Aiming at finding a general and broadly applicable route to dibenzocyclooctadiene (DBCOD) lignans, an important class of natural products with wide-ranging biological activities, we applied Pd-catalyzed bis-metallative cyclizations mediated by a [B-Sn] reagent, 1-trimethylstannyl-2,5-dimethyl-2,5-diazaborolidine, to access the core DBCOD systems.
2,2'-Dipropargyl biphenyls are suitable precursors of [B-Sn] reagent mediated cyclizations and their acetylene moieties can be installed by addition of lithium acetylides to 2'-substituted biphenyl aldehydes. Most of these acetylide additions are highly stereoselective and chelating models have been proposed to rationalize their stereochemical results. The viability of the [B-Sn]-mediated cyclizations of these dipropargyl biphenyls depends on the chirality of the biphenyl scaffolding and the configuration of the propargylic center. Models based on steric arguments can be used to rationalize the stereochemical outcomes in successful cyclizations, and the reluctance in others to undergo the cyclization.
A racemic synthesis of steganone was achieved from a 1,2-bisalkylidenecyclooctadiene prepared via the [B-Sn]-mediated cyclization. A novel AD-mix mediated tandem process quickly led to the formation of the key lactone, which was converted to steganone after three steps.
Eight fully substituted DBCOD lignans, including compounds such as kadsuralignan B, tiegusanin D, and schizanrin F, with a tertiary center at C7, were first synthesized using an intermediate prepared by the [B-Sn]-mediated cyclization. The unique conformations of DBCOD intermediates are crucial for different reactivities of certain functional groups (e.g., C-C double bonds, hydroxyl and carbonyl groups), which can explain the stereochemical outcome of related transformations, for example, the hydrogenation reactions, Mitsunobu reactions, electrophilic additions to C-C double bonds and nucleophilic additions to carbonyl groups. The conformations of DBCODs containing C6 and/or C9 carbonyl groups are also discussed based on experimental data. We provide a general approach to the syntheses of highly functionalized DBCOD lignan natural products (>100) and unnatural analogs with different configurations and/or oxidation states at C6, C7, C8 and C9.
|Commitee:||Badjic, Jovica, Mattson, Anita|
|School:||The Ohio State University|
|School Location:||United States -- Ohio|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Keywords:||2, Dibenzocyclooctadiene (dbcod) lignans, Dipropargyl biphenyls, Multicomponent cyclization reactions, Stereoselective acetylide additions|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be