| Prenylated aromatic compounds are common in nature and have been found in a wide variety of sources. Included in this class are the schweinfurthins, the kampanols, and a number of related natural products. Because these materials may not be abundant in their natural sources, chemical synthesis often is necessary to supply sufficient material to explore the full power of their unique bioactivities, and new synthetic approaches often are necessary to access the more complex structures.;The schweinfurthins are one expanding family of prenylated stilbenes that have both intriguing biological activity and very limited availability. The synthesis of schweinfurthin F that was recently completed is the first example of a total synthesis of a natural schweinfurthin containing a hexahydroxanthene core. The total synthesis provided both enantiomers and was used to determine the absolute configuration of the natural product as having 2R,4a R,9aR stereochemistry. Analysis of the bioactivities of the enantiomeric pair also reinforced that the 2R,4a R,9aR-enantiomer is the natural product because its activity profile matched that of the natural schweinfurthin. The total synthesis of schweinfurthin G described here was useful in further developing the chemistry necessary to prepare complex prenylated aromatic compounds. Analogues also have been synthesized in an effort to elucidate important structure-activity-relationships and to improve upon the stability and 'drugability' of the schweinfurthins.;The kampanols were discovered by Singh and co-workers from a fungal culture of Stachybotrys kampalensis, and exhibit inhibitory activity toward the important enzyme farnesyl-protein transferase. Progress toward the total synthesis of these complex pentacyclic prenylated aromatics includes a key reaction utilizing a tandem cascade cyclization/electrophilic aromatic substitution. This novel reaction gives stereoselective formation of four new stereocenters from a non-racemic epoxide and results in three new carbon-carbon bonds.;Many other prenylated aromatics are known and the syntheses of several artostilbenes and mappain, natural products closely related to schweinfurthin C, have been achieved. Advanced intermediates for several other prenylated aromatics (other artostilbenes and grifolinone A) have been synthesized in an effort to develop new chemistry for preparation of isoprenoids with unique structural features. |
