8-epipuupehedione and chromazonarol

The diversity of drimane hydroquinones was significantly expanded by the facile construction of (+)-chromazonarol relevant natural products, isomers, and analogues for the discovery of new pharmaceutical leads. The structure-activity relationship of (+)-chromazonarol relevant (non)-natural products was delineated via the synergistic interaction of the programmable synthesis and bioactivity-guided screening. The first divergent derivatization of (+)-chromazonarol demonstrated that the phenolic hydroxyl group is one inviolable requirement for antifungal effect. Pinpoint modification of (+)-yahazunol manifested the position of hydroxyl group was crucial for both antifungal and antitumor activities. (+)-Albaconol, (+)-neoalbaconol, and two (+)-yahazunol isomers (24 and 25) proved to be the novel pharmaceutical leads. The probable macromolecular targets were estimated to deliver new information about the biological potentials resident in (+)-yahazunol relevant products. This work also featured the first synthesis of (+)-albaconol and (+)-neoalbaconol, the first biological exploration of (+)-dictyvaric acid and improved preparation of (+)-8-epi-puupehedione and a promising pelorol analogue.

Topics: Antifungal Agents; Ascomycota; Dose-Response Relationship, Drug; Fusarium; Humans; Microbial Sensitivity Tests; Molecular Structure; Rhizoctonia; Stereoisomerism; Structure-Activity Relationship; Xanthenes

A new synthetic strategy toward puupehenone-related bioactive metabolites from sclareol oxide, based on a Diels-Alder cycloaddition approach, is described. Utilizing this, marine ent-chromazonarol and the potent angiogenesis inhibitor 8-epipuupehedione have been synthesized.

Topics: Angiogenesis Inhibitors; Chemistry, Organic; Sesquiterpenes; Terpenes; Xanthenes; Xanthones

This paper describes a new artificial cyclase, optically pure 3-o-fluorobenzyloxy-2-hydroxy-2'-(p-methoxybemzyl)-1,1'-binaphthyl.SnCl4, which is effective for the enantioselective cyclization of 2-(polyprenyl)phenol derivatives to afford polycyclic terpenoids bearing a chroman skeleton such as (-)-chromazonarol, (+)-8-epi-puupehedione, a key synthetic intermediate of (+)-wiedendiol, and (-)-11'-deoxytaondiol methyl ether.

Topics: Chromans; Cyclization; Ethers; Stereoisomerism; Terpenes; Xanthenes