Stereoselective synthesis of the published structure of synargentolide A and of one of its stereoisomers

A stereoselective synthesis is described of the structure published for the naturally occurring synargentolide A, an α,β-unsaturated lactone. The key steps of the synthesis were a Brown´s asymmetric allylation and a ring closing metathesis. The spectroscopic data of the synthetic product were very close to those of the natural product but did not exactly match them. An epimer of the published structure was then synthesized according to a similar strategy. Again, the data of the synthetic product did not match those reported for the natural product. It is thus likely that the actual structure of synargentolide A differs from the published one in more than mere stereochemical aspects.Marco Ventura, Juan Alberto, [email protected]

Stereoselective synthesis of a C1-C18 fragment of amphidinolides G and H

A stereoselective synthesis of a C1–C18 segment of the structure of the cytotoxic macrolides amphidinolides G and H is reported. The target compound was retrosynthetically disconnected into three fragments. In the synthetic sense, connection of the fragments was made by means of a Stille coupling and a Julia–Kocienski olefination. Precursors from the chiral pool were used as the starting materials

The Total Synthesis and Biological Properties of the Cytotoxic Macrolide FD-891 and Its Non-Natural (Z)-C12 Isomer

15 páginas, 1 figura, 1 tabla, 10 esquemas -- PAGS nros. 5060-5074A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD-891 and of its non-natural (Z)-C12 isomer is described. Three fragments of the main carbon chain were stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia–Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12–C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be clearedFinancial support has been granted (to J.A.M. and M.C.) by the Spanish Ministry of Education and Science (projects BQU2002–00468 and CTQ2005–06688-C02–01/02, including financial support by FEDER funds), and by the Consellería d′Empresa, Universitat i Ciencia de la Generalitat Valenciana (projects GV05/52, ACOMP06/006 and ACOMP06/008). J.G.-F. and J. M. thank the Spanish Ministry of Education and Science for a FPU pre-doctoral fellowship and a Ramón y Cajal contract, respectively. Partial support (to J.F.D) by the Spanish Ministry of Education and Science (project BFU2004–00358) and by CAM (BIPPED project) is also acknowledgedPeer reviewe