Multicomponent Cyclization Reactions: A General Approach To Dibenzocyclooctadiene Lignan Natural Product

<p>Aiming at finding a general and broadly applicable route to dibenzocyclooctadiene(DBCOD) lignans, an important class of natural products with wide-ranging biologicalactivities, 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.</p><p>2,2’-Dipropargyl biphenyls are suitable precursors of [B-Sn] reagent mediatedcyclizations and their acetylene moieties can be installed by addition of lithium acetylides to2’-substituted biphenyl aldehydes. Most of these acetylide additions are highlystereoselective and chelating models have been proposed to rationalize their stereochemicalresults. The viability of the [B-Sn]-mediated cyclizations of these dipropargyl biphenylsdepends on the chirality of the biphenyl scaffolding and the configuration of the propargyliccenter. Models based on steric arguments can be used to rationalize the stereochemicaloutcomes in successful cyclizations, and the reluctance in others to undergo the cyclization.</p><p>A racemic synthesis of steganone was achieved from a 1,2-bisalkylidenecyclooctadieneprepared via the [B-Sn]-mediated cyclization. A novel AD-mix mediated tandem processquickly led to the formation of the key lactone, which was converted to steganone after threesteps.</p><p>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 anintermediate prepared by the [B-Sn]-mediated cyclization. The unique conformations ofDBCOD intermediates are crucial for different reactivities of certain functional groups (e.g.,C-C double bonds, hydroxyl and carbonyl groups), which can explain the stereochemicaloutcome of related transformations, for example, the hydrogenation reactions, Mitsunobureactions, electrophilic additions to C-C double bonds and nucleophilic additions to carbonylgroups. The conformations of DBCODs containing C6 and/or C9 carbonyl groups are alsodiscussed based on experimental data. We provide a general approach to the syntheses ofhighly functionalized DBCOD lignan natural products (>100) and unnatural analogs withdifferent configurations and/or oxidation states at C6, C7, C8 and C9.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

The Ohio State University

Year dc:date

2012

Author dc:creator

• Gong, Wei

Contributors dc:contributor

• RajanBabu, thaliyil

• Chemistry
• dibenzocyclooctadiene (DBCOD) lignans
• Multicomponent Cyclization Reactions
• 2,2&rsquo
• -Dipropargyl biphenyls
• stereoselective acetylide additions

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1356546833

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1356546833