step of synthetic sequence was the cyclization of the latter under Heck reaction conditions, which yielded the tetracyclic skeleton of the target compound with complete diastereoselectivity. The participation of an acetate group is decisive, both for the course of the Heck reaction and for the stereoselectivity of the process.
ABSTRACT
The first enantiospecific syntheses of neopetrosiquinones A (6) and B (7), two merosesquiterpenes isolated from the deep-water sponge Neopetrosia cf. proxima, from the labdane diterpene trans-communic acid (10) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen-DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (7) and of the synthetic intermediates 8 and 9 against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound 9 (IC50 = 4.1 µM), which was twice as active as natural compound 7 (IC50 = 8.3 µM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzoquinones/pharmacology , Diterpenes/chemistry , Sesquiterpenes/chemical synthesis , Sesquiterpenes/pharmacology , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Benzoquinones/chemistry , Cell Proliferation/drug effects , Cyclic N-Oxides , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Marine Biology , Mercaptoethanol/analogs & derivatives , Molecular Structure , Porifera/chemistry , Sesquiterpenes/isolation & purification , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Synthesis of the putative structure of the marine natural 15-oxopuupehenoic acid has been achieved starting from commercial (-)-sclareol. Key steps of the synthetic sequence are the Robinson annulation of a ß-ketoester and methyl vinyl ketone and an unprecedented cyclization of the resulting α,ß-enone, which is mediated by tin(IV) chloride in the presence of N-phenylselenophthalimide. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.
Subject(s)
Biological Products/chemistry , Diterpenes/chemistry , Phthalimides/chemistry , Sesquiterpenes/chemical synthesis , Cyclization , Molecular Structure , Sesquiterpenes/chemistry , Tin Compounds/chemistryABSTRACT
A very efficient method for synthesizing spirolactones is reported. Treatment of δ,ε-unsaturated carboxylic acids with iodine and triphenylphosphine under mild conditions leads to the corresponding spiro γ-lactones in high yield and with complete stereoselectivity. Utilizing this, the first synthesis of the terpene spirolactones (-)-isoambreinolide, (+)-vitexifolin D and (+)-vitedoin B has been achieved.