Part I: Total Synthesis of (+/-)-Pallambins C and D, and, Part II: Gold-Catalyzed Tandem Cyclization towards Substituted Bicyclo[3.2.1]Octenone Derivatives: Lead to Total Synthesis of Dhilirolides A-D.

摘要

Naturally occurring pallambins A-D isolated from the Chinese liverwort Pallavicinia ambigua are classified as modified labdane-type diterpenoids, many of which exhibit interesting biological activities. From a structural perspective, pallambins C and D are consisting of trienes and an unprecedented ladder-shaped [6-5-5-5] tetracyclic skeleton bearing seven contiguous stereogenic centers. Furthermore, the bridge of the bicyclo[3.2.1]octane segment is densely substituted with two methyl groups on the bridge-heads and a vinyl group on the carbon bridge. The skeletal novelty and potential bioactivities of pallambins C and D inspired us to explore their total synthesis. In this thesis, the first total synthesis of (+/-)-pallambins C and D is described.;In Chapter 1, a general introduction to the natural occurrence, structural features and biological potency of pallavicinin family is presented briefly. In addition, the background of pallambins C and D including isolation, structural elucidation and retrosynthetic analysis is emphasized.;In Chapter 2, detailed synthesis of (+/-)-pallambins C and D involving a linear 38 steps starting from the known (+/-)-Wieland-Miescher ketone is discussed. The synthetic approach features the following two key conversions: a) a domino process including Grob fragmentation and intramolecular aldol cyclization to build up the bicyclo[3.2.1]octanone embedded in the target molecules; b) a thiourea/palladium -catalyzed alkoxycarbonylative annulation to assemble the fused tetrahydrofuran/gamma -lactone bicyclic framework.;Chaper 3 provides a conclusion of this research work.;Chapter 4 is concerned with the experimental details.