Síntesis enantioselectiva de guayanos y norguayanos naturales a partir de (+)-dihidrocarvona.

Abstract

The guaianes constitute (are) a large group of natural occurring compounds with a wide spectrum of biological activities and which are presents in terrestrial as well as marine organism. 10?-Acetoxy-7?H-guaia-4,11-dien-3-one, easily obtained from (+)-dihydrocarvone, is a good intermediate for the synthesis of 1H,10H,7?H-guaianes. Radical deoxygenation of the parent alcohol afforded 1?H,10?H and 1?H,10?H diastereomers. Basic epimerization at C? of the 1?H,10?H derivative afforded the 1?H,10?H-diastereomer. The fourth diastereomer (1?H,10?H) was obtained by Li-Amine reduction of the acetoxy derivative. The spectral features of the four diasteromers have been correlated and the structure and absolute configuration of 1?H,10?H-7?H-guaia-4,11-dien-3-one isolated from Pleocarphus revolutus has been confirmed. (+)-Pechueloic acid, its methyl ester and the reported structure for (+)-aciphyllene have been obtained by chemical transformation of the corresponding enones. The structure of natural (+)-aciphyllene has been corrected to 1?H,7?H,10?H-guaia-4,11-diene obtained by deoxygenation of the 1?H,10?H guaiadienone. A new synthetic approach to (-)-clavukerin A is described. In this synthesis the tri-nor-guaiane framework is obtained by degradation of the isopropylene side chain of (+)-1?H,7?H,10?H-guaia-4,11-dien-3-one. Selective ozonolysis-Criegge rearrangement afforded 5?-hydroxy and 5?-acetoxy tri-nor-guaiane derivatives, which eliminate separately to give in good yield (-)-1?H,2?H-tri-nor-guaia-5,7-dien-9-one. Its deoxygenation at C3 afforded (-)-clavukerin A. The parent compound can be obtained from commercially available (-)-santonin or (+)-dihydrocarvone. From the discovery of the antimalarial drug artemisinin, peroxy compounds have generated a great interest due to their range of biological activities, and hence a significant work in the synthesis of these compounds has resulted. The first total synthesis of four stereoisomers of 4?-hydroxy-1?,7?-peroxy-10?H-guaia-5-ene is reported starting from the readily available (+)-dihydrocarvone. These compounds have been synthesized from dienes (-)-isoguaiene and (-)-10-epi-isoguaiene by tandem ene hydroperoxylation-[4+2] cycloaddition with O2 followed by selective reduction. The structure of the natural 4?-hydroxy-1?,7?-peroxy-10?H-guaia-5-ene isolated from Liabum floribundum has been confirmed. Compounds (-)-isoguaiene and (-)-10-epi-isoguaiene could be prepared by C-3 and C-10 deoxygenation of 10?-Acetoxy-7?H-guaia-4,11-dien-3-one. On the other hand, transformation of 10?-Acetoxy-7?H-guaia-4,11-dien-3-one into alismoxyde and 4-epi-alismoxyde has been carried out by reduction of the corresponding tosylhydrazone, treatment with LiAlH4 and selective H2O addition to the C3-C4 doble bond to afford 4-epi-alismoxyde or alismoxyde depending on the method addition.